Abstract Periprosthetic joint infection (PJI) represents substantial clinical and economic burdens. This study evaluated patient and procedure characteristics and resource utilization associated with ...revision arthroplasty for PJI. The Nationwide Inpatient Sample (Q4 2005–2010) was analyzed for 235,857 revision THA (RTHA) and 301,718 revision TKA (RTKA) procedures. PJI was the most common indication for RTKA, and the third most common reason for RTHA. PJI was most commonly associated with major severity of illness (SOI) in RTHA, and with moderate SOI in RTKA. RTHA and RTKA for PJI had the longest length of stay. Costs were higher for RTHA/RTKA for PJI than for any other diagnosis except periprosthetic fracture. Epidemiologic differences exist in the rank, severity and populations for RTHA and RTKA for PJI.
BackgroundUnderstanding the causes of failure and the types of revision total hip arthroplasty performed is essential for guiding research, implant design, clinical decision-making, and health-care ...policy. The purpose of the present study was to evaluate the mechanisms of failure and the types of revision total hip arthroplasty procedures performed in the United States with use of newly implemented ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) diagnosis and procedure codes related specifically to revision total hip arthroplasty in a large, nationally representative population.MethodsThe Healthcare Cost and Utilization Project Nationwide Inpatient Sample database was used to analyze clinical, demographic, and economic data from 51,345 revision total hip arthroplasty procedures performed between October 1, 2005, and December 31, 2006. The prevalence of revision procedures was calculated for population subgroups in the United States that were stratified according to age, sex, diagnosis, census region, primary payer class, and type of hospital. The cause of failure, the average length of stay, and total charges were also determined for each type of revision arthroplasty procedure.ResultsThe most common type of revision total hip arthroplasty procedure performed was all-component revision (41.1%), and the most common causes of revision were instability/dislocation (22.5%), mechanical loosening (19.7%), and infection (14.8%). Revision total hip arthroplasty procedures were most commonly performed in large, urban, nonteaching hospitals for Medicare patients seventy-five to eighty-four years of age. The average length of hospital stay for all types of revision arthroplasties was 6.2 days, and the average total charges were $54,553. However, the average length of stay, average charges, and procedure frequencies varied considerably according to census region, hospital type, and type of revision total hip arthroplasty procedure performed.ConclusionsHip instability and mechanical loosening are the most common indications for revision total hip arthroplasty in the United States. As further experience is gained with the new diagnosis and procedure codes specifically related to revision total hip arthroplasty, this information will be valuable in directing future research, implant design, and clinical decision-making.Level of EvidencePrognostic Level II. See Instructions to Authors for a complete description of levels of evidence.
Background
Revision THA and TKA are growing and important clinical and economic challenges. Healthcare systems tend to combine revision joint replacement procedures into a single service line, and ...differences between revision THA and revision TKA remain incompletely characterized. These differences carry implications for guiding care and resource allocation. We therefore evaluated epidemiologic trends associated with revision THAs and TKAs.
Questions/purposes
We sought to determine differences in (1) the number of patients undergoing revision TKA and THA and respective demographic trends; (2) differences in the indications for and types of revision TKA and THA; (3) differences in patient severity of illness scoring between THA and TKA; and (4) differences in resource utilization (including cost and length of stay LOS) between revision THA and TKA.
Methods
The Nationwide Inpatient Sample (NIS) was used to evaluate 235,857 revision THAs and 301,718 revision TKAs between October 1, 2005 and December 31, 2010. Patient characteristics, procedure information, and resource utilization were compared across revision THAs and TKAs. A revision burden (ratio of number of revisions to total number of revision and primary surgeries) was calculated for hip and knee procedures. Severity of illness scoring and cost calculations were derived from the NIS. As our study was principally descriptive, statistical analyses generally were not performed; however, owing to the large sample size available to us through this NIS analysis, even small observed differences presented are likely to be highly statistically significant.
Results
Revision TKAs increased by 39% (revision burden, 9.1%–9.6%) and THAs increased by 23% (revision burden, 15.4%–14.6%). Revision THAs were performed more often in older patients compared with revision TKAs. Periprosthetic joint infection (25%) and mechanical loosening (19%) were the most common reasons for revision TKA compared with dislocation (22%) and mechanical loosening (20%) for revision THA. Full (all-component) revision was more common in revision THAs (43%) than in TKAs (37%). Patients who underwent revision THA generally were sicker (> 50% major severity of illness score) than patients who underwent revision TKA (65% moderate severity of illness score). Mean LOS was longer for revision THAs than for TKAs. Mean hospitalization costs were slightly higher for revision THA (USD 24,697 +/− USD 40,489 SD) than revision TKA (USD 23,130 +/− USD 36,643 SD). Periprosthetic joint infection and periprosthetic fracture were associated with the greatest LOS and costs for revision THAs and TKAs.
Conclusions
These data could prove important for healthcare systems to appropriately allocate resources to hip and knee procedures: the revision burden for THA is 52% greater than for TKA, but revision TKAs are increasing at a faster rate. Likewise, the treating clinician should understand that while both revision THAs and TKAs bear significant clinical and economic costs, patients undergoing revision THA tend to be older, sicker, and have greater costs of care.
BACKGROUND:The patient-related risk factors for periprosthetic joint infection and postoperative mortality in elderly patients undergoing total hip arthroplasty are poorly understood. The purpose of ...this study was to identify the specific patient comorbidities that are associated with an increased risk of periprosthetic joint infection and of ninety-day postoperative mortality in U.S. Medicare patients undergoing total hip arthroplasty.
METHODS:The Medicare 5% sample claims database was used to calculate the relative risk of periprosthetic joint infection and of ninety-day postoperative mortality as a function of preexisting comorbidities in 40,919 patients who underwent primary total hip arthroplasty between 1998 and 2007. The impact of twenty-nine comorbid conditions on periprosthetic joint infection and on postoperative mortality was examined with use of Cox regression, controlling for age, sex, census region, public assistance, and all other baseline comorbidities. The adjusted hazard ratios for all comorbid conditions were evaluated, and the Wald chi-square statistic was used to rank the degree of association of each condition with periprosthetic joint infection and with postoperative mortality. The Bonferroni-Holm method was used to adjust for the multiple comparisons resulting from the number of comorbid conditions analyzed.
RESULTS:Comorbid conditions associated with an increased adjusted risk of periprosthetic joint infection (in decreasing order of significance, p < 0.05 for all comparisons) were rheumatologic disease (hazard ratio HR = 1.71), obesity (HR = 1.73), coagulopathy (HR = 1.58), and preoperative anemia (HR = 1.36). Comorbid conditions associated with an increased adjusted risk of ninety-day postoperative mortality (in decreasing order of significance, p < 0.05 for all comparisons) were congestive heart failure (HR = 2.11), metastatic cancer (HR = 3.14), psychosis (HR = 1.85), renal disease (HR = 1.98), dementia (HR = 2.04), hemiplegia or paraplegia (HR = 2.62), cerebrovascular disease (HR = 1.40), and chronic pulmonary disease (HR = 1.32).
CONCLUSIONS:We identified specific patient comorbidities that were independently associated with an increased risk of periprosthetic joint infection and of ninety-day postoperative mortality in Medicare patients who had undergone total hip arthroplasty. This information is important when counseling elderly patients regarding the risks of periprosthetic joint infection and mortality following total hip arthroplasty, as well as for risk adjustment of publicly reported total hip arthroplasty outcomes.
LEVEL OF EVIDENCE:Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Understanding the cause of failure and type of revision total knee arthroplasty (TKA) procedures performed in the United States is essential in guiding research, implant design, and clinical decision ...making in TKA. We assessed the causes of failure and specific types of revision TKA procedures performed in the United States using newly implemented ICD-9-CM diagnosis and procedure codes related to revision TKA data from the Nationwide Inpatient Sample (NIS) database. Clinical, demographic, and economic data were reviewed and analyzed from 60,355 revision TKA procedures performed in the United States between October 1, 2005 and December 31, 2006. The most common causes of revision TKA were infection (25.2%) and implant loosening (16.1%), and the most common type of revision TKA procedure reported was all component revision (35.2%). Revision TKA procedures were most commonly performed in large, urban, nonteaching hospitals in Medicare patients ages 65 to 74. The average length of hospital stay (LOS) for all revision TKA procedures was 5.1 days, and the average total charges were $49,360. However, average LOS, average charges, and procedure frequencies varied considerably by census region, hospital type, and procedure performed.
Level of Evidence:
Level II, economic and decision analysis. See Guidelines for Authors for a complete description of levels of evidence.
BackgroundHard-on-hard bearings offer the potential to improve the survivorship of total hip arthroplasty implants. However, the specific indications for the use of these advanced technologies remain ...controversial. The purpose of this study was to characterize the epidemiology of bearing surface utilization in total hip arthroplasty in the United States with respect to patient, hospital, geographic, and payer characteristics.MethodsThe Nationwide Inpatient Sample database was used to analyze bearing type and demographic characteristics associated with 112,095 primary total hip arthroplasties performed in the United States between October 1, 2005, and December 31, 2006. The prevalence of each type of total hip arthroplasty bearing was calculated for population subgroups as a function of age, sex, census region, payer class, and hospital type.ResultsThe most commonly reported bearing was metal-on-polyethylene (51%) followed by metal-on-metal (35%) and ceramic-on-ceramic (14%). Metal-on-polyethylene bearings were most commonly reported in female Medicare patients who were sixty-five to seventy-four years old, while metal-on-metal and ceramic-on-ceramic bearings were most commonly reported in privately insured male patients who were less than sixty-five years old. Thirty-three percent of patients over sixty-five years old had a hard-on-hard bearing reported. There was substantial regional variation in bearing usage; the highest prevalence of metal-on-polyethylene bearings was reported in the Northeast and at nonteaching hospitals, and the highest prevalence of metal-on-metal bearings was reported in the South and at teaching hospitals.ConclusionsThe usage of total hip arthroplasty bearings varies considerably by patient characteristics, hospital type, and geographic location throughout the United States. Despite uncertain advantages in older patients, hard-on-hard bearings are commonly used in patients over the age of sixty-five years. Further study is necessary to define the appropriate indications for these advanced technologies in total hip arthroplasty.
Background
Patient, surgeon, health system, and device factors are all known to influence outcomes in THA. However, patient-related factors associated with an increased risk of early failure are ...poorly understood, particularly in elderly patients.
Questions/purposes
We identified specific demographic and clinical characteristics associated with increased risk of early revision in Medicare patients with THA.
Methods
The Medicare 5% national sample administrative database was used to calculate the relative risk of revision within 12 months following primary THA as a function of baseline medical comorbidities in 56,030 Medicare patients who underwent primary THA between 1998 and 2010. The impact of 29 comorbid conditions on risk of early revision was examined using Cox regression, controlling for age, sex, race, US Census region, socioeconomic status, and all other baseline comorbidities.
Results
Depression, rheumatologic disease, psychoses, renal disease, chronic urinary tract infection, and congestive heart failure were associated with revision THA within 12 months of the index arthroplasty (p ≤ 0.038 for all comparisons; risk factors listed in order of significance).
Conclusions
This information is important when counseling elderly patients with THA regarding the risk of early failure and for risk stratifying publicly reported outcomes in Medicare patients with THA.
Level of Evidence
Level II, prognostic study. See Instructions for Authors for a complete description of levels of evidence.
PURPOSE OF REVIEWThe environment experienced during critical windows of development can ‘programme’ long-term health and risk of metabolic diseases such as type 2 diabetes in the offspring. The ...purpose of this review is to discuss potential epigenetic mechanisms involved in the developmental programming of type 2 diabetes by early nutrition.
RECENT FINDINGSMaternal and more recently paternal nutrition have been shown to play key roles in metabolic programming of the offspring. Although the exact mechanisms are still not clear, epigenetic processes have emerged as playing a plausible role. Epigenetic dysregulation is associated with several components that contribute to type 2 diabetes risk, including altered feeding behaviour, insulin secretion and insulin action. It may also contribute to transgenerational risk transmission.
