The Impact of Surgeon Volume on Unicompartmental Knee Arthroplasty Survivorship: A Michigan Arthroplasty Registry Collaborative Quality Initiative Database Analysis.

BACKGROUND: The utilization of unicompartmental knee arthroplasty (UKA) has remained low when compared to total knee arthroplasty (TKA), possibly due to higher rates of revision and reoperation. This study aimed to quantify surgeon UKA case-volumes and measure the effect of surgeon volume on early revision. We hypothesized that surgeons who have high case volumes would have lower revision rates compared to medium- and low-volume surgeons. METHODS: Primary UKAs were performed between February 2012 and November 2021, and associated revisions were identified utilizing the Michigan Arthroplasty Registry Collaborative Quality Initiative. Surgeon information, including total cases and annual UKA volume, was collected. Case volume per year was stratified as High (≥ 35 cases per year), Medium (15 to 34 cases per year), and low (< 15 cases per year). RESULTS: There were a total of 15,542 UKAs performed. Of these, 701 (4.5%) were revised, and 412 (58.8%) revisions occurred within 2 years. Of the 287 surgeons who performed an UKA in the registry, 237 (82.6%) were low-volume surgeons, 36 (12.5%) were medium-volume, and 14 (4.9%) were high-volume. High-volume surgeons were more likely to operate on older patients (P < 0.01), Medicare patients (P < 0.01), and patients who had American Society of Anesthesiologists scores of III and IV (P < 0.01). High-volume surgeons had significantly lower 5-year revision rates compared to medium and low-volume surgeons (high: 4.3% (95% confidence interval: 3.7 to 4.9), medium: 5.2% (4.4 to 6.1), low: 7.2% (6.4 to 8.0); P < 0.001). In comparison, the 5-year revision rate for TKA in Michigan was 3.0% (95% confidence interval: 2.9 to 3.1). CONCLUSIONS: When UKAs were performed by high-volume surgeons in the state of Michigan, there was better survivorship when compared to low-and medium-volume surgeons. High-volume surgeons were more likely to perform UKA on older patients, Medicare patients, and patients who had American Society of Anesthesiologists scores of III and IV. The revision rate for the high-volume surgeons still exceeded the 5-year revision rate for TKA in Michigan.

How Much Perioperative Pain and Dysfunction Underlie the HOOS JR and KOOS JR?

BACKGROUND: The Hip Disability and Osteoarthritis Outcome Score Joint Replacement (HOOS JR) and Knee Injury and Osteoarthritis Outcome Score Joint Replacement (KOOS JR) scores represent pain and dysfunction as a single number ranging from 0 (extreme pain and dysfunction) to 100 (no pain or functional limitations). However, scores between 0 and 100 lack a simple interpretation because they reflect varying combinations of pain levels and dysfunction. Given that most adverse events and improvement occur within the first 90 days after surgery, a deeper understanding of the level of pain and dysfunction may reveal missed opportunities for patient care. QUESTIONS/PURPOSES: (1) What does a given preoperative or postoperative HOOS JR and KOOS JR score indicate about pain and ability to perform daily activities? (2) How much of a change in score (that is, delta) is needed to indicate significant improvement in pain control and daily functioning? METHODS: The Michigan Arthroplasty Registry Collaborative Quality Initiative contains more than 95% of THAs and TKAs performed in Michigan. Between January 2017 and March 2019, 84,175 people in the registry underwent primary THA or TKA and were potentially eligible for this retrospective, comparative study of the first 90 postoperative days. Eighty-four percent (70,608 of 84,175) were excluded because their surgeons did not attain a target survey collection proportion of 70% and another 6% (5042) were missing covariate information or surveys, leaving 10% (8525) for analysis. The mean age and percentage of women were 65 ± 11 years and 55% (2060 of 3716), respectively, for patients undergoing THA and 67 ± 9 years and 61% (2936 of 4809), respectively, for those undergoing TKA. There were no clinically meaningful differences between patients who were analyzed and those who were excluded except for lower representation of non-White patients in the analyzed group. For interpretation, patient responses to Question 7 (pain) and Question 6 (function) from the Patient-Reported Outcomes Measurement Information System global items (PROMIS-10) were dichotomized into "much pain" (rating of pain 4 to 10 of 10) versus "less pain" (rating of ≤ 3) and "good function" (able to perform most activities) versus "poor function" (not able to perform most activities) and combined into four pain-function categories. We examined the mean preoperative and postoperative HOOS JR and KOOS JR scores for each pain-function category, adjusted for patient characteristics. We calculated the size of the delta associated with an increase to a more favorable category postoperatively (versus staying in the same or worse category) via multivariable logistic regression that controlled for patient characteristics. RESULTS: Patients in the least favorable "much pain, poor function" category preoperatively had adjusted mean scores of 40 (95% confidence interval 39 to 41) for both the HOOS JR and KOOS JR. Those with mixed levels of pain and function had mean scores between 46 and 55. Those in the most favorable "less pain, good function" category had means of 60 (95% CI 58 to 62) and 59 (95% CI 58 to 61) for the HOOS JR and KOOS JR, respectively. The adjusted delta to achieve a pain level of ≤ 3 or the ability to perform most activities was 30 (95% CI 26 to 36) on the HOOS JR and 27 (95% CI 22 to 29) on the KOOS JR scales. CONCLUSION: These adjusted means of the HOOS JR and KOOS JR provide context for understanding the levels of pain and dysfunction for individuals as well for patients reported in other studies. Potential quality improvement efforts could include tracking the proportion of patients with THA or TKA who achieved a sufficient delta to attain pain levels of ≤ 3 or the ability to perform most activities. Future studies are needed to understand pain and function represented by the HOOS JR and KOOS JR at 1 to 2 years, how these may differ by patient subgroups, and whether scores can be improved through quality improvement efforts. LEVEL OF EVIDENCE: Level III, therapeutic study.

