A phylum-level phylogenetic classification of zygomycete fungi based on genome-scale data.

Zygomycete fungi were classified as a single phylum, Zygomycota, based on sexual reproduction by zygospores, frequent asexual reproduction by sporangia, absence of multicellular sporocarps, and production of coenocytic hyphae, all with some exceptions. Molecular phylogenies based on one or a few genes did not support the monophyly of the phylum, however, and the phylum was subsequently abandoned. Here we present phylogenetic analyses of a genome-scale data set for 46 taxa, including 25 zygomycetes and 192 proteins, and we demonstrate that zygomycetes comprise two major clades that form a paraphyletic grade. A formal phylogenetic classification is proposed herein and includes two phyla, six subphyla, four classes and 16 orders. On the basis of these results, the phyla Mucoromycota and Zoopagomycota are circumscribed. Zoopagomycota comprises Entomophtoromycotina, Kickxellomycotina and Zoopagomycotina; it constitutes the earliest diverging lineage of zygomycetes and contains species that are primarily parasites and pathogens of small animals (e.g. amoeba, insects, etc.) and other fungi, i.e. mycoparasites. Mucoromycota comprises Glomeromycotina, Mortierellomycotina, and Mucoromycotina and is sister to Dikarya. It is the more derived clade of zygomycetes and mainly consists of mycorrhizal fungi, root endophytes, and decomposers of plant material. Evolution of trophic modes, morphology, and analysis of genome-scale data are discussed.

An enigmatic fossil fungus from the 410 Ma Rhynie chert that resembles Macrochytrium (Chytridiomycota) and Blastocladiella (Blastocladiomycota).

Litter layers in the Lower Devonian (~ 410 Ma) Rhynie chert were inhabited by a wide variety of saprotrophic fungi, however, only a few of these organisms have been described formally. A new microfungus, Trewinomyces annulifer gen. et sp. nov., occurs as tufts on decaying land plant axes from the Rhynie chert. The fungus consists of an intramatrical rhizoidal system and an erect extramatrical hypha (stalk) that bears a single, terminal sporangium. One or two successive rings often are present in the stalk immediately below the sporangium base. Overall morphology of T. annulifer resembles the extant genera Macrochytrium (Chytridiomycota) and Blastocladiella (Blastocladiomycota). However, the rhizoids are septate or pseudoseptate, a feature not known in extant zoosporic fungi, and thus render the systematic affinities of T. annulifer unresolved. Trewinomyces annulifer offers a rare view of the morphology of a distinctive Early Devonian saprotrophic microfungus.

Readmissions after diagnosis of surgical site infection following knee and hip arthroplasty.

CONTEXT: Surgical site infection (SSI) after total hip and knee arthroplasty is a common postoperative complication. We sought to determine readmission rates and costs for total hip and knee arthroplasty complicated by SSI. DESIGN: The Thomson Reuters MarketScan database was searched for patients who underwent knee or hip arthroplasty in 2007. From these data, patients who received a diagnosis of SSI and were readmitted after diagnosis were identified. SETTING: A population of 31 to 45 million individuals receiving insurance coverage. Patients who underwent knee or hip arthroplasty who experienced a hospitalization for SSI in the year after surgery were analyzed. OUTCOME MEASURES: Total readmission rates and costs per readmission at 30, 60, and 90 days and 1 year after diagnosis of SSI. RESULTS: Of the 76,289 case patients with hip or knee replacement in 2007, 1,026 (1.3%) had a hospitalization for SSI within the year after surgery. Among these patients, 310 (30.2%) were subsequently rehospitalized in the year after initial hospitalization specifically due to SSI-related issues. These rehospitalizations were associated with a mean hospital stay of [Formula: see text] days and a median cost of $20,001 (interquartile range [IQR], $14,057-$30,551). A total of 517 subjects had a subsequent "all-cause" hospitalization during the year after SSI. These rehospitalizations were associated with a mean hospital stay of [Formula: see text] days and a median cost of $19,870 (IQR, $13,913-$29,728). CONCLUSIONS: Readmissions during the year after SSI diagnosis accounted for 1,072 hospital admissions and cost over $25.5 million. These readmissions are costly and might be a future target for decreased reimbursement.

Factors affecting the unmet demand for pharmacists: state-level analysis.

