Effect of documented and undocumented psychiatric conditions on length of stay and discharge destination after total knee arthroplasty.

INTRODUCTION: Length of stay (LOS) and readmissions are quality metrics linked to physician payments and substantially impact the cost of care. This study aims to evaluate the effect of documented and undocumented psychiatric conditions on LOS, discharge location, and readmission following total knee arthroplasty (TKA). METHODS: Retrospective review of all primary, unilateral TKA from 2015 to 2020 at a high-volume, academic orthopedic hospital was conducted. Patients were separated into three cohorts: patients with a documented psychiatric diagnosis (+Dx), patients without a documented psychiatric diagnosis but with an actively prescribed psychiatric medication (-Dx), and patients without a psychiatric diagnosis or medication (control). Patient demographics, LOS, discharge location, and 90 days readmissions were assessed. RESULTS: A total of 2935 patients were included; 1051 patients had no recorded psychiatric medications (control); 1884 patients took at least one psychiatric medication, of which 1161 (61.6%) were in the-Dx and 723 (38.4%) were in the +Dx cohort. Operative time (+Dx, 103.4 ± 29.1 and -Dx, 103.1 ± 28.5 vs. 93.6 ± 26.2 min, p < 0.001 for both comparisons) and hospital LOS stay (+ Dx, 3.00 ± 1.70 and -Dx, 3.01 ± 1.83 vs. 2.82 ± 1.40 days, p = 0.021 and p = 0.006, respectively) were greater for patients taking psychiatric medications when compared to the control group. Patients taking psychiatric medication with or without associated diagnosis were significantly more likely to be discharged to a secondary facility-22.8% and 20.9%, respectively-compared to controls, at 12.5% (p < 0.001). Ninety-day readmission rates did not differ between the control and both psychiatric groups (p = 0.693 and p = 0.432, respectively). CONCLUSION: TKA patients taking psychiatric medications with or without a documented psychiatric diagnosis have increased hospital LOS and higher chances of discharge to a secondary facility. Most patients taking psychiatric medication also had no associated diagnosis. Payment models should consider the presence of undocumented psychiatric diagnoses when constructing metrics. Surgeons and institutions should also direct their attention to identifying, recording, and managing these patients to improve outcomes. LEVEL III EVIDENCE: Retrospective Cohort Study.

Understanding the adverse event experience in the S-TRAC adjuvant trial of sunitinib for high-risk renal cell carcinoma.

Until recently, the sole treatment for patients with nonmetastatic renal cell carcinoma (RCC) was nephrectomy followed by observation. As metastatic RCC (mRCC) remains largely incurable (5-year survival rate ∼12%), adjuvant treatment, with potential to prevent/delay disease recurrence, is needed. In November 2017, sunitinib was approved in the USA as the first adjuvant therapy for patients at high risk for recurrent RCC postnephrectomy based on results from the S-TRAC trial. Patients eligible for adjuvant treatment have no evidence of disease and may be less willing to tolerate side effects. Therefore, proactive adverse event management is critical for keeping patients on adjuvant treatment and requires understanding the subtle differences in the adverse event profile of sunitinib in the adjuvant versus metastatic RCC setting.

Subsidence Following Revision Total Hip Arthroplasty Using Modular and Monolithic Components.

BACKGROUND: The ideal femoral component in revision total hip arthroplasty (rTHA) remains undetermined; however, tapered, fluted, titanium (TFT) stems are now widely used with favorable results in all types of revision scenarios. With both modular and monoblock TFT stem options, neither has been proven to be superior. Femoral stem subsidence has been linked to aseptic loosening, instability, and leg length discrepancy. This study aims to assess stem subsidence of modular and monoblock TFT stems at a single urban orthopedic specialty hospital within a tertiary academic medical center. METHODS: Electronic medical records of rTHAs performed between January 2013 and March 2018 utilizing modular and monoblock TFT stems were examined. Data collected included baseline demographics, surgical indication, femoral Paprosky classification, and stem subsidence at most recent follow up (3 months to 3 years). Two-sample t-tests and chi-squared tests were used for statistical analysis. RESULTS: A total of 186 patients (106 modular, 80 monoblock) were included in the analysis. Modular stems underwent significantly greater subsidence than monoblock stems at latest radiographic follow-up (3.9 ± 2.6 vs 2.3 ± 2.5 mm, P < .001). A significantly greater proportion of modular stems underwent >5 mm of subsidence at latest follow-up (29.2% vs 11.3%, P < .001). CONCLUSION: Monoblock TFT stems have displayed promising clinical results in prior studies, and now have been shown to decrease the incidence of postoperative subsidence. With the potential for stem subsidence to lead to aseptic loosening, limb length discrepancy, and instability, the orthopedic surgeon should weigh the risks and benefits of utilizing modular vs monoblock TFT stems in rTHA.

