Patients considering total joint arthroplasty often search for information online regarding surgery; however, little is known about the specific topics that patients search for and the nature of the ...information provided. Google compiles frequently asked questions associated with a search term using machine learning and natural language processing. Links to individual websites are provided to answer each question. Analysis of this data may help improve understanding of patient concerns and inform more effective counseling.
Search terms were entered into Google for total hip and total knee arthroplasty. Frequently asked questions and associated websites were extracted to a database using customized software. Questions were categorized by topic; websites were categorized by type. JAMA Benchmark Criteria were used to assess website quality. Pearson’s chi-squared and Student’s t-tests were performed as appropriate.
A total of 620 questions (305 total knee arthroplasties, 315 total hip arthroplasties) were extracted with 602 associated websites. The most popular question topics were Specific Activities (23.5%), Indications/Management (15.6%), and Restrictions (13.4%). Questions related to Pain were more common in the TKA group (23.0% vs 2.5%, P < .001) compared to THA. The most common website types were Academic (31.1%), Commercial (29.2%), and Social Media (17.1%). JAMA scores (0-4) were highest for Government websites (mean 3.92, P = .005).
The most frequently asked questions on Google related to total joint arthroplasty are related to arthritis management, rehabilitation, and ability to perform specific tasks. A sizable proportion of health information provided originate from non-academic, non-government sources (64.4%), with 17.1% from social media websites.
The purpose of this study was to determine the prevalence of unexpected positive cultures noted at the time of revision surgery for periprosthetic fracture (PPF) after total hip or knee arthroplasty. ...Moreover, we evaluated whether this finding should be considered clinically significant and what type of treatment, if any, was required.
This was a single-center retrospective review of 270 patients undergoing surgery for PPFs from December 2010 to December 2021. Exclusion criteria included: open fractures; history of infection at fractured joint; non-operatively treated patients; and intraoperative fractures. The primary end point was the prevalence of unexpected positive cultures noted at the time of revision surgery. This was defined as one or more positive cultures in a PPF that the surgeon had preoperatively classified as aseptic according to the 2018 International Consensus Meeting. Data collection included patient demographics, medical histories, preoperative investigations, postoperative microbiology, and treatment.
During the study period, 159 patients were admitted with PPFs of the hip and 61 with PPFs of the knee. The mean age was 70 years (range, 32 to 93 years). Unexpected positive cultures were diagnosed postoperatively in 15 patients (6.8%; 10 hips, 5 knees). The most prevalent organism was Staphylococcus epidermidis (35.0%). Of those 15 patients, 6 required a surgical revision for infection. None of the patient-related risk factors were found to be associated with an increased risk of unexpected positive cultures. The comparison between infected and noninfected patients showed a significant association between preoperative C-reactive protein >10 mg/mL (P = .04), loose implant (P = .07), and infection.
The prevalence of unexpected positive cultures was 6.8% in our study cohort. Although surgical treatment may be required, the majority of patients seem to require no treatment. Larger series are required to investigate the clinical importance of this rare finding.
III.
Patients who have bilateral hip arthritis can be treated with bilateral total hip arthroplasty (bTHA) in either a staged or simultaneous fashion. The goal of this study was to determine whether ...staged and simultaneous posterior bTHA patients differ in regard to (1) patient-reported outcome measures, (2) 90-day complication rates, and (3) discharge dispositions and cumulative lengths of stay.
Patients who (1) underwent simultaneous bTHA or staged bTHA (within 12 months) using the posterior approach, and (2) completed preoperative and 1-year postoperative Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement surveys were included in the study. A total of 266 patients (87 simultaneous bTHA and 179 staged bTHA) were included. Chart review was performed to collect patient-level variables, postoperative complications, discharge dispositions, and lengths of stay.
Staged bTHA patients had higher Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement, Lower Extremity Activity Scale, and Veterans RAND 12-Item Health Survey physical component scores compared to simultaneous bTHA patients at 6 weeks after surgery (P = .019, .006, and .008, respectively), but these differences did not meet the minimal clinically important difference threshold for any questionnaire. Simultaneous bTHA was associated with higher rate of periprosthetic fractures (P = .034) and discharge to a location other than home (P < .001).
