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Introduction: Around one-third of Americans reported they were unwilling to get a COVID-19 vaccine in April 2021. This focus group study aimed to provide insights on the factors contributing to unvaccinated adults' hesitancy or refusal to get vaccinated with COVID-19 vaccines., Method: Ipsos recruited 59 unvaccinated US adults who were vaccine hesitant (i.e., conflicted about or opposed to receiving a COVID-19 vaccination) using the Ipsos KnowledgePanel. Trained facilitators led a total of 10 focus groups via video-conference in March and April 2021. Two coders manually coded the data from each group using a coding frame based on the focus group discussion guide. The coding team collaborated in analyzing the data for key themes., Results: Data analysis of transcripts from the focus groups illuminated four main themes associated with COVID-19 vaccine hesitancy: lack of trust in experts and institutions; concern about the safety of COVID-19 vaccines; resistance towards prescriptive guidance and restrictions; and, despite personal reluctance or unwillingness to get vaccinated, acceptance of others getting vaccinated., Discussion: Vaccine confidence communication strategies should address individual concerns, describe the benefits of COVID-19 vaccination, and highlight evolving science using factural and neutral presentations of information to foster trust., Competing Interests: Noel Brewer has served on paid advisory boards for Merck and received research grants from Merck and Pfizer. The remaining authors declare to have no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Acute kidney injury (AKI) is a serious complication after major surgery, which may lead to increased morbidity and mortality. The aim of this study was to identify cost and determinants of AKI after total joint arthroplasty., Methods: A retrospective case-controlled study was conducted with 1719 primary elective total hip or knee replacements performed from January 2004 through September 2015 at an urban teaching hospital. Patients who developed AKI were matched in a 1:3 ratio with those in a control group who did not develop AKI based on age, sex, race, operated joint, and comorbidities including hypertension and diabetes. Increased postoperative serum creatinine was considered indicative of AKI., Results: Fifty-four patients (3.1%) had AKI that was significantly associated with increased length of hospital stay (8.07 days) compared with that of the control group (4.50 days, P < .0001) and incurred significantly higher hospital charges ($224,533) than those of the control group ($142,753, P < .0001). We identified high body mass index, undergoing bilateral surgery in one session, high estimated blood loss, and longer duration of surgery as significant risk factors for AKI in univariate analysis. Elevated preoperative creatinine, large postoperative drop in hemoglobin, and high American Society of Anesthesiologists physical status scores were significant independent predictors of AKI in multivariate analysis., Conclusions: Health-care providers and patients should work together to manage risk factors and to lower the risk of morbidity and mortality, longer in-hospital stay, and high associated costs of AKI.