Safety and effectiveness of classical and alternative sunitinib dosing schedules for metastatic renal cell carcinoma: a meta-analysis.

The optimal dosing schedule to maintain the effectiveness of sunitinib for metastatic renal cell carcinoma - while reducing toxicity - remains an important clinical question. A meta-analysis of randomized trials and observational studies assessed the relative treatment effects of 4/2, 2/1 and transitional-2/1 schedules on outcomes and adverse events using Bayesian network meta-analysis methods. Treatment with 2/1 reduced the risk of disease progression or death by 25% and had lower odds of hand-and-foot syndrome compared with the 4/2. A numerical but not 'statistical' benefit in progression-free survival was observed with the transitional-2/1 compared with 4/2. Alternative schedules with the 2/1 and transitional-2/1 may be more clinically beneficial in metastatic renal cell carcinoma than the 4/2 schedule.

Nonmodular Stems Are a Viable Alternative to Modular Stems in Revision Total Hip Arthroplasty.

BACKGROUND: Nonmodular and modular femoral stems have been associated with complications after revision total hip arthroplasty (rTHA). As such, the ideal femoral component for rTHA remains undecided. This study aims to report outcomes of titanium, tapered-fluted, modular and nonmodular femoral components in rTHA. METHODS: From January 1, 2013 to September 30, 2017, all rTHAs using modular or nonmodular femoral stems were identified. Demographic data including age, gender, and American Society of Anesthesiologists scores were collected. Surgical details including operative time and implant cost were also collected. Clinical outcomes including length of stay, dislocation, infection, fracture, reoperation, and re-revision were collected. Statistical analysis was performed using chi-square test and Student's t-test for all categorical and continuous variables, respectively. RESULTS: One hundred forty-six rTHA cases (103 modular and 43 nonmodular) were identified with an average follow-up of 29 months (range 3-59 months). Nonmodular stems had a significantly lower cost when compared to modular implants (modular stems 120.8% higher cost; P < .001). The surgical time of nonmodular components was significantly greater (193 minutes vs 163 minutes; P = .029). There were no differences observed in any other surgical details or clinical outcomes assessed, including length of stay (P = .323), rate of re-revision of the femoral implant (P = .389), rate of re-operation (P = .383), and postop complications (P = .241), including infection (P = .095), dislocation (P = .778), and fracture (P = .959). CONCLUSIONS: Nonmodular components provide encouraging clinical results with significantly lower costs compared to modular implants in rTHA. The use of titanium, tapered-fluted, nonmodular components may offer a more cost-effective approach to rTHA compared to their modular counterparts.

Effect of Baseline Characteristics on the Pain Response to Pregabalin in Fibromyalgia Patients with Comorbid Depression.

Objective: To evaluate the effect of baseline characteristics on the treatment response to pregabalin in fibromyalgia (FM) patients with depression. Design: Post hoc analysis from a randomized, double-blind, placebo-controlled, two-way crossover study of pregabalin (300 or 450 mg/day, twice daily). Subjects: A total of 193 FM patients taking an antidepressant for comorbid depression. Methods: The effect of patient baseline characteristics on the treatment response to pregabalin vs placebo was assessed for the primary efficacy end point (mean pain score on an 11-point numeric rating scale). Variables were analyzed using a linear mixed effects model with sequence, period, and treatment as fixed factors, and subject within sequence and within subject error as random factors. Results: Pregabalin significantly improved mean pain scores vs placebo irrespective of age, duration of FM, number of prior FM medications, depression diagnosis, shorter-term depression (<10 years), prior or no prior opioid use, pain severity, anxiety severity, and sleep disruption severity (all P < 0.05). Compared with placebo, pregabalin did not significantly affect mean pain scores in patients with comorbid insomnia, irritable bowel syndrome, or gastroesophageal reflux disease; severe FM; a diagnosis of depression before FM, longer-term depression (≥ 10 years), more severe depression, or who were taking a high dose of antidepressant. Conclusions: Pregabalin significantly improved mean pain scores when compared with placebo for the majority of baseline characteristics assessed in FM patients taking an antidepressant for comorbid depression.

