DAS28(3)CRP is a reliable measure of disease activity in pregnant women with rheumatoid arthritis.

OBJECTIVES: The disease activity of rheumatoid arthritis (RA) in pregnancy is most commonly assessed with the modified Disease Activity Score (DAS)-28, the DAS28(3)CRP. However, the performance of the DAS28(3)CRP in pregnancy has not been compared to musculoskeletal ultrasound (MSK-US) as a gold standard. We performed a prospective pilot study to test the hypothesis that pregnancy-related factors limit the reliability of the DAS28(3)CRP. METHODS: Pregnant women with RA were recruited from an Obstetric Rheumatology clinic and assessed during pregnancy (second (T2) and third (T3) trimesters) and postpartum with DAS28(3)CRP and MSK-US scores, with quantification of power Doppler (PD) signal in small joints (hands and feet). Age-matched non-pregnant women with RA underwent equivalent assessments. PD scores were calculated as mean scores of all joints scanned. RESULTS: We recruited 27 pregnant and 20 non-pregnant women with RA. DAS28(3)CRP was sensitive and specific for active RA in pregnancy and postpartum as defined by positive PD signal, but not in non-pregnancy. There were significant correlations between DAS28(3)CRP and PD scores throughout pregnancy (T2, r=0.82 (95% CI [0.42, 0.95], p<0.01); T3, r=0.68 (95% CI [0.38, 0.86], p<0.01)) and postpartum, r=0.84 (95% CI [0.60, 0.94], p<0.01), while this correlation in non-pregnancy was weaker (r=0.47 (95% CI [0, 0.77], p<0.05). CONCLUSIONS: This pilot study found that DAS28(3)CRP is a reliable measure of disease activity in pregnant women with RA. Based on these data, pregnancy does not appear to confound clinical evaluation of the tender and/or swollen joint counts.

What is the impact of sex hormones on the pathogenesis of rheumatoid arthritis?

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease and has a female predominance of around 3:1. The relationship between sex hormones and RA has been of great interest to researchers ever since Philip Hench's observations in the 1930's regarding spontaneous disease amelioration in pregnancy. Extensive basic scientific work has demonstrated the immunomodulatory actions of sex hormones but this therapeutic potential has not to date resulted in successful clinical trials in RA. Epidemiological data regarding both endogenous and exogenous hormonal factors are inconsistent, but declining estrogen and/or progesterone levels in the menopause and post-partum appear to increase the risk and severity of RA. This review assimilates basic scientific, epidemiological and clinical trial data to provide an overview of the current understanding of the relationship between sex hormones and RA, focusing on estrogen, progesterone and androgens.

Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission.

Anecdotal evidence suggests that Coronavirus disease 2019 (COVID-19), caused by the coronavirus SARS-CoV-2, exhibits differences in morbidity and mortality between sexes. Here, we present a meta-analysis of 3,111,714 reported global cases to demonstrate that, whilst there is no difference in the proportion of males and females with confirmed COVID-19, male patients have almost three times the odds of requiring intensive treatment unit (ITU) admission (OR = 2.84; 95% CI = 2.06, 3.92) and higher odds of death (OR = 1.39; 95% CI = 1.31, 1.47) compared to females. With few exceptions, the sex bias observed in COVID-19 is a worldwide phenomenon. An appreciation of how sex is influencing COVID-19 outcomes will have important implications for clinical management and mitigation strategies for this disease.

Mechanisms determining the amelioration of rheumatoid arthritis in pregnancy: A systematic review.

