Frailty is associated with in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands: the COVID-OLD study.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. OBJECTIVE: The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. METHODS: This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. RESULTS: A total of 1,376 patients were included (median age 78 years (interquartile range 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3-3.0)) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8-4.3)). CONCLUSIONS: The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms.

Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry).

BACKGROUND: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. OBJECTIVES: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. METHODS: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. RESULTS: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). CONCLUSION: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

Increased expression of microRNA-155 in peripheral blood mononuclear cells from psoriasis patients is related to disease activity.

BACKGROUND: MicroRNAs (miRNAs) gene expression regulators are altered in psoriasis suggesting their role in the pathogenesis. OBJECTIVE: To study expression changes of inflammation and toll-like receptor (TLR)-related miRNAs, miRNA-155, let-7i, miRNA-21, miRNA-146a and miRNA-223 in peripheral mononuclear cells (PBMCs) and miRNA-21, miRNA-146a and miRNA-223 in plasma, from chronic plaque-type psoriasis patients who were treatment-naive or had undergone a washout period (n = 11). MiRNAs were evaluated at baseline and after 11 (9-12) months [median (25th-75th percentile range)] of methotrexate (MTX) or topical (betamethasone plus calcipotriene) treatment. METHODS: MiRNA expression was analysed with quantitative real-time reverse transcription-polymerase chain reaction. Matched controls were studied. RESULTS: Psoriasis patients presented, at baseline, increased expression of miRNA-155, let-7i, miRNA-146a, miRNA-21 and miRNA-223 in PBMCs, plus miRNA-21, miRNA-146a and miRNA-223 in plasma. Receiver-operator characteristic (ROC) curve analysis and area under the curve (AUC) showed that expression of these miRNAs have the potential to distinguish between psoriasis and controls. At baseline, miRNA-155 expression in PBMCs correlated with Psoriasis Area Severity Index (PASI) [12 (8-14)] (Spearman r: 0.7140, P < 0.05) suggesting a role in psoriasis. After MTX or topical treatment, reduction in PASI was observed [87.5% (75-100)]; miRNA-155 expression in PBMCs decreased; plasma miRNA-21, miRNA-146a and miRNA-223 were down-regulated. ROC analysis showed that miRNA-155 expression in PBMCs from psoriasis patients have the potential to distinguish between patients' samples at baseline and after treatment (AUC: 0.942, sensitivity: 0.91; specificity: 0.91 values; maximum likelihood ratio =10). After treatment, miRNA-146a expression in PBMCs increased; miRNA-155/miRNA-146a ratio decreased, suggestive of a regulatory feedback; let-7i expression decreased; miRNA-21 and miRNA-223 remained elevated. CONCLUSION: In this exploratory study, psoriasis patients presented increased expression of miRNA-155 in PBMCs that correlated with PASI and decreased with disease remission. MiRNA-21, miRNA-146a and miRNA-223 in PBMCs and plasma were increased at baseline and differentially modulated, underscoring different roles of TLR-related miRNAs in psoriasis.

Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis.

Genetic biomarkers could be useful for orienting treatment of patients with rheumatoid arthritis (RA), but none has been convincingly validated yet. Putative biomarkers include 14 single nucleotide polymorphisms that have shown association with response to TNF inhibitors (TNFi) in candidate gene studies and that we assayed here in 755 RA patients. Three of them, in the PTPRC, IL10 and CHUK genes, were significantly associated with response to TNFi. The most significant result was obtained with rs10919563 in PTPRC, which is a confirmed RA susceptibility locus. Its RA risk allele was associated with improved response (B=0.33, P=0.006). This is the second independent replication of this biomarker (P=9.08 × 10(-8) in the combined 3003 RA patients). In this way, PTPRC has become the most replicated genetic biomarker of response to TNFi. In addition, the positive but weaker replication of IL10 and CHUK should stimulate further validation studies.

The development and application of an oncology Therapy-Related Symptom Checklist for Adults (TRSC) and Children (TRSC-C) and e-health applications.