OBJECTIVE: To describe the relationship between state-level Aggregate Demand Index (ADI) data and market factors reflecting both supply and demand: unemployment rates, pharmacy graduates, community pharmacy prescription growth rates, and Medicare Part D. DESIGN: Cross-sectional time series analysis using state-level data. SETTING: U.S. labor market for pharmacists, from 2001 to 2010. INTERVENTION: Model ADI data for states (dependent variable) against five independent variables: previous year ADI, unemployment rates, pharmacy graduates, prescription growth rates, and Medicare Part D. MAIN OUTCOME MEASURES: Significance and predictive ability of the model, sign of the variables studied, and R2. RESULTS: In the two-way (state and time) fixed-effects model, all variables were significant and R2 was 0.79. Contributions to state-level ADIs were, in rank order, previous year ADI, unemployment rates, pharmacy graduates, and prescription growth rates. The model predicted 2010 ADI values for 44 of 51 states within ±10%. The model depicts the independent contributions of each variable for the short (∼1 year) and longer term. Although the nature of ADI data precludes quantitative predictions about the pharmacist job market, the model results show marketplace directions (up or down) and comparative impacts. CONCLUSION: The model demonstrated that unemployment rates, pharmacy graduates, prescription growth rates, and Medicare Part D contributed significantly to state-level ADIs between 2001 and 2010. The relationships uncovered should be monitored and reexamined as new data emerge in order to anticipate the directions of the pharmacist job market.

A measure of treatment response: patient and physician satisfaction with traditional NSAIDs for osteoarthritis control.

PURPOSE: The clinical response to traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) varies substantially. The objective of this study was to describe physicians' and patients' perceptions of response to tNSAIDs as measured by satisfaction with control of patients' osteoarthritis (OA). PATIENTS AND METHODS: A cross-sectional survey was undertaken in 2009 in Germany, Spain, and the UK. Linked physician and patient questionnaires collected data on OA management, degree of pain and disability, and satisfaction with OA control. RESULTS: The study included 363 treating physicians and 713 patients receiving tNSAIDs. Patient mean (standard deviation) age was 65.5 (11.0) years (range 36-94 years); 60% were women; 86% were white; and one-quarter were obese. Dissatisfaction with control of patients' OA was expressed by physicians or their patients, or both, for 51% of patients, including 208 patients (31%) with mild OA and 478 patients (60%) with moderate or severe OA. Overall, 37% of patients reported dissatisfaction and 34% had a physician who reported dissatisfaction. Patient and physician assessments were the same in 70% of cases; Cohen's κ coefficient was 0.34 (95% confidence interval 0.26-0.41), indicating fair agreement. Of those reporting dissatisfaction, most physicians (79%) and patients (64%) believed that the current control was the best that could be achieved. The most common reasons for which physicians reported dissatisfaction were inadequate response (56%), side effects (11.1%), and poor tolerance (7.8%). CONCLUSION: One-half of patients or their treating physicians were dissatisfied with the control of OA provided by tNSAID therapy; moreover, most believed it was the best control that could be achieved.

Paleomycology of the Princeton Chert II. Dark-septate fungi in the aquatic angiosperm Eorhiza arnoldii indicate a diverse assemblage of root-colonizing fungi during the Eocene.

Tissues of the extinct aquatic or emergent angiosperm, Eorhiza arnoldii incertae sedis, were extensively colonized by microfungi, and in this study we report the presence of several types of sterile mycelia. In addition to inter- and intracellular proliferation of regular septate hyphae, the tissues contain monilioid hyphae with intercalary branching. These filamentous mycelia are spatially associated with two distinct morphotypes of intracellular microsclerotia. These quiescent structures are morphologically similar to loose and cerebriform microsclerotia found within the living tissues of some plants, which have been attributed to an informal assemblage of dematiaceous ascomycetes, the dark-septate endophytes. While there are significant challenges to interpreting the ecology of fossilized fungi, these specimens provide evidence for asymptomatic endophytic colonization of the rooting structures of a 48.7 million year old aquatic angiosperm.

Paleomycology of the Princeton Chert I. Fossil hyphomycetes associated with the early Eocene aquatic angiosperm, Eorhiza arnoldii.