Does Duration of Neuropathic Pain Impact the Effectiveness of Pregabalin?

BACKGROUND: Patients with chronic pain conditions such as neuropathic pain frequently experience delays in diagnosis and treatment. Ideally, all patients should be treated in a timely manner, but in those patients with more established disease it is important to know that approved treatments remain effective. METHODS: This was a pooled analysis of 19 randomized placebo-controlled trials of pregabalin for peripheral neuropathic pain conditions, including diabetic peripheral neuropathy, postherpetic neuralgia, and post-traumatic/postsurgical pain. Patients were divided into 5 pain duration categories based on time since onset of pain (< 6 months, 6 months to < 1 year, 1 year to < 2 years, 2 years to < 5 years, and ≥ 5 years). Mean change in pain score at endpoint, vs. placebo, was assessed for each category, together with changes in Patient Global Impression of Change (PGIC) responders ("very much" or "much" improved at endpoint). RESULTS: The analysis included 5,783 patients (n = 3,619 pregabalin; n = 2,164 placebo). Mean baseline pain scores were similar across the pain duration categories (range 6.3 to 6.5). Pregabalin significantly improved pain score at endpoint, vs. placebo, in all patients together (treatment difference [95% confidence interval], -0.59 [-0.67, -0.52], P < 0.0001) and similarly in each pain duration category (P < 0.0001 for each). There were significantly more PGIC responders with pregabalin, vs. placebo, for all patients (45.0% vs. 30.9%, P < 0.0001) and each category separately (P < 0.001 for each). There were no consistent, significant differences in treatment response between the different pain duration categories. CONCLUSIONS: Pregabalin significantly improves pain irrespective of the length of time since onset of neuropathic pain.

Burden of illness in fibromyalgia patients with comorbid depression.

OBJECTIVES: To assess the burden of fibromyalgia (FM) in patients with FM taking antidepressant medication for comorbid depression. METHODS: Symptom burden, impact on work and activity, and healthcare resource utilisation (HCRU) was examined at randomisation in patients enrolled in a clinical trial. Symptom burden was estimated based on self-reported health status measures. The Work Productivity and Activity Impairment: Specific Health Problem scale adapted to FM and a separate HCRU questionnaire were completed. The relationship between FM severity and burden was evaluated. RESULTS: The total population analysed comprised 193 patients; 71 (36.8%) had moderate FM and 119 (61.7%) severe FM. Patients had moderate pain, severe impairment in functioning due to FM, sleep disruption, mild anxiety, and mild depression. In the 7 days preceding randomisation, an average of 58.0% overall work impairment was reported, with 15.2% of working hours missed and 54.0% productivity while at work. In the 3 months preceding randomisation, on average, 5.0 visits per patient were made to healthcare professionals. Physical treatments were used by 34.7% and supplements by 31.6% of patients. Prescription and non-prescription medications, as well as professional services providing help with activities of daily living (ADL) that are impacted by FM, were used by >75% of patients. In addition, 50.4 hours of unpaid help was provided for ADL assistance. Total out-of-pocket expenditures were US$307.1, €410.4, or C$211.3, depending on location. FM burden worsened with increasing FM severity. CONCLUSIONS: This study demonstrates the significant burden of FM in patients with comorbid depression treated with an antidepressant.

Pregabalin Improves Pain Scores in Patients with Fibromyalgia Irrespective of Comorbid Osteoarthritis.

OBJECTIVE: Fibromyalgia (FM) is a chronic pain disorder with patients frequently suffering from comorbid conditions, including osteoarthritis (OA). Data on how FM patients with comorbid OA respond to recommended therapies (such as pregabalin) could help their treatment. DESIGN: This was a pooled exploratory analysis of three randomized placebo-controlled clinical trials of pregabalin in FM patients to assess the impact of comorbid OA on the response to pregabalin. METHODS: Patients were divided into those with and without comorbid OA. Difference in change in least squares (LS) mean pain score at endpoint (assessed by 0-10 numeric rating scale, controlled for baseline pain score) with pregabalin (300 mg/day and 450 mg/day) vs placebo was assessed. Changes in Patient Global Impression of Change (PGIC) responders and Fibromyalgia Impact Questionnaire (FIQ) total score were also assessed. RESULTS: There were 1665 patients in the analysis set (558, placebo; 552, pregabalin 300 mg/day; 555, pregabalin 450 mg/day), including 296 with comorbid OA. Pregabalin 450 mg/day significantly improved the LS mean (95% confidence interval) difference in pain score vs placebo in patients with (0.99 [0.44, 1.55], P < 0.001), and without (0.64 [0.39, 0.89], P < 0.001) OA. Improvements with pregabalin 300 mg/day with (0.31 [-0.25, 0.86], P = 0.276) and without (0.51 [0.25, 0.76], P < 0.001) OA were not consistently significant. Improvements in PGIC and FIQ total score were observed in patients with and without comorbid OA. CONCLUSIONS: FM patients with or without comorbid OA respond to treatment with pregabalin 450mg/day with significant improvements in pain intensity scores. These data could provide guidance to healthcare professionals treating these patients.

Complications of Total Hip Arthroplasty: Standardized List, Definitions, and Stratification Developed by The Hip Society.

BACKGROUND: Reporting of complications after total hip arthroplasty (THA) is not standardized, and it is done inconsistently across various studies on the topic. Advantages of standardizing complications include improved patient safety and outcomes and better reporting in comparative studies. QUESTIONS/PURPOSES: The purpose of this project was to develop a standardized list of complications and adverse events associated with THA, develop standardized definitions for each complication, and stratify the complications. A further purpose was to validate these standardized THA complications. METHODS: The Hip Society THA Complications Workgroup proposed a list of THA complications, definitions for each complication, and a stratification scheme for the complications. The stratification system was developed from a previously validated grading system for complications of hip preservation surgery. The proposed complications, definitions, and stratification were validated with an expert opinion survey of members of The Hip Society, a case study evaluation, and analysis of a large administrative hospital system database with a focus on readmissions. RESULTS: One hundred five clinical members (100%) of The Hip Society responded to the THA complications survey. Initially, 21 THA complications were proposed. The validation process reduced the 21 proposed complications to 19 THA complications with definitions and stratification that were endorsed by The Hip Society (bleeding, wound complication, thromboembolic disease, neural deficit, vascular injury, dislocation/instability, periprosthetic fracture, abductor muscle disruption, deep periprosthetic joint infection, heterotopic ossification, bearing surface wear, osteolysis, implant loosening, cup-liner dissociation, implant fracture, reoperation, revision, readmission, death). CONCLUSIONS: Acceptance and use of these standardized, stratified, and validated THA complications and adverse events could advance reporting of outcomes of THA and improve assessment of THA by clinical investigators. LEVEL OF EVIDENCE: Level V, therapeutic study.

Disparities in Discharge Destination After Lower Extremity Joint Arthroplasty: Analysis of 7924 Patients in an Urban Setting.