Background: Patients with morbid obesity, defined as a BMI greater than 40 kg/m 2 , and super obesity, defined as a BMI greater than 50 kg/m 2 , increasingly present for total hip replacement. There is disagreement in the literature whether these individuals have greater surgical risks and costs for the episode of care, and the magnitude of those risks and costs. There also is no established threshold for obesity as defined by BMI in identifying increased complications, risks, and costs of care. Until recently, analysis of higher BMI data was limited to small cohorts from hospital-based data banks, based on BMI or height and weight only, often as part of a multivariate analysis. On October 1, 2010 the Centers for Medicare & Medicaid Services added a fifth digit to the BMI data, V85.xx, in the Medicare data bank, which allowed data mining of cases of patients with higher BMI. To our knowledge, our study is the first large retrospective Medicare data mining study, which allows us to examine BMI levels greater than 40 and 50 kg/m 2 to delineate risks, complications, and costs for these patients., Questions/purposes: We sought to quantify (1) the surgical risk, and (2) the costs associated with complications after THA in patients who were morbidly obesity (BMI ≥ 40 kg/m 2 ) or super obese (BMI ≥ 50 kg/m 2 )., Methods: This is a retrospective study of patients, using Medicare hospital claims data, who underwent THA. The ICD-9 Clinical Modification (CM) diagnosis code V85.4x was used to identify patients with morbid obesity and with super obesity from October 1, 2010 through December 31, 2014. Patients without any BMI-related diagnosis codes were used as the control group. Twelve complications occurring during the 90 days after THA were analyzed using multivariate Cox models adjusting for patient demographic, comorbidities, and institutional factors. In addition, hospital charges and payments were compared from primary surgery through the subsequent 90 days., Results: Patients with morbid obesity had increased postoperative complications including prosthetic joint infection (hazard ratio [HR], 3.71; 95% CI, 3.2-4.31; p < 0.001), revision (HR, 1.91; 95% CI, 1.69-2.16; p < 0.001), and wound dehiscence (HR, 3.91; 95% CI, 3.14-4.86; p < 0.001). In addition, patients with morbid obesity had increased risk of deep vein thrombosis (HR, 1.43; 95% CI, 1.14-1.79; p < 0.002), pulmonary embolism (HR, 1.57; 95% CI, 1.25-1.99; p < 0.001), implant failure (HR, 1.48; 95% CI, 1.3-1.68; p < 0.001), acute renal failure (HR, 1.68; 95% CI, 1.56-1.80; p < 0.001), and all-cause readmission (HR, 1.48; 95% CI, 1.40-1.56; p < 0.001). However, death (HR, 0.94 95% CI, 0.73-1.19 p < 0.592), acute myocardial infarction (HR, 0.94; 95% CI, 0.74-1.2 p < 0.631), and dislocation (HR 1.07; 95% CI, 0.85-1.34; p < 0.585) were not different between patients in the control and morbidly obese groups. Super obese patients had an increased risk of infection (HR, 6.48; 95% CI, 4.54-9.25; p < 0.001), wound dehiscence (HR, 9.81; 95% CI, 6.31-15.24; p < 0.001), and readmission (HR, 2.16; 95% CI, 1.84-2.54; p < 0.001) compared with patients with normal BMI. Controlling for patient and institutional factors, each THA had mean total hospital charges of USD 88,419 among patients who were super obese compared with USD 73,827 for the control group, a difference of USD 14,591. Medicare payment for the patients who were super obese also was higher, but only by USD 3631., Conclusions: Patients who are super obese are at increased risk for serious complications compared with patients with morbid obesity, whose risks are elevated relative to patients whose BMI is less than 40 kg/m 2 . Costs of care for patients who were super obese, likewise, were increased. We present BMI outcomes to allow an objective basis for patient counseling, risk stratification, maintaining access to orthopaedic surgical care, and maintaining hospital operating margins., Level of Evidence: Level III, therapeutic study.

Robust modeling of CNS transport integrates molecular fluxes at the microvascular blood-brain barrier and epithelial choroid plexus blood-cerebrospinal fluid (CSF) barrier. Normal activity of solute transporters, channels and aquaporins, in the cerebral endothelium and choroidal epithelium, sets the microenvironment composition for neurons and glia. Conversely, perturbed transport/permeability at the barrier interfaces causes interstitial fluid dyshomeostasis (e.g. edema) arising in neural disorders. Critically-important transependymal solute/water distribution between brain and CSF needs more attention. This treatise encourages procuring transport data simultaneously for blood-brain barrier, blood-CSF barrier and CSF. In situ perfusion and multicompartmental analyses (tracers, microdialysis) provide dynamic assessments of molecular transfer among various CNS regions. Diffusion, active transport and convection are distorted by disease- and age-associated alterations in barrier permeability and CSF turnover (sink action). Clinical complications result from suboptimal conveyance of micronutrients (folate), catabolites (β-amyloid) and therapeutic agents (antibiotics) within the CNS. Neurorestorative therapies for stroke, traumatic brain injury, multiple sclerosis and brain tumors are facilitated by insight on molecular and cellular trafficking through the choroid plexus-CSF nexus. Knowledge is needed about fluxes of growth factors, neurotrophins, hormones and leukocytes from ventricular CSF into the hippocampus, subventricular zone and hypothalamus. CSF and brain removal of potentially toxic catabolites and neuropeptides merits further investigation to manage the degeneration of Alzheimer's disease and normal pressure hydrocephalus. Novel therapies will rely on delineating peptide and drug distributions across the blood-brain barrier and choroid plexus-CSF, and how they modulate the intervening neural-glial networks and neurogenic sites. Multicompartmental transport modeling is key to devising specific pharmacologic targeting and thus impactful CSF translational research for CNS disorders.

Background: Obtaining an orthopaedic surgery residency is competitive. Advisors must understand what factors may help unmatched candidates reapply successfully., Questions/purposes: We determined (1) the attitude of leaders of orthopaedic surgery residency programs toward interviewing unmatched students; (2) whether a surgical internship or a research year is preferred in considering reapplicants; (3) the importance of United States Medical Licensing Examination (USMLE) scores, recommendations, and Alpha Omega Alpha (AOA) membership; and (4) whether academic and nonacademic programs evaluate reapplicants differently., Methods: We sent an anonymous 19-question survey to 151 Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedic surgery residency programs in five waves, 1 week apart (December 5, 2009-January 5, 2010). Investigators were blinded to the respondents' identities., Results: Ninety-one of the 151 programs (60%) responded. Sixty-eight of the 91 programs (75%) stated they rarely accept unmatched applicants. Sixty-eight programs (75%) agreed an unmatched applicant should do a surgery internship for 1 year. Of the 36 programs that recommended a research year, 32 were academic programs. Academic programs were more likely than nonacademic programs to view as important new recommendations (85% versus 67%), minimum scores of 220 on Step I (67% versus 49%) and Step II (64% versus 36%), and AOA membership (85% versus 67%)., Conclusions: By completing a surgical internship, unmatched students may increase their chances of matching. Students considering academic programs should ensure their academic record meets certain benchmarks and may consider a research year but risk limiting their acceptance to academic programs.

Systemic sclerosis (scleroderma) is a connective tissue disorder of unknown etiology. This rare, chronic, multisystem disorder encompasses a number of variations leading to focal and systemic classifications, which includes features such as skin thickening. The changes within the skin microstructure have led to numerous surgical complications. In a review of the orthopedic literature, we found no reports describing surgical outcomes or the success of skin closures in procedures related to the hip for patients with scleroderma. We present a case of a 74-year-old man with a history of scleroderma who underwent a bipolar hemiarthroplasty to repair a right transcervical femoral neck fracture. The risk factors associated with wound healing and effects of skin contractures in systemic sclerosis patients are reviewed.

Previous classifications of severity for total knee arthroplasty revisions have been based largely on bone loss of the femur and tibia. These approaches failed to address the more technically difficult issues in revision surgery such as surgical exposure, contractures, extremity alignment, implant removal, soft tissue stability (in the anteroposterior and in the sagittal planes), extensor mechanism integrity, and patellar revisability. Through the Knee Society, the authors developed a severity index that incorporated these latter factors into one measure. The current authors describe the application of the Knee Society Index of Severity for failed total knee arthroplasty and its method of scoring.

Compared with primary knee replacement, total knee arthroplasty revision surgery is a more complex procedure and accounts for greater expenditures of healthcare resources at each clinical stage. Overall, patients having revision procedures have poorer functional outcomes and higher complication rates than patients having primary arthroplasty. Despite the expanded scope of revision problems and the rapidly emerging technology in revision surgery, the long-term success of any method remains in question. Because there is little consensus on the timing of revision surgery, optimal surgical reconstruction, and the type of prosthesis to be implanted, the Knee Society began development of an Index of Severity for Failed Total Knee Arthroplasty. Fifty-four percent of Knee Society members completed an 82-item questionnaire that determined their clinical impression about potential risk factors for the outcomes of revision surgery for failed total knee replacements. Using these results, a consensus group developed the final version of the index. The result of the nominal group process was the Knee Society Index of Severity, which was based on eight distinct domains. Each domain was divided into attributes and weights based on the questionnaire responses and consensus meeting. Actual case scenarios from five institutions were used to test interrater reliability and validity. The interrater reliability of the average score of all ratings was 0.95; the correlation of the criterion rating with the mean rating was 0.77. When three outliers were not included, the Pearson product correlation increased to 0.92. These data support the application of the Knee Society Index of Severity as a critical component of risk factor studies, effectiveness research, and cost-effectiveness analysis involving revisions of total knee replacements.