BACKGROUND: Studies found that treatment symptoms of concern to oncology/hematology patients were greatly under-identified in medical records. On average, 11.0 symptoms were reported of concern to patients compared to 1.5 symptoms identified in their medical records. A solution to this problem is use of an electronic symptom checklist that can be easily accessed by patients prior to clinical consultations. PURPOSE: Describe the oncology Therapy-Related Symptom Checklists for Adults (TRSC) and Children (TRSC-C), which are validated bases for e-Health symptom documentation and management. The TRSC has 25 items/symptoms; the TRSC-C has 30 items/symptoms. These items capture up to 80% of the variance of patient symptoms. Measurement properties and applications with outpatients are presented. E-Health applications are indicated. METHODS: The TRSC was developed for adults (N = 282) then modified for children (N = 385). Statistical analyses have been done using correlational, epidemiologic, and qualitative methods. Extensive validation of measurement properties has been reported. RESULTS: Research has found high levels of patient/clinician satisfaction, no increase in clinic costs, and strong correlations of TRSC/TRSC-C with medical outcomes. A recently published sequential cohort trial with adult outpatients at a Mayo Clinic community cancer center found TRSC use produced a 7.2% higher patient quality of life, 116% more symptoms identified/managed, and higher functional status. DISCUSSION, IMPLICATIONS, AND FOLLOW-UP: An electronic system has been built to collect TRSC symptoms, reassure patients, and enhance patient-clinician communications. This report discusses system design and efforts made to provide an electronic system comfortable to patients. Methods used by clinicians to promote comfort and patient engagement were examined and incorporated into system design. These methods included (a) conversational data collection as opposed to survey style or standardized questionnaires, (b) short response phrases indicating understanding of the reported symptom, (c) use of open-ended questions to reduce long lists of symptoms, (d) directed questions that ask for confirmation of expected symptoms, (e) review of symptoms at designated stages, and (d) alerting patients when the computer has informed clinicians about patient-reported symptoms. CONCLUSIONS: An e-Health symptom checklist (TRSC/TRSC-C) can facilitate identification, monitoring, and management of symptoms; enhance patient-clinician communications; and contribute to improved patient outcomes.

Addressing the Unmet Needs of Patients With Rapidly Progressive Neurological Disease: A Case Report of Palliative Care in Creutzfeldt-Jakob Disease (CJD).

Creutzfeldt-Jacob disease (CJD) is a rare neurodegenerative disorder that typically progresses rapidly and unrelentingly. Providing comfort and support for patients with CJD presents significant challenges for clinicians and caregivers. In comparison to the more typical disease progression experienced in dementias, the trajectory of CJD differs significantly. This case report delves into these differences and emphasizes the need for the development of guidelines for healthcare professionals and families who care for individuals with CJD. Such guidelines would help facilitate better care and support for patients and their families throughout the course of this devastating illness.

Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis.

OBJECTIVE: To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA). METHODS: Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays. RESULTS: The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79). CONCLUSIONS: Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.

Early Guided Palliative Care Communication for Patients With COVID-19 Receiving ECMO.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) combined with COVID-19 presents challenges (eg, isolation, anticipatory grief) for patients and families. OBJECTIVE: To (1) describe characteristics and outcomes of patients with COVID-19 receiving ECMO, (2) develop a practice improvement strategy to implement early, semistructured palliative care communication in ECMO acknowledgment meetings with patients' families, and (3) examine family members' experiences as recorded in clinicians' notes during these meetings. METHODS: Descriptive observation of guided, in-depth meetings with families of patients with COVID-19 receiving ECMO, as gathered from the electronic medical record of a large urban academic medical center. Most meetings were held within 3 days of initiation of ECMO. RESULTS: Forty-three patients received ECMO between March and October 2020. The mean patient age was 44 years; 63% of patients were Hispanic/Latino, 19% were Black, and 7% were White. Documentation of the ECMO acknowledgment meeting was completed for 60% of patients. Fifty-six percent of patients survived to hospital discharge. Family discussions revealed 7 common themes: hope, reliance on faith, multiple family members with COVID-19, helping children adjust to a new normal, visitation restrictions, gratitude for clinicians and care, and end-of-life discussions. CONCLUSION: Early and ongoing provision of palliative care is feasible and useful for highlighting a range of experiences related to COVID-19. Palliative care is also useful for educating patients and families on the benefits and limitations of ECMO therapy.