BACKGROUND: Discharge destination is an important factor to consider to maximize care coordination and manage patient expectations after total joint arthroplasty (TJA). It also has significant impact on the cost-effectiveness of these procedures given the significant cost of post-acute inpatient care. Therefore, understanding factors that impact discharge destination after TJA is critical. METHODS: An evaluation of socioeconomic, geographic, and racial/ethnic factors associated with discharge destination to either home or institution (ie, rehabilitation, skilled nursing facility, and so forth) following joint arthroplasty of the lower extremity was conducted. We analyzed data on patients admitted between 2011 and 2014 for primary or revision hip or knee arthroplasty at a single institution. Bivariate and multivariate statistical techniques were applied to determine associations. RESULTS: Included in the analysis were 7924 cases of lower extremity joint procedures, of which 4836 (61%), 785 (10%), and 2770 (35%) were of female gender, low socioeconomic status, and nonwhite race/ethnicity, respectively. A total of 5088 (64%) and 2836 (36%) cases were discharged to home and institution, respectively. Significant predictors of discharge to an institution in the multivariate analysis include SES (low and middle SES [odds ratio {OR}: 1.27, 95% confidence interval {CI}: 1.02-1.57, P = .029; and OR: 1.26, 95% CI: 1.10-1.44, P = .001]), age (OR: 1.05, 95% CI: 1.049-1.060, P < .001), female gender (OR: 1.69, 95% CI: 1.52-1.89, P < .001) and TKA procedure (OR: 1.48, 95% CI: 1.33-1.64, P < .001). Patients of nonblack race/ethnicity were more likely to be discharged home (white OR: 0.84, 95% CI: 0.72-0.98, P = .027; other OR: 0.80, 95% CI: 0.67-0.95, P = .009). CONCLUSION: Socioeconomic status and race/ethnicity are important factors related to discharge destination following TJA. Thoroughly understanding and addressing these factors may help increase the rates of discharge to home as opposed to institution.

Early Results of Medicare's Bundled Payment Initiative for a 90-Day Total Joint Arthroplasty Episode of Care.

BACKGROUND: In 2011 Medicare initiated a Bundled Payment for Care Improvement (BPCI) program with the goal of introducing a payment model that would "lead to higher quality, more coordinated care at a lower cost to Medicare." METHODS: A Model 2 bundled payment initiative for Total Joint Replacement (TJR) was implemented at a large, tertiary, urban academic medical center. The episode of care includes all costs through 90 days following discharge. After one year, data on 721 Medicare primary TJR patients were available for analysis. RESULTS: Average length of stay (LOS) was decreased from 4.27 days to 3.58 days (Median LOS 3 days). Discharges to inpatient facilities decreased from 71% to 44%. Readmissions occurred in 80 patients (11%), which is slightly lower than before implementation. The hospital has seen cost reduction in the inpatient component over baseline. CONCLUSION: Early results from the implementation of a Medicare BPCI Model 2 primary TJR program at this medical center demonstrate cost-savings. LEVEL OF EVIDENCE: IV economic and decision analyses-developing an economic or decision model.

Cost Analysis of Total Joint Arthroplasty Readmissions in a Bundled Payment Care Improvement Initiative.

BACKGROUND: The Bundled Payment for Care Improvement (BPCI) Initiative is a Centers for Medicare and Medicaid Services program designed to promote coordinated and efficient care. This study seeks to report costs of readmissions within a 90-day episode of care for BPCI Initiative patients receiving total knee arthroplasty (TKA) or total hip arthroplasty (THA). METHODS: From January 2013 through December 2013, 1 urban, tertiary, academic orthopedic hospital admitted 664 patients undergoing either primary TKA or THA through the BPCI Initiative. All patients readmitted to our hospital or an outside hospital within 90-days from the index episode were identified. The diagnosis and cost for each readmission were analyzed. RESULTS: Eighty readmissions in 69 of 664 patients (10%) were identified within 90-days. There were 53 readmissions (45 patients) after THA and 27 readmissions (24 patients) after TKA. Surgical complications accounted for 54% of THA readmissions and 44% of TKA readmissions. These complications had an average cost of $36,038 (range, $6375-$60,137) for THA and $38,953 (range, $4790-$104,794) for TKA. Eliminating the TKA outlier of greater than $100,000 yields an average cost of $27,979. Medical complications of THA and TKA had an average cost of $22,775 (range, $5678-$82,940) for THA and $24,183 (range, $3306-$186,069) for TKA. Eliminating the TKA outlier of greater than $100,000 yields an average cost of $11,682. CONCLUSION: Hospital readmissions after THA and TKA are common and costly. Identifying the causes for readmission and assessing the cost will guide quality improvement efforts.

Evaluating Guideline-recommended Pain Medication Use Among Patients with Newly Diagnosed Fibromyalgia.