TH1 cytokines have recently been detected in rheumatoid arthritis (RA) and osteoarthritis (OA). For this reason we studied the TH-1-promoting cytokine IL-12 in synovial membranes from patients with RA and OA. IL-12 transcripts and protein were analyzed by reverse transcriptase-polymerase chain reaction (PCR) and immunohistochemistry, respectively. In addition, IL-12 transcripts were quantitated by competitive PCR. IL-12 transcripts (p40) were detected in 8 of 13 patients with RA and in 10 of 18 patients with OA. Their levels did not differ significantly between RA and OA. IL-12 heterodimer protein was detected by immunostaining using an anti-IL-12p70 mAb. Double labeling with anti-IL-12p70 and anti-CD68 mAbs showed that synovial lining cells and monocytes/macrophages expressed IL-12 p70 protein. The presence of IL-12 p70 protein in the synovial membranes of patients with RA and OA suggests that IL-12 may play an important immunoregulatory role in these diseases by perpetuating inflammation., (Copyright 1998 Academic Press.)

The synovial membrane in osteoarthritis (OA) often exhibits inflammatory infiltrates, but the role of T cells in these infiltrates is not known. T-cell activation antigens were analyzed by immunohistochemistry, and T-cell cytokine transcripts were measured by competitive PCR in synovial membranes from patients with OA and rheumatoid arthritis (RA). Lymphoid cell aggregates, containing primarily CD3+ T lymphocytes, were found in 65% of patients with OA. Mononuclear cells expressing the activation antigens CD69, CD25, CD38, CD43, CD45RO, and HLA class II were present in both patient groups, although in higher numbers in patients with RA. Interleukin 2 (IL-2) transcripts were found in 10 of 18 patients with OA versus 12 of 13 patients with RA (P = 0.03). Gamma interferon (IFN-gamma) transcripts were detected in 9 of 18 patients with OA versus 10 of 13 patients with RA (not significant), whereas IL-10 transcripts were found in nearly all patients. IL-4 and IL-5 were not detected in any patients. The levels of IFN-gamma and IL-2 transcripts, normalized for T-cell number equivalents, were not statistically different between OA and RA, but the levels of IFN-gamma, normalized for total cell number equivalents, were lower in OA than in RA (P = 0.01). Synovial membranes that expressed IL-2 and IFN-gamma transcripts were more likely to have heavier infiltrations of T cells and cells bearing activation markers than synovial membranes that did not express these cytokines. The presence of activated T cells and TH1 cytokine transcripts in chronic joint lesions of patients with OA suggests that T cells contribute to chronic inflammation in a large proportion of these patients.

The effectiveness and safety of warfarin were compared with those of a low-molecular-weight heparin (dalteparin) for the prevention of deep-vein thrombosis after total hip arthroplasty in a prospective, randomized, multi-institutional trial. Patients who were older than eighteen years of age and were scheduled to have an elective primary or revision total hip arthroplasty were eligible; 580 patients were randomized, 550 had the operation and received prophylaxis, and 382 had evaluable venograms. Prophylaxis was provided either with warfarin beginning the night before the operation or with dalteparin beginning two hours before the operation and was continued until venography was performed. Bleeding was assessed on the basis of intraoperative blood loss, transfusion requirements, a decrease in hematocrit, and clinically identified bleeding complications. The prevalence of deep-vein thrombosis was found to be significantly lower in the patients who had received dalteparin than in those who had received warfarin (twenty-eight [15 per cent] of 192 patients compared with forty-nine [26 per cent] of 190 patients; p = 0.006). Deep-vein thrombosis occurred in the calf veins of twenty-one patients (11 per cent) who had received dalteparin and of forty-three patients (23 per cent) who had received warfarin; this difference was significant (p = 0.003). Proximal deep-vein thrombosis occurred in ten patients (5 per cent) who had received dalteparin and in sixteen patients (8 per cent) who had received warfarin; however, with the numbers available, no significant difference could be detected (p = 0.185). We also could not detect a significant difference with regard to the intraoperative and postoperative blood loss, the decrease in hematocrit, and the prevalence of major bleeding complications between the two groups; however, the patients who had received dalteparin had a significantly higher prevalence of bleeding complications involving the operative site (p = 0.03), and a significantly greater percentage required postoperative transfusions (p = 0.001). We concluded that preoperative prophylaxis with dalteparin is significantly more effective than that with warfarin in preventing deep-vein thrombosis after total hip arthroplasty. The greater effectiveness of dalteparin must be considered, however, in light of an increased need for postoperative transfusions and an increase in the prevalence of wound-related bleeding complications.

