Association of hospital and surgeon procedure volume with patient-centered outcomes of total knee replacement in a population-based cohort of patients age 65 years and older

OBJECTIVE: To study the association between procedure volume and patient-centered outcomes such as functional status. METHODS: We performed an observational study of a stratified random sample of Medicare beneficiaries who underwent primary total knee replacement (TKR) in 2000. Low-volume surgeons were defined as surgeons performing < or =6 TKRs per year in the Medicare population, and low-volume centers were defined as those in which < or =25 TKRs per year were performed. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) functional status score (0-100 scale; 100 = best) 2 years after TKR. We defined a WOMAC functional status score of <60 as a poor functional outcome. Analyses were adjusted for sociodemographic factors, preoperative functional status, and comorbidities. RESULTS: Fifty-eight percent of 1,597 eligible patients agreed to participate. Twelve percent of participating patients had a WOMAC score <60 2 years following TKR. Patients operated upon by low-volume surgeons in low-volume hospitals were twice as likely to have a poor WOMAC functional status score as patients operated upon by higher volume surgeons and in higher volume hospitals (odds ratio 2.1, 95% confidence interval 1.1-4.2). CONCLUSION: Patients operated upon in low-volume hospitals by low-volume surgeons had worse functional outcomes 2 years after TKR. These findings add a new and important dimension to the discussion of whether to promote selective referral of procedures such as TKR to high-volume centers.     

Increasing body mass index z-score is continuously associated with complications of overweight in children, even in the healthy weight range

CONTEXT: Overweight/obesity in children is increasing. Incidence data for medical complications use arbitrary cutoff values for categories of overweight and obesity. Continuous relationships are seldom reported. OBJECTIVES: The objective of this study is to report relationships of child body mass index (BMI) z-score as a continuous variable with the medical complications of overweight. DESIGN: This study is a part of the larger, prospective cohort Growth and Development Study. SETTING: Children were recruited from the community through randomly selected primary schools. Overweight children seeking treatment were recruited through tertiary centers. PARTICIPANTS: Children aged 6-13 yr were community-recruited normal weight (n = 73), community-recruited overweight (n = 53), and overweight treatment-seeking (n = 51). Medical history, family history, and symptoms of complications of overweight were collected by interview, and physical examination was performed. Investigations included oral glucose tolerance tests, fasting lipids, and liver function tests. MAIN OUTCOME MEASURE: Adjusted regression was used to model each complication of obesity with age- and sex-specific child BMI z-scores entered as a continuous dependent variable. RESULTS: Adjusted logistic regression showed the proportion of children with musculoskeletal pain, obstructive sleep apnea symptoms, headaches, depression, anxiety, bullying, and acanthosis nigricans increased with child BMI z-score. Adjusted linear regression showed BMI z-score was significantly related to systolic and diastolic blood pressure, insulin during oral glucose tolerance test, total cholesterol, high-density lipoprotein, triglycerides, and alanine aminotransferase. CONCLUSION: Child's BMI z-score is independently related to complications of overweight and obesity in a linear or curvilinear fashion. Children's risks of most complications increase across the entire range of BMI values and are not defined by thresholds.     

Audience Segmentation as a Social-Marketing Tool in Health Promotion: Use of the Risk Perception Attitude Framework in HIV Prevention in Malawi

Objectives. We sought to determine whether individuals'' risk perceptions and efficacy beliefs could be used to meaningfully segment audiences to assist interventions that seek to change HIV-related behaviors.Methods. A household-level survey of individuals (N = 968) was conducted in 4 districts in Malawi. On the basis of responses about perceptions of risk and beliefs about personal efficacy, we used cluster analysis to create 4 groups within the risk perception attitude framework: responsive (high risk, strong efficacy), avoidance (high risk, weak efficacy), proactive (low risk, strong efficacy), and indifference (low risk, weak efficacy). We ran analysis of covariance models (controlling for known predictors) to determine how membership in the risk perception attitude framework groups would affect knowledge about HIV, HIV-testing uptake, and condom use.Results. A significant association was found between membership in 1 or more of the 4 risk perception attitude framework groups and the 3 study variables of interest: knowledge about HIV (F_{8, 956} = 20.77; P < .001), HIV testing uptake (F_{8, 952} = 10.91; P < .001), and condom use (F_{8, 885} = 29.59; P < .001).Conclusions. The risk perception attitude framework can serve as a theoretically sound audience segmentation technique that can be used to determine whether messages should augment perceptions of risk, beliefs about personal efficacy, or both.Malawi has been greatly affected by AIDS. In 2007, approximately 68 000 deaths in Malawi were attributable to this pandemic,¹ and AIDS prevalence is currently estimated at 11.9% among Malawian adults, a figure that has changed little since 2004.² Prevalence of HIV infection in the southern region of the country is 17.6%. As of 2005, life expectancy for women in Malawi was 42 years, and life expectancy for men was 41 years.³ The number of orphans in the country who have lost either parent to AIDS almost tripled in 6 years, from 201 000 in 2001 to 560 000 in 2007.¹ Approximately 840 000 adults in Malawi are currently living with HIV.There is an urgent need for long-term strategies to promote behaviors that protect Malawians from HIV infection. A number of efforts to address the growing problem are currently under way, including provision of antiretroviral treatments and promotion of HIV testing and counseling. It is only recently that comprehensive programs to prevent AIDS transmission have been undertaken, one of which is the Malawi BRIDGE project, described here.     

Geographic diversity of low-volume hospitals in total knee replacement: implications for regionalization policies

BACKGROUND/OBJECTIVES: Centers performing low volumes of total knee replacements (TKR) have worse outcomes of TKR than higher volume centers. Regionalization policies that shift patients to higher volume centers are being considered as a means of improving TKR outcomes. We sought to describe geographic diversity in the distribution of low-volume centers and examine state level characteristics associated with states that have a higher proportion of low-volume centers and/or a higher proportion of TKRs performed in low-volume centers. METHODS: We used U.S. Census data and geocoded Medicare claims to ascertain state-level demographic factors, procedure volume, and TKR rates and to conduct our state level analysis. We defined 2 outcomes: 1) proportion of all hospitals with a low annual TKR volume (<26 per year in the Medicare population); and 2) proportion of all TKRs in the Medicare population performed in low-volume centers. We examined linear associations among the 2 outcomes and state factors, and used multivariate regression to identify factors associated independently with these outcomes. RESULTS: Half of hospitals performing TKR in the Medicare population were low-volume centers, accounting for 13% of TKRs. Multivariate analysis revealed lower TKR rates, higher proportion of rural areas and larger state area were associated with a higher proportion of low-volume hospitals in a state. Lower proportion of elderly residents, higher population density and higher proportion of rural areas predicted a higher proportion of TKRs performed in low-volume centers. CONCLUSIONS: The distribution of low-volume hospitals among U.S. states varies substantially. Regionalization of TKR may require different strategies in states with small and large numbers of low-volume centers.     

Caspase 3 is not essential for the induction of anergy or multiple pathways of CD8+ T-cell death

T-cell death is a fundamental process that is intricately regulated at multiple phases during T-cell differentiation, tolerance induction and the decline of the immune response. Caspase 3 is a crucial molecule regulating both mitochondrial and death receptor apoptotic pathways and therefore we were interested in examining the role of caspase 3 in T cells. Using P14 and H-Y CD8(+) TCR-transgenic models, our analysis has shown that caspase 3 is not required for thymic negative selection. In addition, caspase 3 does not play a prominent role in the contraction phase following acute viral infection, nor clonal deletion of CD8(+) T cells under tolerizing conditions. Surprisingly, our studies demonstrate that caspase 3 was not required for the induction of CD8(+) T-cell anergy in vivo, contrary to published reports using CD4(+) T cells. Therefore, these results demonstrate that caspase 3 is not essential in CD8(+) T cells for multiple forms of thymic or peripheral tolerance, nor the contraction phase after an acute anti-viral response.     

c‐Rel but not NF‐κB1 is important for T regulatory cell development

Regulatory T (Treg) cells are crucial for maintaining peripheral tolerance and controlling T‐cell responses. The generation of Treg in the thymus requires TCR triggering and CD28 costimulation. Engagement of these receptors induces a number of signalling pathways, including the activation of NF‐κB via PKCθ and the Bcl‐10/CARMA1/MALT complex. Previous studies have shown that PKCθ, Bcl‐10 and CARMA1 are important for Treg development. It is unclear, however, whether different members of the NF‐κB family contribute to Treg development or homeostasis. In this study, we show that Treg numbers are reduced in the absence of c‐Rel but not NF‐κB1 (p50). Furthermore, using mixed bone marrow chimeras from WT and KO animals, we demonstrate that the requirement for PKCθ, Bcl‐10 and c‐Rel is T‐cell intrinsic, and cannot be rescued by the presence of WT cells. Therefore, c‐Rel and NF‐κB1 have differential roles in Treg development.     

Synovial fluid proteins differentiate between the subtypes of juvenile idiopathic arthritis

Objective

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory diseases, and no clinically useful prognostic markers to predict disease outcome in children with JIA are currently available. Synovial fluid likely reflects the proteins present in the inflamed synovium. The purpose of this study was to delineate the synovial fluid proteome and determine whether protein expression differs in the different subtypes of JIA.

Methods

Synovial fluid samples obtained from children with oligoarticular JIA, polyarticular JIA, or systemic JIA were compared. Two‐dimensional gel electrophoresis for protein separation and matrix‐assisted laser desorption ionization−time‐of‐flight mass spectrometry and quadripole time‐of‐flight mass spectrometry for protein identification were used for this study. Synovial fluid cells were analyzed by polymerase chain reaction (PCR) for the presence of haptoglobin messenger RNA (mRNA).

Results

The synovial fluid proteome of the samples was delineated. The majority of proteins showed overexpression in JIA synovial fluid as compared with noninflammatory control samples. There were 24 statistically significantly differentially expressed spots (>2‐fold change; P < 0.05) between the subtypes of JIA. PCR analysis revealed haptoglobin mRNA, suggesting that haptoglobin is locally produced in an inflamed joint in JIA.

Conclusion

Despite the similar histologic appearance of inflamed joints in patients with different subtypes of JIA, there are differences in protein expression according to the subtype of JIA. Haptoglobin is differentially expressed between the subtypes of JIA and is locally produced in an inflamed joint in JIA. Haptoglobin and other differentially expressed proteins may be potential biomarkers in JIA.

     

Cyclooxygenase-2 deficiency increases epidermal apoptosis and impairs recovery following acute UVB exposure

The cyclooxygenases, COX-1 and COX-2, are involved in cutaneous responses to both acute and chronic UV exposure. In the present study, wild-type (WT), COX-1-/- and COX-2-/- mice were used to determine the influence of the individual isoform on mouse skin responses to acute UVB treatment. Immunohistochemistry and Western analysis indicated that COX-2, and not COX-1, was induced by UVB (2.5 or 5.0 kJ/m2), but that COX-1 remained the major source of prostaglandin E2 production. UVB exposure significantly increased epidermal apoptosis in all genotypes compared to untreated mice. However, while the number of apoptotic cells in WT and COX-1-/- mice were about equal, the number of apoptotic cells was 2.5-fold greater in COX-2-/- mice. Apoptosis in WT and COX-2-/- mice peaked at 24 h post-exposure. The increased apoptosis and reduced proliferation in COX-2-/- mice resulted in about a 50% decrease in epidermal thickness at 24-48 h post-exposure compared to about a 50% increase in epidermal thickness in WT mice. UVB-induced cell replication, as measured by BrdU labeling, was reduced in COX-2-/- compared to WT mice at 24-96 h. However, by 96 h post-exposure, both WT and COX-2-/- mice showed epidermal hyperplasia. The data indicate that COX-2 induction initially protects against the acute sunburn effects of UVB, but that continuous induction of COX-2 may contribute to skin cancer in chronic UVB exposure.