Serious adverse events and 30-day hospital readmission rate following elective total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Elective total knee arthroplasty (TKA) is a common surgery which has evolved rapidly. However, there are no recent large systematic reviews of serious adverse event (SAE) rate and 30-day readmission rate (30-dRR) or an indication of whether surgical methods have improved. METHODS: To obtain a pooled estimate of SAE rate and 30-dRR following TKA, we searched Medline, Web of Science, Cochrane Library, and Google Scholar databases. Data were extracted by two authors following PRISMA guidelines. Eligibility criteria were defined prior to a comprehensive search. Studies were eligible if they were published in 2007 or later, described sequelae of TKA with patient N > 1000, and the SAE or 30-dRR rate could be calculated. SAEs included return to operating room, death or coma, venous thromboembolism (VTE), deep infection or sepsis, myocardial infarction, heart failure or cardiac arrest, stroke or cerebrovascular accident, or pneumonia. RESULTS: Of 248 references reviewed, 28 are included, involving 10,153,503 patients; this includes 9,483,387 patients with primary TKA (pTKA), and 670,116 patients with revision TKA (rTKA). For pTKA, the SAE rate was 5.7% (95% CI 4.4-7.2%, I2 = 100%), and the 30-dRR was 4.8% (95% CI 4.3-5.4%, I2 = 100%). For rTKA, the SAE rate was 8.5% (95% CI 8.3-8.7%, I2 = 77%), while the 30-dRR was 7.2% (95% CI 6.4-8.0%, I2 = 81%). Odds of 30-dRR following pTKA were about half that of rTKA (OR 0.57, 95% CI 0.53-0.62%, p < 0.001, I2 = 45%). Of patients who received pTKA, the commonest SAEs were VTE (1.22%; 95% CI 0.83-1.70%) and genitourinary complications including renal insufficiency or renal failure (1.22%; 95% CI 0.83-1.67%). There has been significant improvement in SAE rate and 30-dRR since 2010 (χ2 test < 0.001). CONCLUSIONS: TKA procedures have a relatively low complication rate, and there has been a significant improvement in SAE rate and 30-dRR over the past decade.

Delayed Healing in Metatarsal Fractures: Role of Low-Intensity Pulsed Ultrasound Treatment.

The most common fracture in primary care is metatarsal fracture, but it is controversial whether to treat this fracture conservatively or surgically. We performed a cohort study to contrast metatarsal fractures that heal normally with fractures that show delayed healing. We analyzed 5% Medicare Standard Analytic Files, selecting all metatarsal fractures in 2011 to 2013, excluding patients with multiple fractures. Delayed healing was defined as treatment >14 days postfracture with either low-intensity pulsed ultrasound or surgery. Treatment for delayed healing was identified using the Current Procedural Terminology and International Classification of Diseases, Revision 9, Clinical Modification codes. Among 9482 metatarsal fractures, 256 (2.7%) showed delayed healing. Patients with delayed healing were younger (p < .0001); more likely to receive specialist referral (p < .001); more likely to have obesity (p = .005), psychosis (p = .003), chronic lung disease (p = .012), or iron deficiency anemia (p = .016); and more likely to receive surgery before ultrasound (p < .0001). Patients more likely to be treated with surgery than ultrasound included younger patients (p < .0001), obese patients (p = .02), and patients who first see a specialist (p < .05).

Nonunion and Reoperation After Internal Fixation of Proximal Femur Fractures: A Systematic Review.

Nonunion after fixation of a proximal femur fracture is associated with increased disability, pain, and cost to both patient and health care system. Understanding the effect of fixation method and fracture pattern on healing is important to optimize healing. The authors evaluated surgical healing, nonunion rate, and reoperation rate after internal fixation of proximal femur fracture, especially since the year 2000. They performed a systematic review of all published records from PubMed, Embase, and the Cochrane Review system. The burden of proximal femoral fracture extends beyond acute disability, as it carries a high risk of long-term morbidity and mortality. Choice of fixation method for high-risk fractures is critical to reduce nonunion and reoperation rates. [Orthopedics. 2019; 42(2):e162-e171.].

