The performance of anti-cyclic citrullinated peptide assays in diagnosing rheumatoid arthritis: a systematic review and meta-analysis.

OBJECTIVES: We assessed the ability of anti-cyclic citrullinated peptide (CCP) tests to diagnose rheumatoid arthritis (RA), comparing the effect of manufacturer assay type, study design (single- and two-gated) and duration of disease (early vs. established). METHODS: We searched seven databases for relevant diagnostic studies containing data on CCP tests in known or suspected RA patients. We used a bivariate model to produce summary estimates for test sensitivity, specificity, and positive and negative likelihood ratios. Summary Receiver Operating Characteristic (sROC) curves were derived to compare early versus established RA. RESULTS: 83 studies were identified and included. For individual manufacturer tests there was considerable variation in both pooled sensitivity (range 67-83%) and specificity (range 90-96%) estimates. This heterogeneity was also observed when grouping studies into two-gated and single-gated designs. Study design and disease duration impacted on sensitivity, with single-gated study designs and early RA patients resulting in lower estimates than two-gated and established disease, respectively. CONCLUSIONS: This review highlights the large number of CCP tests that are now commercially available and the considerable variation in their diagnostic performance. This variation, although partly influenced in this analysis by the study design (single-gated vs. two-gated), seems to have different levels of impact depending on the manufacturers. The Thermo Fisher Scientific EliA and Inova Diagnostics Quanta Lite (CCP2) tests showed the least between-study variation in sensitivity and specificity suggesting they have the most consistent diagnostic performance overall.

A Pilot Study: Testing of the Psychological Conditions Scale Among Hospital Nurses.

OBJECTIVE: The aim of this study was to test the reliability and validity of the Psychological Conditions Scale (PCS), a measure of drivers of engagement in hospital-based nurses. BACKGROUND: Research suggests drivers of engagement are positive links to patient, employee, and hospital outcomes. Although this scale has been used in other occupations, it has not been tested in nursing. METHODS: A cross-sectional, methodological study using a convenience sample of 200 nurses in a large Magnet® hospital in New Jersey. RESULTS: Cronbach's α's ranged from .64 to .95. Principal components exploratory factor analysis with oblique rotation revealed that 13 items loaded unambiguously in 3 domains and explained 76% of the variance. Mean PCS scores ranged from 3.62 to 4.68 on a 5-point Likert scale. CONCLUSIONS: The scale is an adequate measure of drivers of engagement in hospital-based nurses. Leadership efforts to promote the facilitators of engagement are recommended.

Health Care in the Community: Developing Academic/Practice Partnerships for Care Coordination and Managing Transitions.

The delivery of health care is quickly changing from an acute care to a community-based setting. Faculty development and mastery in the use of new technologies, such as high-definition simulation and virtual communities are crucial for effective student learning outcomes. Students' benefits include opportunities for hands-on experience in various patient care scenarios, realtime faculty feedback regarding their critical reasoning and clinical performance, interdisciplinary collaboration, and access to a nonthreatening learning environment. The results of this study provide some evidence of the benefits of developing faculty and nursing curricula that addresses the shift from an ilness-based, acute hospital model, to a community and population health-based preventive model.

Real-World Persistence with Ocrelizumab in Multiple Sclerosis: a Systematic Review.

In clinical trials, the percentage of patients discontinuing treatment with ocrelizumab due to adverse events was low. However, real-world populations are often more diverse than randomized controlled trials (RCTs), therefore it is important to assess discontinuation rates in real-world studies. This systematic literature review (SLR) was conducted to identify real-world discontinuation and persistence data for ocrelizumab in studies of patients with relapsing remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Searches were conducted in MEDLINE and Embase to identify relevant real-world studies that met pre-determined Population, Intervention, Comparison, Outcomes, and Study (PICOS) criteria. Only articles published in English were included, but the study country was not restricted. A total of 30 studies were included, with the majority reporting real-world persistence data that appear to be similar to or better than in the pivotal clinical trials, with only 1 study reporting higher discontinuation rates due to adverse events compared with the clinical trials. Other studies identified reported that the risk of discontinuation was higher for other disease-modifying therapies (DMTs) compared with ocrelizumab, and adherence was also higher for ocrelizumab versus other DMTs. These findings have clinical relevance, as other studies have reported improved clinical outcomes and lower care costs for patients that are persistent or adherent to other DMTs.

Low molecular weight heparin downregulates tissue factor expression and activity by modulating growth factor receptor-mediated induction of nuclear factor-κB.