Although there have been many studies focusing on the increasingly important assessment of patients' satisfaction, few studies have specifically addressed this tissue for total hip arthroplasty (THA). The goals of this study were to measure patients' satisfaction with THA and to evaluate the relationships of expectations and outcome to patients' satisfaction. A total of 180 patients were surveyed 2 to 3 years after THA about their experiences with THA. Patients cited 45 different expectations, which were grouped into five categories reflecting improvement in pain, walking, psychological state, essential activities, and nonessential activities. Overall, 89% of patients were satisfied with the results of surgery. Lower rates of satisfaction were found in patients who had a better preoperative condition (as measured by the surgeons with The Hospital for Special Surgery Hip Scale), in patients who expected improvement in nonessential activities, and in patients who reported worse postoperative condition (as measured by self-assessment with the Hip Rating Questionnaire and the Medical Outcomes Study Short-form General Health Survey). Patients were also asked how they came to THA. Nearly 50% of patients were first referred to an orthopaedist by family or friends or based on their own knowledge. Seventy-four percent either had subsequently referred others for THA or would have done so if they knew someone with hip pain. This study demonstrates that satisfaction with THA is a complex phenomenon, affected by expectations, outcome, and what patients know about the procedure from their community network. A better understanding of THA satisfaction will enable better future selection of patients and an additional dimension of outcome, both of which are important to patients and payers.

A lack of consensus regarding the indications for total hip arthroplasty (THA) and total knee arthroplasty (TKA) has been cited as one reason for the variations in the rates of THA and TKA across the United States. The purposes of this study were to survey orthopaedists in a specific geographic area (New York City) regarding the candidacy of patients with osteoarthritis for THA or TKA and to compare indications for THA between orthopaedists at two academic medical centers, The Hospital for Special Surgery in the United States and McGill University in Canada. Orthopaedists were sent mail surveys asking about indications, factors affecting outcomes, and factors that might modify decisions for surgery. Approximately 45% of orthopaedists who performed THA and TKA in New York City in 1992 completed the surveys. Although there were wide variations among surgeons, most surgeons required at least severe pain daily, rest pain several days per week, transfer pain either several days per week (THA) or daily (TKA), and destruction of most of the joint space on radiograph. Younger age, comorbidity, technical difficulties, and lack of motivation modified the decision against surgery, whereas the desire to be independent and return to work swayed the decision for surgery. Most surgeons rated that patients with severe pain, osteoarthritis, or rheumatoid arthritis would have a high likelihood of an excellent outcome, whereas those with comorbidity and certain technical factors would have only a moderate likelihood of an excellent outcome. In the U.S.-Canadian survey of THA, in which more than 90% of surgeons responded, Canadian surgeons tended to require more frequent pain and use of assistive devices for walking. Although there was a majority of opinion for several indications, there was no clear consensus among surgeons regarding the indications for THA and TKA. Possible explanations for this are that isolated indications are not as important as integrating and weighing several indications and that the patient's desire to proceed with THA or TKA is an important driving force in the decision to operate.