Risk factors for nonunion of bone fracture in pediatric patients: An inception cohort study of 237,033 fractures.

Adult fracture nonunion risk is related to injury severity and surgical technique, yet nonunion is not fully explained by these risk factors alone; biological risk factors are also important. We test a hypothesis that risk factors associated with pediatric fracture nonunion are similar to adult nonunion risk factors.Inception cohort study in a large payer database of pediatric fracture patients (0-17 years) in the United States in calendar year 2011. Continuous enrollment in the database was required for 12 months, to allow time to capture a nonunion diagnosis. The final database collated demographic descriptors, treatment procedures as per Current Procedural Terminology (CPT) codes, comorbidities as per International Statistical Classification of Diseases and Related Health Problems (ICD-9) codes, and drug prescriptions as per National Drug Code Directory (Red Book) codes. Logistic regression was used to calculate odds ratios (ORs) for variables associated with nonunion.Among 237,033 pediatric fractures in 18 bones, the nonunion rate was 0.85%. Increased nonunion risk was associated with increasing age, male gender, high body-mass index, severe fracture (e.g., open fracture, multiple fractures), and tobacco smoking (all, P < .0001). Nonunion rate varied with fracture location; scaphoid, neck of femur, and tibia/fibula were most likely to go to nonunion. Nonunion ORs were significantly increased for risk factors including; surgical procedure, cardiovascular disease, Vitamin D deficiency, osteoarthritis, osteoporosis, and opioid prescription (all, multivariable P < .001).Nonunion is rare in pediatric patients, but nonunion risk increases with increasing age. We confirm a hypothesis that risk factors for pediatric nonunion are similar to adult nonunion risk factors. Scaphoid fractures in adolescents have nearly the same risk of nonunion as in adults. Opioids should be used cautiously in pediatric patients, as they are associated with a significant and substantial elevation of nonunion risk. LEVEL OF EVIDENCE: Prognostic study, Retrospective, Level II.

Healing, nonunion, and re-operation after internal fixation of diaphyseal and distal femoral fractures: a systematic review and meta-analysis.

PURPOSE: Nonunion is a highly morbid complication that exacerbates the pain, disability and financial burden of distal and diaphyseal femur fractures. This study examined the modern rates of healing, nonunion, and other complications requiring reoperation of different fixation methods for distal and diaphyseal femur fractures. METHODS: A systematic review and meta-analysis of all records from PubMed, Embase and the Cochrane Review system was performed. Included studies had >20 acute, non-pathologic distal or diaphyseal femur fractures treated with primary internal fixation. Excluded were studies on abnormal patient/fracture populations, external fixation, or cement/bone graft use. RESULTS: Thirty-eight studies with 2,829 femoral shaft fractures and 11 studies with 505 distal femur fractures were included. Distal fractures had a lower healing rate (86.6% vs. 93.7%) and a higher re-operation rate (13.4% vs 6.1%) than shaft fractures (p < 0.00001), primarily due to higher rates of mechanical failure (p < 0.00001). Nonunion was the most frequent complication, occurring in 4.7% of distal fractures and 2.8% of shaft fractures. There was no difference between plate and nail fixation of distal fractures in healing, nonunion, or other causes of re-operation. Shaft fractures developed nonunion in 6.6% of unreamed nails and 2.1% of reamed nails (p = 0.002). Nonunion occurred in 2.3% of antegrade nailed fractures and 1.5% of retrograde nailed fractures (p = 0.66). CONCLUSIONS: Approximately one out of every eight distal fractures and one of every 16 shaft fractures requires re-operation. The most common cause of fixation failure is nonunion. Further research is needed to improve outcomes, particularly in distal femur fractures.

Healing of fracture nonunions treated with low-intensity pulsed ultrasound (LIPUS): A systematic review and meta-analysis.

