The effect of patients' sex on physicians' recommendations for total knee arthroplasty

Background

The underuse of total joint arthroplasty in appropriate candidates is more than 3 times greater among women than among men. When surveyed, physicians report that the patient''s sex has no effect on their decision-making; however, what occurs in clinical practice may be different. The purpose of our study was to determine whether patients'' sex affects physicians'' decisions to refer a patient for, or to perform, total knee arthroplasty.

Methods

Seventy-one physicians (38 family physicians and 33 orthopedic surgeons) in Ontario performed blinded assessments of 2 standardized patients (1 man and 1 woman) with moderate knee osteoarthritis who differed only by sex. The standardized patients recorded the physicians'' final recommendations about total knee arthroplasty. Four surgeons did not consent to the inclusion of their data. After detecting an overall main effect, we tested for an interaction with physician type (family physician v. orthopedic surgeon). We used a binary logistic regression analysis with a generalized estimating equation approach to assess the effect of patients'' sex on physicians'' recommendations for total knee arthroplasty.

Results

In total, 42% of physicians recommended total knee arthroplasty to the male but not the female standardized patient, and 8% of physicians recommended total knee arthroplasty to the female but not the male standardized patient (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.4–7.3, p < 0.001; risk ratio [RR] 2.1, 95% CI 1.5–2.8, p < 0.001). The odds of an orthopedic surgeon recommending total knee arthroplasty to a male patient was 22 times (95% CI 6.4–76.0, p < 0.001) that for a female patient. The odds of a family physician recommending total knee arthroplasty to a male patient was 2 times (95% CI 1.04–4.71, p = 0.04) that for a female patient.

Interpretation

Physicians were more likely to recommend total knee arthroplasty to a male patient than to a female patient, suggesting that gender bias may contribute to the sex-based disparity in the rates of use of total knee arthroplasty.Disparity in the use of medical or surgical interventions based on patient characteristics, such as sex, ethnic background or socioeconomic status, is an important health care issue.¹ Women are less likely than men to receive lipid-lowering medication after a myocardial infarction,² receive kidney dialysis,³ be admitted to an intensive care unit,⁴ or undergo cardiac catheterization,⁵ renal transplantation⁶ or total joint arthroplasty.⁷ Although women''s preferences for surgery or the information needed to make an informed decision may differ from men and explain sex-based differences in care,^8,9 subtle or overt gender bias may inappropriately influence physicians'' clinical decision-making.^2,5,7 A more pronounced gender bias might be expected when the clinical decision involves an elective surgical procedure such as total joint arthroplasty.Total hip and knee arthroplasty is the definitive treatment for relieving pain and restoring function in people with moderate to severe osteoarthritis for whom medical therapy has failed.¹⁰ Although age-adjusted rates of total joint arthroplasty are higher among women than among men,¹¹ based on a population-based epidemiologic survey, underuse of arthroplasty is 3 times greater in women.⁷ In prior opinion surveys, more than 93% of referring physicians and orthopedic surgeons have reported that patients'' sex has no effect on their decision to refer a patient for, or perform, total knee arthroplasty.^12,13 However, there may be a difference between what is reported in a survey and what occurs in clinical practice. The purpose of our study was to determine whether physicians would provide the same recommendation about total knee arthroplasty to a male and a female standardized patient presenting to their offices with identical clinical scenarios that differed only by sex.     

Comparison of Mantoux and Tine Tuberculin Skin Tests in BCG-Vaccinated Children Investigated for Tuberculosis

Background

Tuberculin skin tests (TSTs) are long-established screening methods for tuberculosis (TB). We aimed to compare agreement between the intradermal Mantoux and multipuncture percutaneous Tine methods and to quantify risk factors for a positive test result.

Methodology/Principal Findings

1512 South African children younger than 5 years of age who were investigated for tuberculosis (TB) during a Bacille Calmette Guerin (BCG) trial were included in this analysis. Children underwent both Mantoux and Tine tests. A positive test was defined as Mantoux ≥15 mm or Tine ≥ Grade 3 for the binary comparison. Agreement was evaluated using kappa (binary) and weighted kappa (hierarchical). Multivariate regression models identified independent risk factors for TST positivity. The Mantoux test was positive in 430 children (28.4%) and the Tine test in 496 children (32.8%, p<0.0001), with observed binary agreement 87.3% (kappa 0.70) and hierarchical agreement 85.0% (weighted kappa 0.66). Among 173 children culture-positive for Mycobacterium tuberculosis, Mantoux was positive in 49.1% and Tine in 54.9%, p<0.0001 (kappa 0.70). Evidence of digit preference was noted for Mantoux readings at 5 mm threshold intervals. After adjustment for confounders, a positive culture, suggestive chest radiograph, and proximity of TB contact were risk factors for a positive test using both TST methods. There were no independent associations between ethnicity, gender, age, or over-crowding, and TST result.

Conclusions/Significance

The Tine test demonstrated a higher positive test rate than the Mantoux, with substantial agreement between TST methods among young BCG-vaccinated children. TB disease and exposure factors, but not demographic variables, were independent risk factors for a positive result using either test method. These findings suggest that the Tine might be a useful screening tool for childhood TB in resource-limited countries.     

