Thrombopoietin receptor agonist and rituximab combination therapy in patients with refractory primary immune thrombocytopenia.

The aim of our study was to evaluate the efficacy of this therapy in patients with refractory primary immune thrombocytopenia. It is crucial to develop alternative treatment methods for this patient group in order to achieve better response. This combination therapy combines two different mechanisms of action, which is promising in terms of targeting pathophysiology of immune thrombocytopenia. We conducted a retrospective study, which included all patients who were diagnosed with refractory primary immune thrombocytopenia and received TPO-RA and rituximab at the General Hematology Department, Copernicus Memorial Hospital in Lodz, Poland. We assessed the response, time to response and treatment-free remission (TFR). After 1 month of treatment, the complete response (CR1, PLT >100 g/l) was achieved in 62.5% patients, and response (R1, PLT >30 g/l) was achieved in 62.5% patients. The median PLT was 175 × 10 9 /l. Within 1 month of treatment, 87.5% of patients achieved TFR. Adequately, after 6 months, CR6 and R6 was 62.5 and 75%. The median PLT was 182 × 10 9 /l. Treatment-free remission 6 months after completion was in 50% of patients. The study group achieved response to treatment, which suggests that combination of TPO-RA and rituximab is effective and relatively well tolerated. Prospective study on larger group of patients is needed to better evaluate the efficiency and safety of this treatment.

Antithrombin Deficiency Is Associated with Prothrombotic Plasma Fibrin Clot Phenotype.

BACKGROUND: Deficiency of antithrombin increases risk of venous thromboembolism. We hypothesized that antithrombin deficiency affects fibrin clot structure and function. METHODS: We evaluated 148 patients (age: 38 [32-50] years; 70% women) with genetically confirmed antithrombin deficiency and 50 healthy controls. Fibrin clot permeability (Ks) and clot lysis time (CLT) along with thrombin generation capacity were assessed before and after antithrombin activity normalization in vitro. RESULTS: Antithrombin-deficient patients had lower antithrombin activity (-39%) and antigen levels (-23%) compared with controls (both p < 0.01). Prothrombin fragment 1 + 2 levels were 26.5% higher in patients with antithrombin deficiency than in controls along with 94% increased endogenous thrombin potential (ETP) and 108% higher peak thrombin (all p < 0.01). Antithrombin deficiency was associated with 18% reduced Ks and 35% prolonged CLT (both p < 0.001). Patients with type I (n = 65; 43.9%) compared with type II antithrombin deficiency (n = 83; 56.1%) had 22.5% lower antithrombin activity (p < 0.001) and despite similar fibrinogen levels, 8.4% reduced Ks, 18% prolonged CLT, and 30% higher ETP (all p < 0.01). Reduced Ks was associated with lower antithrombin antigen level (ß = - 6.1, 95% confidence interval [CI]: -1.7 to -10.5), while prolonged CLT was associated with lower antithrombin antigen (ß = - 69.6, 95% CI: -9.6 to -129.7), activity (ß = - 2.4, 95% CI: -0.3 to -4.5), higher PAI-1 (ß = 12.1, 95% CI: 7.7-16.5), and thrombin-activatable fibrinolysis inhibitor levels (ß = 3.8, 95% CI: 1.9-5.7). Addition of exogenous antithrombin reduced ETP (-42%) and peak thrombin (-21%), and improved Ks (+8%) and CLT (-12%; all p < 0.01). CONCLUSION: Our study suggests that enhanced thrombin generation and prothrombotic plasma fibrin clot phenotype can contribute to increased risk of thrombosis in patients with antithrombin deficiency.

The Economic Burden of Non-Alcoholic Steatohepatitis: A Systematic Review.