BACKGROUND: The phenomenon of pregnancy-induced remission of rheumatoid arthritis (RA) was first reported by Philip Hench in 1938. Despite extensive efforts, the underlying scientific basis has remained elusive. A number of different potential mechanisms have been investigated. We have undertaken a systematic review of the available peer-reviewed articles involving pregnant patients with RA in order to establish the depth of current scientific understanding of this important topic. METHODS: This review was conducted according to guidelines of preferred reporting items for systematic reviews and meta-analyses. Studies were identified by a thorough search of multiple databases including Medline, PubMed and EMBASE. Search terms used were different combinations of the keywords: rheumatoid arthritis, inflammatory arthritis, pregnancy, mechanisms, disease activity, relapse and remission. Non-English language articles and studies that were not directly relevant were excluded. Two independent reviewers (CR and KA) screened the retrieved articles by reading the title and abstract to identify studies that addressed potential mechanisms determining RA activity in pregnancy. Articles were further refined after reading the full text. A data extraction sheet was developed for the purpose of this review and used by the independent reviewers. RESULTS: After exclusion of irrelevant, duplicate and foreign language articles, a final total of 37 original articles were identified. The largest body of literature concerned glycosylation of immunoglobulins, with 9 published articles. There is evidence of an association between increasing levels of galactosylation of immunoglobulins and reduced RA disease activity in pregnancy. Other identified articles comprised 5 on cytokine changes in pregnancy, 5 on human leucocyte antigen (HLA) incompatibility, 5 on changes in peripheral blood mononuclear cell (PBMC) gene expression; 4 on changes in corticosteroids; 3 on pregnancy associated α2-glycoprotein; 2 on changes in rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA); and 1 each on microchimerism, gamma delta T cells, regulatory T cells, and mannose-binding lectin. The results of these studies were heterogenous and occasionally conflicting. Selected studies varied greatly in terms of population size, methodology and use of controls and disease activity assessments. CONCLUSION: This systematic review has found that the cause of the pregnancy-induced amelioration of RA remains to be determined, despite extensive efforts. It is unclear which of the various transitory changes in pregnancy may be responsible for initiating downstream anti-inflammatory immunological mechanisms. We discuss limitations of the current literature and suggest areas for future study.

Real benefits of ultrasound evaluation of hand and foot synovitis for better characterisation of the disease activity in rheumatoid arthritis.

OBJECTIVES: Optimal management of rheumatoid arthritis (RA) depends on accurate evaluation of disease activity. Foot synovitis is not included in the most used RA outcome measure (DAS-28 score). The aim of this study was to investigate how musculoskeletal ultrasound (MSK-US) examination of hand and feet correlate with the disease activity score (DAS-28 score). We also explored whether performing MSK-US assessments of hands alone compared with hands and feet underestimates the disease activity in RA. METHODS: This is a real-life cross-sectional study of 101 patients (51 with RA and 50 with other musculoskeletal conditions) with inflammatory small joint pain, who underwent MSK-US examination of hands and feet. RESULTS: MSK-US-detected hand synovitis was found in 18/51 (35.3%) RA patients and 16/50 (32%) of those with other musculoskeletal conditions (p = 0.96), while foot synovitis was detected in 18/51 (35.3%) and 12/50 (24%) patients, respectively (p = 0.78). DAS-28 did not correlate with any of the US outcome measures in patients with RA. Six out of 13 (46.1%) RA patients in remission, 7/14 (50%) with low disease activity and 18/32 (56.2%) with moderate disease activity (according to DAS-28 definition) had active synovitis as assessed by the MSK-US examination of their hands and feet. MSK-US-detected synovitis led to treatment escalation in 26/51 (51%) RA patients. CONCLUSION: This study emphasises that MSK-US examination of hands and feet has led to optimised management of the majority of RA patients, which would have not been possible otherwise, because of the lack of correlation between DAS-28 assessment and MSK-US outcomes. KEY POINTS: • The most used disease activity score in rheumatoid arthritis (DAS-28) did not correlate with US outcome measures derived from hands and feet examination. • DAS-28 did not differentiate between RA patients with subclinical active synovitis versus well-controlled disease on US. • As a result of US examination of the hands and feet, 51% RA patients had their immunosuppressive treatment optimised.

Severe gangrene in a patient with anti-RNP positive limited cutaneous systemic sclerosis/rheumatoid arthritis overlap syndrome caused by vasculopathy and vasculitis.

In this paper, we describe a case of a male patient with anti-U1RNP positive limited cutaneous systemic sclerosis/rheumatoid arthritis overlap syndrome, who presented acutely with rapidly progressive digital ischemia, which lead to extensive gangrene. Management with conventional vasodilator therapy was unsuccessful. There were constitutional symptoms and a marked inflammatory response in the absence of evidence of infection, implying a component of vasculitis underlying the presentation. Treatment with immunosuppression and intravenous immunoglobulin led to resolution of the inflammatory process with no further progression of tissue necrosis. Here we discuss pertinent issues raised by the case, including the management of digital ischemia and gangrene in this context and the relevance of the anti-U1RNP in systemic sclerosis overlap syndromes.

A 26-week feasibility study comparing the efficacy and safety of modified-release prednisone with immediate-release prednisolone in newly diagnosed cases of giant cell arteritis.

