Perioperative Sleep Quality Disturbances in Total Joint Arthroplasty is Multifactorial.

BACKGROUND: Sleep quality following arthroplasty procedures is important for patient recovery and satisfaction, but remains poorly understood. The purpose of this study was to report risk factors for sleep disturbances in the perioperative period in patients undergoing primary total joint arthroplasty procedures. METHODS: Sleep surveys were prospectively collected on 751 consecutive patients undergoing total joint arthroplasty at our institution between June 2019 and February 2021 at their preoperative and postoperative visits (2 and 6 weeks). Data were collected on patient demographics, opioid use (preoperatively and postoperatively) as well as tobacco and alcohol use, and specific medical diagnosis that may influence sleep patterns (ie, depression). Statistical analyses were performed using the Student's t-tests and 1-way analysis of variances. RESULTS: For both total hip and total knee patients, worse sleep patterns preoperatively were found in patients who used opioids prior to surgery (P < .001), were current smokers (P < .001), and were aged less than 65 years (P < .001). Postoperative persistent opioid use (more than 3 months) was seen in patients who had worse reported sleep quality preoperatively (P < .001). In comparison to total hip arthroplasty, patients who underwent total knee arthroplasty were more likely to report less sleep in the postoperative period. Patients who were current smokers (compared to nonsmokers or previous smokers) (P = .014) had worse sleep quality at all time points that persisted at 6 weeks, although these differences were seen more in total hip patients than in total knee patients (P = .006 versus P = .059). CONCLUSIONS: Sleep quality disturbances around the time of surgery appear to be multifactorial. LEVEL OF EVIDENCE: Therapeutic Level III.

Methods and evaluation metrics for reducing material waste in the operating room: a scoping review.

BACKGROUND: Operating rooms contribute up to 70% of total hospital waste. Although multiple studies have demonstrated reduced waste through targeted interventions, few examine processes. This scoping review highlights methods of study design, outcome assessment, and sustainability practices of operating room waste reduction strategies employed by surgeons. METHODS: Embase, PubMed, and Web of Science were screened for operating room-specific waste-reduction interventions. Waste was defined as hazardous and non-hazardous disposable material and energy consumption. Study-specific elements were tabulated by study design, evaluation metrics, strengths, limitations, and barriers to implementation in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. RESULTS: A total of 38 articles were analyzed. Among them, 74% of studies had pre- versus postintervention designs, and 21% used quality improvement instruments. No studies used an implementation framework. The vast majority (92%) of studies measured cost as an outcome, whereas others included disposable waste by weight, hospital energy consumption, and stakeholder perspectives. The most common intervention was instrument tray optimization. Common barriers to implementation included lack of stakeholder buy-in, knowledge gaps, data capture, additional staff time, need for hospital or federal policies, and funding. Intervention sustainability was discussed in few studies (23%) and included regular waste audits, hospital policy change, and educational initiatives. Common methodologic limitations included limited outcome evaluation, narrow scope of intervention, and inability to capture indirect costs. CONCLUSION: Appraisal of quality improvement and implementation methods are critical for developing sustainable interventions for reducing operating room waste. Universal evaluation metrics and methodologies may aid in both quantifying the impact of waste reduction initiatives and understanding their implementation in clinical practice.

Platelet-Rich Plasma Injections for Shoulder Adhesive Capsulitis Are at Least Equivalent to Corticosteroid or Saline Solution Injections: A Systematic Review of Prospective Cohort Studies.

PURPOSE: To evaluate the role of platelet-rich plasma (PRP) for adhesive capsulitis (AC) as compared with other injectables. METHODS: A literature search of the PubMed and Embase online databases was performed to identify articles evaluating injection therapy for the treatment of AC. The inclusion criteria included prospective studies comparing PRP against alternative injectables with a minimum of 15 patients in each treatment arm and a minimum 12-week follow-up period. Pain scores, range of motion, and function scores were the primary outcomes assessed. RESULTS: Five articles comparing PRP with corticosteroid or saline solution injections met the inclusion criteria. A total of 157 patients were treated with PRP, with a follow-up duration ranging from 3 to 6 months. All 5 studies showed statistically significant improvements in pain scores, motion, and function scores in patients receiving PRP, corticosteroid, and saline solution injections. However, PRP was consistently superior on intergroup analyses in all but 1 study. In 4 studies, pain and function scores favored PRP over control at final follow-up (range in mean difference, -2.2 to 0.69 for visual analog scale pain score [n = 5] and -50.5 to -4.0 for Shoulder Pain and Disability Index score [n = 3]), whereas 3 studies found greater improvement in shoulder motion after PRP (range in mean difference, 0.7° to 34.3° for forward flexion and -2.3° to 20.4° for external rotation [n = 4]). One study found no significant difference between PRP and corticosteroid injections but noted that the results were comparable. CONCLUSIONS: According to a limited number of prospective studies, PRP injections for AC are at least equivalent to corticosteroid or saline solution injections and often lead to improved pain, motion, and functional outcomes at 3- to 6-month follow-up. Given the small number of studies, with design heterogeneity, there is insufficient evidence to routinely recommend PRP for AC. However, the results are promising and do support considering PRP as an adjunct treatment option for AC, especially for patients refractory and/or averse to corticosteroids or alternative treatment modalities. LEVEL OF EVIDENCE: Level II, systematic review of Level I and II studies.

B Cell-Activating Factor Antagonism Attenuates the Growth of Experimental Abdominal Aortic Aneurysm.

B cell-activating factor (BAFF), part of a tumor necrosis factor family of cytokines, was recently identified as a regulator of atherosclerosis; however, its role in aortic aneurysm has not been determined. Here, the study examined the effect of selective BAFF antagonism using an anti-BAFF antibody (blocks binding of BAFF to receptors BAFF receptor 3, transmembrane activator and CAML interactor, and B-cell maturation antigen) and mBaffR-mFc (blocks binding of BAFF to BAFF receptor 3) on a murine model of abdominal aortic aneurysm (AAA). In a prevention strategy, the antagonists were injected before the induction of AAA, and in an intervention strategy, the antagonists were injected after the induction of AAA. Both strategies attenuated the formation of AAA. In the intervention group, BAFF antagonism depleted most of the mature B-cell subsets in spleen and circulation, leading to enhanced resolution of inflammation in AAA as indicated by decreased infiltration of B cells and proinflammatory macrophages and a reduced number of apoptotic cells. In AAA tissues, B cells and macrophages were found in close contact. In vitro, B cells, irrespective of treatment with BAFF, impaired the efferocytosis activity of macrophages, suggesting a direct innate role of B cells on macrophage function. Altogether, BAFF antagonism affects survival of the mature B cells, promotes resolution of inflammation in the aorta, and attenuates the growth of AAA in mice.

Sex-Based Differences Among Experimental Swine Abdominal Aortic aneurysms.

BACKGROUND: Female sex protects against abdominal aortic aneurysms (AAAs); however, the mechanisms behind these sex-based differences remain unknown. The purpose of this study was to explore the role of sex and sex hormones in AAA formation among swine. MATERIALS AND METHODS: Using a previous validated model, infrarenal AAA were surgically created in uncastrated male (n = 8), female (n = 5), and castrated male (n = 4) swine. Aortic dilation was measured on postoperative day 28 during the terminal procedure and compared to initial aortic diameter measured during the index procedure. Tissue was analyzed for immunohistochemistry, cytokine array, gelatin zymography, serum 17ß-estradiol, and testosterone assay. RESULTS: Uncastrated males had significantly larger maximal aortic dilation compared to castrated males (113.5% ± 11.4% versus 38.1% ± 4.5%, P = 0.0012). Females had significantly higher mean aortic dilation compared to castrated males (96.2% ± 7.5% versus 38.1% ± 4.5%, P = 0.0004). Aortic diameters between females and uncastrated males were not significantly different on day 28. Female swine had significantly higher concentrations of 17ß-estradiol compared with uncastrated males (1590 ± 873.3 ng/mL versus 95.2 ± 2.3 ng/mL, P = 0.047), with no significant difference between females and castrated males. Uncastrated male AAA demonstrated significantly more elastin degradation compared with female and castrated males (P = 0.01 and <0 .01, respectively). No differences existed for T-cells or smooth muscle cells between groups. Multiple proinflammatory cytokines were elevated within uncastrated male aortic walls compared to females and castrated males. CONCLUSIONS: Sex hormones, specifically 17ß-estradiol and testosterone, influence experimental swine AAA formation as demonstrated by increased aneurysm size, collagen turnover, and elastolysis in uncastrated males in processes reflective of human disease.