INTRODUCTION: Bone fractures fail to heal and form nonunions in roughly 5% of cases, with little expectation of spontaneous healing thereafter. We present a systematic review and meta-analysis of published papers that describe nonunions treated with low-intensity pulsed ultrasound (LIPUS). METHODS: Articles in PubMed, Ovid MEDLINE, CINAHL, AMED, EMBASE, Cochrane Library, and Scopus databases were searched, using an approach recommended by the Methodological Index for Non-Randomized Studies (MINORS), with a Level of Evidence rating by two reviewers independently. Studies are included here if they reported fractures older than 3 months, presented new data with a sample N≥12, and reported fracture outcome (Heal/Fail). RESULTS: Thirteen eligible papers reporting LIPUS treatment of 1441 nonunions were evaluated. The pooled estimate of effect size for heal rate was 82% (95% CI: 77-87%), for any anatomical site and fracture age of at least 3 months, with statistical heterogeneity detected across all primary studies (Q=41.2 (df=12), p<0.001, Tau2=0.006, I2=71). With a stricter definition of nonunion as fracture age of at least 8 months duration, the pooled estimate of effect size was 84% (95% CI: 77%-91.6%; heterogeneity present: Q=21 (df=8), p<0.001, Tau2=0.007, I2=62). Hypertrophic nonunions benefitted more than biologically inactive atrophic nonunions. An interval without surgery of <6months prior to LIPUS was associated with a more favorable result. Stratification of nonunions by anatomical site revealed no statistically significant differences between upper and lower extremity long bone nonunions. CONCLUSIONS: LIPUS treatment can be an alternative to surgery for established nonunions. Given that no spontaneous healing of established nonunions is expected, and that it is challenging to test the efficacy of LIPUS for nonunion by randomized clinical trial, findings are compelling. LIPUS may be most useful in patients for whom surgery is high risk, including elderly patients at risk of delirium, or patients with dementia, extreme hypertension, extensive soft-tissue trauma, mechanical ventilation, metabolic acidosis, multiple organ failure, or coma. With an overall average success rate for LIPUS >80% this is comparable to the success of surgical treatment of non-infected nonunions.

When Is a Fracture Not "Fresh"? Aligning Reimbursement With Patient Outcome After Treatment With Low-Intensity Pulsed Ultrasound.

OBJECTIVE: The clinical value of low-intensity pulsed ultrasound (LIPUS) for fresh fracture is known. Yet, in the absence of a definition of what "fresh" is, payers have adopted study inclusion criteria drawn from randomized clinical trials as de facto definitions of which patients should be treated, with "fresh" defined as <1 week old. Patients with fracture may thus be ineligible for LIPUS treatment after week 1, which potentially denies access to patients who could benefit from LIPUS. We seek to characterize the inflection point at which heal rate declines. DESIGN: Prospective cohort. SETTING: Food and Drug Administration-mandated nationwide postmarketing surveillance registry. PATIENTS: Observational cohort of 5983 registry enrollees. INTERVENTION: LIPUS, 20 min/d. MAIN OUTCOME MEASURE: Fracture heal rate. Logistic regression was used to model the odds ratio of nonunion from week 1 to week 12. Covariates in the model included age, gender, body mass index, open fracture, and smoking. RESULTS: We estimated the time point at which a fracture responds to LIPUS as well as during the first week after fracture. There was significant bone-to-bone variation; metatarsal was "fresh" until week 7, ankle until week 9, humerus until week 10, and femur and radius until week 12. Healing was significantly impacted by patient age, body mass index, and open fracture (all, P ≤ 0.02). CONCLUSIONS: Our results suggest that fractures of the metatarsal, femur, humerus, ankle, and radius respond to LIPUS treatment, as if they were still fresh at least 6 weeks longer than the eligibility allowed under current coverage policies. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Bone fracture nonunion rate decreases with increasing age: A prospective inception cohort study.