OBJECTIVE: A feasibility study to assess efficacy and safety of modified release (MR) prednisone (Lodotra™) compared to immediate release (IR) prednisolone in patients with newly diagnosed giant cell arteritis (GCA). METHODS: Twelve patients with new diagnosis of GCA were initially treated with high-dose prednisolone (40-60 mg) daily for 4 weeks and then randomized to two open arms to continue tapering steroid treatment with either standard IR prednisolone or MR prednisone. Patients were reviewed every 2 weeks either face to face or by telephone, for a total of 26 weeks. Disease activity, steroid-related side effects, sleep disturbance, fatigue scores and blood tests were systematically monitored. The primary endpoint (efficacy) was defined as the proportion of patients achieving persistent clinical disease control (without features of active disease and remaining flare free at 26 weeks) in each arm. RESULTS: At 26 weeks, 6/7 patients taking MR prednisone were in persistent control, compared with 4/5 receiving IR prednisone. One patient in each group suffered a disease flare necessitating an increased steroid dose. There were no statistically significant differences between the groups in terms of reduction in inflammatory markers, Health Assessment Questionnaire, visual analogue scale, fatigue and improvement in EuroQol 5D scores. CONCLUSION: This trial shows that MR prednisone appears to be a safe and effective treatment for GCA with a similar outcome profile to standard IR prednisolone.

The role of IL-12/23 in T cell-related chronic inflammation: implications of immunodeficiency and therapeutic blockade.

In this review we discuss the divergent role of two closely related cytokines, IL-12 and IL-23, in shaping immune responses. In light of current therapeutic developments using biologic agents to block these two pathways, a better understanding of the immunological function of these cytokines is pivotal.

Self-Monitoring of Blood Glucose (SMBG) in insulin- and non-insulin-using adults with diabetes: consensus recommendations for improving SMBG accuracy, utilization, and research.

Current clinical guidelines for diabetes care encourage self-monitoring of blood glucose (SMBG) to improve glycemic control. Specific protocols remain variable, however, particularly among non-insulin-using patients. This is due in part to efficacy studies that neglect to consider (1) the performance of monitoring equipment under real-world conditions, (2) whether or how patients have been taught to take action on test results, and (3) the physiological, behavioral, and social circumstances in which SMBG is carried out. As such, a multidisciplinary group of specialists, including several endocrinologists, a health psychologist, a diabetes nurse practitioner, and a patient advocate (the Panel), discuss within this review article how the potential of SMBG might be fully realized in today's healthcare environment. The resulting recommendations cover technological, clinical, behavioral, and research considerations with the aim of achieving short- and long-term benefits, ranging from fewer hypoglycemic episodes to lower complication-related costs. The panel also made suggestions for designing future studies that increase the ability to discern optimal models of SMBG utilization for individuals with diabetes who may, or may not, use insulin.

Predicted blood glucose from insulin administration based on values from miscoded glucose meters.

OBJECTIVES: The proper use of many types of self-monitored blood glucose (SMBG) meters requires calibration to match strip code. Studies have demonstrated the occurrence and impact on insulin dose of coding errors with SMBG meters. This paper reflects additional analyses performed with data from Raine et al. (JDST, 2:205-210, 2007). It attempts to relate potential insulin dose errors to possible adverse blood glucose outcomes when glucose meters are miscoded. METHODS: Five sets of glucose meters were used. Two sets of meters were autocoded and therefore could not be miscoded, and three sets required manual coding. Two of each set of manually coded meters were deliberately miscoded, and one from each set was properly coded. Subjects (n = 116) had finger stick blood glucose obtained at fasting, as well as at 1 and 2 hours after a fixed meal (Boost((R)); Novartis Medical Nutrition U.S., Basel, Switzerland). Deviations of meter blood glucose results from the reference method (YSI) were used to predict insulin dose errors and resultant blood glucose outcomes based on these deviations. RESULTS: Using insulin sensitivity data, it was determined that, given an actual blood glucose of 150-400 mg/dl, an error greater than +40 mg/dl would be required to calculate an insulin dose sufficient to produce a blood glucose of less than 70 mg/dl. Conversely, an error less than or equal to -70 mg/dl would be required to derive an insulin dose insufficient to correct an elevated blood glucose to less than 180 mg/dl. For miscoded meters, the estimated probability to produce a blood glucose reduction to less than or equal to 70 mg/dl was 10.40%. The corresponding probabilities for autocoded and correctly coded manual meters were 2.52% (p < 0.0001) and 1.46% (p < 0.0001), respectively. Furthermore, the errors from miscoded meters were large enough to produce a calculated blood glucose outcome less than or equal to 50 mg/dl in 42 of 833 instances. Autocoded meters produced zero (0) outcomes less than or equal to 50 mg/dl out of 279 instances, and correctly coded manual meters produced 1 of 416. CONCLUSIONS: Improperly coded blood glucose meters present the potential for insulin dose errors and resultant clinically significant hypoglycemia or hyperglycemia. Patients should be instructed and periodically reinstructed in the proper use of blood glucose meters, particularly for meters that require coding.