Treatment of cancer patients with low molecular weight heparin (LMWH) appears to have beneficial effects. In this study, the influence of low molecular weight heparin (LMWH) on tissue factor (TF) expression and activity in five cell lines from various tissues was analysed and explored. Incubation of cells with LMWH (0-2000µg/ml) resulted in the downregulation of TF mRNA expression which was both LMWH concentration-dependent and time-dependent. Downregulation of TF was also measured as decreased cellular TF antigen and activity. Consistently, incubation of cells with LMWH suppressed the nuclear localisation and the transcriptional activity of NFκB. Decreased TF mRNA was largely achievable by incubating the cells with an NFκB inhibitor alone whilst incubation with betulinic acid to activate NFκB reversed the inhibitory influence of LMWH. Cells were also incubated with a range of concentrations of EGF (0-10ng/ml), bFGF (0-20ng/ml) or VEGF (0-4ng/ml) in the presence or absence of LMWH (200µg/ml) for 24h and TF antigen measured. Inclusion of LMWH reduced TF expression in response to EGF, bFGF or VEGF but TF expression was partially restored by increasing concentrations of the growth factors. We conclude that LMWH downregulates TF expression in vitro through a mechanism that involves interference with the function of growth factors which in turn is mediated through the downregulation of the transcriptional activity of NFκB. This mechanism may also explain some of the beneficial influences attributed to LMWH therapy in the treatment of cancer patients.

Development and validation of Gaucher disease type 1 (GD1)-specific patient-reported outcome measures (PROMs) for clinical monitoring and for clinical trials.

BACKGROUND: Disease-specific patient-reported outcome measures (PROMs) are fundamental to understanding the impact on, and expectations of, patients with genetic disorders, and can facilitate constructive and educated conversations about treatments and outcomes. However, generic PROMs may fail to capture disease-specific concerns. Here we report the development and validation of a Gaucher disease (GD)-specific PROM for patients with type 1 Gaucher disease (GD1) a lysosomal storage disorder characterized by hepatosplenomegaly, thrombocytopenia, anemia, bruising, bone disease, and fatigue. RESULTS AND DISCUSSION: The questionnaire was initially developed with input from 85 patients or parents of patients with GD1 or GD3 in Israel. Owing to few participating patients with GD3, content validity was assessed for patients with GD1 only. Content validity of the revised questionnaire was assessed in 33 patients in the US, France, and Israel according to US Food and Drug Administration standards, with input from a panel of six GD experts and one patient advocate representative. Concept elicitation interviews explored patient experience of symptoms and treatments, and a cognitive debriefing exercise explored patients' understanding and relevance of instructions, items, response scales, and recall period. Two versions of the questionnaire were subsequently developed: a 24-item version for routine monitoring in clinical practice (rmGD1-PROM), and a 17-item version for use in clinical trials (ctGD1-PROM). Psychometric validation of the ctGD1-PROM was assessed in 46 adult patients with GD1 and re-administered two weeks later to examine test-retest reliability. Findings from the psychometric validation study revealed excellent internal consistency and strong evidence of convergent validity of the ctGD1-PROM based on correlations with the 36-item Short Form Health Survey. Most items were found to show moderate, good, or excellent test-retest reliability. CONCLUSIONS: Development of the ctGD1-PROM represents an important step forward for researchers measuring the impact of GD and its respective treatment.

Quality of life in patients with gastroenteropancreatic tumours: A systematic literature review.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract (GI-NETs) or the pancreas (P-NETs). They are relatively uncommon, accounting for 2% of all gastrointestinal malignancies. The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy, biological therapies, and peptide receptor radionuclide therapy. Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease. Health-related quality of life (HRQoL) is increasingly important as a concept reflecting the patients' perspective in conjunction with the disease presentation, severity and treatment. AIM: To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019. METHODS: The PRISMA guiding principles were applied. MEDLINE, Embase and the Cochrane library were searched. Data extracted from the publications included type of study, patient population data (mid-gut/hind-gut/GI-NET/P-NET), sample size, intervention/comparators, HRQoL instruments, average and data spread of overall and sub-scores, and follow-up time for data collection. RESULTS: Forty-three publications met the inclusion criteria. The heterogeneous nature of the different study populations was evident; the percentage of female participants ranged between 30%-60%, whilst average age ranged from 53.8 to 67.0 years. Eight studies investigated GI-NET patients only, six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour. The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (n = 28) with consistent results across studies; the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies. A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms. The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients; it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients' HRQoL. CONCLUSION: HRQoL instruments offer a means to monitor patients' general disease condition, disease progression and their physical and mental well-being. Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack, however, validation and a defined minimal clinical important difference specifically for GI-NET and P-NET patients.