Are Short Stems Associated With Higher Fracture Rates and Early Revision Rates in Primary Total Hip Arthroplasty? A Noninferiority Analysis.

BACKGROUND: This study aimed to determine if "short" femoral stems were noninferior to (at least as good as) standard-length stems in regards to 90-day periprosthetic fracture and 1-year revision rates. METHODS: Using the MARCQI implant registry, a retrospective study of statewide data was carried out on 64,084 total hip arthroplasties (THAs) between 2012 and 2017. We noticed an increase in the use of "short" uncemented femoral hip stems during THA. Chi-square tests were used to test homogeneity of categorical variables. The covariates included in the analyses were identified using modern epidemiological methods. A Type I probability of 0.05 was used as the level of statistical significance. Inverse probability of treatment weighting (IPTW) was used to mitigate confounding variables. RESULTS: One hundred and seven stems were implanted by surgeons in the state of Michigan. They were classified according to the Khanuja Classification System as Type 2A (trapezoidal, double-tapered calcar loading, n = 3,281), Type 3 (calcar loading with lateral flare, n = 1,898), and Type 4 (shortened, tapered, conventional, n = 19,580), and were compared to standard-length, type 5, stems (n = 33,322) in regards to the 2 outcomes (periprosthetic fractures and 1-year revision rates). Overall, 1-year revision and the 90-day fracture rates were 1.3% (791/57,853) and 1.1% (631/57,968), respectively. Noninferiority was established for all short stems at the clinical threshold of an odds ratio (OR) of 1.5 with P-values <0.05 for 90-day fractures. In regards to 1-year revision rates, noninferiority was also established for Type 3 and 4 stems (P < .05). CONCLUSION: The increased use of "short stems" in Michigan did not lead to increased 1-year revision or 90-day fracture rates.

Early Survivorship of Uncemented Total Knee Arthroplasty Varies by Age and Sex Based on Data From the Michigan Arthroplasty Registry Collaborative Quality Initiative.

BACKGROUND: Outcome data for newer uncemented total knee arthroplasty (TKA) designs has been mixed. Registry studies showed worse survivorship, but clinical trials have not demonstrated differences compared to cemented designs. There has been renewed interest in uncemented TKA with modern designs and improved technology. The utilizations of uncemented knees in Michigan, 2-year outcomes, and the effects of age and sex were evaluated. METHODS: A statewide database from 2017 through 2019 was analyzed for incidence, distribution, and early survivorship of cemented versus uncemented TKAs. There was 2-year minimum follow-up. Kaplan-Meier survival analysis was used to generate time to first revision cumulative percent revision curves. The impacts of age and sex were examined. RESULTS: Use of uncemented TKAs increased from 7.0 to 11.3%. Uncemented TKAs were more commonly men, younger, heavier, American Society of Anesthesiologists score > 2, and opioid users (P < .05). At 2 years, overall cumulative percent revision was higher in uncemented (2.44% [2.00, 2.99]) versus cemented (1.76% [1.64, 1.89]), particularly in women uncemented (2.41 [1.87, 3.12]) versus cemented (1.64 [1.50, 1.80]). Revision rates were greater with uncemented women >70 years (1.2% 1 year, 1.02% 2 years) versus < 70 years (0.56%, 0.53%), notably uncemented were inferior in both groups (P < .05). Men, regardless of age, had similar survivorships with both cemented and uncemented designs. CONCLUSION: The use of an uncemented TKA had an increased risk of early revision compared to cemented. This finding, however, was only apparent in women, especially those >70 years old. Surgeons should consider cement fixation in women >70 years.