BACKGROUND: Fracture nonunion risk is related to severity of injury and type of treatment, yet fracture healing is not fully explained by these factors alone. We hypothesize that patient demographic factors assessable by the clinician at fracture presentation can predict nonunion. METHODS: A prospective cohort study design was used to examine ~2.5 million Medicare patients nationwide. Patients making fracture claims in the 5% Medicare Standard Analytic Files in 2011 were analyzed; continuous enrollment for 12months after fracture was required to capture the ICD-9-CM nonunion diagnosis code (733.82) or any procedure codes for nonunion repair. A stepwise regression analysis was used which dropped variables from analysis if they did not contribute sufficient explanatory power. In-sample predictive accuracy was assessed using a receiver operating characteristic (ROC) curve approach, and an out-of-sample comparison was drawn from the 2012 Medicare 5% SAF files. RESULTS: Overall, 47,437 Medicare patients had 56,492 fractures and 2.5% of fractures were nonunion. Patients with healed fracture (age 75.0±12.7SD) were older (p<0.0001) than patients with nonunion (age 69.2±13.4SD). The death rate among all Medicare beneficiaries was 4.8% per year, but fracture patients had an age- and sex-adjusted death rate of 11.0% (p<0.0001). Patients with fracture in 14 of 18 bones were significantly more likely to die within one year of fracture (p<0.0001). Stepwise regression yielded a predictive nonunion model with 26 significant explanatory variables (all, p≤0.003). Strength of this model was assessed using an area under the curve (AUC) calculation, and out-of-sample AUC=0.710. CONCLUSIONS: A logistic model predicted nonunion with reasonable accuracy (AUC=0.725). Within the Medicare population, nonunion patients were younger than patients who healed normally. Fracture was associated with increased risk of death within 1year of fracture (p<0.0001) in 14 different bones, confirming that geriatric fracture is a major public health issue. Comorbidities associated with increased risk of nonunion include past or current smoking, alcoholism, obesity or morbid obesity, osteoarthritis, rheumatoid arthritis, type II diabetes, and/or open fracture (all, multivariate p<0.001). Nonunion prediction requires knowledge of 26 patient variables but predictive accuracy is currently comparable to the Framingham cardiovascular risk prediction.

Epidemiology of Fracture Nonunion in 18 Human Bones.

Importance: Failure of bone fracture healing occurs in 5% to 10% of all patients. Nonunion risk is associated with the severity of injury and with the surgical treatment technique, yet progression to nonunion is not fully explained by these risk factors. Objective: To test a hypothesis that fracture characteristics and patient-related risk factors assessable by the clinician at patient presentation can indicate the probability of fracture nonunion. Design, Setting, and Participants: An inception cohort study in a large payer database of patients with fracture in the United States was conducted using patient-level health claims for medical and drug expenses compiled for approximately 90.1 million patients in calendar year 2011. The final database collated demographic descriptors, treatment procedures as per Current Procedural Terminology codes; comorbidities as per International Classification of Diseases, Ninth Revision codes; and drug prescriptions as per National Drug Code Directory codes. Logistic regression was used to calculate odds ratios (ORs) for variables associated with nonunion. Data analysis was performed from January 1, 2011, to December 31, 2012. Exposures: Continuous enrollment in the database was required for 12 months after fracture to allow sufficient time to capture a nonunion diagnosis. Results: The final analysis of 309 330 fractures in 18 bones included 178 952 women (57.9%); mean (SD) age was 44.48 (13.68) years. The nonunion rate was 4.9%. Elevated nonunion risk was associated with severe fracture (eg, open fracture, multiple fractures), high body mass index, smoking, and alcoholism. Women experienced more fractures, but men were more prone to nonunion. The nonunion rate also varied with fracture location: scaphoid, tibia plus fibula, and femur were most likely to be nonunion. The ORs for nonunion fractures were significantly increased for risk factors, including number of fractures (OR, 2.65; 95% CI, 2.34-2.99), use of nonsteroidal anti-inflammatory drugs plus opioids (OR, 1.84; 95% CI, 1.73-1.95), operative treatment (OR, 1.78; 95% CI, 1.69-1.86), open fracture (OR, 1.66; 95% CI, 1.55-1.77), anticoagulant use (OR, 1.58; 95% CI, 1.51-1.66), osteoarthritis with rheumatoid arthritis (OR, 1.58; 95% CI, 1.38-1.82), anticonvulsant use with benzodiazepines (OR, 1.49; 95% CI, 1.36-1.62), opioid use (OR, 1.43; 95% CI, 1.34-1.52), diabetes (OR, 1.40; 95% CI, 1.21-1.61), high-energy injury (OR, 1.38; 95% CI, 1.27-1.49), anticonvulsant use (OR, 1.37; 95% CI, 1.31-1.43), osteoporosis (OR, 1.24; 95% CI, 1.14-1.34), male gender (OR, 1.21; 95% CI, 1.16-1.25), insulin use (OR, 1.21; 95% CI, 1.10-1.31), smoking (OR, 1.20; 95% CI, 1.14-1.26), benzodiazepine use (OR, 1.20; 95% CI, 1.10-1.31), obesity (OR, 1.19; 95% CI, 1.12-1.25), antibiotic use (OR, 1.17; 95% CI, 1.13-1.21), osteoporosis medication use (OR, 1.17; 95% CI, 1.08-1.26), vitamin D deficiency (OR, 1.14; 95% CI, 1.05-1.22), diuretic use (OR, 1.13; 95% CI, 1.07-1.18), and renal insufficiency (OR, 1.11; 95% CI, 1.04-1.17) (multivariate P < .001 for all). Conclusions and Relevance: The probability of fracture nonunion can be based on patient-specific risk factors at presentation. Risk of nonunion is a function of fracture severity, fracture location, disease comorbidity, and medication use.