There were statistically significant, but likely not clinically meaningful differences in patient-reported outcomes for staged and simultaneous bTHA patients at 6 weeks after surgery. Surgeons should be aware of the higher periprosthetic fracture risk and greater likelihood of discharge to a rehabilitation facility associated with simultaneous bTHA. Further research should aim to understand which patients may benefit most from simultaneous bTHA.
Background: Bisphenol A (BPA) is a high-production-volume chemical commonly used in the manufacture of polycarbonate plastic Low-level concentrations of BPA in animals and possibly in humans may ...cause endocrine disruption. Whether ingestion of food or beverages from polycarbonate containers increases BPA concentrations in humans has not been studied. Objectives: We examined the association between use of polycarbonate beverage containers and urinary BPA concentrations in humans. Methods: We conducted a nonrandomized intervention of 77 Harvard College students to compare urinary BPA concentrations collected after a washout phase of 1 week to those taken after an intervention week during which most cold beverages were consumed from polycarbonate drinking bottles. Paired t-tests were used to assess the difference in urinary BPA concentrations before and after polycarbonate bottle use. Results: The geometric mean urinary BPA concentration at the end of the washout phase was 1.2 µg/g creatinine, increasing to 2.0 µg/g creatinine after 1 week of polycarbonate bottle use. Urinary BPA concentrations increased by 69% after use of polycarbonate bottles (p < 0.0001). The association was stronger among participants who reported ≥ 90% compliance (77% increase; p < 0.0001) than among those reporting < 90% compliance (55% increase; p = 0.03), but this difference was not statistically significant (p = 0.54). Conclusions: One week of polycarbonate bottle use increased urinary BPA concentrations by twothirds. Regular consumption of cold beverages from polycarbonate bottles is associated with a substantial increase in urinary BPA concentrations irrespective of exposure to BPA from other sources.
Non-small cell lung cancers (NSCLCs) with activating mutations in the kinase domain of the epidermal growth factor receptor (EGFR) demonstrate dramatic, but transient, responses to the reversible ...tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Some recurrent tumors have a common secondary mutation in the EGFR kinase domain, T790M, conferring drug resistance, but in other cases the mechanism underlying acquired resistance is unknown. In studying multiple sites of recurrent NSCLCs, we detected T790M in only a small percentage of tumor cells. To identify additional mechanisms of acquired resistance to gefitinib, we used NSCLC cells harboring an activating EGFR mutation to generate multiple resistant clones in vitro. These drug-resistant cells demonstrate continued dependence on EGFR and ERBB2 signaling for their viability and have not acquired secondary EGFR mutations. However, they display increased internalization of ligand-activated EGFR, consistent with altered receptor trafficking. Although gefitinib-resistant clones are cross-resistant to related anilinoquinazolines, they demonstrate sensitivity to a class of irreversible inhibitors of EGFR. These inhibitors also show effective inhibition of signaling by T790M-mutant EGFR and killing of NSCLC cells with the T790M mutation. Both mechanisms of gefitinib resistance are therefore circumvented by irreversible tyrosine kinase inhibitors. Our findings suggest that one of these, HKI-272, may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib.
When evaluating the results of clinical research studies, readers need to know that patients perceive effect sizes, not p values. Knowing the minimum clinically important difference (MCID) and the ...patient-acceptable symptom state (PASS) threshold for patient-reported outcome measures helps us to ascertain whether our interventions result in improvements that are large enough for patients to care about, and whether our treatments alleviate patient symptoms sufficiently. Prior studies have developed the MCID and PASS threshold for the Hip Disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS JR) and Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) anchored on satisfaction with surgery, but to our knowledge, neither the MCID nor the PASS thresholds for these instruments anchored on a single-item PASS question have been described.
(1) What are the MCID (defined here as the HOOS/KOOS JR change score associated with achieving PASS) and PASS threshold for the HOOS JR and KOOS JR anchored on patient responses to the single-item PASS instrument? (2) How do patient demographic factors such as age, gender, and BMI correlate with MCID and PASS thresholds using the single-item PASS instrument?