Non-Inferiority of Aspirin for Venous Thromboembolism Prophylaxis After Hip Arthroplasty in a Statewide Registry.

BACKGROUND: Uncertainty remains surrounding the use of aspirin as a sole chemoprophylactic agent to reduce the risk of venous thromboembolism (deep vein thrombosis or pulmonary embolism) and bleeding after primary total hip arthroplasty. METHODS: We performed a non-inferiority analysis of a retrospective cohort of patients undergoing total hip arthroplasty from April 1, 2013 to December 31, 2018. Cases were retrieved from the Michigan Arthroplasty Registry Collaborative Quality Initiative database and performed by 355 surgeons at 61 hospitals throughout Michigan. Surgical setting ranged from small community hospitals to large academic and non-academic centers. The primary outcomes were post-operative venous thromboembolism event or death and bleeding event. RESULTS: Of the 59,747 patients included, 32,878 (55.03%) were female, and the mean age was 64.5. A total of 462 (0.77%) composite venous thromboembolism events occurred. There were 221 (0.71%) and 129 (0.80%) venous thromboembolism events in patients receiving aspirin only and anticoagulants only, respectively. Aspirin was non-inferior to anticoagulants for composite venous thromboembolism events (odds ratio 0.99, 95% confidence interval 0.79-1.26, P < .001). Bleeding events occurred in 767 (1.28%) patients, with 304 (0.97%) and 281 (1.74%) bleeding events in patients receiving aspirin only and anticoagulants only, respectively. Aspirin was non-inferior to anticoagulants for bleeding events (odds ratio 0.62, 95% confidence interval 0.52-0.74, P < .001). CONCLUSION: Aspirin is not inferior to other anticoagulants as pharmacologic venous thromboembolism prophylaxis with regards to post-operative risk of venous thromboembolism or bleeding. Sole use of aspirin for venous thromboembolism prophylaxis after total hip arthroplasty should be considered in the appropriate patient.

Support vector machines for automated snoring detection: proof-of-concept.

BACKGROUND: Snoring has been shown to be associated with adverse physical and mental health, independent of the effects of sleep disordered breathing. Despite increasing evidence for the risks of snoring, few studies on sleep and health include objective measures of snoring. One reason for this methodological limitation is the difficulty of quantifying snoring. Conventional methods may rely on manual scoring of snore events by trained human scorers, but this process is both time- and labor-intensive, making the measurement of objective snoring impractical for large or multi-night studies. METHODS: The current study is a proof-of-concept to validate the use of support vector machines (SVM), a form of machine learning, for the automated scoring of an objective snoring signal. An SVM algorithm was trained and tested on a set of approximately 150,000 snoring and non-snoring data segments, and F-scores for SVM performance compared to visual scoring performance were calculated using the Wilcoxon signed rank test for paired data. RESULTS: The ability of the SVM algorithm to discriminate snore from non-snore segments of data did not differ statistically from visual scorer performance (SVM F-score = 82.46 ± 7.93 versus average visual F-score = 88.35 ± 4.61, p = 0.2786), supporting SVM snore classification ability comparable to visual scorers. CONCLUSION: In this proof-of-concept, we established that the SVM algorithm performs comparably to trained visual scorers, supporting the use of SVM for automated snoring detection in future studies.

Updated assays for inhibin B and AMH provide evidence for regular episodic secretion of inhibin B but not AMH in the follicular phase of the normal menstrual cycle.

