Disease activity and patient-reported outcomes in patients with rheumatoid arthritis and Sjogren\u27s syndrome enrolled in a large observational US registry

The objective of this study was to compare rheumatoid arthritis (RA) disease activity and patient-reported outcomes (PROs) in a national sample of patients with RA with/without Sjogren\u27s syndrome (SS). Adults with RA from a large observational US registry (Corrona RA) with known SS status between 22 April 2010 and 31 July 2018 and a visit 12 (+/- 3) months after index date were identified (n = 36,256/52,757). SS status: determined from a yes/no variable reported at enrolment into the Corrona RA registry and follow-up visits. Index date: date that SS status was recorded (yes/no). Patients received biologic or targeted synthetic disease-modifying antirheumatic drugs as part of standard care. Patients with RA only were followed for \u3e /= 12 months to confirm the absence of SS. Patients were frequency- and propensity-score matched (PSM) 1:1 and stratified by disease duration and treatment response-associated variables, respectively. Clinical Disease Activity Index (CDAI) and PROs 12 months after index visit were compared in patients with and without SS. Baseline characteristics in 283 pairs of PSM patients were balanced. Mean change in CDAI score was numerically lower in patients with RA and SS than patients with RA only (8.8 vs 9.3). Reductions in PROs of pain, fatigue and stiffness were two- to threefold lower for patients with RA and SS versus RA only. Reductions in RA disease activity and RA-related PROs were lower in patients with RA and SS versus those with RA only. Our data indicate that SS adds to treatment challenges; physicians may wish to consider SS status when managing patients with RA

Prevalence of Sjogren\u27s syndrome associated with rheumatoid arthritis in the USA: an observational study from the Corrona registry

The objectives of this analysis were to assess the prevalence of Sjogren\u27s syndrome (SS) associated with rheumatoid arthritis (RA) and to compare baseline characteristics of patients with RA with and without SS. Adult patients with RA from a large observational US registry (Corrona RA), with \u3e /= 1 visit for assessment of SS status between 22 April 2010 and 28 February 2018, were considered. Patients with RA with versus without SS were compared. SS status was determined from a yes/no variable and reported at enrollment into the Corrona RA registry and follow-up visits. Outcomes were unadjusted prevalence of SS in patients with RA, prevalence of SS by RA disease duration, and baseline characteristics in patients with RA by SS status. Of 24,528 eligible patients, 7870 (32.1%) had a diagnosis of RA and SS. The unadjusted overall rate for SS prevalence in patients with RA was 0.30 (95% confidence interval 0.29, 0.31). SS prevalence increased with increasing RA duration. Patients with RA with versus without SS were more likely to be older, female, and seropositive; had a longer RA duration; higher disease activity; and a higher incidence of comorbidities (hypertension, cardiovascular disease, malignancies, and serious infections), erosive disease, and subcutaneous nodules at index date. Patients with RA and SS had a higher disease burden than those with RA only. The prevalence of SS increased as duration of RA increased. RA with SS was associated with seropositivity, more severe RA, extra-articular manifestations, and comorbidities.Key Points* The overall prevalence of SS among patients with RA was 30%.* The prevalence of SS increased with increasing RA disease duration.* Identifying specific clinical characteristics of patients with RA with SS, such as a greater incidence of extra-articular manifestations and comorbidities, may help clinicians to better characterize this patient population

Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis

Differentiating patients with higher cerebral dysfunction from patients with psychiatric or acute medical illness using the BNI screen for higher cerebral functions

The BNI Screen for Higher Cerebral Functions (BNIS) was administered to 41 patients with known cerebral dysfunction, 22 psychiatric patients (some of whom were psychotic) without documented brain lesions, and 22 medical inpatients without neurological or psychiatric diagnoses. Patients with cerebral dysfunction scored significantly lower than the medical and psychiatric patients (p \u3c 0.05). Utilizing the recommended cutoff score of 47, 40 of the 41 brain-dysfunctional patients were correctly classified as impaired, but only seven of the medical and five of the psychiatric patients were correctly classified. Using age-based T-scores, 36 of the 41 brain-dysfunctional patients (87.8%) were correctly classified. Specificity improved slightly, but these numbers were still low (55%), primarily because psychotic patients performed like neurological patients (100%). This study provides further empirical validation of this screening instrument in identifying patients with brain disorders

Screening for more than level of cognitive functioning: the BNI screen for higher cerebral functions

OBJECTIVE: This paper describes the BNI Screen for Higher Cerebral Functions (BNIS) and reviews studies that comment on its reliability, validity, and clinical and research utility. The ability of the BNIS to assess non-cognitive higher brain functions is also described. METHODS: We reviewed the original administration manual, studies published in the BNI Quarterly of the Barrow Neurological Institute, and peer-reviewed studies on the BNI Screen identified by an academic database, PubMed and Google Scholar. Thirty-two studies were reviewed that describe normative data, psychometric properties, sensitivity and specificity estimates, the relationship of demographic factors to test performance, and its research utility. RESULTS: The BNIS is a time efficient screening test often taking no longer than 12-18 minutes. In addition to cognitive functioning, it aids in assessing conation, awareness of memory impairment, and affects expression and perception. Sensitivity estimates ranged from 80% to 92.3%. Specificity estimates ranged from 38.9% to 90%. Its construct, concurrent, and predictive validity have been supported by a series of international studies using different language translations of the test. CONCLUSION: The BNIS is a useful screening test for identifying patients with underlying brain disorders that uniquely measures domains of functioning not sampled by other existing screening tests