Heal rate of metatarsal fractures: A propensity-matching study of patients treated with low-intensity pulsed ultrasound (LIPUS) vs. surgical and other treatments.

INTRODUCTION: Whether to treat metatarsal fractures conservatively or surgically is controversial. We test a hypothesis that metatarsal fractures treated conservatively with non-invasive low-intensity pulsed ultrasound (LIPUS) obtain heal rates comparable to current surgical techniques. PATIENTS AND METHODS: This is a retrospective observational cohort study, using patient outcomes from a prospectively-collected LIPUS registry required by the U.S. Food & Drug Administration. Registry data were collected over a 5-year period and were reviewed and validated by a registered nurse. Data required for analysis were days-to-treatment (DTT) with LIPUS and a dichotomous outcome of healed versus failed, as assessed by clinical and radiographic criteria. Registry patients (DTT<365days) were propensity-matched to metatarsal fracture patients from a health claims database that includes medical and drug expenses for ∼90.1 million patients. The propensity match was based on patient demographic data (age, gender, body weight, fracture severity, and smoking status). RESULTS: A total of 594 metatarsal fractures were treated with LIPUS, including 161 Jones fractures. Compared to patients in the claims database, LIPUS-treated patients were more likely to: be overweight or obese; be male; have open fracture; and smoke (all, P<0.0001), suggesting that these variables were perceived as nonunion risk factors by prescribing physicians. After propensity-matching, none of these differences between the registry and the health claims database remained significant. The heal rate with LIPUS treatment was 97.3%, comparable to the heal rate of 95.3% among claims patients in 2011 who did not receive LIPUS (P=0.0654). When fresh fractures (0-90days) and delayed unions (91-365days) were analyzed separately, the LIPUS fresh fracture heal rate was superior to claims patients (P=0.0381), and the delayed union heal rate was comparable. After exclusion of registry patients who received surgery, heal rate with LIPUS alone (97.4%) was significantly better (P<0.0097) than the heal rate for matched patients in 2011 (94.2%). CONCLUSIONS: LIPUS significantly improved the heal rate of metatarsal fractures <1year old without surgery (P=0.0097). Metatarsal fractures treated with LIPUS alone have a heal rate comparable to fractures treated by surgical intervention.

Biological Risk Factors for Nonunion of Bone Fracture.