STUDY QUESTION: What is the daily variation in serum inhibin B (InhB) and anti-Müllerian hormone (AMH) in relation to the LH surge in women of reproductive age. SUMMARY ANSWER: AMH is secreted in a biphasic follicular/luteal pattern in women with higher AMH secretion, while InhB secretion is episodic in the early to mid-follicular phase and immediately after the LH surge but not in the luteal phase. WHAT IS KNOWN ALREADY: In women of reproductive age with a mean serum AMH >1 ng/ml, levels are highest in Days 2-7 of the cycle. InhB concentrations are highest in the follicular phase of the cycle. STUDY DESIGN, SIZE, DURATION: In this cohort study conducted in an academic center, blood samples were collected daily from 20 women during one normal menstrual cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: Regularly menstruating 30- to 40-year-old women had daily serum InhB, AMH, LH and FSH levels measured. Intracycle variability of InhB and AMH were assessed after aligning to the LH surge. MAIN RESULTS AND THE ROLE OF CHANCE: When classified into quartiles of AMH concentration, the lowest AMH levels did not vary across the cycle; the highest AMH levels showed a mid-follicular increase, mid-cycle decrease and mid-luteal increase. A surge of InhB was noted following the LH surge in 16/20 cycles. Episodic increases in InhB occurred in 17/20 cycles prior to the LH surge. In the luteal phase, InhB decreased or became undetectable and did not demonstrate episodic secretion. Old and new assays for AMH and InhB were compared in all samples, with the AMH assays demonstrating good correlation (Rsq = 0.9625) but the InhB assays showing less correlation (Rsq = 0.4903). LIMITATIONS, REASONS FOR CAUTION: The study population is small and in the mid-to-late reproductive age group. Single daily sampling may not detect more frequent variability (i.e. pulses) in hormone levels. WIDER IMPLICATIONS OF THE FINDINGS: These data suggest different regulatory mechanisms for InhB and AMH secretion, and confirm an 'aging ovary' pattern of AMH and InhB secretion, which is consistent with decreased ovarian reserve. We also demonstrated comparability of the AMH Gen II assay with the previous version in standard usage but our data raised concerns about comparability of the InhB Gen II assay. STUDY FUNDING/COMPETING INTEREST(S): General Clinical Research Center for phlebotomy work has been supported in part by NIH grant UL1RR024986. Recruitment and data analyses were supported by the Center for Integrated Approaches to Complex Diseases (SD Harlow, Director). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

A 24-hour approach to the study of health behaviors: temporal relationships between waking health behaviors and sleep.

BACKGROUND: Although sleep is often associated with waking health behaviors (WHB) such as alcohol consumption, caffeine use, smoking, and exercise, the causal direction of these relationships is unclear. PURPOSE: The present study used time series data to examine the temporal dynamics of WHB and sleep characteristics in participants of the Study of Women's Health Across the Nation Sleep Study. METHODS: Three hundred three women completed daily assessments of WHB and wore wrist actigraphs to measure sleep characteristics for the duration of the study (mean = 29.42 days, SD = 6.71). RESULTS: Vector autoregressive modeling revealed that weekly patterns of sleep and WHB best predicted subsequent sleep and WHB suggesting that the associations between WHB and sleep persist beyond their immediate influence. Some WHB predicted some subsequent sleep characteristics, but sleep did not predict subsequent WHB. CONCLUSIONS: These novel findings provide insight into the temporal dynamics of 24-h behaviors and encourage consideration of both sleep and WHB in health promotion and behavior change efforts.

Individualized Surgeon Reports in a Statewide Registry.

ABSTRACT: Despite progress with the development of joint replacement registries in the United States, surgeons may have limited opportunities to determine the cumulative outcome of their own patients or understand how those outcomes compare with their peers; this information is important for quality improvement. In order to provide surgeons with accurate data, it is first necessary to have a registry with complete coverage and patient matching. Some international registries have accomplished this. Building on a comprehensive statewide registry in the United States, a surgeon-specific report has been developed to provide surgeons with survivorship and complication data, which allows comparisons with other surgeons in the state. This article describes funnel plots, cumulative sum reports, complication-specific data, and patient-reported outcome measure data, which are provided to hip and knee arthroplasty surgeons with the goal of improving quality, decreasing variability in the delivery of care, and leading to improved value and outcomes for hip and knee arthroplasty in the state of Michigan.

Role and therapeutic targets of P2X7 receptors in neurodegenerative diseases.