Amino-Acid Co-Variation in HIV-1 Gag Subtype C: HLA-Mediated Selection Pressure and Compensatory Dynamics

Background

Despite high potential for HIV-1 genetic variation, the emergence of some mutations is constrained by fitness costs, and may be associated with compensatory amino acid (AA) co-variation. To characterize the interplay between Cytotoxic T Lymphocyte (CTL)-mediated pressure and HIV-1 evolutionary pathways, we investigated AA co-variation in Gag sequences obtained from 449 South African individuals chronically infected with HIV-1 subtype C.

Methodology/Principal Findings

Individuals with CTL responses biased toward Gag presented lower viral loads than individuals with under-represented Gag-specific CTL responses. Using methods that account for founder effects and HLA linkage disequilibrium, we identified 35 AA sites under Human Leukocyte Antigen (HLA)-restricted CTL selection pressure and 534 AA-to-AA interactions. Analysis of two-dimensional distances between co-varying residues revealed local stabilization mechanisms since 40% of associations involved neighboring residues. Key features of our co-variation analysis included sites with a high number of co-varying partners, such as HLA-associated sites, which had on average 55% more connections than other co-varying sites.

Conclusions/Significance

Clusters of co-varying AA around HLA-associated sites (especially at typically conserved sites) suggested that cooperative interactions act to preserve the local structural stability and protein function when CTL escape mutations occur. These results expose HLA-imprinted HIV-1 polymorphisms and their interlinked mutational paths in Gag that are likely due to opposite selective pressures from host CTL-mediated responses and viral fitness constraints.     

BMI Independently Predicts Younger Age at Hip and Knee Replacement

Obesity has been identified as a risk factor for the development of hip and knee osteoarthritis (OA) and may play a role in exacerbating existing disease. Therefore, we hypothesized that obese patients would present for hip and knee replacement surgery at a younger age than nonobese patients. From our registry, we performed a cross‐sectional study of 841 hip and 804 knee replacement patients. Patients were categorized by BMI ≤25 kg/m², 25.1–29.9 kg/m², 30–34.9 kg/m², and ≥35 kg/m². Linear regression modeling was used to examine the relationship between BMI and age at surgery. Hip and knee replacement patients' mean age at surgery was 7.1 and 7.9 years younger, respectively, if their BMI was ≥35 kg/m² when compared to patients with a BMI ≤25 kg/m² (P = 0.002). BMI was a significant independent (of gender, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, surgeon, and comorbidity) predictor of age at knee replacement (P < 0.05). WOMAC scores were significantly worse preoperatively in patients with a BMI ≥35 kg/m² compared to those with a BMI ≤25 kg/m² (P < 0.05). Our study indicates that obese patients, especially those with a BMI ≥35 kg/m², presented for and underwent joint replacement surgery at a younger age as compared to nonobese patients.     

FDTD analysis of a noninvasive hyperthermia system for brain tumors

ABSTRACT: BACKGROUND: Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40--4[DEGREE SIGN]C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. METHODS: The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. RESULTS: The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. CONCLUSIONS: The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.     

Broad and Gag-biased HIV-1 epitope repertoires are associated with lower viral loads

Background

HLA class-I alleles differ in their ability to control HIV replication through cell-mediated immune responses. No consistent associations have been found between the breadth of Cytotoxic T Lymphocytes (CTL) responses and the control of HIV-1, and it is unknown whether the size or distribution of the viral proteome-wide epitope repertoire, i.e., the intrinsic ability to present fewer, more or specific viral epitopes, could affect clinical markers of disease progression.

Methodology/Principal Findings

We used an epitope prediction model to identify all epitope motifs in a set of 302 HIV-1 full-length proteomes according to each individual''s HLA (Human Leukocyte Antigen) genotype. The epitope repertoire, i.e., the number of predicted epitopes per HIV-1 proteome, varied considerably between HLA alleles and thus among individual proteomes. In a subgroup of 270 chronically infected individuals, we found that lower viral loads and higher CD4 counts were associated with a larger predicted epitope repertoire. Additionally, in Gag and Rev only, more epitopes were restricted by alleles associated with low viral loads than by alleles associated with higher viral loads.

Conclusions/Significance

This comprehensive analysis puts forth the epitope repertoire as a mechanistic component of the multi-faceted HIV-specific CTL response. The favorable impact on markers of disease status of the propensity to present more HLA binding peptides and specific proteins gives impetus to vaccine design strategies that seek to elicit responses to a broad array of HIV-1 epitopes, and suggest a particular focus on Gag.     

A new subgenus ofEpoligosita [Hym.: Trichogrammatidae] and egg parasite ofTingiae [Het.] from Southern India

SubgenusEpoligositina nov. of the genusEpoligosita with a type speciesEpoligosita (Epoligositina) duliniae sp. nov., a new record as egg parasite of the morinda Tingid,Dulinius conchatus Dist. has been described and illustrated.