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.

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.

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.

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.

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.

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.

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.

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.

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.

Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and estrone over the menopausal transition.

BACKGROUND: Previous reports have noted that dehydroepiandrosterone-sulfate (DHEAS) increases prior to the final menstrual period (FMP) and remains stable beyond the FMP. How DHEAS concentrations correspond with other sex hormones across the menopausal transition (MT) including androstenedione (A4), testosterone (T), estrone (E1), and estradiol (E2) is not known. Our objective was to examine how DHEAS, A4, T, E1, and E2 changed across the MT by White vs. African-American (AA) race/ethnicity. METHODS: We conducted a longitudinal observational analysis of a subgroup of women from the Study of Women's Health Across the Nation observed over 4 visits prior to and 4 visits after the FMP (n = 110 women over 9 years for 990 observations). The main outcome measures were DHEAS, A4, T, E1, and E2. RESULTS: Compared to the decline in E2 concentrations, androgen concentrations declined minimally over the MT. T (ß 9.180, p < 0.0001) and E1 (ß 11.365, p < 0.0001) were higher in Whites than in AAs, while elevations in DHEAS (ß 28.80, p = 0.061) and A4 (ß 0.2556, p = 0.052) were borderline. Log-transformed E2 was similar between Whites and AAs (ß 0.0764, p = 0.272). Body mass index (BMI) was not significantly associated with concentrations of androgens or E1 over time. CONCLUSION: This report suggests that the declines in E2 during the 4 years before and after the FMP are accompanied by minimal changes in DHEAS, A4, T, and E1. There are modest differences between Whites and AAs and minimal differences by BMI.

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.

Combined intra- and post-cardiac arrest hypothermic-targeted temperature management in a rat model of asphyxial cardiac arrest improves survival and neurologic outcome compared to either strategy alone.

AIM: Post-cardiac arrest hypothermic-targeted temperature management (HTTM) improves outcomes in preclinical cardiac arrest studies. However, inadequate understanding of the mechanisms and therapeutic windows remains a barrier to optimization. We tested the hypothesis that combined intra- and post-cardiac arrest HTTM provides a synergistic outcome benefit compared to either strategy alone. METHODS: Rats subjected to 8-min asphyxial cardiac arrest were block randomized to 4 treatment groups (n=12/group): NTTM) normothermic-targeted temperature management; 1-24 HTTM) HTTM initiated 1h post-ROSC and maintained for 24h; Intra-1 HTTM) HTTM initiated at CPR onset and maintained for 1h; and Intra-24 HTTM) HTTM initiated at CPR onset and maintained for 24h. HTTM was induced by nasopharyngeal cooling and maintained using an automated temperature regulation system. Target temperature range was 36.5-37.5°C for NTTM and 32.0-34.0°C for HTTM. Post-arrest neurologic function score (NFS) was measured daily, and rats surviving 72h were euthanized for histological analysis of neurodegeneration. RESULTS: Target brain temperature was achieved 7.8±3.3min after initiating intra-arrest cooling. The survival rate was 42%, 50%, 50%, and 92% in the NTTM, 1-24 HTTM, Intra-1 HTTM, and Intra-24 HTTM groups, respectively (p<0.05, Intra-24 group vs. all other groups). The rate of survival with good neurologic function (NFS≥450) was 33% in the Intra-24 HTTM group vs. 0% in all other groups (mid p<0.05). Hippocampal CA1 sector neurodegeneration was significantly reduced in the Intra-24 HTTM group compared to all other groups (p<0.05). CONCLUSION: Combined intra- and post-cardiac arrest HTTM has greater outcome benefits than either strategy alone.

Characterizing the trajectories of vasomotor symptoms across the menopausal transition.