The P2X7 receptor (P2X7R), a non-selective cation channel modulated by adenosine triphosphate (ATP), localizes to microglia, astrocytes, oligodendrocytes, and neurons in the central nervous system, with the most incredible abundance in microglia. P2X7R partake in various signaling pathways, engaging in the immune response, the release of neurotransmitters, oxidative stress, cell division, and programmed cell death. When neurodegenerative diseases result in neuronal apoptosis and necrosis, ATP activates the P2X7R. This activation induces the release of biologically active molecules such as pro-inflammatory cytokines, chemokines, proteases, reactive oxygen species, and excitotoxic glutamate/ATP. Subsequently, this leads to neuroinflammation, which exacerbates neuronal involvement. The P2X7R is essential in the development of neurodegenerative diseases. This implies that it has potential as a drug target and could be treated using P2X7R antagonists that are able to cross the blood-brain barrier. This review will comprehensively and objectively discuss recent research breakthroughs on P2X7R genes, their structural features, functional properties, signaling pathways, and their roles in neurodegenerative diseases and possible therapies.

Total Hip and Knee Arthroplasty Implant Revision Risk to 5 Years From a State-wide Arthroplasty Registry in Michigan.

Background: Information on the revision risk of implants is useful for improving the quality of care for elective hip and knee arthroplasty. The purpose of this study was to report on the revision risk of implants using a state-wide registry in the United States. Methods: The Michigan Arthroplasty Registry Collaborative Quality Initiative systematically collects data on elective primary and revision hip and knee arthroplasty cases in Michigan. It contained data on 139,970 hip and 245,499 knee arthroplasty cases from February 15, 2012, to December 31, 2021. Kaplan-Meier estimates of revision risk were computed using time to first revision as the dependent variable, and the results were computed and expressed as the cumulative percent revision (CPR). CPR estimates were computed for all implants having at least 500 cases in the Michigan Arthroplasty Registry Collaborative Quality Initiative dataset. Results: At 5-years postoperatively, elective primary conventional total hip arthroplasty implant stem/cup combinations had CPR values from 0.95% (0.39%-2.30%, 95% confidence intervals [CI]) to 5.77% (4.22%-7.85%, 95% CI), and elective primary total knee arthroplasty CPR ranged from 1.10% (0.64%-1.89%, 95% CI) to 12.52% (8.37%-18.50%, 95% CI). Unicondylar knee arthroplasty CPR at 5-years went from 4.23% (3.54%-5.06%, 95% CI) to 7.13% (6.20%-8.20%, 95% CI). Conclusions: The wide variation in CPR points to the need for surgeons to choose implants wisely to improve quality of care.

Limiting the Surveillance Period to 90 Days Misses a Large Portion of Infections in the First Year After Total Hip and Knee Arthroplasty.

Background: In 2013, the Centers for Disease Control and Prevention reduced the periprosthetic joint infection (PJI) surveillance period from 1 year to 90 days for total hip (THA) and knee arthroplasty (TKA). Our aim was to determine how the reduced surveillance window impacts capture of PJIs. Material and methods: Primary and revision THA and TKA cases were retrospectively identified in a statewide registry from October 1, 2015, to September 30, 2018. Infections were defined using the Periprosthetic Joint/Wound Infection measure (Centers for Medicare and Medicaid Services). We compared the cumulative incidence of infected primary and revision THA (pTHA/rTHA) and TKA (pTKA/rTKA) at 0-90 days and 91-365 days postoperatively. Results: A total of 136,491 patients were included, 59.59% female, mean age 65.8 years, and mean body mass index 32.3 kg/m2. The overall rate of PJI diagnosed by 1 year was 1.33%. The percent of infections diagnosed between 0-90 days and 91-365 days were pTHA 76.78% and 23.22%, rTHA 74.12% and 25.88%, pTKA 57.67% and 42.33%, and rTKA 53.78% and 46.22%, respectively. More infections were diagnosed after 90 days in pTKA than in pTHA and in rTKA than in rTHA (P < .0001). There was a higher risk of infection throughout the year when comparing rTKA to rTHA (P = .0374) but not when comparing pTKA to pTHA (P = .0518). Conclusion: A substantial portion of infections are missed by the 90-day surveillance period. More infections are missed after TKA than after THA. Extension of the surveillance period would allow for identification of opportunities for quality improvement.

Genetic polymorphisms and obesity influence estradiol decline during the menopause.

