Asymptotic results with generalized estimating equations for longitudinal data

We consider the marginal models of Liang and Zeger [Biometrika 73 (1986) 13-22] for the analysis of longitudinal data and we develop a theory of statistical inference for such models. We prove the existence, weak consistency and asymptotic normality of a sequence of estimators defined as roots of pseudo-likelihood equations.Comment: Published at http://dx.doi.org/10.1214/009053604000001255 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Asymptotic Results with Generalized Estimating Equations for Longitudinal data II

We consider the marginal models of Liang and Zeger (1986) for the analysis of longitudinal data and we develop a theory of statistical inference for such models. We prove the existence, weak consistency and asymptotic normality of a sequence of estimators defined as roots of pseudo-likelihood equations.Generalized estimating equations, Generalized linear model, Consistency, Asymptotic normality

Predictors of survival in a cohort of patients with polymyositis and dermatomyositis: effect of corticosteroids, methotrexate and azathioprine

Introduction: The idiopathic inflammatory myopathies are rare diseases for which data regarding the natural history, response to therapies and factors affecting mortality are needed. We performed this study to examine the effects of treatment and clinical features on survival in polymyositis and dermatomyositis patients. Methods: A total of 160 consecutive patients (77 with polymyositis and 83 with dermatomyositis) seen at the University of Michigan from 1997 to 2003 were included. Medical records were abstracted for clinical, laboratory and therapeutic data, including initial steroid regimen and immunosuppressive use. State vital records were utilized to derive mortality and cause of death data. Survival was modeled by left-truncated Kaplan-Meier estimation and Cox regression. Results: The 5- and 10-year survival estimates were 77% (95% CI = 66 to 85), and 62% (95% CI = 48 to 73), respectively, and the rates were similar for polymyositis and dermatomyositis. Survival between the sexes was similar through 5 years and significantly lower thereafter for males (10-year survival: 18% male, 73% female; P = 0.002 for 5- to 10-year interval). The sex disparity was restricted to the polymyositis group. Increased age at diagnosis and non-Caucasian race were associated with lower survival. Intravenous versus oral corticosteroid use was associated with a higher risk of death among Caucasians (HR = 10.6, 95% CI = 2.1 to 52.8). Early survival between patients treated with methotrexate versus azathioprine was similar, but survival at 10 years was higher for the methotrexate-treated group (76% vs 52%, P = 0.046 for 5- to 10-year interval). Conclusions: Patients treated initially with intravenous corticosteroids had higher mortality, which was likely related to disease severity. Both methotrexate and azathioprine showed similar early survival benefits as first-line immunosuppressive drugs. Survival was higher between 5 and 10 years in the methotrexate-treated group, but could not be confirmed in multivariable modeling for the full follow-up period. Other important predictors of longterm survival included younger age, female sex and Caucasian race.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90025/1/IIM_ART2012.pdf1611

Predictors of survival in a cohort of patients with polymyositis and dermatomyositis: effect of corticosteroids, methotrexate and azathioprine

Abstract Introduction The idiopathic inflammatory myopathies are rare diseases for which data regarding the natural history, response to therapies and factors affecting mortality are needed. We performed this study to examine the effects of treatment and clinical features on survival in polymyositis and dermatomyositis patients. Methods A total of 160 consecutive patients (77 with polymyositis and 83 with dermatomyositis) seen at the University of Michigan from 1997 to 2003 were included. Medical records were abstracted for clinical, laboratory and therapeutic data, including initial steroid regimen and immunosuppressive use. State vital records were utilized to derive mortality and cause of death data. Survival was modeled by left-truncated Kaplan-Meier estimation and Cox regression. Results The 5- and 10-year survival estimates were 77% (95% CI = 66 to 85), and 62% (95% CI = 48 to 73), respectively, and the rates were similar for polymyositis and dermatomyositis. Survival between the sexes was similar through 5 years and significantly lower thereafter for males (10-year survival: 18% male, 73% female; P = 0.002 for 5- to 10-year interval). The sex disparity was restricted to the polymyositis group. Increased age at diagnosis and non-Caucasian race were associated with lower survival. Intravenous versus oral corticosteroid use was associated with a higher risk of death among Caucasians (HR = 10.6, 95% CI = 2.1 to 52.8). Early survival between patients treated with methotrexate versus azathioprine was similar, but survival at 10 years was higher for the methotrexate-treated group (76% vs 52%, P = 0.046 for 5- to 10-year interval). Conclusions Patients treated initially with intravenous corticosteroids had higher mortality, which was likely related to disease severity. Both methotrexate and azathioprine showed similar early survival benefits as first-line immunosuppressive drugs. Survival was higher between 5 and 10 years in the methotrexate-treated group, but could not be confirmed in multivariable modeling for the full follow-up period. Other important predictors of long-term survival included younger age, female sex and Caucasian race.http://deepblue.lib.umich.edu/bitstream/2027.42/112905/1/13075_2011_Article_3467.pd

Участь фармацевтів в управлінні застосуванням ліків рослинного походження людьми похилого віку