Coxa Vara Deformity in Fibrous Dysplasia/McCune-Albright Syndrome: Prevalence, Natural History and Risk Factors: A Two-Center Study.

This study aimed to evaluate the prevalence of and risk factors for coxa vara deformity in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). This study was conducted at the National Institutes of Health and Leiden University Medical Center. All patients with any subtype of FD/MAS, FD involving the proximal femur, one or more X-rays available and age <30 years were included. X-rays were scored for the neck-shaft angle (NSA). Varus deformity was defined as NSA <110 degrees or >10 degrees below age-specific values. Risk factors for deformity were assessed by nested case-control analysis, comparing patients and femurs with and without deformity, and by linear mixed effects model, modeling temporal NSA decrease (the natural course of the NSA) in non-operated femurs with two or more X-rays. Assessed variables included growth hormone excess, hyperthyroidism, hypophosphatemia, >25% of the femur affected, calcar destruction, radiolucency, and bilateral involvement. In total 180 patients were studied, 57% female. Mean ± SD baseline age was 13.6 ± 7.5 years; median follow-up 5.4 (interquartile range [IQR], 11.1) years. Sixty-three percent (63%) were diagnosed with MAS. A total of 94 patients were affected bilaterally; 274 FD femurs were analyzed; 99 femurs had a varus deformity (36%). In the nested case-control analysis, risk factors were as follows: presence of MAS (p < 0.001), hyperthyroidism (p < 0.001), hypophosphatemia (p < 0.001), high percentage of femur affected (p < 0.001), and calcar destruction (p < 0.001). The linear mixed effects model included 114 femurs, identified risk factors were: growth hormone excess (ß = 7.2, p = 0.013), hyperthyroidism (ß = 11.3, p < 0.001), >25% of the femur affected (ß = 13.2, p = 0.046), calcar destruction (ß = 8.3, p = 0.004), radiolucency (ß = 3.9, p = 0.009), and bilateral involvement (ß = 9.8, p = 0.010). Visual inspection of the graph of the model demonstrated most progression of deformity if NSA <120 degrees with age < 15 years. In conclusion, in tertiary care centers, the prevalence of FD/MAS coxa vara deformity was 36%. Risk factors included presence of MAS, high percentage of femur affected, calcar destruction, radiolucency, NSA <120 degrees and age < 15 years. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The Corpse: Time for Another Look A Review of the Culture of Embalming, Viewing and the Social Construction.

Embalming of the dead is more common in the United States than anywhere else in the world. Battles far from home during the Civil War with concern for contagion from dead bodies being shipped home compelled President Lincoln to direct the troops to use embalming to allow the return of the Union dead to their homes. Viewings were common with war heroes and culminated with the viewing of Lincoln himself. In the 20th century embalming became a tradition despite substantial evidence indicating environmental and occupational hazards related to embalming fluids and carbon dioxide generated from manufacturing steel coffins before placing in concrete burial vaults. Embalming is promoted and considered helpful to the grieving process. Embalmers are expected to produce an illusion of rest, an image that in some ways disguises death for the benefit of mourners. The dead are carefully displayed in a condition of liminal repose where the 'true' condition is hidden, and death is removed from the actual event. In this paper we highlight the spiritual and cultural complexities of embalming related issues. We propose an innovative process to empower people facing serious illness, and their families to make shared and informed decisions, especially when death is an expected outcome.

Long Bone Fractures in Fibrous Dysplasia/McCune-Albright Syndrome: Prevalence, Natural History, and Risk Factors.