OBJECTIVES: Obesity and genetic variation in aromatase and type 1 17-ß hydroxysteroid dehydrogenase (HSD) could influence the E2 trajectory of decline during the menopause transition. DESIGN AND PARTICIPANTS: E2 trajectories during the menopause transition (phenotype) were identified using 5934 data points acquired annually from 681 women in Study of Women's Health across the Nation (SWAN), a multiethnic study of the mid-life. E2 trajectories were related to CYP19 and type I 17-ßHSD single-nucleotide polymorphisms (SNPs) and obesity. RESULTS: (log) E2 trajectories began to decline precipitously 2 years before the final menstrual period (FMP). The trajectory of the (log) E2 decline varied with genotypes and obesity. (log) E2 rates of decline were greater in nonobese women than in obese women, P < 0·05. Women with the CYP19rs936306 CT variant had (log) E2 rate of decline that was 54% as rapid as the rate of decline of women with the TT variant, P < 0·05. (log) E2 rate of decline in women with the CYP19rs749292 GG variant was two-thirds the rate of (log) E2 decline in women with the AG variant, P < 0·05. (log) Rates of E2 decline with 17-ßHSD SNPs (rs2830, rs592389, and rs615942) varied according to genotype within obesity groups. Within each obesity group, (log) E2 rate of decline was greater in heterozygous variants and much less in homozygotes (P < 0·05). Obese women with selected CYP19 and 17-ß HSD gene variants had remarkably different E2 trajectories around the FMP, resulting in different postmenopausal E2 levels. The rate of the E2 decline and the subsequent postmenopausal E2 levels may be relevant to oestrogen-sensitive chronic diseases including cancers.

Are inflammatory and coagulation biomarkers related to sleep characteristics in mid-life women?: Study of Women's Health across the Nation sleep study.

STUDY OBJECTIVES: Inflammation and pro-coagulation biomarkers may be a link between sleep characteristics and risk for cardiometabolic disorders. We tested the hypothesis that worse sleep characteristics would be associated with C-reactive protein (CRP), fibrinogen, factor VIIc, and plasminogen activator inhibitor (PAI)-1 in a multi-ethnic subsample of mid-life women enrolled in the Study of Women's Health across the Nation. DESIGN: Cross-sectional. MEASUREMENTS AND RESULTS: African American, Chinese, and Caucasian women (N=340) participated in 3 days of in-home polysomnographic (PSG) monitoring and had measures of inflammation and coagulation. Regression analyses revealed that each of the biomarkers were associated with indicators of sleep disordered breathing after adjusting for age, duration between sleep study and blood draw, site, menopausal status, ethnicity, residualized body mass index, smoking status, and medications that affect sleep or biomarkers. Among African American women, those who had higher levels of CRP had shorter PSG-sleep duration and those who had higher levels of fibrinogen had less efficient sleep in multivariate models. CONCLUSIONS: These results suggest that inflammation and pro-coagulation processes may be an important pathway connecting sleep disordered breathing and cardiometabolic disorders in women of these ethnic groups and that inflammation may be a particularly important pathway in African Americans.

Association of Aspirin With Prevention of Venous Thromboembolism in Patients After Total Knee Arthroplasty Compared With Other Anticoagulants: A Noninferiority Analysis.