The Eocene (~ 48.7 Ma, Ypresian-Lutetian) Princeton Chert of British Columbia, Canada, has long been recognized as a significant paleobotanical locality, and a diverse assemblage of anatomically preserved fossil plants has been extensively documented. Co-occurring fossil fungi also have been observed, but the full scope of their diversity has yet to be comprehensively assessed. Here, we present the first of a series of investigations of fossilized fungi associated with the silicified plants of the Princeton Chert. This report focuses on saprotrophic, facultative-aquatic hyphomycetes observed in cortical aerenchyma tissue of an enigmatic angiosperm, Eorhiza arnoldii. Our use of paleontological thin sections provides the opportunity to observe and infer developmental features, making it possible to more accurately attribute two hyphomycetes that were observed in previous studies. These comprise multiseptate, holothallic, chlamydospore-like phragmoconidia most similar to extant Xylomyces giganteus and basipetal phragmospore-like chains of amerospores like those of extant Thielaviopsis basicola. We also describe a third hyphomycete that previously has not been recognized from this locality; biseptate, chlamydosporic phragmoconidia are distinguished by darkly melanized, inflated apical cells and are morphologically similar to Brachysporiella rhizoidea or Culcitalna achraspora.

Triassic leech cocoon from Antarctica contains fossil bell animal.

Our understanding of the evolution of life on Earth is limited by the imperfection of the fossil record. One reason for this imperfect record is that organisms without hard parts, such as bones, shells, and wood, have a very low potential to enter the fossil record. Occasionally, however, exceptional fossil deposits that preserve soft-bodied organisms provide a rare glimpse of the true biodiversity during past periods of Earth history. We here present an extraordinary find of a fossil ciliate that is encased inside the wall layer of a more than 200 Ma leech cocoon from Antarctica. The microfossil consists of a helically contractile stalk that attaches to a main body with a peristomial feeding apparatus and a large C-shaped macronucleus. It agrees in every aspect with the living bell animals, such as Vorticella. Vorticellids and similar peritrichs are vital constituents of aquatic ecosystems worldwide, but so far have lacked any fossil record. This discovery offers a glimpse of ancient soft-bodied protozoan biotas, and also highlights the potential of clitellate cocoons as microscopic "conservation traps" comparable to amber.

Antarctic glossopterid diversity on a local scale: the presence of multiple megasporophyll genera, Upper Permian, Mt. Achernar, Transantarctic Mountains, Antarctica.

PREMISE OF THE STUDY: The glossopterids are a group of plants that thrived during a time of global warming similar to what is happening on the Earth today as well as the transition from archaic plant groups to the ancestors of modern groups. The diversity of the glossopterid clade is based on the megasporangiate structures assigned to the group, because the vegetative and pollen-bearing structures vary little. The presence of numerous reproductive genera from a single Upper Permian locality in the central Transantarctic Mountains provides important data on local glossopterid diversity in Antarctica. METHODS: Impression/compression fossils were imaged with a Leica 5000C digital camera on a dissecting microscope or a Fujifilm FinePix S1pro digital camera. KEY RESULTS: Two megasporangiate taxa are described: Scutum leiophyllum, which represents the first confirmed record of the genus in Antarctica, and Lidgettoniopsis ramulus, a new morphology consisting of a pinnate structure with oppositely attached megasporophylls. Plumsteadia ovata specimens indicate that this genus can be larger than previously recorded and illustrate the vegetative surface with a distinct midrib. CONCLUSIONS: The presence of a laminar, multiovulate structure and a pinnate structure at the same site indicates that local-level glossopterid diversity in Antarctica is greater than previously hypothesized. The discovery of a new megasporophyll morphology in Antarctica (confirming the presence of three distinctive morphologies on the continent) shows that Antarctic glossopterid heterogeneity is on a par with other Gondwanan continents. The diversity of the Antarctic landscape reveals that high polar latitudes can sustain a diverse ecosystem during times of global warming.

Effects of targeting higher vancomycin trough levels on clinical outcomes and costs in a matched patient cohort.