The purpose of this study was to develop a method for directly measuring bone density of femoral neck sections. Three types of density were measured. Real density equals wet weight divided by the actual volume of bone tissue (real volume). Apparent density equals wet weight divided by the total volume occupied by the bone plus the pore spaces (total sample volume). Ash density equals the ash weight divided by the real volume. Corticocancellous cross-sections of the femoral neck were analyzed for density at two levels: level 1, proximal neck and level 3, distal neck. Density measurements were compared with histomorphometric measurements performed on cross-sections at the midportion of the femoral neck (level 2) and with a clinical radiographic measure of bone density (cortical index 3 cm below the lesser trochanter). No correlation was found between apparent density and either real (r = .12, P = .62) or ash density (r = -.09, P = .72) within a given femoral neck section. There was, however, a strong correlation between real and ash density (r = .93, P = .0001). This was expected because real and ash densities are both reflections of bone mineralization. Apparent density showed better correlation, when comparing level 1 with level 3 sections (r = .76, P = .0001), than did ash (r = .57, P = .01) or real density (r = .55, P = .01). There was no correlation between either real or ash density with any histomorphometric parameter. Apparent density was moderately correlated with total bone area expressed as a percentage of cross-sectional area (r = .66, P = .008). This finding tends to validate the direct measurement of apparent density in that both apparent density and total bone area are measurements of the concentration of bone in space. No significant correlation was found between any of the density measurements and the cortical index at 3 cm. This underscores the necessity for precisely qualifying any definition or discussion of bone quality. The success or failure of hip implants may be at least partially determined by the ability of the bone to withstand the insult of implantation of the prosthesis and to adapt successfully to the new mechanical environment. This study represents an early phase of defining parameters that may have prognostic value in long-term implant fixation.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease affecting primarily young women. Osteonecrosis of the femoral head produces significant morbidity in these patients. The clinical and radiographic results of 33 total hip arthroplasties (THA) in 25 patients were studied. The Hospital for Special Surgery hip rating was good or excellent in all surviving index primary hip arthroplasties at a median follow-up of 47 months. Overall survival probability was 94.6% at 5 years and 81.8% at 9 years using survivorship analysis. Perioperative morbidity was minimal. Total hip arthroplasty using contemporary techniques and current management protocols can provide reliable functional improvement in patients with osteonecrosis secondary to SLE.

We developed a sensitive radioimmunoassay (CYCLO-Trac SP) that specifically measures cyclosporine A in serum, plasma and whole blood of transplant patients. The specific monoclonal antibody was from Sandoz and the tracer was an 125I derivative of cyclosporine C. The assay is performed at room temperature for 1 h followed by a 20 min centrifugation. The sensitivities of the assays are 2.6 ng/mL and 8.7 ng/mL for the serum/plasma assay and the whole blood assay, respectively. Within-run and between-run CVs for both types of assays using cyclosporine concentrations of 80 and 58 ng/mL (serum) and 186 and 199 ng/mL (whole blood) were less than 5% and 9%, respectively. Averaged recovery of serum/plasma and whole blood assays at various levels ranged from 93% to 115%. Interferences by bilirubin, triglyceride, cholesterol, hemoglobin, OKT-3, azathioprine, methylprednisolone and 20 other drugs were insignificant. Multicenter proficiency studies showed an excellent correlation between the CYCLO-Trac SP and the specific 3H-Sandimmune assay from Sandoz: whole blood assay (r = 0.998) and serum assay (r = 0.997).

Disorders of hemoglobin synthesis affect the musculoskeletal system by either causing replacement of bone by hematopoietic tissue, precipitating bone and soft tissue ischemia and necrosis, or a combination of both processes. Less frequently, joints are involved by synovial ischemia, synovial deposition of iron, or microfracture of subchondral bone. Osteopenia is a significant problem in both thalassemia and sickle cell anemia and may result in vertebral and long bone fractures. Growth disturbances are frequently seen but are not often appreciated until adolescence because of improved hematologic management. The cause of the growth problems is multifactorial and may be related to hormonal deficiencies, iron overload, hypoxia, or local trauma to the growth plate secondary to significant osteopenia.