BACKGROUND: The global prevalence of non-alcoholic steatohepatitis (NASH) is increasing, such that NASH is predicted to become the leading cause of liver transplantation (LT) in the US by 2025. Despite this, data on the economic burden of NASH are limited. OBJECTIVES: This systematic literature review aimed to summarise and critically evaluate studies reporting on the economic burden of NASH and identify evidence gaps for subsequent research. METHODS: Medline, EMBASE, the Cochrane Library and EconLit were searched up to 6 January 2021 for English language articles published from January 2010 to January 2021 inclusive that reported economic outcomes of a NASH population or subpopulation. Evidence was presented and synthesised using narrative data analysis, and quality was assessed by two reviewers using an 11-item checklist developed for economic evaluations and adapted to cost of illness. RESULTS: Fourteen studies were included, of which five presented data on costs and resource use, four on costs only and five on resource use only. Overall, NASH is associated with a significant and increasing economic burden in terms of healthcare resource utilisation (HCRU) and direct and indirect costs. This burden was higher among NASH patients with advanced (fibrosis stage 3-4) versus early (fibrosis stage 0-2) disease, symptomatic versus asymptomatic disease and for patients with complications or comorbidities versus those without. In LT patients, those with NASH as the primary indication had greater HCRU and higher costs compared with non-NASH indications such as hepatitis B and C viruses. Considerable variability in HCRU and costs was seen across the US and Europe, with the highest costs seen in the US. The quality of the included studies was variable, and the studies themselves were heterogeneous in terms of study methodology, patient populations, comorbidities, follow-up time and outcomes measured. CONCLUSIONS: This review highlights a general scarcity of NASH-specific economic outcomes data. Despite this, the identified studies show that NASH is associated with a significant economic burden in terms of increased HCRU, and high direct medical and non-medical costs and societal burden that increases with disease severity or when patients have complications or comorbidity. More national-level NASH prevalence data are needed to generate accurate forecasts of HCRU and costs in the coming decades. FUNDING: Novo Nordisk A/S, Søborg, Denmark.

It is important to know the cost of treating different diseases because this helps to guide how healthcare resources and funds are used. Non-alcoholic steatohepatitis (NASH) is a serious liver disease that can lead to liver scarring (cirrhosis), liver transplantation and early death, and the number of people with NASH is growing around the world. Fourteen studies published over the past 10 years have investigated the costs of treating patients with NASH. Patients with NASH generally use more healthcare services with a higher cost than the general population or patients with type 2 diabetes. In people with more serious liver disease, such as liver transplant patients, NASH tends to be more expensive and use more healthcare services than other serious liver diseases such as hepatitis. Costs and use of health services are particularly high in patients with more severe NASH, or those who have other diseases or complications in addition to NASH (such as type 2 diabetes or kidney failure).

Back to life, back to reality: A multi-level dynamic network analysis of student mental health upon return to campus during the COVID-19 pandemic.

Lockdown measures during the COVID-19 pandemic resulted in drastic disruptions of university students' everyday life and study mode, such as marked reductions in face-to-face teaching activities. Previous research on student mental health during the pandemic found that prolonged campus relocation had negative effects on students' mental well-being. However, these studies focussed on the initial lockdown period, or periods of active lockdown measures. This longitudinal study collected 456 observations of 23 undergraduate students in the Netherlands using ecological momentary assessment data on mental health related items (anxiety, stress, social context) during the first two weeks of on-campus teaching after prolonged lockdown measures. Using multi-level dynamic network modelling, we analysed the temporal and contemporaneous interplay of students' mental health factors following the return to campus in September 2021. On average, students reported low to medium scores on stress and anxiety both before and after the assessment period. Results of network analyses showed that students experienced social unease in relation to accumulating difficulties at university and vice versa. Furthermore, there were clusters of different states of social unease next to clusters of stress, anger, loss of control, and feeling upset. Lastly, we found beneficial effects of self-efficacy on experiencing social comfort in university. We discuss implications and concrete examples of interventions in universities, such as the promotion of self-efficacy, providing guidance in structuring study load, as well as help with stress management. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03196-7.

Autoimmune thrombocytopenia: Current treatment options in adults with a focus on novel drugs.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by platelet destruction and reduced platelet production resulting in decreased platelet level and an increased risk of bleeding. Based on the immunologic mechanism of ITP, front-line standard therapy consists of corticosteroids and intravenous immunoglobulins (IVIG). If patients do not respond to the first-line treatment, or if continuous therapy is required, the disorder is called refractory ITP, and second-line therapy is indicated. This treatment may consist of rituximab, thrombopoietin receptor agonists, splenectomy, or cytotoxic drugs. Despite significant advances, many patients do not respond to any the treatments listed below, and new treatment options need to be developed for this relapsed and refractory group. Recent clinical studies have indicated promising outcomes for novel drugs, either as single agents or in combination with traditional drugs. This review discusses the latest and the most promising novel drugs for ITP in adults.

A Systematic Literature Review and Network Meta-Analysis Comparing Once-Weekly Semaglutide with Other GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Previously Receiving Basal Insulin.

INTRODUCTION: Once-weekly semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that is currently available as 1.0 mg and 0.5 mg dose for the treatment of type 2 diabetes (T2D). Currently, no head-to-head trial investigating once-weekly semaglutide as an add-on to basal insulin vs other GLP-1 receptor agonists (GLP-1 RAs) is available. The aim of this study was to conduct a network meta-analysis (NMA) to assess the efficacy and safety of once-weekly semaglutide vs other GLP-1 RAs in patients with T2D inadequately controlled on basal insulin. METHODS: A systematic literature review was performed to identify all trials of GLP-1 RAs as an add-on to basal insulin in patients with T2D. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in an NMA), including the change from baseline in glycated hemoglobin (HbA1c), body weight, and systolic blood pressure, and the incidence of nausea, vomiting, and diarrhea. Data were synthesized using a NMA and a Bayesian framework. RESULTS: In total, eight studies were included across the base-case analyses. The results demonstrate that once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA1c (- 0.88% to - 1.39% vs comparators) and weight (- 1.49 to - 4.69 kg vs comparators) and similar odds of experiencing nausea, vomiting, or diarrhea vs all GLP-1 RA comparators. Once-weekly semaglutide 1.0 mg was also equally effective at reducing systolic blood pressure compared with liraglutide 1.8 mg. Once-weekly semaglutide 0.5 mg significantly reduced HbA1c vs the majority of other GLP-1 RAs, except liraglutide 1.8 mg QD. The odds of experiencing nausea were significantly lower with once-weekly semaglutide 0.5 mg compared with all GLP-1 RA comparators. CONCLUSION: Once-weekly semaglutide 1.0 mg as an add-on to basal insulin is likely to be the most efficacious GLP-1 RA for reducing HbA1c and weight from baseline after 6 months of treatment. The efficacy of once-weekly semaglutide is not associated with a significant increase in the incidence of gastrointestinal side-effects vs other GLP-1 RAs. FUNDING: Novo Nordisk.

A Systematic Literature Review and Network Meta-Analysis Comparing Once-Weekly Semaglutide with Other GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Previously Receiving 1-2 Oral Anti-Diabetic Drugs.

INTRODUCTION: Once-weekly semaglutide is a new glucagon-like peptide-1 (GLP-1) analogue administered at a 1.0 or 0.5 mg dose. As head-to-head trials assessing once-weekly semaglutide as an add-on to 1-2 oral anti-diabetic drugs (OADs) vs other GLP-1 receptor agonists (GLP-1 RAs) are limited, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of once-weekly semaglutide vs GLP-1 RAs in patients with type 2 diabetes (T2D) inadequately controlled on 1-2 OADs. METHODS: A systematic literature review (SLR) was conducted in order to identify trials of GLP-1 RAs in patients inadequately controlled on 1-2 OADs. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in a NMA), which included the key outcomes of change from baseline in glycated hemoglobin (HbA1c), systolic blood pressure (SBP), and weight, as well as discontinuation due to adverse events (AEs). Data were synthesized using a NMA and a Bayesian framework. RESULTS: In total, 26 studies were included across the base case analyses. Once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA1c and weight vs all GLP-1 RA comparators. Once-weekly semaglutide 0.5 mg also achieved significantly greater reductions in HbA1c and weight compared with the majority of other GLP-1 RAs. Both doses of once-weekly semaglutide were associated with similar odds of discontinuation due to AEs compared with other GLP-1 RAs. CONCLUSION: Overall, once-weekly semaglutide 1.0 mg as an add-on to 1-2 OADs is the most efficacious GLP-1 RA in terms of the reduction of HbA1c and weight from baseline after 6 months of treatment. In addition, the analysis suggests that once-weekly semaglutide is well tolerated and not associated with an increase in discontinuations due to AEs compared with other GLP-1 RAs. FUNDING: Novo Nordisk.

A Network Meta-Analysis Comparing Semaglutide Once-Weekly with Other GLP-1 Receptor Agonists in Japanese Patients with Type 2 Diabetes.

INTRODUCTION: Semaglutide once-weekly (QW) is a novel glucagon-like peptide-1 (GLP-1) analogue administered at a 0.5 or 1.0 mg dose. In the absence of head-to-head trials between semaglutide QW and other GLP-1 receptor agonists (GLP-1 RAs) in a Japanese population, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of semaglutide QW vs GLP-1 RAs in Japanese patients with type 2 diabetes (T2DM), with a specific focus on the comparison between semaglutide 0.5 mg QW and dulaglutide 0.75 mg QW. METHODS: A systematic review (SR) and supplementary Japanese searches were conducted to identify trials of GLP-1 RAs in Japanese patients on diet and exercise, who have previously received 0-1 oral antidiabetic drugs (OADs). Data at 52-56 weeks were extracted for the following outcomes (feasible for analysis in an NMA): glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), weight, systolic blood pressure (SBP), and overall hypoglycemia. The data were synthesized using an NMA and a Bayesian framework. RESULTS: Four trials, identified from the SR and Japanese-specific searches, were relevant for inclusion in the NMA. When compared to dulaglutide 0.75 mg QW, semaglutide 0.5 mg QW was shown to provide significant reductions in HbA1c [- 0.61% (12.3 mmol/mol)], weight (- 1.45 kg), SBP (- 5.03 mmHg), and FPG (- 1.26 mmol/L). No significant differences in the proportion of patients achieving a HbA1c level < 7% (53 mmol/mol) or the risk of overall hypoglycemia were observed between semaglutide 0.5 mg QW and dulaglutide 0.75 mg QW. CONCLUSION: Overall, semaglutide 0.5 mg QW was associated with significant reductions from baseline in HbA1c, weight, SBP, and FPG compared with dulaglutide 0.75 mg QW in Japanese patients with T2DM. These data may provide valuable evidence for clinical decision-making, cost-effectiveness analyses, and health technology appraisal (HTA) requirements. FUNDING: Novo Nordisk Pharma Ltd.

Asymptomatic atrial fibrillation in patients with atrial fibrillation and implanted pacemaker.

INTRODUCTION: Atrial fibrillation is the most common chronic arrhythmia. Due to diagnostic difficulties, the exact prevalence of silent atrial fibrillation is not precisely defined. AIM: The main aim of the present study was to assess the prevalence of asymptomatic atrial fibrillation and the relation between clinical status and presence of symptoms of atrial fibrillation. MATERIAL AND METHODS: Fifty patients with implanted pacemaker with atrial fibrillation recording function and diagnosed paroxysmal atrial fibrillation were enrolled to the study in order to detect episodes of atrial fibrillation. Episodes lasting >1min were included into analysis. Patients were evaluated for presence of atrial fibrillation symptoms. RESULTS: A total of 870 atrial fibrillation episodes were registered, the majority (93%) were asymptomatic. Episodes occurred more often during the day than during the night (p<0.001). Asymptomatic episodes occurred 13 times more frequently than symptomatic (p<0.001). Majority of episodes lasting up to 5min were asymptomatic, while episodes lasting over 24h were usually symptomatic (p<0.001). Furthermore, there were association between silent atrial fibrillation and lower HR (p=0.003), higher percentage of atrial (p=0.01) and ventricular pacing (p<0.001), male gender (p<0.001), presence of atrioventricular block (p<0.003), lower NYHA class (p<0.002), and calcium channel blockers (p=0.033) and diuretics intake (p<0.001). CONCLUSION: In patients with bradycardia permanent pacemakers and paroxysmal atrial fibrillation, the proportion of asymptomatic episodes is very high. It was observed that shorter duration of the episodes, male gender, lower heart rate, presence of atrioventricular block, lower NYHA class, higher percentage of atrial and ventricular pacing, Ca2+ blockers, and diuretics intake predisposed to silent atrial fibrillation.