OBJECTIVE: The aim of the study was to investigate the heterogeneity of temporal patterns of vasomotor symptoms (VMS) over the menopausal transition and identify factors associated with these patterns in a diverse sample of women. METHODS: The Study of Women's Health Across the Nation is a multisite longitudinal study of women from five racial/ethnic groups transitioning through the menopause. The analytic sample included 1,455 women with nonsurgical menopause and a median follow-up of 15.4 years. Temporal patterns of VMS and associations with serum estradiol and follicle-stimulating hormone, race/ethnicity, body mass index, and demographic and psychosocial factors were examined using group-based trajectory modeling. RESULTS: Four distinct trajectories of VMS were found: onset early (11 years before the final menstrual period) with decline after menopause (early onset, 18.4%), onset near the final menstrual period with later decline (late onset, 29.0%), onset early with persistently high frequency (high, 25.6%), and persistently low frequency (low, 27.0%). Relative to women with persistently low frequency of VMS, women with persistently high and early onset VMS had a more adverse psychosocial and health profile. Black women were overrepresented in the late onset and high VMS subgroups relative to white women. Obese women were underrepresented in the late onset subgroup. In multivariable models, the pattern of estradiol over the menopause was significantly associated with the VMS trajectory. CONCLUSIONS: These data distinctly demonstrate heterogeneous patterns of menopausal symptoms that are associated with race/ethnicity, reproductive hormones, premenopause body mass index, and psychosocial characteristics. Early targeted intervention may have a meaningful impact on long-term VMS.

Higher Leptin and Adiponectin Concentrations Predict Poorer Performance-based Physical Functioning in Midlife Women: the Michigan Study of Women's Health Across the Nation.

BACKGROUND: Excess fat mass is a greater contributor to functional limitations than is reduced lean mass or the presence of obesity-related conditions. The impact of fat mass on physical functioning may be due to adipokines, adipose-derived proteins that have pro- or anti-inflammatory properties. METHODS: Serum samples from 1996 to 2003 that were assayed for leptin, adiponectin, and resistin were provided by 511 participants from the Michigan site of the Study of Women's Health Across the Nation. Physical functioning performance was assessed annually during study visits from 1996 to 2003. RESULTS: Among this population of Black and White women (mean baseline age = 45.6 years, SD = 2.7 years), all of whom were premenopausal at baseline, higher baseline leptin concentrations predicted longer stair climb, sit-to-rise, and 2-pound lift times and shorter forward reach distance (all p < .01). This relationship persisted after adjustment for age, BMI, percent skeletal muscle mass, race/ethnicity, economic strain, bodily pain, diabetes, knee osteoarthritis, and C-reactive protein. Baseline total adiponectin concentrations did not predict any mobility measures but did predict quadriceps strength; a 1 µg/mL higher adiponectin concentration was associated with 0.64 Nm lower quadriceps strength (p = .02). Resistin was not associated with any of the physical functioning performance measures. Change in the adipokines was not associated with physical functioning. CONCLUSION: In this population of middle-aged women, higher baseline leptin concentrations predicted poorer mobility-based functioning, whereas higher adiponectin concentrations predicted reduced quadriceps strength. These findings suggest that the relationship between the adipokines and physical functioning performance is independent of other known correlates of poor functioning.

Fast estimation of regression parameters in a broken-stick model for longitudinal data.

Estimation of change-point locations in the broken-stick model has significant applications in modeling important biological phenomena. In this article we present a computationally economical likelihood-based approach for estimating change-point(s) efficiently in both cross-sectional and longitudinal settings. Our method, based on local smoothing in a shrinking neighborhood of each change-point, is shown via simulations to be computationally more viable than existing methods that rely on search procedures, with dramatic gains in the multiple change-point case. The proposed estimates are shown to have [Formula: see text]-consistency and asymptotic normality - in particular, they are asymptotically efficient in the cross-sectional setting - allowing us to provide meaningful statistical inference. As our primary and motivating (longitudinal) application, we study the Michigan Bone Health and Metabolism Study cohort data to describe patterns of change in log estradiol levels, before and after the final menstrual period, for which a two change-point broken stick model appears to be a good fit. We also illustrate our method on a plant growth data set in the cross-sectional setting.

An actigraphy study of sleep and pain in midlife women: the Study of Women's Health Across the Nation Sleep Study.