OBJECTIVES: To compare pain medication treatment changes across cohorts of newly diagnosed patients with fibromyalgia (FM) treated with guideline-recommended medications or opioids. METHODS AND DESIGN: Retrospective claims data analysis examined adult commercial health plan members newly diagnosed with FM (initial diagnosis = index date) from January 2008 to February 2012. Patients had 6-month pre-index and 12-month postindex periods and received pain medication within 6 months postindex; cohorts were based on the first postindex medication. Guideline-recommended medication cohorts were anti-epileptic drug (AED), serotonin-norepinephrine reuptake inhibitor (SNRI), selective serotonin reuptake inhibitor (SSRI), and tricyclic antidepressant (TCA). Short-acting and long-acting opioid (SAO, LAO) cohorts were also identified. Pairwise comparisons with the SAO cohort were conducted. Cox proportional hazards regressions modeled the likelihood of receiving guideline-recommended therapy. RESULTS: The final sample was 96,175 patients (mean age 47.3 years; 72.5% female), distributed into SAO (57%), SSRI (22%), AED (10%), SNRI (6%), TCA (3%), and LAO (2%) cohorts. The SAO cohort had the most discontinuation (49% vs. 6% to 22%, P < 0.01) and the least augmentation (29% vs. 35% to 50%, P < 0.01). Regression analyses indicated that patients with (vs. without) pre-index guideline-recommended medications were 2 to 4 times more likely to receive them postindex. Patients in the opioid cohorts were about half as likely to receive subsequent guideline-recommended medications. CONCLUSIONS: Opioid use was widespread among patients with FM. Once patients received opioids postdiagnosis, the likelihood of receiving guideline-recommended medications was small. These real-world results indicate an opportunity may exist for improved FM management using recommended therapies in clinical practice.

Time to improvement of pain and sleep quality in clinical trials of pregabalin for the treatment of fibromyalgia.

OBJECTIVE: To determine the time to immediate and sustained clinical improvement in pain and sleep quality with pregabalin in patients with fibromyalgia. DESIGN: A post hoc analysis of four 8- to 14-week phase 2-3, placebo-controlled trials of fixed-dose pregabalin (150-600 mg/day) for fibromyalgia, comprising 12 pregabalin and four placebo treatment arms. PATIENTS: A total of 2,747 patients with fibromyalgia, aged 18-82 years. METHODS: Pain and sleep quality scores, recorded daily on 11-point numeric rating scales (NRSs), were analyzed to determine time to immediate improvement with pregabalin, defined as the first of ≥2 consecutive days when the mean NRS score was significantly lower for pregabalin vs placebo in those treatment arms with a significant improvement at endpoint, and time to sustained clinical improvement with pregabalin, defined as a ≥1-point reduction of the baseline NRS score of patient responders who had a ≥30% improvement on the pain NRS, sleep NRS, or Fibromyalgia Impact Questionnaire (FIQ) from baseline to endpoint, or who reported "much improved" or "very much improved" on the Patient Global Impression of Change (PGIC) at endpoint. RESULTS: Significant improvements in pain and sleep quality scores at endpoint vs placebo were seen in 8/12 and 11/12 pregabalin treatment arms, respectively (P < 0.05). In these arms, time to immediate improvements in pain or sleep occurred by day 1 or 2. Time to sustained clinical improvement occurred significantly earlier in pain, sleep, PGIC, and FIQ responders (P < 0.02) with pregabalin vs placebo. CONCLUSIONS: Both immediate and sustained clinical improvements in pain and sleep quality occurred faster with pregabalin vs placebo.

Can Administrative Data Be Used to Analyze Complications Following Total Joint Arthroplasty?

We hypothesized that the Centers for Medicare and Medicaid Services Limited Dataset (CMS-LDS) could be used to validate the complications associated with total hip and knee arthroplasty (THA and TKA) endorsed by the Hip and Knee Societies. Using ICD-9 procedure and diagnosis codes, cases were extracted from the first three quarters of the 2009 CMS-LDS to allow all complications within 90-days be captured in the same calendar year. We were unable to validate the Hip and Knee Societies' complications as we could not connect readmissions or outpatient visits to index admissions. In addition, well-known complications were not detected, raising concerns about coding accuracy and stratification. Furthermore, the assignment of outpatient and inpatient codes allows for duplication of complications which may falsely elevate the true incidence.

A comprehensive drug safety evaluation of pregabalin in peripheral neuropathic pain.