Pharmacologic inhibition of transient receptor channel vanilloid 4 attenuates abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, leukocyte infiltration, and vascular remodeling. This study investigates the role of TRPV4 channels, which are transmembrane calcium channels that can regulate vascular tone, in modulating AAA formation. The elastase-treatment model of AAA in C57BL6 (WT) mice and Angiotensin II treatment model in ApoE-/- mice were used to confirm our hypotheses. The administration of a specific TRPV4 antagonist, GSK2193874, in elastase-treated WT mice and in AngII-treated ApoE-/- mice caused a significant attenuation of aortic diameter, decrease in pro-inflammatory cytokines (IL-1ß, IL-6, IL-17, MCP-1, MIP-1α, MIP-2, RANTES, and TNF-α), inflammatory cell infiltration (CD3 + T cells, macrophages, and neutrophils), elastic fiber disruption, and an increase in smooth muscle cell α-actin expression compared to untreated mice. Similarly, elastase-treated TRPV4-/- mice had a significant decrease in AAA formation, aortic inflammation, and vascular remodeling compared to elastase-treated WT mice on Day 14. In vitro studies demonstrated that the inhibition of TRPV4 channels mitigates aortic smooth muscle cell-dependent inflammatory cytokine production as well as decreases neutrophil transmigration through aortic endothelial cells. Therefore, our results suggest that TRPV4 antagonism can attenuate aortic inflammation and remodeling via decreased smooth muscle cell activation and neutrophil transendothelial migration during AAA formation.

Porcine Model of Infrarenal Abdominal Aortic Aneurysm.

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called ß-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease. Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone. Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% ± 47.4% at day 7, 105.4% ± 58.1% at day 14, and 113.5% ± 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p < 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease. Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN.

ZFP148 (Zinc-Finger Protein 148) Binds Cooperatively With NF-1 (Neurofibromin 1) to Inhibit Smooth Muscle Marker Gene Expression During Abdominal Aortic Aneurysm Formation.

Objective- The goal of this study was to determine the role of ZFP148 (zinc-finger protein 148) in aneurysm formation. Approach and Results- ZFP148 mRNA expression increased at day 3, 7, 14, 21, and 28 after during abdominal aortic aneurysm formation in C57BL/6 mice. Loss of ZFP148 conferred abdominal aortic aneurysm protection using ERTCre+ ZFP148 flx/flx mice. In a third set of experiments, smooth muscle-specific loss of ZFP148 alleles resulted in progressively greater protection using novel transgenic mice (MYH [myosin heavy chain 11] Cre+ flx/flx, flx/wt, and wt/wt). Elastin degradation, LGAL3, and neutrophil staining were significantly attenuated, while α-actin staining was increased in ZFP148 knockout mice. Results were verified in total cell ZFP148 and smooth muscle-specific knockout mice using an angiotensin II model. ZFP148 smooth muscle-specific conditional mice demonstrated increased proliferation and ZFP148 was shown to bind to the p21 promoter during abdominal aortic aneurysm formation. ZFP148 smooth muscle-specific conditional knockout mice also demonstrated decreased apoptosis as measured by decreased cleaved caspase-3 staining. ZFP148 bound smooth muscle marker genes via chromatin immunoprecipitation analysis mediated by NF-1 (neurofibromin 1) promote histone H3K4 deacetylation via histone deacetylase 5. Transient transfections and chromatin immunoprecipitation analyses demonstrated that NF-1 was required for ZFP148 protein binding to smooth muscle marker genes promoters during aneurysm formation. Elimination of NF-1 using shRNA approaches demonstrated that NF-1 is required for binding and elimination of NF-1 increased BRG1 recruitment, the ATPase subunit of the SWI/SWF complex, and increased histone acetylation. Conclusions- ZFP148 plays a critical role in multiple murine models of aneurysm formation. These results suggest that ZFP148 is important in the regulation of proliferation, smooth muscle gene downregulation, and apoptosis in aneurysm development.

A novel swine model of abdominal aortic aneurysm.