OBJECTIVE: We examined whether women reporting nighttime pain would have more actigraphy-measured evidence for disturbed sleep and would report feeling less rested compared with women without nighttime pain. METHODS: Up to 27 consecutive nights of actigraphy and sleep diary data from each participant were analyzed in this community-based study of 314 African-American (n = 118), white (n = 141), and Chinese (n = 55) women, aged 48 to 58 years, who were premenopausal, perimenopausal, or postmenopausal and were participating in the Study of Women's Health Across the Nation Sleep Study. Dependent variables were actigraphy-measured movement and fragmentation index, total sleep time, sleep efficiency, and diary self-report of "feeling rested" after waking up. All outcomes were fitted using linear mixed-effects models to examine covariate-adjusted associations between the independent variable (nighttime pain severity) and sleep outcomes. RESULTS: Higher pain severity scores were associated with longer sleep duration but reduced sleep efficiency and less restful sleep. Women reporting nocturnal vasomotor symptoms had more sleep-related movement and sleep fragmentation, had reduced sleep efficiency, and were less likely to feel rested after wakening whether or not they reported pain. CONCLUSIONS: Midlife women who report higher nighttime pain levels have more objective evidence for less efficient sleep, consistent with self-reported less restful sleep. Nocturnal vasomotor symptoms also can contribute to restlessness and wakefulness in midlife women.

Masturbation frequency and sexual function domains are associated with serum reproductive hormone levels across the menopausal transition.

OBJECTIVE: To determine whether reproductive hormones are related to sexual function during the menopausal transition. DESIGN: The Study of Women's Health Across the Nation (SWAN) is a multiethnic cohort study of the menopausal transition located at seven US sites. At baseline, the 3302 community-based participants, aged 42-52, had an intact uterus and at least one ovary and were not using exogenous hormones. Participants self-identified as White, Black, Hispanic, Chinese, or Japanese. At baseline and at each of the 10 follow-up visits, sexual function was assessed by self-administered questionnaires, and blood was drawn to assay serum levels of T, estradiol, FSH, SHBG, and dehydroepiandrosterone sulfate. MAIN OUTCOME MEASURES: Self-reported frequency of masturbation, sexual desire, sexual arousal, orgasm, and pain during intercourse. RESULTS: Masturbation, sexual desire, and arousal were positively associated with T. Masturbation, arousal, and orgasm were negatively associated with FSH. Associations were modest. Estradiol was not related to any measured sexual function domain. Pain with intercourse was not associated with any hormone. CONCLUSIONS: Reproductive hormones were associated with sexual function in midlife women. T was positively associated, supporting the role of androgens in female sexual function. FSH was negatively associated, supporting the role of menopausal status in female sexual function. The modest associations in this large study suggest that the relationships are subtle and may be of limited clinical significance.

Actigraphy-defined measures of sleep and movement across the menstrual cycle in midlife menstruating women: Study of Women's Health Across the Nation Sleep Study.

OBJECTIVE: This study aims to evaluate patterns in actigraphy-defined sleep measures across the menstrual cycle by testing the hypothesis that sleep would be more disrupted in the premenstrual period (ie, within the 14 d before menses). METHODS: A community-based longitudinal study of wrist actigraphy-derived sleep measures was conducted in 163 (58 African American, 78 white, and 27 Chinese) late-reproductive-age (mean [SD], 51.5 [2.0] y) women from the Study of Women's Health Across the Nation Sleep Study. Daily measures of sleep (sleep efficiency [%] and total sleep time [minutes]) and movement during sleep (mean activity score [counts]) were characterized using wrist actigraphy across a menstrual cycle or 35 days, whichever was shorter. Data were standardized to 28 days to account for unequal cycle lengths and divided into four weekly segments for analyses. RESULTS: Sleep efficiency declined gradually across the menstrual cycle, but the decline became pronounced on the fourth week (the premenstrual period). Compared with the third week, sleep efficiency declined by 5% (P < 0.0001) and mean total sleep time was 25 minutes less (P = 0.0002) on the fourth week. We found no significant differences between the mean for the second week and the mean for the third week. The association of weekly segments with sleep efficiency or total sleep time was modified by sociodemographic and lifestyle factors, including body mass index, race, study site, financial strain, marital status, and smoking. CONCLUSIONS: Among late-reproductive-age women, sleep varies systematically across the menstrual cycle, including a gradual decline in sleep efficiency across all weeks, with a more marked change premenstrually during the last week of the menstrual cycle. These sleep changes may be modified by altering lifestyle factors.