Elicitation of Health-Related Utility in Perianal Fistula in Crohn's Disease.

BACKGROUND AND OBJECTIVE: Perianal fistulae are a common complication of Crohn's disease (CD) and pose a substantial burden on quality of life. Data capturing health-related utility associated with perianal fistulae in CD are scarce. The current study aims to value health states related to different stages of the disease to quantitatively evaluate the impact of complex perianal fistulae on CD patients' quality of life. METHODS: Eight health state descriptions associated with complex perianal fistulae in CD were developed following qualitative research with patients and validation by clinicians. Following pre-testing, a survey was administered online in two samples of UK respondents: the general population and patients with CD. A choice-based valuation technique, the time trade-off (TTO), was used for direct utility measurement. CD patients also valued their current health state using the TTO. Exclusion criteria for respondents displaying logical inconsistencies were applied. RESULTS: Usable responses were received from 835 respondents, reflective of the UK population in age and sex, in the general population survey and 162 CD patients in the patient survey. Non-remission states were valued much lower than the remission state by both samples, ranging from 0.20 for proctectomy with a negative outcome to 0.66 for chronic symptomatic fistulae with mild symptoms. Patients currently experiencing fistulae reported lower values for current health than those without fistulae. CONCLUSION: Low utility values were assigned to the non-remission health states for perianal fistulae in CD by the general public and patients with CD. This demonstrates the high humanistic burden of inadequately managed perianal fistula in CD.

Identification of morphological differences between avian influenza A viruses grown in chicken and duck cells.

Although wild ducks are considered to be the major reservoirs for most influenza A virus subtypes, they are typically resistant to the effects of the infection. In contrast, certain influenza viruses may be highly pathogenic in other avian hosts such as chickens and turkeys, causing severe illness and death. Following in vitro infection of chicken and duck embryo fibroblasts (CEF and DEF) with low pathogenic avian influenza (LPAI) viruses, duck cells die more rapidly and produce fewer infectious virions than chicken cells. In the current study, the morphology of viruses produced from CEF and DEF cells infected with low pathogenic avian H2N3 was examined. Transmission electron microscopy showed that viruses budding from duck cells were elongated, while chicken cells produced mostly spherical virions; similar differences were observed in viral supernatants. Sequencing of the influenza genome of chicken- and duck-derived H2N3 LPAI revealed no differences, implicating host cell determinants as responsible for differences in virus morphology. Both DEF and CEF cells produced filamentous virions of equine H3N8 (where virus morphology is determined by the matrix gene). DEF cells produced filamentous or short filament virions of equine H3N8 and avian H2N3, respectively, even after actin disruption with cytochalasin D. These findings suggest that cellular factors other than actin are responsible for the formation of filamentous virions in DEF cells. The formation of elongated virions in duck cells may account for the reduced number of infectious virions produced and could have implications for virus transmission or maintenance in the reservoir host.

Low molecular weight heparin suppresses tissue factor-mediated cancer cell invasion and migration in vitro.

Elevated expression of tissue factor (TF) has been associated with an increased risk of thrombosis in the majority of cancers. Moreover, treatment of cancer patients with low molecular weight heparin (LMWH) appears to have beneficial effects that reach beyond controlling the immediate hypercoagulable state. In this study, we investigated the influence of the treatment of cancer cells with LMWH (0-2,000 µg/ml) on cell invasiveness and migration in cancer cell lines from five separate tissues; pancreatic, breast, colocarcinoma, ovarian and melanoma. The rate of cell invasion across collagen IV-coated membranes was suppressed in all cell lines tested on incubation with 2,000 µg/ml LMWH, but BxPC-3 and MDA-MB-231 cells also responded to the lowest concentration of 20 µg/ml LMWH. Furthermore, the rate of cell migration was reduced to varying extents in all of the cell lines tested on incubation with 20 µg/ml or higher concentrations of LMWH. The decrease in the rates of invasion and migration also strongly correlated with the reduction in TF protein expression and TF activity in these cells following incubation with LMWH. Moreover, the LMWH-mediated decreases in cellular invasion in the most affected cell lines (BxPC-3 and MDA-MB-231) were restored by transfection of the cells with the mammalian pCMV-XL5-TF expression vector allowing independent overexpression of TF. In conclusion, LMWH appears to suppress the rate of cancer cell invasion and migration in vitro, through a mechanism that is at least in part dependent on the TF protein expression and activity in cancer cells.