Drug Evaluation in Rheumatoid Arthritis

Pulmonary thromboembolism is an extremely common cause of respiratory distress, unremitting heart failure, and sudden death in elderly persons.     

Thrombocytopoietic properties of oncostatin M

Oncostatin M (OM) is a 28-kD glycoprotein that exhibits a panoply of biologic effects. Based on histologic observations of increased splenic megakaryocytes in nude mice implanted with an OM-secreting cell line, the thrombocytopoietic properties of OM in mice were investigated in culture and in vivo. Alone, OM did not induce megakaryocytic colony formation, but in combination with murine interleukin-3 (IL-3), OM markedly enhanced colony formation. The effects of OM on colony formation were similar to those of IL-6. OM alone augmented acetylcholinesterase in short-term marrow cultures. In normal mice, the administration of OM augmented platelet counts without increasing other circulating blood cell counts. The increment in counts exceeded that observed with IL-6. The kinetics of the OM response suggested that maximal increases in platelets occurred 3 days after the cessation of OM administration, irrespective of the duration of administration. In irradiated mice, OM administration accelerated platelet recovery and prevented the decrease in red blood cells observed in irradiated control animals. The data show that OM behaves as a megakaryocytic maturation factor in vitro and augments platelet production in vivo. Based on these animal data, OM may have potential clinical utility as a thrombocytopoietic agent.     

Using the cardiac depression scale in men recovering from coronary artery bypass surgery

Aims. To examine the utility and validate the use of the Cardiac Depression Scale in patients who had first‐time coronary artery bypass graft surgery. Background. The Beck Depression Inventory, though frequently used, may not be sufficiently sensitive for use in cardiac patients. The Cardiac Depression Scale has been shown to identify the range of depression in medical cardiac patients. Design. Survey. Methods. The Beck Depression Inventory and Cardiac Depression Scale were administered to 120 men at hospital discharge, as well as six, 12 and 36 weeks postoperatively. Cronbach’s α scores were calculated for the measures at each point. Changes in scores over time were analysed using repeated measures analysis of variance. Associations between the measures scores were calculated using Pearson product–moment correlations. Agreement between the measures’ dichotomised scores (depression/no depression) was examined using Cohen’s Kappa statistic. Results. Internal consistency was similar for the Beck Depression Inventory (0·793–0·904) and Cardiac Depression Scale (0·859–0·910). Depression scores decreased over time with the Beck Depression Inventory [F(2·50, 175·29) = 22·27, p < 0·001] and Cardiac Depression Scale [F(2·68, 190·37) = 13·18, p < 0·001]. The measures had similar power [Cohen’s f = 0·65 (Beck Depression Inventory) and 0·43 (Cardiac Depression Scale)] to reveal changes over time. The continuous scores were highly correlated at each point [0·737 (p < 0·001)–0·819 (p < 0·001)]. However, when dichotomised scores were compared, the chance corrected level of agreement was less impressive [0·198 (p = 0·014)–0·381 (p < 0·001)]. Conclusions. The Cardiac Depression Scale may have utility for use with surgical cardiac patients. However, continued examination of this measure of depression is warranted. Relevance to clinical practice. Given the prevalence of depression and its negative impact on coronary artery disease, it is important to identify even mild depression in cardiac patients. Using a measure of depression specifically for cardiac patients, rather than a generic measure, may best accomplish this goal.     

A Systematic Review of the Patient- and Carer-Related Factors Affecting the Experience of Pain for Advanced Cancer Patients Cared for at Home

Context

Effective pain management is a priority in the palliative care of advanced cancer patients. A body of research is emerging examining the factors that influence the management and experience of pain for such individuals. Identifying such factors should allow for the development of targeted interventions to improve pain management in the home while ultimately reducing unnecessary suffering for the patient.

COVID-19 and biomarkers of thrombosis: focus on von Willebrand factor and extracellular vesicles

Journal of Thrombosis and Thrombolysis - COVID-19, caused by the SARS-CoV-2 virus, is responsible for a pandemic of unparalleled portion over the past century. While the acute phase of infection...     