Many risk factors for fracture nonunion are well supported in the orthopaedic literature, including location of the fracture site, surgical treatment, bone displacement, type of fixation, treatment delay, comminution, inadequate treatment, and wound infection. However, evidence from a systematic review suggests that patient-related or biological causes of nonunion may not be as well understood. Understanding the biological causes of nonunion is important for several reasons. Risk factors might identify patients prone to nonunion who could benefit from more aggressive intervention, and a clear idea of nonunion risk could be important when choosing between competing therapeutic options. Risk factors also can inform the design of clinical trials and clarify patient inclusion and exclusion criteria, so that small studies can yield more definitive answers. Finally, an understanding of patient risk profiles may enable clinicians to counsel patients more effectively and to set appropriate expectations for success. Patient age appears to be a strong risk factor for nonunion in some bones, a weak risk factor for nonunion in other bones, and perhaps not a significant risk factor for nonunion in certain bones. This observation suggests that there can be substantial bone-to-bone variation in nonunion risk. Age also may be a surrogate for the prevalence of risk factors that potentially increase with age, such as smoking, diabetes, obesity, or nonsteroidal anti-inflammatory drug (NSAID) use. Smoking has been replicated as a risk factor for nonunion only in retrospective studies involving the humerus and tibia. Smoking appears to have an important effect on nonunion, yet the incremental risk may be rather small, except in context with additional risk factors. Diabetes has been confirmed as a risk factor for nonunion only in retrospective studies involving the foot and ankle. Nonunion risk from diabetes alone may be small and the context of additional risk factors crucial; this could account for why it has been so difficult to predict nonunion in the individual patient. Prediction of fracture nonunion in the individual patient is a difficult problem. Fracture nonunion may be influenced by complex interactions between biological and surgical risk factors, and the nonunion rate varies from bone to bone. A randomized clinical trial may not appropriately control for all potential correlates and confounders and may require impractical sample sizes. A large claims-based study of real-world fracture-healing outcomes is needed to provide guidance for randomized clinical trials that can test risk factors more rigorously.

Hyaluronic Acid Injections Are Associated with Delay of Total Knee Replacement Surgery in Patients with Knee Osteoarthritis: Evidence from a Large U.S. Health Claims Database.

BACKGROUND: The growing prevalence of osteoarthritis (OA) and the medical costs associated with total knee replacement (TKR) surgery for end-stage OA motivate a search for agents that can delay OA progression. We test a hypothesis that hyaluronic acid (HA) injection is associated with delay of TKR in a dose-dependent manner. METHODS AND FINDINGS: We retrospectively evaluated records in an administrative claims database of ~79 million patients, to identify all patients with knee OA who received TKR during a 6-year period. Only patients with continuous plan enrollment from diagnosis until TKR were included, so that complete medical records were available. OA diagnosis was the index event and we evaluated time-to-TKR as a function of the number of HA injections. The database included 182,022 patients with knee OA who had TKR; 50,349 (27.7%) of these patients were classified as HA Users, receiving ≥1 courses of HA prior to TKR, while 131,673 patients (72.3%) were HA Non-users prior to TKR, receiving no HA. Cox proportional hazards modelling shows that TKR risk decreases as a function of the number of HA injection courses, if patient age, gender, and disease comorbidity are used as background covariates. Multiple HA injections are therefore associated with delay of TKR (all, P < 0.0001). Half of HA Non-users had a TKR by 114 days post-diagnosis of knee OA, whereas half of HA Users had a TKR by 484 days post-diagnosis (χ2 = 19,769; p < 0.0001). Patients who received no HA had a mean time-to-TKR of 0.7 years; with one course of HA, the mean time to TKR was 1.4 years (χ2 = 13,725; p < 0.0001); patients who received ≥5 courses delayed TKR by 3.6 years (χ2 = 19,935; p < 0.0001). CONCLUSIONS: HA injection in patients with knee OA is associated with a dose-dependent increase in time-to-TKR.

Prothrombin Time and Activated Partial Thromboplastin Time Testing: A Comparative Effectiveness Study in a Million-Patient Sample.