STUDY OBJECTIVE: To compare clinical outcomes and costs in patients treated with the new vancomycin guidelines recommending goal serum trough concentrations of 15-20 mg/L versus patients treated with vancomycin doses targeting trough concentrations 5-20 mg/L prior to the new guidelines. DESIGN: Retrospective quasi-experimental study. SETTING: Urban level I trauma center. PATIENTS: A total of 200 patients treated with vancomycin for at least 72 hours for confirmed, complicated methicillin-resistant Staphylococcus aureus (MRSA) bacteremia during one of two study phases relative to the implementation of the vancomycin dosing guidelines targeting serum trough concentrations of 15-20 mg/L: 2005-2007 (preperiod phase) and 2008-2010 (postperiod phase). One hundred patients in each phase were matched in a 1:1 ratio according to diagnosis, any concomitant nephrotoxic agents (e.g., aminoglycosides, colistin, acyclovir), and age ± 5 years. MEASUREMENTS AND MAIN RESULTS: Patients in the preperiod had significantly lower success rates with vancomycin than those in the postperiod (45% vs 60%, p=0.034). Median length of stay (LOS) was not significantly higher in patients in the preperiod versus postperiod (15 days vs 13.5 days; p=0.28), and patients in the preperiod received a longer median duration of vancomycin versus those in the postperiod (13 days vs 8.5 days; p<0.001). No statistically significant difference was noted in total hospital costs for patients treated with vancomycin during the preperiod versus the postperiod ($32,754 vs $27,709, p=0.147). However, total drug and monitoring costs of vancomycin were significantly higher for patients in the postperiod. Initial vancomycin trough levels were significantly lower in patients in the preperiod versus postperiod (12.3 mg/L vs 15.8 mg/L, p=0.02). Patients in the preperiod had lower rates of nephrotoxicity than those in the postperiod, although this difference was not statistically significant (15% vs 18%; p=0.85). Median (interquartile range) LOS was significantly longer in patients who developed nephrotoxicity compared with patients who did not develop nephrotoxicity (17 days [11.5-36.5 days] vs 14 days [9-24 days], p=0.017). Costs associated with measurement of serum creatinine concentrations and vancomycin trough levels as well as labor were significantly higher in patients who developed nephrotoxicity. CONCLUSION: Higher vancomycin trough concentrations improved outcomes in patients with complicated MRSA bacteremia. In addition, more aggressive dosing was shown to significantly decrease overall duration of vancomycin therapy, which may affect total hospital LOS and cost. Patients who experienced nephrotoxicity had a significantly longer hospital LOS. Additional studies evaluating optimal therapy for MRSA bacteremia in a larger cohort of matched patients are warranted.

Fossil fungi with suggested affinities to the Endogonaceae from the Middle Triassic of Antarctica.

Documented fossil evidence of zygomycetous fungi is rare. A conspicuous fungal fossil, Jimwhitea circumtecta gen. et sp. nov., occurs in permineralized peat from the Middle Triassic of Antarctica. The fossil is interpreted as a mantled zygosporangium that buds from a macrogametangium subtended by a sac-like macrosuspensor. The macrogametangium is united at its tip with a microgametangium which is subtended by a micro-suspensor. This configuration is strikingly similar to the zygosporangium-gametangia complexes seen in certain modern Endogonaceae. Co-occurring with J. circumtecta are isolated propagules closely resembling the zygosporangium of J. circumtecta and a portion of a sporocarp containing zygosporangia embedded in a gleba. Several of the sporangia are borne on ovoid or elongate structures, which we interpret as gametangia. These fossils offer an exceptionally detailed view of the morphology and reproductive biology of early Mesozoic zygomycetes.

Pharmacy effect on adherence to antidiabetic medications.

BACKGROUND: There have been a number of studies relating medication adherence to patient characteristics. There is less research on influence of health care providers on patients' medication-taking behavior. OBJECTIVES: To evaluate the pharmacy-level effect on medication adherence for patients receiving antidiabetic medications. RESEARCH DESIGN: This was a hypothesis-driven retrospective study using cross-sectional design and insurance claims data. The main analytical interest was the pharmacy-level effect on proportion of days covered as the measure of medication adherence. Multilevel random and mixed-effect models were used to tease out the pharmacy-level effect on patient outcomes. SUBJECTS: The study population consisted individuals aged 18-64 years, insured under employer-sponsored private health plans. RESULTS: We estimated models with and without covariates. In both models, pharmacy cluster effect was statistically significant (P<0.001). In the model without covariates, pharmacy cluster effect accounted for 12.8% (95% confidence interval, 12.4%-13.1%) of total variance in adherence, whereas in the model with covariates pharmacies accounted for 12.1% (95% confidence interval, 11.6%-12.4%) of total variance. Covariates associated significantly with adherence were age, sex, mail order pharmacy, and prescription drug copay. CONCLUSIONS: The results suggest significant variation in medication adherence attributable to pharmacy factor, independent of other effects. The underlying reason could be varying level of influence from pharmacies' efforts to inform or influence patients to take medications in prescribed manners. More research is necessary to better understand the effect of specific pharmacy characteristics and practice styles differences.