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare bone and endocrine disorder arising along a broad spectrum. Long-bone fractures are a common, painful, and potentially disabling complication. However, fracture prevalence and risk factors have not been well-established, making it difficult to predict which patients are at risk for a severe course. Clinical and imaging data were reviewed from two large, well-phenotyped cohorts (National Institutes of Health [NIH] in the United States and the Leiden University Medical Center [LUMC] in the Netherlands) to identify long-bone fractures at FD sites. Skeletal burden score was quantified using bone scintigraphy. Multiple linear regressions were performed to identify clinical associations with fractures. A total of 419 patients were included (186 NIH, 233 LUMC); 194 (46%) had MAS endocrinopathies. Median age at last follow-up was 30.2 years (range 3.2-84.6, interquartile range [IQR] 25.5), and median skeletal burden score was 16.6 (range 0-75, IQR 33). A total of 48 (59%) patients suffered one or more lifetime fracture (median 1, range 0-70, IQR 4). Median age at first fracture was 8 years (range 1-76, IQR 10). Fracture rates peaked between 6 and 10 years of age and decreased thereafter. Lifetime fracture rate was associated with skeletal burden score (ß = 0.40, p < 0.01) and MAS hyperthyroidism (ß = 0.22, p = 0.01). Younger age at first fracture was associated with skeletal burden score (ß = -0.26, p = 0.01) and male sex (ß = -0.23, p = 0.01). Both skeletal burden score >25 and age at first fracture ≤7 years were associated with a higher total number of lifetime fractures (median 4, range 1-70, IQR 5 versus median 1, range 1-13, IQR 1) (p < 0.01). In conclusion, higher skeletal burden score and MAS hyperthyroidism are associated with long-bone fractures in FD/MAS. Both skeletal burden score ≥25 and age at first fracture ≤7 years are associated with a higher lifetime long-bone fracture risk and may predict a more severe clinical course. These results may allow clinicians to identify FD/MAS patients at risk for severe disease who may be candidates for early therapeutic interventions. © 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Genotype-Phenotype Correlation in Fibrous Dysplasia/McCune-Albright Syndrome.

CONTEXT: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare bone and endocrine disorder resulting in fractures, pain, and disability. There are no targeted or effective therapies to alter the disease course. Disease arises from somatic gain-of-function variants at the R201 codon in GNAS, replacing arginine by either cysteine or histidine. The relative pathogenicity of these variants is not fully understood. OBJECTIVE: This work aimed 1) to determine whether the most common GNAS variants (R201C and R201H) are associated with a specific clinical phenotype, and 2) to determine the prevalence of the most common GNAS variants in a large patient cohort. METHODS: This retrospective cross-sectional analysis measured the correlation between genotype and phenotype characterized by clinical, biochemical, and radiographic data. RESULTS: Sixty-one individuals were genotyped using DNA extracted from tissue or circulating cell-free DNA. Twenty-two patients (36.1%) had the R201C variant, and 39 (63.9%) had the R201H variant. FD skeletal disease burden, hypophosphatemia prevalence, fracture incidence, and ambulation status were similar between the 2 groups. There was no difference in the prevalence of endocrinopathies, ultrasonographic gonadal or thyroid abnormalities, or pancreatic involvement. There was a nonsignificant association of cancer with the R201H variant. CONCLUSION: There is no clear genotype-phenotype correlation in patients with the most common FD/MAS pathogenic variants. The predominance of the R201H variant observed in our cohort and reported in the literature indicates it is likely responsible for a larger burden of disease in the overall population of patients with FD/MAS, which may have important implications for the future development of targeted therapies.

Association study of ghrelin receptor gene polymorphisms in rheumatoid arthritis.

OBJECTIVES: Ghrelin is a newly characterised growth hormone (GH) releasing peptide widely distributed that may play an important role in the regulation of metabolic balance in inflammatory diseases such as rheumatoid arthritis (RA) by decreasing the pro-inflammatory Th1 responses. In this study we investigated the possible contribution of several polymorphisms in the functional Ghrelin receptor to RA susceptibility. METHODS: A screening of 3 single nucleotide polymorphisms (SNPs) was performed in a total of 950 RA patients and 990 healthy controls of Spanish Caucasian origin. Genotyping of all 3 SNPs was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. RESULTS: We observed no statistically significant deviation between RA patients and controls for the GHSR SNPs analysed. In addition, we performed a haplotype analysis that did not reveal an association with RA susceptibility. The stratification analysis for the presence of shared epitope (SE), rheumatoid factor (RF) or antibodies anti cyclic citrullinated peptide (anti-CCP) did not detect significant association of the GHSR polymorphisms with RA. CONCLUSIONS: These findings suggest that the GHSR gene polymorphisms do not appear to play a major role in RA genetic predisposition in our population.

Investigation of CD69 as a new candidate gene for rheumatoid arthritis.