[The latest recommendations on the use of new oral anticoagulants in routine practice]. / Najnowsze zalecenia dotyczace zastosowania nowych doustnych antykoagulantów w rutynowej praktyce.

The use of non-vitamin K antagonist oral anticoagulants (NOACs) has become a breakthrough in anticoagulant treatment and it is expected to rise significantly in upcoming years. The use of conventional anticoagulants have several limitations: subcutaneous administration of heparin, or close monitoring of INR during application of vitamin K antagonists. In the last decade, target-specific oral anticoagulants (TSOAC) including dabigatran, rivaroxaban, apixaban, edoxaban have been marketed for prophylaxis and treatment. Therefore, it is crucial to understand the potential uses, side effects, and management of these agents in routine practice. NOACs have major pharmacologic advantages, including a rapid onset and offset of action, fewer drug interactions than conventional anticoagulants, and predictable pharmacokinetics. These agents are gaining popularity among both physicians and patients because of their easiness of administration and the eliminating the requirement for regular coagulation monitoring. In this review, we focus on discussing practical recommendations for the use of NOACs and the risks and benefits of incorporating them into routine practice.

Is there the gap in public health literature in Europe?

INTRODUCTION AND OBJECTIVE: The growing expectations for the effectiveness of public health increase the demand for scientific literature, concerning research, reviews and other forms of information. The bibliographic databases are of crucial importance for researchers and policy makers. The objective of this study is to estimate the supply of scientific literature related to public health in selected European countries, which are available to a wide range of users. MATERIALS AND METHODS: Analysis of the number of bibliographic records on topics related to public health was based on searches in Ovid MEDLINE (R) in May and June 2011. According to MeSH terms, 11 keywords and names of 13 European countries were used in the search. Publications from the years 2001-2010 were analyzed. A number of publications indexed under 'public health', and related to selected countries were compared with the size of the population of those countries, GDP, total expenditure on health and burden of disease (DALYS's). RESULTS: The most popular topic was 'health policy', whereas the topics 'occupational health' and 'environmental health' were less prevalent. There were no significant changes in the number of publications in 2001-2010. The number of articles indexed under 'public health' had significant positive correlation with national GDP, expenditure on health and population size, and negative with DALY's. CONCLUSIONS: According to the criteria accepted in this study, the Nordic countries--Finland, Sweden and Norway--were very productive in this respect. Poland and other Central European Countries were less productive.

Methods of assessment of magnesium status in humans: a systematic review.

To understand humans' requirements for magnesium and the effect of magnesium on health, it is important to identify sensitive and population-specific biomarkers of magnesium status. Thus, we assessed the effectiveness of different magnesium status biomarkers through a systematic review of published magnesium supplementation and depletion trials in healthy humans. The methods used in this study included a structured search on Ovid MEDLINE, EMBASE (Ovid) and Cochrane databases up to September 2008, followed by the use of formal inclusion/exclusion criteria, data extraction, validity assessment, and meta-analysis. A total of 20 potential biomarkers of magnesium status were assessed from 21 included publications. The majority of studies included were magnesium supplementation studies. Fewer magnesium depletion studies were identified. Available data analysis suggests that serum/plasma magnesium concentration, red blood cell (RBC) concentration and urinary magnesium excretion responded to dietary manipulation. For other biomarkers with available data, it was not possible to draw any conclusions about their usefulness as magnesium status biomarkers. The lack of data prevented detailed subgroup analysis. In conclusion, although limited data were available, serum/plasma magnesium concentration, RBC magnesium concentration and urinary magnesium excretion appear to be useful biomarkers of magnesium status in the general population. Further high-quality studies are needed to assess the effectiveness of existing and newly developed biomarkers, especially in populations that are vulnerable to magnesium deficiency.