Bridging for an isolated subtherapeutic INR: an evaluation of clinical practice patterns, outcomes, and costs from an anticoagulation clinic.

No formal recommendations support bridging patients taking warfarin for a subtherapeutic international normalized ratio (INR). This study aimed to: (1) characterize practices at one anticoagulation clinic, (2) evaluate adverse events, and (3) compare cost of bridging versus withholding bridging for subtherapeutic INR. A retrospective chart review of 320 patients having 546 isolated subtherapeutic INR episodes included patients with an INR below their therapeutic range, preceded by two INRs within or above range. Bridged episodes required more frequent follow-up visits to achieve therapeutic INR (2.5 ± 1.0 vs. 2.2 ± 0.6; P = 0.097), but fewer days until the INR returned to therapeutic range (6.8 ± 5.0 vs. 18.9 ± 16.0; P < 0.0001). The strongest predictor of bridging was the magnitude the INR fell below the therapeutic range, where those with a severely-low INR were 30-fold more likely to be bridged (P < 0.0001), and moderately-low INR episodes were 6-fold more likely to be bridged compared with mildly-low INR (P < 0.0001). Those at high thromboembolic risk were more likely to be bridged than at low-risk (OR 3.39 [1.50-7.68]; P = 0.0034). Increasing age reduced the likelihood of being bridged (OR 0.97 [0.95-0.99]; P = 0.0118). Adverse events were infrequent in both the bridged and non-bridged; thrombosis (2.0 vs. 0.7%), major bleeding (2.0 vs. 1.3%), minor bleeding (4.1 vs. 3.1%) and bruising (18.4 vs. 3.6%). Incremental cost difference of bridging was significantly greater for total cost ($967.13) and its components, direct medical ($951.32), transportation ($2.73) and productivity cost ($13.08). It is unclear if bridging for an isolated subtherapeutic INR reduces thrombosis risk, but it is associated with higher costs.

Transportation cost of anticoagulation clinic visits in an urban setting.

BACKGROUND: Patients being managed on warfarin make frequent or regular visits to anticoagulation monitoring appointments. International studies have evaluated transportation cost and associated time related to anticoagulation clinic visits. To our knowledge, no studies have evaluated the cost of transportation to such clinic visits in the United States. OBJECTIVE: To describe the methods of transportation and estimate the average total cost of transportation to and from an anticoagulation clinic in an urban setting. METHODS: We prospectively conducted a survey of patients treated at the Harper Anticoagulation Clinic located in Detroit, Michigan, during November 2010. The survey was given to patients while waiting at their regularly scheduled clinic appointments and included questions regarding mode of transportation, distance traveled in miles, parking payment, and time missed from work for clinic appointments. The mean distance traveled was translated into cost assuming 50 cents per mile based on 2010 estimates by the Internal Revenue Service. RESULTS: Sixty patients responded to the 11-item survey; response rates for individual items varied because participants were instructed to skip questions that did not pertain to them. Of the 47 participants responding to demographic questions, 70.2% were female, and 46.8% were older than 60 years. Transportation by private vehicle (80.0%), either driven by patients (41.7%) or someone else (38.3%), was the most common method reported. Use of private automobile translated into a cost of $11.19 per round trip. Other means of transportation identified include a ride from a medical transportation service (10.0%), bus (5.0%), walking (3.3%), and taxi (1.7%). The mean (SD) distance traveled to the clinic for all methods of transportation was 8.34 (7.7) miles. We estimated the average cost of round-trip transportation to be $10.78 weighted for all transportation modes. This is a direct nonmedical cost that is paid for by most patients out of pocket. However, 9 of 44 (20.5%) responded that their insurance plans provided at least some coverage for their rides to the anticoagulation clinic. Most participants stated that they did not take any time off work for clinic visits (88%) primarily because a large proportion of the study population was unemployed or retired. CONCLUSION: The round-trip cost of transportation to an anticoagulation clinic in an urban setting in the United States may translate into a substantial expense, ranging from weekly appointments ($560 annually) to once monthly appointments ($130 annually).

Potential reduction in neural tube defects associated with use of Metafolin-fortified oral contraceptives in the United States.