OBJECTIVE: Few large-animal models exist for the study of aortic aneurysms. ß-Aminopropionitrile (BAPN) is a compound known to cause aortic aneurysms by inhibiting lysyl oxidase, a collagen cross-linking enzyme. It is hypothesized that BAPN plus aneurysm induction surgery would result in significant aneurysm formation in swine with biologic properties similar to human disease. METHODS: Initial experiments were performed in uncastrated male swine not treated with BAPN (surgery alone). Subsequently, uncastrated male swine were fed BAPN (0.15 g/kg) for 7 days before undergoing surgery; the infrarenal aorta was circumferentially dissected and measured, balloon dilated, and perfused with elastase (500 units) and type I collagenase (8000 units), with extraluminal elastase application. In the BAPN groups, daily BAPN feedings continued until swine harvest at postoperative days 7, 14, and 28. RESULTS: Swine undergoing surgery alone (n = 12) had significantly less dilation at 28 days compared with BAPN + surgery swine (51.9% ± 29.2% [0%-100%] vs 113.5% ± 30.2% [52.9%-146.2%]; P < .0003). Mean aortic dilation in animals undergoing treatment with surgery and BAPN was 86.9% ± 47.4% (range, 55.6%-157.1%), 105.4% ± 58.1% (50%-133.3%), and 113.5% ± 30.2% (52.9%-146.2%) at 7, 14, and 28 days, respectively. In the BAPN + surgery group, significant elastolysis was present at all time points, whereas aortic wall collagen content was not significantly different. Smooth muscle cells were significantly depleted at 14 and 28 days, and M1 macrophages were increased at 14 and 28 days (P < .05, all). Matrix metalloproteinase 2 was elevated at 7 days (P < .05). Multiple proinflammatory cytokines were elevated within the aortic wall of BAPN + surgery swine. CONCLUSIONS: BAPN plus surgery resulted in significantly larger aortic aneurysms than surgery alone and was critical to aneurysm formation in this novel swine model. Hallmarks of human disease, such as elastin fragmentation, smooth muscle cell depletion, macrophage infiltration, matrix metalloproteinase activation, and proinflammatory cytokine expression, were observed in BAPN-treated swine. This model better parallels many of the characteristics of human AAAs and may be suitable for prehuman drug trials.

Resolvin D1 decreases abdominal aortic aneurysm formation by inhibiting NETosis in a mouse model.

OBJECTIVE: Resolvins have been shown to attenuate inflammation, whereas NETosis, the process of neutrophils releasing neutrophil extracellular traps (NETs), produces increased inflammation. It is hypothesized that treatment of animals with resolvin D1 (RvD1) would reduce abdominal aortic aneurysm (AAA) formation by inhibiting NETosis. METHODS: Wild-type 8- to 12-week-old C57BL/6 male mice (n = 47) and apolipoprotein E-deficient (ApoE-/-) mice (n = 20) were used in two models to demonstrate the effects of RvD1 on AAA growth. In the topical elastase AAA model, wild-type mice were divided into three groups: a deactivated elastase control group, in which sham surgery was performed using deactivated elastase and mice were intravenously injected with phosphate-buffered saline (PBS) once a day until harvest; an elastase group, in which active elastase was used to induce AAA and mice were injected with PBS daily until harvest; and an RvD1-treated group, in which AAA was induced and mice were injected with RvD1 daily until harvest. In the angiotensin II (Ang II)-induced AAA model, ApoE-/- mice were fed a high-fat diet and implanted with osmotic infusion pumps containing Ang II (1000 ng/kg/min). The Ang II model was divided into two groups: an Ang II control group, in which Ang II was delivered and mice were injected with PBS daily until harvest; and an RvD1-treated group, in which Ang II was delivered and mice were injected with RvD1 daily until harvest. On postoperative day 3, day 14, or day 28, aortic and blood samples were collected for Western blot, histology, cytokine array, enzyme-linked immunosorbent assay, and gelatin zymography after aortic diameter measurement. RESULTS: The day 14 RvD1-treated group demonstrated 42% reduced AAA diameter compared with the elastase group (P < .001). On postoperative day 3, the RvD1-treated group showed decreased levels of NETosis markers citrullinated histone H3 (P = .04) and neutrophil elastase (P = .002) compared with the elastase group. Among important cytokines involved in AAA formation, interleukin (IL) 1ß was downregulated (P = .02) whereas IL-10, a protective cytokine, was upregulated (P = .01) in the RvD1-treated group. Active matrix metalloproteinase 2 also decreased in the RvD1-treated group (P = .03). The RvD1-treated group in the Ang II AAA model, a second model, demonstrated reduced AAA diameter compared with the Ang II control group on day 28 (P < .046). The RvD1-treated group showed decreased levels of citrullinated histone H3 on day 3 (P = .002). Cytokines interferon γ, IL-1ß, C-X-C motif chemokine ligand 10, monocyte chemotactic protein 1, and regulated on activation, normal T cell expressed and secreted (RANTES) were all decreased on day 28 (P < .05). CONCLUSIONS: RvD1-mediated inhibition of NETosis may represent a future medical treatment for the attenuation of AAA growth.