Between July 2020 and September 2021, a total of 10,970 patients underwent one primary unilateral THA or TKA and completed at least one of the three surveys (preoperative HOOS or KOOS JR, 1-year postoperative HOOS or KOOS JR, and 1-year postoperative single-item anchor) at one large, academic medical center. Of those, only patients with data for all three surveys were eligible, leaving 13% (1465 total; 783 THAs and 682 TKAs) for analysis. Despite this low percentage, the overall sample size was large, and there was little difference between completers and noncompleters in terms of demographics or baseline patient-reported outcome measure scores. Patients undergoing bilateral total joint arthroplasty or revision total joint arthroplasty and those without all three surveys at 1 year of follow-up were excluded. A receiver operating characteristic curve analysis, leveraging a 1-year, single-item PASS (that is, "Do you consider that your current state is satisfactory?" with possible answers of "yes" or "no") as the anchor was then used to establish the MCID and PASS thresholds among the 783 included patients who underwent primary unilateral THA and 682 patients who underwent primary unilateral TKA. We also explored the associations of age at the time of surgery (younger than 65 years or 65 years and older), gender (men or women), BMI (< 30 or ≥ 30 kg/m 2 ), and baseline Patient-Reported Outcome Measure Information System-10 physical and mental component scores (< 50 or ≥ 50) for each of the MCID and PASS thresholds through stratified analyses.
For the HOOS JR, the MCID associated with the PASS was 23 (95% CI 18 to 31), with an area under the receiver operating characteristic curve of 0.75, and the PASS threshold was 81 (95% CI 77 to 85), with an area under the receiver operating characteristic curve of 0.81. For the KOOS JR, the MCID was 16 (95% CI 14 to 18), with an area under the receiver operating characteristic curve of 0.75, and the PASS threshold was 71 (95% CI 66 to 73) with an area under the receiver operating characteristic curve of 0.84. Stratified analyses indicated higher change scores and PASS threshold for younger men undergoing THA and higher PASS thresholds for older women undergoing TKA.
Here, we demonstrated the utility of a single patient-centered anchor question, raising the question as to whether simply collecting a postoperative PASS is an easier way to measure success than collecting preoperative and postoperative patient-reported outcome measures and then calculating MCIDs and the substantial clinical benefit.
Level III, therapeutic study.
Wilms tumor is a pediatric kidney cancer associated with inactivation of the WT1 tumor-suppressor gene in 5 to 10% of cases. Using a high-resolution screen for DNA copy-number alterations in Wilms ...tumor, we identified somatic deletions targeting a previously uncharacterized gene on the X chromosome. This gene, which we call WTX, is inactivated in approximately one-third of Wilms tumors (15 of 51 tumors). Tumors with mutations in WTX lack WT1 mutations, and both genes share a restricted temporal and spatial expression pattern in normal renal precursors. In contrast to biallelic inactivation of autosomal tumor-suppressor genes, WTX is inactivated by a monoallelic "single-hit" event targeting the single X chromosome in tumors from males and the active X chromosome in tumors from females.
The use of body mass index (BMI) cutoff values has been suggested for proceeding with total knee arthroplasty (TKA) in obese patients. However, the relationship between obesity severity and early ...reoperations after TKA is poorly defined. This study evaluated whether increased World Health Organization (WHO) obesity class was associated with risk, severity, and timing of reintervention within one year after TKA.
There were 8,674 patients from our institution who had a BMI ≥ 30 and underwent unilateral TKA for primary osteoarthritis between 2016 and 2021. Patients were grouped by WHO obesity class: 4,456 class I (51.5%), 2,527 class II (29.2%), and 1,677 class III (19.4%). A chart review was performed to determine patient characteristics and identify patients who underwent any closed or open reintervention requiring anesthesia within the first postoperative year. Regression analyses were performed to identify variables associated with increased odds ratios (ORs) for requiring a reintervention, its timing, and invasiveness.
There were 158 patients (1.8%) who required at least one reintervention, and 15 patients (0.2%) required at least 2 reinterventions. Reintervention rates for obesity classes I, II, and III were 1.8% (n = 81), 2.0% (n = 51), and 1.4% (n = 23), respectively. There were 65 closed procedures (41.1%), 47 minor procedures (29.7%), 34 open with or without liner exchange (21.5%), and 12 revisions with component exchange (7.6%). Obesity class was not associated with reintervention rate (P = .3), timing (P = .36), or invasiveness (P = .93). Diabetes (odds ratio OR = 2.47; P = .008) was associated with a need for reintervention. Non-Caucasian race (OR = 1.7; P = .01) and Charlson comorbidity index (OR = 2.1; P = .008) were associated with earlier reintervention. No factors were associated with the invasiveness of reintervention.
The WHO obesity class did not associate with rate, timing, or invasiveness of reintervention after TKA in obese patients. These findings suggest that policies that restrict the indication for elective TKA based only on a BMI limit have limited efficacy in reducing early reintervention after TKA in obese patients.
III.
A concept that currently steers the development of cancer therapies has been that agents directed against specific proteins that facilitate tumorigenesis or maintain a malignant phenotype will have ...greater efficacy, less toxicity and a more sustained response relative to traditional cytotoxic chemotherapeutic agents. The clinical success of the targeted agent Imatinib mesylate as an inhibitor of the tyrosine kinase associated with the breakpoint cluster region-Abelson oncogene locus (BCR-ABL) in the treatment of Philadelphia-positive chronic myelogenous leukemia (CML) has served as a paradigm. While intellectually gratifying, the selective targeting of a single driver event by a small molecule, e.g., kinase inhibitor, to dampen a tumor-promoting pathway in the treatment of solid tumors is limited by many factors. Focus can alternatively be placed on targeting fundamental cellular processes that regulate multiple events, e.g., protein degradation, through the Ubiquitin (Ub)+Proteasome System (UPS). The UPS plays a critical role in modulating numerous cellular proteins to regulate cellular processes such as signal transduction, growth, proliferation, differentiation and apoptosis. Clinical success with the proteasome inhibitor bortezomib revolutionized treatment of B-cell lineage malignancies such as Multiple Myeloma (MM). However, many patients harbor primary resistance and do not respond to bortezomib and those that do respond inevitably develop resistance (secondary resistance). The lack of clinical efficacy of proteasome inhibitors in the treatment of solid tumors may be linked mechanistically to the resistance detected during treatment of hematologic malignancies. Potential mechanisms of resistance and means to improve the response to proteasome inhibitors in solid tumors are discussed.
Significant geographic variability in gastrointestinal (GI) cancer-related death has been reported in the United States. We aimed to evaluate both modifiable and nonmodifiable factors associated with ...intercounty differences in mortality due to GI cancer.
Data from the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research platform were used to calculate county-level mortality from esophageal, gastric, pancreatic, and colorectal cancers. Multivariable linear regression models were fit to adjust for county-level covariables, considering both patient (eg, sex, race, obesity, diabetes, alcohol, and smoking) and structural factors (eg, specialist density, poverty, insurance prevalence, and colon cancer screening prevalence). Intercounty variability in GI cancer-related mortality explained by these covariables was expressed as the multivariable model R2.
There were significant geographic disparities in GI cancer-related county-level mortality across the US from 2010–2019 with the ratio of mortality between 90th and 10th percentile counties ranging from 1.5 (pancreatic) to 2.1 (gastric cancer). Counties with the highest 5% mortality rates for gastric, pancreatic, and colorectal cancer were primarily in the Southeastern United States. Multivariable models explained 43%, 61%, 14%, and 39% of the intercounty variability in mortality rates for esophageal, gastric, pancreatic, and colorectal cancer, respectively. Cigarette smoking and rural residence (independent of specialist density) were most strongly associated with GI cancer–related mortality.
Both patient and structural factors contribute to significant geographic differences in mortality from GI cancers. Our findings support continued public health efforts to reduce smoking use and improve care for rural patients, which may contribute to a reduction in disparities in GI cancer–related death.
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The highest rates of death from gastrointestinal cancers occur in rural counties and in the Southeastern United States, with differences in county-level mortality from esophagus, stomach, pancreas, and colon cancer being associated with higher rates of smoking, diabetes, and obesity.
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