BACKGROUND: A substantial fraction of all American healthcare expenditures are potentially wasted, and practices that are not evidence-based could contribute to such waste. We sought to characterize whether Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) tests of preoperative patients are used in a way unsupported by evidence and potentially wasteful. METHODS AND FINDINGS: We evaluated prospectively-collected patient data from 19 major teaching hospitals and 8 hospital-affiliated surgical centers in 7 states (Delaware, Florida, Maryland, Massachusetts, New Jersey, New York, Pennsylvania) and the District of Columbia. A total of 1,053,472 consecutive patients represented every patient admitted for elective surgery from 2009 to 2012 at all 27 settings. A subset of 682,049 patients (64.7%) had one or both tests done and history and physical (H&P) records available for analysis. Unnecessary tests for bleeding risk were defined as: PT tests done on patients with no history of abnormal bleeding, warfarin therapy, vitamin K-dependent clotting factor deficiency, or liver disease; or aPTT tests done on patients with no history of heparin treatment, hemophilia, lupus anticoagulant antibodies, or von Willebrand disease. We assessed the proportion of patients who received PT or aPTT tests who lacked evidence-based reasons for testing. CONCLUSIONS: This study sought to bring the availability of big data together with applied comparative effectiveness research. Among preoperative patients, 26.2% received PT tests, and 94.3% of tests were unnecessary, given the absence of findings on H&P. Similarly, 23.3% of preoperative patients received aPTT tests, of which 99.9% were unnecessary. Among patients with no H&P findings suggestive of bleeding risk, 6.6% of PT tests and 7.1% of aPTT tests were either a false positive or a true positive (i.e. indicative of a previously-undiagnosed potential bleeding risk). Both PT and aPTT, designed as diagnostic tests, are apparently used as screening tests. Use of unnecessary screening tests raises concerns for the costs of such testing and the consequences of false positive results.

Treatment of chronic (>1 year) fracture nonunion: heal rate in a cohort of 767 patients treated with low-intensity pulsed ultrasound (LIPUS).

BACKGROUND: Established fracture nonunions rarely heal without secondary intervention. Revision surgery is the most common intervention, though non-surgical options for nonunion would be useful if they could overcome nonunion risk factors. Our hypothesis is that low-intensity pulsed ultrasound (LIPUS) can enhance heal rate (HR) in fractures that remain nonunion after one year, relative to the expected HR in the absence of treatment, which is expected to be negligible. METHODS: We collated outcomes from a prospective patient registry required by the U.S. Food & Drug Administration. Patient data were collected over a 4-year period beginning in 1994 and were individually reviewed and validated by a registered nurse. Patients were only included if they had four data points available: date when fracture occurred; date when LIPUS treatment began; date when LIPUS treatment ended; and a dichotomous outcome of healed vs. failed, assessed by clinical and radiological criteria. Data were used to calculate two derived variables: days to treatment (DTT) with LIPUS, and days on treatment (DOT) with LIPUS. Every validated chronic nonunion patient (DTT>365 days) with complete data is reported. RESULTS: Heal rate for chronic nonunion patients (N=767) treated with LIPUS was 86.2%. Heal rate was 82.7% among 98 patients with chronic nonunion ≥5 years duration, and 12 patients healed after chronic nonunion >10 years (HR=63.2%). There was more patient loss to follow-up, non-compliance, and withdrawal, comparing chronic nonunion patients to all other patients (p<0.0001). Patient age was the only factor associated with failure to heal among chronic nonunions (p<0.004). Chronic nonunion patients averaged 3.1 surgical procedures prior to LIPUS, but some LIPUS-treated patients were able to heal without revision surgery. Among 91 patients who received LIPUS ≥90 days after their last surgery, HR averaged 85.7%, and the time from last surgery to index use of LIPUS averaged 449.6 days. CONCLUSIONS: Low-intensity pulsed ultrasound enhanced HR among fractures that had been nonunion for at least 1 year, and even healed fractures that had been nonunion >10 years. LIPUS resulted in successful healing in the majority of nonunions without further surgical intervention.

A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients.