Pregabalin is a commonly used therapy currently recommended as first-line treatment for a number of neuropathic pain (NeP) conditions. Since licensure, a number of clinical trials of pregabalin in different NeP conditions have been completed from which additional data on safety and tolerability can be drawn. In this analysis, patient-level data from 31 randomized clinical trials of pregabalin in peripheral NeP sponsored by Pfizer were pooled and assessed for incidence of adverse events (AEs). Incidence by age, disease condition, and race, together with risk differences and time to onset and resolution of AEs, was assessed. In total, 7,510 patients were included: 4,884 on pregabalin (representing 805 patient-years treatment) and 2,626 on placebo. Pregabalin vs. placebo risk analysis identified 9 AEs with a risk difference, for which the lower limit of the 95% confidence interval (CI) was > 1%: dizziness (risk difference [95% CI]: (17.0 [15.4 to 18.6]), somnolence (10.8 [9.5 to 12.1]), peripheral edema (5.4 [4.3 to 6.4]), weight increase (4.7 [3.9 to 5.5]), dry mouth (2.9 [2.1 to 3.8]), constipation (2.3 [1.5 to 3.2]), blurred vision (2.2 [1.6 to 2.9]), balance disorder (2.0 [1.5 to 2.5]), and euphoric mood (1.6 [1.2 to 2.0]). The most common AEs, dizziness and somnolence, typically emerged within the first 1 to 2 weeks of treatment and resolved 1 to 2 weeks later, without resulting in cessation of treatment. The data from this review provide information, indicating which AEs may be expected in patients treated with pregabalin, and suggest that careful dose titration to the highest tolerable dose is the most appropriate approach in clinical practice.

Prior authorization in the treatment of patients with pDPN and FM.

PURPOSE: To determine prior authorization (PA) impact on healthcare utilization, costs, and pharmacologic treatment patterns for painful diabetic peripheral neuropathy (pDPN) and fibromyalgia (FM). METHODS: This retrospective, observational, longitudinal cohort study used medical and pharmacy claims data. Newly diagnosed patients treated for FM or pDPN between 7/1/2007 and 12/31/2011 were included. PA and no PA groups were matched by propensity score 4:1. Medical resource utilization, direct medical and pharmacy costs, and treatment pattern differences were compared. Pre and postindex differences between PA and no PA cohorts were determined by difference in difference analysis. RESULTS: Analysis of 2,315 FM patients (1,852 PA; 463 no PA) demonstrated greater increases in postindex all-cause costs ($197; P = 0.6673) and disease-related costs ($72; P = 0.4186) in the PA cohort. Analysis of 1,300 pDPN patients (1,040 PA; 260 no PA) demonstrated postindex all-cause cost increases of $1,155 more in the no PA cohort (P = 0.6248); disease-related costs decreased $2,809 more in the no PA cohort (P = 0.4312). Treatment patterns were similar between cohorts; opioid usage was higher in the FM PA cohort (P = 0.0082). CONCLUSIONS: There was no evidence of statistically significant differences between PA and no PA cohorts in either FM or pDPN populations for total all-cause or disease-related costs.

Cytokine Receptor-like Factor 1 (CRLF1) and Its Role in Osteochondral Repair.

BACKGROUND: Since cytokine receptor-like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. METHODS: The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow-derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno-associated virus (AAV) or AAV containing CRLF1 was determined by morphological, histological, and micro computer tomography (CT) analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were determined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes using real-time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. RESULTS: Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondrogenic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and cardiotrophin-like Cytokine (CLC) stimulated catabolic events via STAT3 activation. CONCLUSION: A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.

Laceration of the Sciatic Nerve After Closed Reduction of a Dislocated Total Hip Arthroplasty.

Sciatic nerve injury after closed reduction of a dislocated total hip arthroplasty (THA) is an exceedingly rare but tremendously devastating complication. Closed reduction is the standard of care and is typically associated with a low complication rate. There have only been seven sciatic nerve injuries after closed reduction of a dislocated THA reported in the literature, and none were secondary to nerve laceration. We report a case of sciatic nerve laceration after attempted closed reduction of a dislocated THA. This resulted in complete loss of sensory and motor sciatic nerve function. This case highlights the importance of a detailed neurologic examination before and after closed reduction of a dislocated total hip, the importance of using careful reduction maneuvers, and transitioning to open reduction when necessary.