Importance: There has been significant debate in the surgical and medical communities regarding the appropriateness of using aspirin alone for venous thromboembolism (VTE) prophylaxis following total knee arthroplasty (TKA). Objective: To determine the acceptability of aspirin alone vs anticoagulant prophylaxis for reducing the risk of postoperative VTE in patients undergoing TKA. Design, Setting, and Participants: Noninferiority study of a retrospective cohort of TKA cases submitted to the Michigan Arthroplasty Registry Collaborative Quality Initiative at 29 member hospitals, ranging from small community hospitals to large academic and nonacademic medical centers in Michigan. The study included 41 537 patients who underwent primary TKA between April 1, 2013, and October 31, 2015. Clinical events were monitored for 90 days after surgery. Data were analyzed between September and October 2016. Exposures: The method of pharmacologic prophylaxis: neither aspirin nor anticoagulants for 668 patients (1.6%), aspirin only for 12 831 patients (30.9%), anticoagulant only (eg, low-molecular-weight heparin, warfarin, and Xa inhibitors) for 22 620 patients (54.5%), and both aspirin/anticoagulant for 5418 patients (13.0%). Most patients were also using intermittent pneumatic compression stockings. Main Outcome and Measures: The primary composite outcome was the first occurrence of VTE or death. The noninferiority margin was specified as 0.3. The secondary outcome was bleeding events. Results: Of the 41 537 patients, 14 966 were men (36%), and the mean age was 65.8 years. A VTE event occurred in 573 of 41 537 patients (1.38%); 32 of 668 (4.79%) who received no pharmacologic prophylaxis, 149 of 12 831 (1.16%) treated with aspirin alone, 321 of 22 620 (1.42%) with anticoagulation alone, and 71 of 5418 (1.31%) prescribed both aspirin and anticoagulation. Aspirin only was noninferior for the composite VTE outcome compared with those receiving other chemoprophylaxis (adjusted odds ratio, 0.85; 95% CI, 0.68-1.07, P for inferiority = .007). Bleeding occurred in 457 of 41 537 patients (1.10%), 10 of 668 (1.50%) without prophylaxis, 116 of 12 831 (0.90%) in the aspirin group, 258 of 22 620 (1.14%) with anticoagulation, and 73 of 5418 (1.35%) of those receiving both. Aspirin alone was also noninferior for bleeding complications (adjusted odds ratio, 0.80; 95% CI, 0.63-1.00, P for inferiority <.001). Conclusions and Relevance: In this study of patients undergoing TKA, aspirin was not inferior to other anticoagulants in the postoperative rate of VTE or death. Aspirin alone may provide similar protection from postoperative VTE compared with other anticoagulation treatments.

Estradiol rates of change in relation to the final menstrual period in a population-based cohort of women.

CONTEXT/OBJECTIVE: The aim was to characterize rates of change in serum estradiol (E2) levels across the menopausal transition and into early postmenopause. SETTING/PARTICIPANTS: We studied the Michigan Bone Health and Metabolism Study cohort of 629 women with median age of 38 yr (interquartile range, 7) at the 1992-1993 baseline with annual assessment of E2 levels over the subsequent 15-yr period. DESIGN/MAIN OUTCOME MEASURES: The purpose was to describe patterns of acceleration/deceleration in (log)E2 rates of change before and after the final menstrual period (FMP) using nonparametric and piecewise regression modeling. RESULTS: Between -10 to -2 yr to the FMP, mean fitted serum E2 population values were relatively stable. The 95% confidence bands around the slight increase in E2 rate of change 5 yr prior to the FMP included the value of no change. The fitted population mean E2 value declined 67% from 64.5 pg/ml (se = 3.6) to 21 pg/ml (se = 1.2) in the 4 yr between -2 < FMP < +2. A second significant mean E2 rate of change was identified from 6-8 yr after FMP. Fitted population mean E2 values declined 18% from 18.1 pg/ml (se = 1.3) at FMP = 6 to 14.8 pg/ml (se = 1.3) at FMP = 8. In nonobese women, the mean E2 percent decline was 42% from FMP = 6 to FMP = 8, whereas in obese women, the mean E2 percent decline over this time was 31%. CONCLUSIONS: Population mean serum E2 levels were sustained until approximately 2 yr prior to the FMP. In the ensuing 4-yr period, E2 levels declined 67%. A secondary E2 decline, commencing about 6 yr after the FMP, was observed in nonobese but not obese women.

Follicle stimulating hormone and its rate of change in defining menopause transition stages.

CONTEXT/OBJECTIVE: The objective of the study was to identify menopause transition stages using acceleration or deceleration patterns of FSH rates of change from the late reproductive years to postmenopause. SETTING/PARTICIPANTS: Participants were the Michigan Bone Health and Metabolism Study cohort of 629 women, aged 24-44 yr (in 1992/3), with 5757 annual FSH data points over a 14-yr period. DESIGN/MAIN OUTCOME MEASURES: The study was designed to relate acceleration/deceleration patterns in FSH rate of change to time to final menstrual period (FMP) and chronological age using nonparametric and piecewise regression modeling. RESULTS: Four major FSH stages, based on rate of FSH change patterns, were identifiable in relation to the FMP. In FSH stage 1, the rate of FSH change increased modestly up to -7 yr prior to the FMP; in FSH stage 2 (-7 to -2 yr prior to FMP), there was a major acceleration in FSH rate of change. FSH stage 3 had an acute increase in FSH rate of change (-2 to +1 yr around the FMP), with average FSH level of 34 mIU/ml. The fourth, or plateau, FSH stage began at 1 yr after FMP when the average FSH level was 54 mIU/ml. During the yr 28-60, there were eight age-specific epochs defined by significant changes of FSH trajectory accelerations or decelerations and rate of change. CONCLUSIONS: Four menopause transition stages bounding the FMP and eight epochs in chronological aging from age 28 to 60 yr were defined by changes of FSH trajectory accelerations/decelerations and rates of change. This timing information, combined with knowledge of FSH levels and menstrual cycle characteristics, can help discern the likely status of women with respect to their reproductive viability and menopause transition stage.