A cross-sectional comparison of three self-reported functional indices in scleroderma

OBJECTIVES: In scleroderma, outcome measures such as skin score provide only limited information about the functional impact of the disease. The requirement for validated and convenient instruments that reliably reflect disease morbidity is now recognized. This study compares the Disability Index of the Health Assessment Questionnaire (HAQ-DI) with two more recently developed scleroderma-specific tools: scleroderma-visual analogue scales (scleroderma-VAS) and the UK scleroderma Functional Score (UKFS). In addition, the use of clinical and laboratory measures as predictors of disease severity have been examined. METHODS: One hundred and fifteen consecutive patients were studied. Subjects completed the 20-item HAQ-DI, the scleroderma-VAS and a questionnaire related to hand and muscle function (UKFS). Clinical details, measurement of maximal hand-spread, fist-closure and investigations for internal organ involvement were recorded. RESULTS: Over 68% of patients with diffuse disease had moderate to severe disease on the UKFS, compared with 44% with limited disease. The mean UKFS in diffuse disease was 14.7 (s.d. 9.1) and 10.6 (s.d. 8.5) in the limited subset (P=0.02). The mean HAQ-DI in diffuse disease was 1.23 (s.d. 0.77) and 0.79 (s.d. 0.75) in the limited subset (P=0.005). The HAQ-DI showed significant correlation with UKFS (r=0.9; P < 0.001). Several clinical and laboratory measures were associated with higher HAQ-DI and UKFS. CONCLUSIONS: This is the first comparative study of the UKFS and the HAQ-DI. These data show a strong correlation between assessment methods. Higher scores correlated with clinical and laboratory indicators of severe disease. Used together, these inexpensive tools assess general and organ-specific symptoms, as well as functional limitation.     

Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters

OBJECTIVE: TGPO autoantibodies (aAbs) that bind simultaneously to thyroglobulin (Tg) and thyroperoxidase (TPO) are present in the serum of patients with autoimmune thyroid diseases (AITD) and have been found to differ from monospecific Tg and TPO aAbs. To obtain further insights on the prevalence defined as the rate of occurrence and significance of TGPO aAbs in a large population, we carried out a collaborative study involving 15 European teams. METHODS: Serum samples from 3122 patients with various thyroid and non-thyroid diseases and normal subjects were assayed using a novel TGPO aAb detection kit. This test was designed so that TGPO aAbs are trapped between the Tg-coated solid phase and the soluble TPO labeled with a radioiodinated monoclonal antibody. RESULTS: Only three out of the 220 normal subjects (prevalence of 1.4%) were found to have positive TGPO aAb levels, which were mainly observed in the patients with AITD: the group of patients suffering from Hashimoto's thyroiditis had a TGPO aAb prevalence of 40.5% (n=437 patients), those with Graves' disease, a prevalence of 34.6% (n=645) and those with post-partum thyroiditis, 16.0% (n=243). Among the non-AITD patients with positive TGPO aAb levels, the TGPO aAb prevalence ranged from 20.7% among those with thyroid cancer (n=246) to 0% among those with toxic thyroid nodules (n=47). Among the patients with non-thyroid diseases, the TGPO aAb prevalence ranged from 9.8% in the case of Biermer's pernicious anemia (n=78) to 0% in that of premature ovarian failure (n=44). It is worth noting that the groups showing the highest TGPO aAb prevalence also contained the patients with the highest TGPO aAb titers. Statistical comparisons between the TGPO aAb prevalences in the various groups showed that TGPO aAb could be used as a parameter to distinguish between the groups of Hashimoto's and Graves' patients and between the women with post-partum thyroiditis and the post-partum women with only Tg and/or TPO aAb established during early pregnancy. Unexpectedly, the correlations between TGPO aAbs and Tg and TPO aAbs were found to depend mainly on the assay kit used. CONCLUSION: High TGPO aAb titers are consistently associated with AITD but the reverse was not found to be true. TGPO aAbs are a potentially useful tool, however, for establishing Hashimoto's diagnosis, and would be worth testing in this respect with a view to using them for routine AITD investigations.     

Herpes zoster and impaired cell-associated immunity to the varicella-zoster virus in patients with Hodgkin's disease.

Thirty-two patients with Hodgkin's disease and 12 normal donors were studied for their in vitro lymphocyte responsiveness to a membrane-associated varicella-zoster (VZ) antigen. When compared to the normal donors, patients with Hodgkin's disease in whom radiotherapy was recently completed and those with active, recurrent disease had markedly impaired cell-associated immunity to VZ antigen. In addition, there was a suggestion that patients in long-term remission who had received primary combined modality therapy (radiotherapy plus chemotherapy) had an impaired response when compared to normal persons or to patients who had received single modality therapy. Newly diagnosed, untreated patients with Hodgkin's disease did not differ significantly from normal persons as a group but two of six were unresponsive to the VZ antigen whereas all normal subjects were responsive. Most patients in remission for at least one year following therapy had normal in vitro responsiveness. In two patients herpes zoster developed after the demonstration of absent in vitro lymphocyte reactivity to the VZ antigen.