The aim of this study was to investigate the CD69 gene as a new functional candidate gene for rheumatoid arthritis (RA) genetic predisposition. A case-control association study including 933 RA patients and 800 healthy individuals was conducted. Five haplotype-tagging single nucleotide polymorphisms (SNPs) (rs929615, rs3176806, rs4763299, rs11052877, and rs3176789) covering the CD69 gene coding, 5' and 3' untranslated regions were selected as CD69 genetic markers and genotyped using a Taqman 5' allelic discrimination assay. No statistically significant differences were observed in the single marker association study with regard to either genotypic or allelic frequencies when considering the rs929615, rs3176806, rs4763299, rs11052877, and rs3176789 CD69 SNPs independently. According to these findings, no statistically significant skewing was observed between the RA patients and the controls in the distribution of CD69 haplotypes. In summary, our results do not support a major role for the CD69 gene polymorphisms in RA genetic predisposition in our population.

The IL23R Arg381Gln non-synonymous polymorphism confers susceptibility to ankylosing spondylitis.

OBJECTIVES: Recent results have shown that the IL23R gene, coding for a subunit of the interleukin-23 receptor, is strongly associated with autoimmunity. The aim of the current study was to investigate, for the first time, the possible involvement of the IL23R gene in genetic susceptibility to ankylosing spondylitis (AS). METHODS: We carried out a case-control association study in which 365 patients with AS and 500 blood bank donors were included. Eight single nucleotide polymorphisms (SNPs) spanning the IL23R gene were selected as genetic markers for our association study and were genotyped using a Taqman 5' allelic discrimination assay. RESULTS: Interestingly, we observed association of two of eight IL23R genotyped SNPs. The strongest effect was conferred by the non-synonymous rs11209026 (Arg381Gln) SNP (odds ratio 0.46 95% confidence interval 0.2 to 0.7 p = 0.001). Similarly, the IL23R rs1343151 SNP showed association with AS genetic susceptibility (odds ratio 0.68 95% confidence interval 0.55 to 0.83 p = 0.0002). After a conditional case-control test we observed that the effect of these two genetic variants was independent of linkage disequilibrium. CONCLUSIONS: These results suggest that the IL23R gene seems to be involved in AS genetic predisposition.

The Multimorbidity Index: A Tool for Assessing the Prognosis of Patients from Their History of Illness.

BACKGROUND: The Multimorbidity (MM) Index predicts the prognosis of patients from their diagnostic history. In contrast to existing approaches with broad diagnostic categories, it treats each diagnosis as a separate independent variable using individual International Classification of Disease, Revision 9 (ICD-9) codes. OBJECTIVE: This paper describes the MM Index, reviews the published data on its accuracy, and provides procedures for implementing the Index within electronic health record (EHR) systems. Methods: The MM Index was tested on various patient populations by using data from the United States Department of Veterans Affairs data warehouse and claims data within the Healthcare Cost and Utilization Project of the Agency for Health Care Research and Quality. RESULTS: In cross-validated studies, the MM Index outperformed prognostic indices based on physiological markers, such as CD4 cell counts in HIV/AIDS, HbAlc levels in diabetes, ejection fractions in heart failure, or the 13 physiological markers commonly used for patients in intensive care units. When predicting the prognosis of nursing home patients by using the cross-validated area under a receiver operating characteristic (ROC) curve, the MM Index was 15 percent outperformed the Quan variant of the Charlson Index, 27 percent more accurate than the Deyo variant of the Charlson Index, and 22 percent more accurate than the von Walraven variant of the Elixhauser Index. For patients in intensive care units, the MM Index was 13 percent outperformed the cross-validated area under ROC associated with Elixhauser's categories. The MM Index also demonstrated greater accuracy than a number of commercially available measures of illness severity; including a fivefold greater accuracy than the All Patient Refined Diagnosis-Related Groups and a threefold greater accuracy than All Payer Severity-Adjusted Diagnosis-Related Groups. CONCLUSION: The MM Index is statistically more accurate than many existing measures of prognosis. The magnitude of improvement is large and may lead to a clinically meaningful difference in patient care. Given the large improvements in accuracy, the use of the MM Index for policy and comparative effectiveness analysis is recommended.