Sex steroid hormone profiles are related to sleep measures from polysomnography and the Pittsburgh Sleep Quality Index.

STUDY OBJECTIVES: To relate reproductive hormones (and the preceding 7-year rates of their change) to objectively and subjectively assessed sleep measures, independent of age, vasomotor symptom frequency, depressive symptoms, and body size. DESIGN: A cross-sectional sleep substudy nested in the Study of Women's Health Across the Nation (SWAN), a longitudinal study of the menopausal transition. SETTING: Community-based. PARTICIPANTS: 365 Caucasian, African American, and Chinese women. MEASUREMENTS AND RESULTS: Sleep duration, continuity, and architecture were measured during two nights of in-home polysomnography (PSG) studies. Participants completed the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, sleep diaries for medication, vasomotor symptoms, lifestyle information and questionnaires for depressive symptoms. Blood collected annually in the years prior to sleep study was assayed for follicle stimulating hormone (FSH), estradiol (E2), and total testosterone (T). More rapid rate of FSH change was significantly associated with higher delta sleep percent, longer total sleep time (TST), but less favorable self-reported sleep quality (PSQI). Baseline E2 was modestly and negatively associated with sleep quality. Women in the lowest total testosterone quartile at baseline had more wake time after sleep onset (WASO) than women in the highest quartile. Lower E2/T ratio, an index reflecting the increasing androgenic environment with the menopause transition, was associated with less WASO. CONCLUSIONS: More rapid rate of FSH change was associated with longer sleep duration but poor sleep quality. Women with higher T or who were closer to the completion of the transition process (as indexed by a lower E2/T) had less sleep discontinuity (less WASO).

Application of a Causal Discovery Algorithm to the Analysis of Arthroplasty Registry Data.

Improving the quality of care for hip arthroplasty (replacement) patients requires the systematic evaluation of clinical performance of implants and the identification of "outlier" devices that have an especially high risk of reoperation ("revision"). Postmarket surveillance of arthroplasty implants, which rests on the analysis of large patient registries, has been effective in identifying outlier implants such as the ASR metal-on-metal hip resurfacing device that was recalled. Although identifying an implant as an outlier implies a causal relationship between the implant and revision risk, traditional signal detection methods use classical biostatistical methods. The field of probabilistic graphical modeling of causal relationships has developed tools for rigorous analysis of causal relationships in observational data. The purpose of this study was to evaluate one causal discovery algorithm (PC) to determine its suitability for hip arthroplasty implant signal detection. Simulated data were generated using distributions of patient and implant characteristics, and causal discovery was performed using the TETRAD software package. Two sizes of registries were simulated: (1) a statewide registry in Michigan and (2) a nationwide registry in the United Kingdom. The results showed that the algorithm performed better for the simulation of a large national registry. The conclusion is that the causal discovery algorithm used in this study may be a useful tool for implant signal detection for large arthroplasty registries; regional registries may only be able to only detect implants that perform especially poorly.

The Michigan Arthroplasty Registry Collaborative Quality Initiative Experience: Improving the Quality of Care in Michigan.

The Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI) is a regional quality improvement effort that is focused on hip and knee arthroplasty. From its inception in 2012, MARCQI has grown to include data from 66 hospitals and surgery centers, and contains over 209,000 fully abstracted cases in its database. Using high-quality risk-standardized outcomes data, MARCQI drives quality improvement through a collaborative and nonpunitive structure. Quality improvement initiatives have included transfusion reduction, infection prevention, venous thromboembolism reduction, and reduction of discharge to nursing homes. In addition, MARCQI focuses on postmarket surveillance of implants by computing revision-risk estimates based on the cases that were registered prior to the end of 2016. This paper describes the impact of MARCQI on the quality of hip and knee arthroplasty care in the state of Michigan since its inception in 2012, and it briefly summarizes the recently released 5-year report.