Tamsulosin attenuates abdominal aortic aneurysm growth.

BACKGROUND: Tamsulosin, an α1A-adrenergic receptor inhibitor, is prescribed to treat benign prostatic hyperplasia in men >60 years of age, the same demographic most susceptible to abdominal aortic aneurysm. The goal of this study was to investigate the effect of tamsulosin on abdominal aortic aneurysm pathogenesis. METHODS: Abdominal aortic aneurysms were induced in WT C57BL/6 male mice (n = 9-18/group), using an established topical elastase abdominal aortic aneurysm model. Osmotic pumps were implanted in mice 5 days before operation to create the model, administering either low dose (0.125 µg/day tamsulosin), high dose (0.250µg/day tamsulosin), or vehicle treatments with and without topical application of elastase. Blood pressures were measured preoperatively and on postoperative days 0, 3, 7, and 14. On postoperative day 14, aortic diameter was measured before harvest. Sample aortas were prepared for histology and cytokine analysis. RESULTS: Measurements of systolic blood pressure did not differ between groups. Mice treated with the low dose of tamsulosin and with the high dose of tamsulosin showed decreased aortic diameter compared with vehicle-treated control (93% ± 24 versus 94% ± 30 versus 132% ± 24, respectively; P = .0003, P = .0003). Cytokine analysis demonstrated downregulation of pro-inflammatory cytokines in both treatment groups compared with the control (P < .05). Histology exhibited preservation of elastin in both low- and high-dose tamsulosin-treated groups (P = .0041 and P = .0018, respectively). CONCLUSION: Tamsulosin attenuates abdominal aortic aneurysm formation with increased preservation of elastin and decreased production of pro-inflammatory cytokines. Further studies are necessary to elucidate the mechanism by which tamsulosin attenuates abdominal aortic aneurysm pathogenesis.

A novel reproducible model of aortic aneurysm rupture.

INTRODUCTION: Given the unknown biologic antecedents before aortic aneurysm rupture, the purpose of this study was to establish a reproducible model of aortic aneurysm rupture. METHODS: We fed 7-week-old apolipoprotein E deficient mice a high-fat diet for 4 weeks and osmotic infusion pumps containing Angiotensin II were implanted. Angiotensin II was delivered continuously for 4 weeks at either 1,000 ng/kg/min (n = 25) or 2,000 ng/kg/min (n = 29). A third group (n = 14) were given Angiotensin II at 2,000 ng/kg/min and 0.2% ß-aminopropionitrile dissolved in drinking water. Surviving mice were killed 28 days after pump placement, aortic diameters were measured, and molecular analyses were performed. RESULTS: Survival at 28 days was significantly different among groups with 80% survival in the 1,000 ng/kg/min group, 52% in the 2,000 ng/kg/min group, and only 14% in the Angiotensin II/ß-aminopropionitrile group (P = .0001). Concordantly, rupture rates were statistically different among groups (8% versus 38% versus 79%, P < .0001). Rates of abdominal aortic aneurysm were 48%, 55%, and 93%, respectively, with statistically higher rates in the Angiotensin II/ß-aminopropionitrile group compared with both the 1,000 ng and 2,000 ng Angiotensin II groups (P = .006 and P = .0165, respectively). Rates of thoracic aortic aneurysm formation were 12%, 52%, and 79% in the 3 groups with a statistically higher rate in the Angiotensin II/ß-aminopropionitrile group compared with 1,000 ng group (P < .0001). CONCLUSIONS: A reproducible model of aortic aneurysm rupture was developed with a high incidence of abdominal and thoracic aortic aneurysm. This model should enable further studies investigating the pathogenesis of aortic rupture, as well as allow for targeted strategies to prevent human aortic aneurysm rupture.