BACKGROUND: Patient age is one of many potential risk factors for fracture nonunion. Our hypothesis is that older patients (≥ 60) with fracture risk factors treated with low-intensity pulsed ultrasound (LIPUS) have similar heal rate (HR) to the population as a whole. We evaluate the impact of age in conjunction with other risk factors on HR in LIPUS-treated patients with fresh fracture (≤ 90 days old). METHODS: The Exogen Bone Healing System is a LIPUS device approved in 1994 to accelerate healing of fresh fracture. After approval, the FDA required a Post-Market Registry to assess performance. Patient data collected from October 1994 until October 1998 were individually reviewed and validated by a registered nurse. Four distinct data elements were required to report a patient: date fracture occurred; date treatment began; date treatment ended; and a dichotomous outcome of healed v. failed, by clinical and radiological criteria. Data were used to calculate two derived variables; days to treatment (DTT) and days on treatment (DOT). Every validated fresh fracture patient with DTT, DOT, and outcome is reported. RESULTS: The validated registry had 5,765 patients with fresh fracture; 73% (N = 4,190) are reported, while 13% of patients were lost to follow-up, 11% withdrew or were non-compliant, and 3% died or are missing outcome. Among treatment-compliant patients, HR was 96.2%. Logistic estimates of the odds ratio for healing are equivalent for patients age 30 to 79 years and all age cohorts had a HR > 94%. Open fracture, current smoking, diabetes, vascular insufficiency, osteoporosis, cancer, rheumatoid arthritis, and prescription NSAIDs all reduced HR, but older patients (≥ 60) had similar HRs to the population as a whole. DTT was significantly shorter for patients who healed (p < 0.0001). CONCLUSIONS: Comorbid conditions in conjunction with aging can reduce fracture HR. Patients with fracture who used LIPUS had a 96% HR, whereas the expected HR averages 93%. Time to treatment was significantly shorter among patients who healed (p < 0.0001), suggesting that it is beneficial to begin LIPUS treatment early. Older patients (≥ 60) with fracture risk factors treated with LIPUS exhibit similar heal rates to the population as a whole.

Low-intensity pulsed ultrasound (LIPUS) can decrease the economic burden of fracture non-union.

OBJECTIVES: Few studies have evaluated the economic burden of surgical and conservative treatment of fracture non-union. An analysis was undertaken of aggregated payer data to determine economic costs of non-unions treated with surgery only vs non-unions treated conservatively with low-intensity pulsed ultrasound (LIPUS) only. METHODS: This study used administrative claims from a health plan database including nearly 80 million people. Patients with a claim for non-union surgery or LIPUS for non-union were identified, from April 2007 until April 2010. A retrospective cohort was formed by pairwise demographic matching among patients who received 'Surgery Only' or 'LIPUS Only'. Date of the first non-union intervention (surgery or LIPUS) was defined as the index date. All medical costs were assessed over 12 months following the index date for the 'Surgery Only' and 'LIPUS Only' cohorts. RESULTS: A total of 1158 matched patients were identified. 'Surgery Only' patients used significantly more healthcare services. In the year following intervention, 'Surgery Only' patients had total medical costs $6289 higher than 'LIPUS Only' patients (Mean = $11,276 vs $4986; p < 0.0001). Outpatient costs accounted for >68% of overall costs in both cohorts, and outpatient costs were significantly higher among the 'Surgery Only' cohort (Mean = $7682 vs $4196; p < 0.0001). Total inpatient costs were also significantly higher among the 'Surgery Only' cohort (Mean = $3302 vs $381; p < 0.0001). LIMITATIONS: Limitations of this work are typical of all studies based on administrative claims data: errors in the database are assumed to distribute randomly between cohorts, and some patients may have been miscoded as to treatment received or costs billed. CONCLUSIONS: 'Surgery Only' patients used significantly and substantially more healthcare services in treatment of fracture non-union. Conservative treatment with 'LIPUS only' for fracture non-union could potentially result in cost savings projected to roughly $1 billion dollars [corrected].