Citations

ObjectiveAssess algorithms for linking patients across de‐identified databases without compromising confidentiality.Data Sources/Study SettingHospital discharges from 11 Mayo Clinic hospitals during January 2008–September 2012 (assessment and validation data). Minnesota death certificates and hospital discharges from 2009 to 2012 for entire state (application data).Study DesignCross‐sectional assessment of sensitivity and positive predictive value (PPV) for four linking algorithms tested by identifying readmissions and posthospital mortality on the assessment data with application to statewide data.Data Collection/Extraction MethodsDe‐identified claims included patient gender, birthdate, and zip code. Assessment records were matched with institutional sources containing unique identifiers and the last four digits of Social Security number (SSNL4).Principal FindingsGender, birthdate, and five‐digit zip code identified readmissions with a sensitivity of 98.0 percent and a PPV of 97.7 percent and identified postdischarge mortality with 84.4 percent sensitivity and 98.9 percent PPV. Inclusion of SSNL4 produced nearly perfect identification of readmissions and deaths. When applied statewide, regions bordering states with unavailable hospital discharge data had lower rates.ConclusionAddition of SSNL4 to administrative data, accompanied by appropriate data use and data release policies, can enable trusted repositories to link data with nearly perfect accuracy without compromising patient confidentiality. States maintaining centralized de‐identified databases should add SSNL4 to data specifications.

ObjectiveSeveral studies have demonstrated small but statistically significant differences in quality‐of‐life (QOL) scores among vestibular schwannoma (VS) treatment modalities. However, does a several‐point difference on a 100‐point scale really matter? The minimal clinically important difference (MCID)—defined as the smallest difference in scores that patients perceive as important and that could lead to a change in management—was developed to answer this important question. While the MCID has been determined for QOL measures used in other diseases, it remains undefined in the VS literature.Study DesignDistribution‐ and anchor‐based techniques were utilized to define the MCID for the Penn Acoustic Neuroma Quality of Life (PANQOL) and 36‐Item Short Form Health Survey (SF‐36).SettingTwo academic referral centers.PatientsPatients with VS (N = 538).InterventionCross‐sectional postal survey.Main Outcome MeasuresMCID for PANQOL domains and total score and SF‐36 Physical and Mental Health Component Summary scores.ResultsThe MCID (median, interquartile range) for the PANQOL total score was 11 points (10‐12); the MCIDs for individual domains were as follows: hearing, 6 (5‐8); balance, 16 (14‐19); facial, 10 (no interquartile range); pain, 11 (10‐13); energy, 13 (10‐17); anxiety, 11 (5‐22); and general, 15 (11‐19). The MCID was 7 points (6‐11) for the SF‐36 Mental Health Component Summary score and 8 points (6‐10) for the Physical Health Component Summary score.ConclusionsThe MCIDs determined in the current study generally exceed differences reported in previous prospective studies, in which conclusions about QOL benefit (or harm) among VS treatment modalities were based on statistical significance alone. Moving forward, these MCIDs should be considered when interpreting results of VS QOL studies.

Abstract A genome-wide association study (GWAS) of prostate cancer in Kaiser Permanente health plan members (7,783 cases, 38,595 controls; 80.3% non-Hispanic white, 4.9% African-American, 7.0% East Asian, and 7.8% Latino) revealed a new independent risk indel rs4646284 at the previously identified locus 6q25.3 that replicated in PEGASUS (N = 7,539) and the Multiethnic Cohort (N = 4,679) with an overall P = 1.0 × 10−19 (OR, 1.18). Across the 6q25.3 locus, rs4646284 exhibited the strongest association with expression of SLC22A1 (P = 1.3 × 10−23) and SLC22A3 (P = 3.2 × 10−52). At the known 19q13.33 locus, rs2659124 (P = 1.3 × 10−13; OR, 1.18) nominally replicated in PEGASUS. A risk score of 105 known risk SNPs was strongly associated with prostate cancer (P < 1.0 × 10−8). Comparing the highest to lowest risk score deciles, the OR was 6.22 for non-Hispanic whites, 5.82 for Latinos, 3.77 for African-Americans, and 3.38 for East Asians. In non-Hispanic whites, the 105 risk SNPs explained approximately 7.6% of disease heritability. The entire GWAS array explained approximately 33.4% of heritability, with a 4.3-fold enrichment within DNaseI hypersensitivity sites (P = 0.004). Significance: Taken together, our findings of independent risk variants, ethnic variation in existing SNP replication, and remaining unexplained heritability have important implications for further clarifying the genetic risk of prostate cancer. Our findings also suggest that there may be much promise in evaluating understudied variation, such as indels and ethnically diverse populations. Cancer Discov; 5(8); 878–91. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 783