SUMMARYEpigenetic processes may represent a central underlying mechanism of developmental programming of type 2 diabetes. During embryonic and foetal development, extensive epigenetic remodelling takes place not only in somatic but also in primordial germ cells. Therefore, concerns have been raised that epigenetic dysregulation induced by a suboptimal early environment could programme altered phenotypes not only in the first generation but also in the subsequent ones. Characterizing these altered epigenetic marks has great implications for identifying individuals at an increased disease risk as well as potentially leading to novel preventive and treatment strategies.
Aims/hypothesis
Levels of the microRNA (miRNA) miR-126-3p are programmed cell-autonomously in visceral adipose tissue of adult offspring born to obese female C57BL/6J mice. The spectrum of miR-126-3p ...targets and thus the consequences of its dysregulation for adipocyte metabolism are unknown. Therefore, the aim of the current study was to identify novel targets of miR-126-3p in vitro and then establish the outcomes of their dysregulation on adipocyte metabolism in vivo using a well-established maternal obesity mouse model.
Methods
miR-126-3p overexpression in 3T3-L1 pre-adipocytes followed by pulsed stable isotope labelling by amino acids in culture (pSILAC) was performed to identify novel targets of the miRNA. Well-established bioinformatics algorithms and luciferase assays were then employed to confirm those that were direct targets of miR-126-3p. Selected knockdown experiments were performed in vitro to define the consequences of target dysregulation. Quantitative real-time PCR, immunoblotting, histology, euglycaemic–hyperinsulinaemic clamps and glucose tolerance tests were performed to determine the phenotypic and functional outcomes of maternal programmed miR-126-3p levels in offspring adipose tissue.
Results
The proteomic approach confirmed the identity of known targets of miR-126-3p (including IRS-1) and identified Lunapark, an endoplasmic reticulum (ER) protein, as a novel one. We confirmed by luciferase assay that Lunapark was a direct target of miR-126-3p. Overexpression of miR-126-3p in vitro led to a reduction in Lunapark protein levels and increased
Perk
(also known as
Eif2ak3
) mRNA levels and small interference-RNA mediated knockdown of Lunapark led to increased
Xbp1
, spliced
Xbp1
,
Chop
(also known as
Ddit3
) and
Perk
mRNA levels and an ER stress transcriptional response in 3T3-L1 pre-adipocytes. Consistent with the results found in vitro, increased miR-126-3p expression in adipose tissue from adult mouse offspring born to obese dams was accompanied by decreased Lunapark and IRS-1 protein levels and increased markers of ER stress. At the whole-body level the animals displayed glucose intolerance.
Conclusions/interpretation
Concurrently targeting IRS-1 and Lunapark, a nutritionally programmed increase in miR-126-3p causes adipose tissue insulin resistance and an ER stress response, both of which may contribute to impaired glucose tolerance. These findings provide a novel mechanism by which obesity during pregnancy leads to increased risk of type 2 diabetes in the offspring and therefore identify miR-126-3p as a potential therapeutic target.
Graphical abstract
Selenium (Se) is a micronutrient with promising breast cancer prevention and treatment potential. There is extensive preclinical evidence of Se mammary carcinogenesis inhibition. Evidence from ...epidemiological studies is, however, unclear and intervention studies are rare. Here, we examine Se chemoprotection, chemoprevention, and chemotherapy effects in breast cancer, focusing on associated cellular and molecular mechanisms. Se exerts its protective actions through multiple mechanisms that involve antioxidant activities, induction of apoptosis, and inhibition of DNA damage, cell proliferation, angiogenesis, and invasion. New aspects of Se actions in breast cancer have emerged such as the impact of genetic polymorphisms on Se metabolism and response, new functions of selenoproteins, epigenetic modulation of gene expression, and long-term influence of early-life exposure on disease risk. Opportunity exists to design interventional studies with Se for breast cancer prevention and treatment taking into consideration these key aspects.
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