OBJECTIVE: The objective of the study was to estimate the potential reduction of neural tube defects (NTDs) through the use of Metafolin-fortified oral contraceptives (OCs) in the United States. STUDY DESIGN: A population-based decision analytic model was developed to estimate the benefits of increased red blood cell (RBC) folate levels through the use of Metafolin-fortified OCs on NTD risk during pregnancy. We modeled women who began the year taking Metafolin-fortified or traditional OCs. Folate levels were derived from the National Health and Nutrition Examination Survey and clinical trial data. NTD risk was estimated by applying a published risk equation to respective RBC folate levels. RESULTS: The number of predicted NTD cases declined by 23.7% to 31.4%, depending on median baseline folate levels in women taking a fortified OC compared with taking a traditional OC. CONCLUSION: Metafolin-fortified OCs have the potential to reduce the number of folate-dependent NTDs among current and recent OC users.

Morphological and functional stasis in mycorrhizal root nodules as exhibited by a Triassic conifer.

Mycorrhizal root nodules occur in the conifer families Araucariaceae, Podocarpaceae, and Sciadopityaceae. Although the fossil record of these families can be traced back into the early Mesozoic, the oldest fossil evidence of root nodules previously came from the Cretaceous. Here we report on cellularly preserved root nodules of the early conifer Notophytum from Middle Triassic permineralized peat of Antarctica. These fossil root nodules contain fungal arbuscules, hyphal coils, and vesicles in their cortex. Numerous glomoid-type spores are found in the peat matrix surrounding the nodules. This discovery indicates that mutualistic associations between conifer root nodules and arbuscular mycorrhizal fungi date back to at least the early Mesozoic, the period during which most of the modern conifer families first appeared. Notophytum root nodules predate the next known appearance of this association by 100 million years, indicating that this specialized form of mycorrhizal symbiosis has ancient origins.

Root suckering in a Triassic conifer from Antarctica: paleoecological and evolutionary implications.

PREMISE OF THE STUDY: Although root suckering and other types of sprouting are well studied in extant woody plants, little is known about the distribution of these traits at a macroevolutionary scale. Anatomically preserved fossil plants represent an excellent but understudied source of information of the distribution of sprouting behavior through time and across taxa. METHODS: A block of silicified peat collected in the Middle Triassic Fremouw Formation at the Fremouw Peak locality, Central Transantarctic Mountains, Antarctica, contains a group of anatomically preserved roots of the fossil conifer Notophytum krauselii that bear young shoots. The specimen was prepared using the standard acetate peel technique and studied in reflected and transmitted light. KEY RESULTS: Young sucker shoots bearing well-preserved leaves are produced in groups in some areas of the Notophytum roots. CONCLUSIONS: The production of root suckers in Notophytum indicates that some of the trees growing in polar forests during the Triassic could respond to environmental stresses by regenerating their vegetative structures and had the potential to reproduce vegetatively. The specimens also represent the first anatomical evidence of root suckering in any fossil seed plant, and its occurrence in an early putative podocarp supports the idea that this trait might be ancestral in at least some extant conifer families.

Antidiabetic prescribing trends and predictors of thiazolidinedione discontinuation following the 2007 rosiglitazone safety alert.

This study aimed to examine the change in antidiabetic medication prescribing trends and predictors of thiazolidinedione (TZD) discontinuation six months after the 2007 rosiglitazone safety alert. We performed a retrospective cohort analysis. Patients with two prescriptions for a TZD between 1 January and 21 May 2007, including one covering 21 May 2007, and continuous enrolment during 2006-2007 were identified from the MarketScan database. Multivariate logistic regression analysis was used to compare characteristics between patients who continued and discontinued each TZD. We identified 40,836 and 37,183 individuals with a current prescription for rosiglitazone and pioglitazone, respectively. Significantly more rosiglitazone (53.5%) compared to pioglitazone users (21.4%) discontinued initial therapy six months after the alert (p<0.001). Approximately 23% of patients who discontinued rosiglitazone were switched to pioglitazone, while <1% was switched from pioglitazone to rosiglitazone. Notably, 19.4% of patients who discontinued rosiglitazone and 36.1% of those who discontinued pioglitazone did not have evidence of any antidiabetic drug at follow-up. There was a significant decrease in metformin and an increase in sitagliptin prescribing in patients who discontinued TZDs. Age, sex, region, cardiovascular comorbidities and physician specialty predicted TZD discontinuation. These findings suggest that FDA advisories may be associated with substantial changes in medication use.