Recent data indicate that the pharmaceutical market for herbal medicines continues to grow steadily, and this enables pharmacists to improve their professional skills in managing the treatment of the elderly with herbal medicines and identify potential problems associated with their use. Aim. To study the practice of using herbal medicines among elderly patients from the pharmacist’s point of view and identify specific recommendations of pharmacists in managing the use of herbal medicines. Materials and methods. A descriptive design study was conducted; the main research tool was a questionnaire for pharmacists. Results. Pharmacists’ responses indicate that the use of herbal medicines in the elderly is common, herbal preparations are used mainly for treating chronic diseases, and in most cases elderly patients associate the quality of treatment with the co-use of traditional medicines with herbal ones; often older patients also have false information about the requested herbal medicines. This means the need for pharmacists to monitor and supervise the use of herbal medicines by the elderly, special attention should be paid to the results of drug-herbal interactions and to regular updating of knowledge in the field of geriatric pharmaceutical care oriented to herbal therapy. Conclusions. Based on the results of the study, the problems associated with the use of herbal medicines in the elderly have been described, and some specific recommendations for pharmacists related to the treatment with herbal medicines in the elderly have been proposed.Дані останніх досліджень свідчать, що фармацевтичний ринок рослинних препаратів продовжує стабільно зростати, що дає можливість фармацевтам поліпшити свої професійні навички з моніторингу лікування старих людей ліками рослинного походження і виявити потенційні проблеми, пов’язані з їх застосуванням. Мета – розглянути практику використання рослинних препаратів серед літніх пацієнтів з погляду фармацевта й окреслити конкретні рекомендації фахівців щодо управління застосуванням рослинних лікарських засобів. Матеріали та методи. Проведено дослідження описового дизайну з використанням основного інструменту – анкети для фармацевтів. Результати дослідження. Відповіді фармацевтів свідчать про те, що застосування рослинних лікарських засобів літніми людьми є звичайним явищем. Пацієнти старшого віку використовують зазначені препарати здебільшого для лікування хронічних захворювань, а якість лікування пов’язують з одночасним застосуванням традиційних ліків і рослинних препаратів; також вони часто мають помилкову інформацію про рослинні препарати. Це визначає необхідність моніторингу та нагляду фармацевтів за використанням рослинних препаратів літніми людьми. Особливу увагу має бути приділено результатам взаємодії ліків і рослинних препаратів, а також регулярному оновленню знань в галузі геріатричної фармацевтичної допомоги, орієнтованої на лікування рослинними препаратами. Висновки. На підставі результатів дослідження описано проблеми, пов’язані із застосуванням літніми людьми лікарських засобів на травах, і запропоновано деякі конкретні рекомендації для фармацевтів, що стосуються лікування рослинними препаратами людей похилого віку

Clinical and serological features of systemic sclerosis in a multicenter African American cohort: Analysis of the genome research in African American scleroderma patients clinical database.

Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort).African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987-2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses.The study population included a total of 1009 African American SSc patients, comprised of 84% women. In total, 945 (94%) patients met the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc, with the remaining 64 (6%) meeting the 1980 ACR or CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) criteria. While 43% were actively employed, 33% required disability support. The majority (57%) had the more severe diffuse subtype and a young age at symptom onset (39.1 ± 13.7 years), in marked contrast to that reported in cohorts of predominantly European ancestry. Also, 1 in 10 patients had a severe Medsger cardiac score of 4. Pulmonary fibrosis evident on computed tomography (CT) chest was present in 43% of patients and was significantly associated with anti-topoisomerase I positivity. 38% of patients with CT evidence of pulmonary fibrosis had a severe restrictive ventilator defect, forced vital capacity (FVC) ≤50% predicted. A significant association was noted between longer disease duration and higher odds of pulmonary hypertension, telangiectasia, and calcinosis. The prevalence of potentially fatal scleroderma renal crisis was 7%, 3.5 times higher than the 2% prevalence reported in the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) cohort.Our study emphasizes the unique and severe disease burden of SSc in African Americans compared to those of European ancestry

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci

<i>HLA</i> and autoantibodies define scleroderma subtypes and risk in African and European Americans and suggest a role for molecular mimicry

Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examined HLA associations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominant HLA-DRB1*08:04 and HLA-DRB1*11:02 alleles were associated with overall SSc risk, and the HLA-DRB1*08:04 allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.4). These African ancestry-predominant alleles may help explain the increased frequency and severity of SSc among the AA population. In the EA population, the HLA-DPB1*13:01 and HLA-DRB1*07:01 alleles were more strongly associated with antitopoisomerase (ATA) and anticentromere antibody-positive subsets of SSc, respectively, than with overall SSc risk, emphasizing the importance of HLA in defining autoantibody subtypes. The association of the HLA-DPB1*13:01 allele with the ATA+ subset of SSc in both AA and EA patients demonstrated a transancestry effect. A direct correlation between SSc prevalence and HLA-DPB1*13:01 allele frequency in multiple populations was observed (r = 0.98, P = 3 × 10−6). Conditional analysis in the autoantibody subsets of SSc revealed several associated amino acid residues, mostly in the peptide-binding groove of the class II HLA molecules. Using HLA &#x3B1; / &#x3B2; allelic heterodimers, we bioinformatically predicted immunodominant peptides of topoisomerase 1, fibrillarin, and centromere protein A and discovered that they are homologous to viral protein sequences from the Mimiviridae and Phycodnaviridae families. Taken together, these data suggest a possible link between HLA alleles, autoantibodies, and environmental triggers in the pathogenesis of SSc

Survival and Predictors of Mortality in Systemic Sclerosis‐Associated Pulmonary Arterial Hypertension: Outcomes From the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106105/1/acr22121.pd