Impact of caring for persons with Alzheimer's disease or dementia on caregivers' health outcomes: findings from a community based survey in Japan.

BACKGROUND: This study assessed how family caregivers for patients with Alzheimer's disease (AD) or dementia in Japan differed from non-caregivers in characteristics and health outcomes (i.e., comorbidities, health-related quality of life [HRQoL], productivity, and resource use). Caregivers were hypothesized to experience significantly poorer outcomes than non-caregivers. METHODS: Data were combined from the 2012 and 2013 National Health and Wellness Survey in Japan (n = 60000). Caregivers for adult relatives with AD or dementia were compared with non-caregivers on: comorbidities (including Patient Health Questionnaire (PHQ-9) cutoff scores suggesting presence/absence of major depressive disorder (MDD)), Work Productivity and Activity Impairment (WPAI), SF-36v2-based HRQoL, and healthcare resource utilization. Sociodemographic characteristics, health characteristics and behaviors, and Charlson comorbidity index (CCI) scores were compared across groups. Propensity matching, based on scores generated from a logistic regression predicting caregiving, was used to match caregivers with non-caregivers with similar likelihood of being caregivers. Bivariate comparisons across matched groups served to estimate outcomes differences due to caregiving. RESULTS: Among 55060 respondents, compared with non-caregivers (n = 53758), caregivers (n = 1302) were older (52.6 vs. 47.5 years), more frequently female (53 % vs. 49 %), married/partnered, frequent alcohol drinkers, current smokers, exercisers, and not employed, and they averaged higher CCI scores (0.37 vs. 0.14), all p < 0.05. Propensity scores incorporated sex, age, body mass index (BMI), exercise, alcohol, smoking, marital status, CCI, insured status, education, employment, income, and children in household. A greedy matching algorithm produced 1297 exact matches, excluding 5 non-matched caregivers. Health utilities scores were significantly lower among caregivers (0.724) vs. non-caregivers (0.764), as were SF-36v2 Physical and Mental Component Summary scores. Caregivers vs. non-caregivers had significantly higher absenteeism, presenteeism-related impairment, overall work impairment (25.8 % vs. 20.4 %, respectively), and activity impairment (25.4 % vs. 21.8 %), more emergency room and traditional provider visits (7.70 vs. 5.35) in the past six months, and more frequent MDD (14 % vs. 9 %), depression, insomnia, anxiety, and pain. CONCLUSIONS: Those providing care for patients with AD or dementia in Japan experienced significantly poorer HRQoL and greater comorbid risk, productivity impairment, and resource use. These findings inform the need for greater support for caregivers and their patients.

Medication use patterns, health care resource utilization, and economic burden for patients with major depressive disorder in Beijing, People's Republic of China.

OBJECTIVE: The objective of the study was to investigate medication usage patterns, health care resource utilization, and direct medical costs of patients with major depressive disorder (MDD) in Beijing, People's Republic of China. METHODS: Data were extracted from a random sample of the Beijing Urban Employee Basic Medical Insurance database. Patients aged ≥18 years, with ≥1 primary diagnosis of MDD and 12-month continuous enrollment after their first observed MDD diagnosis between 2012 and 2013 were identified. Those with a diagnosis of schizophrenia, bipolar disorder, or cancer during the analysis period were excluded. RESULTS: In total 8,484 patients, with a mean age of 57.2 years, were included and 63% were female. The top three commonly observed comorbidities were hypertension (70.9%), anxiety disorder (68.6%), and coronary heart disease (65.1%). Furthermore, 71.4% of patients were treated with antidepressant medications, including 60.5% of patients treated with selective serotonin reuptake inhibitors, followed by noradrenergic and specific serotonergic antidepressants (9.0%) and serotonin-norepinephrine reuptake inhibitors (8.3%). The proportions of patients who discontinued their initial antidepressant within the first and second months after the index date were 45.4% and 77.0%, respectively. Concomitant medications were prescribed for 76.8% of patients. Only 0.42% of patients experienced ≥1 MDD-related hospitalization(s) during the 1-year follow-up, and the average annual number of hospitalization was 1.2 for those hospitalized. The mean length of stay was 33.4 days per hospitalization. All patients had ≥1 MDD-related outpatient visit(s). The mean annual number of outpatient visits per patient was 3.1. The mean annual direct medical costs per patient with MDD was RMB ¥1,694.1 (48.5% for antidepressant medications), and that for hospitalized patients was RMB ¥21,291.0 (15.0% for antidepressant medications). CONCLUSION: In Beijing, the majority of patients with MDD were treated in the outpatient setting only and they received antidepressants. Selective serotonin reuptake inhibitors were the most commonly used antidepressants. However, the duration to antidepressant medication was short, and persistence was low. The economic burden of MDD-related hospitalization was considerable.

Development of a surgical skills curriculum for the training and assessment of manual skills in orthopedic surgical residents.

OBJECTIVE: To develop and conduct a pilot study of a curriculum of 4 surrogate bone training modules to assess and track progress in basic orthopedic manual skills outside the operating room. DESIGN: Four training modules were developed with faculty and resident input. The modules include (1) cortical drilling, (2) drill trajectory, (3) oscillating saw, and (4) pedicle probing. Orthopedic resident's performance was evaluated. Validity and reliability results were calculated using standard analysis of variance and multivariate regression analysis accounting for postgraduate year (PGY) level, number of attempts, and specific outcome target results specific to the simulation module. SETTING: St. Mary's Medical Center in San Francisco, CA. PARTICIPANTS: These modules were tested on 15 orthopedic surgery residents ranging from PGY 1 to PGY 5 experience. RESULTS: The cortical drilling module had a mean success rate of 56% ± 5%. There was a statistically significant difference in performance according to the diameter of the drill used from 33% ± 7% with large diameter to 70% ± 6% with small diameter. The drill trajectory module had a success rate of 85% ± 3% with a trend toward improvement across PGY level. The oscillating saw module had a mean success rate of 25% ± 5% (trajectory) and 84% ± 6% (depth). We observed a significant improvement in trajectory performance during the second attempt. The pedicle probing module had a success rate of 46% ± 10%. CONCLUSION: The results of this pilot study on a small number of residents are promising. The modules were inexpensive and easy to administer. Conclusions of statistical significance include (1) residents who could easily detect changes in surrogate bone thickness with a smaller diameter drill than with a larger diameter drill and (2) residents who significantly improved saw trajectory with an additional attempt at the module.

The role of Wnt/ß-catenin signaling in proliferation and regeneration of the developing basilar papilla and lateral line.

Canonical Wnt/ß-catenin signaling has been implicated in multiple developmental events including the regulation of proliferation, cell fate, and differentiation. In the inner ear, Wnt/ß-catenin signaling is required from the earliest stages of otic placode specification through the formation of the mature cochlea. Within the avian inner ear, the basilar papilla (BP), many Wnt pathway components are expressed throughout development. Here, using reporter constructs for Wnt/ß-catenin signaling, we show that this pathway is active throughout the BP (E6-E14) in both hair cells (HCs) and supporting cells. To characterize the role of Wnt/ß-catenin activity in developing HCs, we performed gain- and loss-of-function experiments in vitro and in vivo in the chick BP and zebrafish lateral line systems, respectively. Pharmacological inhibition of Wnt signaling in the BP and lateral line neuromasts during the periods of proliferation and HC differentiation resulted in reduced proliferation and decreased HC formation. Conversely, pharmacological activation of this pathway significantly increased the number of HCs in the lateral line and BP. Results demonstrated that this increase was the result of up-regulated cell proliferation within the Sox2-positive cells of the prosensory domains. Furthermore, Wnt/ß-catenin activation resulted in enhanced HC regeneration in the zebrafish lateral line following aminoglycoside-induced HC loss. Combined, our data suggest that Wnt/ß-catenin signaling specifies the number of cells within the prosensory domain and subsequently the number of HCs. This ability to induce proliferation suggests that the modulation of Wnt/ß-catenin signaling could play an important role in therapeutic HC regeneration.

The effect of biceps adhesions on glenohumeral range of motion: a cadaveric study.