AbstractAcute pain following amputation can be challenging to treat due to multiple underlying mechanisms and variable clinical responses to treatment. Furthermore, poorly controlled preoperative pain is a risk factor for developing chronic pain. Evidence suggests that epidural analgesia and peripheral nerve blockade may decrease the severity of residual limb pain and the prevalence of phantom pain after lower extremity amputation. We present the perioperative analgesic management of a patient with gangrene of the bilateral upper and lower extremities as a result of septic shock and prolonged vasopressor administration who underwent four‐limb amputation in a single procedure. A multimodal analgesic regimen was utilized, including titration of preoperative opioid and neuropathic pain agents, perioperative intravenous, epidural and peripheral nerve catheter infusions, and postoperative oral medication titration. More than 8 months postoperatively, the patient has satisfactory pain control with no evidence for phantom limb pain. To our knowledge, there have been no publications to date concerning analgesic regimens in four‐limb amputation.

SummaryMitochondrial dysfunction is often observed in aging skeletal muscle and is implicated in age‐related declines in physical function. Early evidence suggests that dietary omega‐3 polyunsaturated fatty acids (n‐3 PUFAs) improve mitochondrial function. Here, we show that 10 weeks of dietary eicosapentaenoic acid (EPA) supplementation partially attenuated the age‐related decline in mitochondrial function in mice, but this effect was not observed with docosahexaenoic acid (DHA). The improvement in mitochondrial function with EPA occurred in the absence of any changes in mitochondrial abundance or biogenesis, which was evaluated from RNA sequencing, large‐scale proteomics, and direct measurements of muscle mitochondrial protein synthesis rates. We find that EPA improves muscle protein quality, specifically by decreasing mitochondrial protein carbamylation, a post‐translational modification that is driven by inflammation. These results demonstrate that EPA attenuated the age‐related loss of mitochondrial function and improved mitochondrial protein quality through a mechanism that is likely linked with anti‐inflammatory properties of n‐3 PUFAs. Furthermore, we demonstrate that EPA and DHA exert some common biological effects (anticoagulation, anti‐inflammatory, reduced FXR/RXR activation), but also exhibit many distinct biological effects, a finding that underscores the importance of evaluating the therapeutic potential of individual n‐3 PUFAs.

Abstract Purpose: Immunotherapeutic strategies to treat patients with renal cell carcinoma (RCC) offer new opportunities for disease management. Further improvements to immunotherapy will require additional understanding of the host response to RCC development. Experimental Design: Using a novel approach to understanding the immune status of cancer patients, we previously showed that patients with a certain immune profile had decreased overall survival. Here, we examine in more detail the phenotypic changes in peripheral blood and the potential consequences of these changes in RCC patients. Results: We found that CD14+HLA-DRlo/neg monocytes were the most predominant phenotypic change in peripheral blood of RCC patients, elevated nearly 5-fold above the average levels measured in healthy volunteers. Intratumoral and peritumoral presence of CD14 cells was an independent prognostic factor for decreased survival in a cohort of 375 RCC patients. The amount of peripheral blood CD14+HLA-DRlo/neg monocytes was found to correlate with the intensity of CD14 staining in tumors, suggesting that the measurement of these cells in blood may be a suitable surrogate for monitoring patient prognosis. The interaction of monocytes and tumor cells triggers changes in both cell types with a loss of HLA-DR expression in monocytes, increases of monocyte survival factors such as GM-CSF in tumors, and increased production of angiogenic factors, including FGF2. Conclusions: Our results suggest a model of mutually beneficial interactions between tumor cells and monocytes that adversely affect patient outcome. Clin Cancer Res; 21(18); 4224–33. ©2015 AACR.

This study's aims were to describe the spirituality of depressed elderly psychiatric inpatients and to examine associations among spirituality, depression, and quality of life (QOL). Forty-five persons participated. Most reported frequent, stable spiritual practices and experiencing spiritual comfort and guidance. Some reported spiritual distress and changes in spirituality. During hospitalization, participants demonstrated increased spiritual well-being (SWB) and peacefulness, and reduced hopelessness, worthlessness, and guilt. Positive associations were found between SWB and QOL and negative associations between SWB and depression.