Significant insulin dose errors may occur if blood glucose results are obtained from miscoded meters.

OBJECTIVE: The objective of this study was to determine inaccuracies of miscoded blood glucose (BG) meters and potential errors in insulin dose based on values from these meters. RESEARCH DESIGN: Fasting diabetic subjects at three clinical centers participated in a 2-hour meal tolerance test. At various times subjects' blood was tested on five BG meters and on a Yellow Springs Instruments laboratory glucose analyzer. Some meters were purposely miscoded. Using the BG values from these meters, along with three insulin dose algorithms, Monte Carlo simulations were conducted to generate ideal and simulated-meter glucose values and subsequent probability of insulin dose errors based on normal and empirical distribution assumptions. RESULTS: Maximal median percentage biases of miscoded meters were +29% and -37%, while maximal median percentage biases of correctly coded meters were only +0.64% and -10.45% (p = 0.000, chi(2) test, df = 1). Using the low-dose algorithm and the normal distribution assumption, the combined data showed that the probability of insulin error of +/-1U, +/-2, +/-3, +/-4, and +/-5U for miscoded meters could be as high as 49.6, 50.0, 22.3, 1.4, and 0.04%, respectively. This is compared to manually, correctly coded meters where the probability of error of +/-1, +/-2, and +/-3U could be as high as 44.6, 7.1, and 0.49%, respectively. There was no instance of a +/-4 or +/-5U insulin dose error with a manually, correctly coded meter. For autocoded meters, the probability of +/-1 and +/-2U could be as high as 35.4 and 1.4%, respectively. For autocoded meters there were no calculated insulin dose errors above +/-2U. The probability of insulin misdosing with either manually, correctly coded or autocoded meters was significantly lower than that with miscoded meters. Results using empirical distributions showed similar trends of insulin dose errors. CONCLUSIONS: Blood glucose meter coding errors may result in significant insulin dosing errors. To avoid error, patients should be instructed to code their meters correctly or be advised to use an autocoded meter that showed superior performance over manually, correctly coded meters in this study.

Self-monitored blood glucose: a common pitfall.

OBJECTIVE: To assess the frequency of user error in selecting the appropriate code for glucose meter strips during performance of self-monitoring of blood glucose. METHODS: The glucose meter code and corresponding glucose strip code were examined in 335 different patients during routine clinic visits. All patients had received instructions in meter use from a clinic nurse, a diabetes educator, or a pharmacist. Of the 335 patients, 134 were excluded from analysis because of unavailability of the meter or strip container or unreadability of the code on the strip container. Age, sex, type of diabetes, treatment method, and most recent glycated hemoglobin (HbA1c) value (before the observation period) were compared for patients with the correct (matching) codes and those for whom the codes did not match. RESULTS: Of the 201 study patients, 26 had type 1 diabetes mellitus and 175 had type 2 diabetes. Overall, 107 patients were being treated with insulin, 16 by continuous subcutaneous insulin infusion. Matching glucose meter and strip codes were found in 169 patients (84%); 32 (16%) had incorrect (nonmatching) codes (P<0.0001). The mean HbA1c was higher in patients with incorrect codes (8.2% versus 7.7%), but the difference was not significant (P = 0.4688). Twelve percent of patients with type 1 diabetes and 17% of patients with type 2 diabetes had incorrect codes; this difference was not significant (P = 0.3674). Codes were incorrect in 12% of patients with type 2 diabetes treated with insulin, in comparison with 20% of those treated with orally administered agents (P = 0.2338). No significant difference was noted between the groups on the basis of age or sex. CONCLUSION: A considerable number of patients with diabetes fail to use glucose meters properly. Clinical decisions based on these data can result in adverse events. We found no significant difference in patients having the wrong code on glucose meters when compared for age,