BACKGROUND: Previous studies have demonstrated that the humerus slides along the long head of the biceps tendon (LHBT). Blocking this motion may result in decreased glenohumeral (GH) range of motion (ROM). The goal of the study was to characterize the excursion of the LHBT and measure the effect of biceps adhesions on GH ROM. MATERIALS AND METHODS: A custom biomechanical testing setup was used to measure the excursion of the LHBT and rotation of the humerus at 0°, 15°, 30°, 60°, and 90° of GH abduction in the scapular plane. An in situ biceps tenodesis with the biceps anchor still intact, thus simulating biceps adhesions, was sequentially performed in 2 positions: 0° abduction and maximum external rotation, followed by 0° abduction and maximum internal rotation. The effect of tenodesis on ROM was measured. RESULTS: There was an average excursion of 19.4 ± 5.4 mm of the LHBT as the humerus was taken through ROM in the scapular plane. Tenodesis in 0° abduction and maximum internal rotation resulted in a significant decrease in GH external rotation of 47.3° ± 12.2° (P = .007) with the arm in 0° abduction. CONCLUSIONS: Tenodesis in maximum internal rotation limited rotation significantly, such that in situ tenodesis without proximal tenotomy should not be performed. Furthermore, in situations where the biceps is at risk for scarring, such as proximal humeral fractures, shoulder arthroplasty, and the stiff shoulder, the biomechanical consequence of biceps adhesions may be similar to in situ tenodesis and may limit ROM and clinical outcomes.

Treatment and outcomes of an Australian cohort of outpatients with bipolar I or schizoaffective disorder over twenty-four months: implications for clinical practice.

BACKGROUND: The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with 'real-world' treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication. METHODS: Participants prescribed either conventional mood stabilizers (CMS; n = 155) alone, or olanzapine with, or without, CMS (olanzapine ± CMS; n = 84) were assessed every 3 months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale - Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data. RESULTS: On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24 months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine ± CMS (61%;) cohorts. CONCLUSIONS: Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.

Optimal screw placement for base plate fixation in reverse total shoulder arthroplasty.

HYPOTHESIS: Scapular cortical thickness has not been fully characterized from the perspective of determining optimal screw placement for securing the glenoid base plate in reverse shoulder arthroplasty. MATERIALS AND METHODS: Twelve fresh frozen cadaveric scapulae underwent high resolution CT scans with 3-dimensional reconstructions and wall thickness analysis. Digital base plates were positioned and virtual screws were placed according to 2 scenarios: A - intraosseous through the entire course and exits a "safe region" with no known neurovascular structures; B - may leave and re-enter the bone and penetrates the thickest cortical region accessible regardless of adjacent structures. RESULTS: For scenario A, the optimal screw configurations were: (superior screw) length = 35 mm, 9° superior, 2° posterior; (inferior screw-A) length = 34 mm, 16° inferior, 5° anterior; (inferior screw-B) length = 31 mm, 31 inferior, 4 posterior; (posterior screw) length 19 mm, 29° inferior, 3° anterior. For scenario B: (superior screw) length = 36 mm, 28° superior, 10° anterior; (inferior screw) length = 35 mm, 19° inferior, 4° anterior; (posterior screw) length 37 mm, 23° superior, 3° anterior. The anterior screw was consistent between scenarios A and B, averaged 29 mm in length and was directed 16° inferior and 14° posterior. CONCLUSION: Thicker cortical regions were present in the lateral aspect of the suprascapular notch, scapular spine base, anterior/superior aspect of inferior pillar and junction of glenoid neck and scapular spine. Regions with high cortical thickness were accessible for both scenarios except for the posterior screw in scenario A.

Magnetic resonance imaging appearance of anterior cruciate ligament reconstruction using Calaxo screws.

Bioabsorbable interference screws are commonly used to secure the graft during anterior cruciate ligament (ACL) reconstruction, in part because they result in less image degradation on subsequent magnetic resonance imaging (MRI). However, some bioabsorbable screws are associated with abnormalities on MRI examination not reported with metallic interference screws. We describe a finding on knee MRI examination after ACL reconstruction using a polylactide carbonate (PLC) bioabsorbable screw that we believe to be previously unreported with any other bioabsorbable screws. The finding raised suspicion of hemorrhage or infection, neither of which were present clinically. Analysis of tissue from the tibial tunnel suggested an explanation for the MRI finding: calcite crystals. An additional five patients with knee MRI examinations after ACL reconstruction using a PLC screw were reviewed and correlated with clinical findings with four having similar imaging abnormalities present. The PLC (Calaxo screw, Smith and Nephew, Andover, MA) screw used in these patients has been recalled in the United States and Europe by the manufacturer after a greater than expected incidence of adverse reactions, and legal action may be pending.