Mortality Rate in Veterans with Multiple Chronic Conditions

Background: Among patients with multiple chronic conditions, there is increasing appreciation of the complex interrelatedness of diseases. Previous studies have focused on the prevalence and economic burden associated with multiple chronic conditions, much less is known about the mortality rate associated with specific combinations of multiple diseases. Objective: Measure the mortality rate in combinations of 11 chronic conditions. Design: Cohort study of veteran health care users. Participants Veterans between 55 and 64 years that used Veterans Health Administration health care services between October 1999 and September 2000. Measurements: Patients were identified as having one or more of the following: COPD, diabetes, hypertension, rheumatoid arthritis, osteoarthritis, asthma, depression, ischemic heart disease, dementia, stroke, and cancer. Mutually exclusive combinations of disease based on these conditions were created, and 5-year mortality rates were determined. Results: There were 741,847 persons included. The number in each group by a count of conditions was: none = 217,944 (29.34%); 1 = 221,111 (29.8%); 2 = 175,228 (23.6%); 3 = 86,447 (11.7%); and 4+ = 41,117 (5.5%). The 5-year mortality rate by the number of conditions was: none = 4.1%; 1 = 6.0%; 2 = 7.8%; 3 = 11.2%; 4+ = 16.7%. Among combinations with the same number of conditions, there was significant variability in mortality rates. Conclusions: Patients with multiple chronic conditions have higher mortality rates. Because there was significant variation in mortality across clusters with the same number of conditions, when studying patients with multiple coexisting illnesses, it is important to understand not only that several conditions may be present but that specific conditions can differentially impact the risk of mortality

Phase-Field Model of Mode III Dynamic Fracture

We introduce a phenomenological continuum model for mode III dynamic fracture that is based on the phase-field methodology used extensively to model interfacial pattern formation. We couple a scalar field, which distinguishes between ``broken'' and ``unbroken'' states of the system, to the displacement field in a way that consistently includes both macroscopic elasticity and a simple rotationally invariant short scale description of breaking. We report two-dimensional simulations that yield steady-state crack motion in a strip geometry above the Griffith threshold.Comment: submitted to PR

ISPOR Code of Ethics 2017 (4th Edition)

As the leading health economics and outcomes research (HEOR) professional society, ISPOR has a responsibility to establish a uniform, harmonized international code for ethical conduct. ISPOR has updated its 2008 Code of Ethics to reflect the current research environment. This code addresses what is acceptable and unacceptable in research, from inception to the dissemination of its results. There are nine chapters: 1 – Introduction; 2 – Ethical Principles respect, beneficence and justice with reference to a non-exhaustive compilation of international, regional, and country-specific guidelines and standards; 3 – Scope HEOR definitions and how HEOR and the Code relate to other research fields; 4 – Research Design Considerations primary and secondary data related issues, e.g., participant recruitment, population and research setting, sample size/site selection, incentive/honorarium, administration databases, registration of retrospective observational studies and modeling studies; 5 – Data Considerations privacy and data protection, combining, verification and transparency of research data, scientific misconduct, etc.; 6 – Sponsorship and Relationships with Others (roles of researchers, sponsors, key opinion leaders and advisory board members, research participants and institutional review boards (IRBs) / independent ethics committees (IECs) approval and responsibilities); 7 – Patient Centricity and Patient Engagement new addition, with explanation and guidance; 8 – Publication and Dissemination; and 9 – Conclusion and Limitations

Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease

Objective: To determine the motor phenotype of LRRK2 G2019S mutation carriers. LRRK2 mutation carriers were previously reported to manifest the tremor dominant motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared with the postural instability and gait difficulty (PIGD) phenotype. Design: Cross-sectional observational study. Setting: Thirteen movement disorders centers. Participants: Nine hundred twenty-five early-onset Parkinson disease cases defined as age at onset younger than 51 years. Main Outcome Measures: LRRK2 mutation status and Parkinson disease motor phenotype: tremor dominant or PIGD. Demographic information, family history of Parkinson disease, and the Unified Parkinson's Disease Rating Scale score were collected on all participants. DNA samples were genotyped for LRRK2 mutations (G2019S, I2020T, R1441C, and Y1699C). Logistic regression was used to examine associations of G2019S mutation status with motor phenotype adjusting for disease duration, Ashkenazi Jewish ancestry, levodopa dose, and family history of Parkinson disease. Results: Thirty-four cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be Ashkenazi Jewish (55.9% vs 11.9%; P < .001) but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (P = .03) and were more likely to have a PIGD phenotype (92.3% vs 58.9%; P = .003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and Ashkenazi Jewish ancestry (odds ratio, 17.7; P < .001). Conclusion: Early-onset Parkinson disease G2019S LRRK2 carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course

Multiple Chronic Conditions: Prevalence, Health Consequences, and Implications for Quality, Care Management, and Costs

Persons with multiple chronic conditions are a large and growing segment of the US population. However, little is known about how chronic conditions cluster, and the ramifications of having specific combinations of chronic conditions. Clinical guidelines and disease management programs focus on single conditions, and clinical research often excludes persons with multiple chronic conditions. Understanding how conditions in combination impact the burden of disease and the costs and quality of care received is critical to improving care for the 1 in 5 Americans with multiple chronic conditions. This Medline review of publications examining somatic chronic conditions co-occurring with 1 or more additional specific chronic illness between January 2000 and March 2007 summarizes the state of our understanding of the prevalence and health challenges of multiple chronic conditions and the implications for quality, care management, and costs

Rare coding variants in ten genes confer substantial risk for schizophrenia

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, PPeer reviewe

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies