Lipid metabolism during pregnancy:Consequences for mother and child

Purpose of review:Accommodating fetal growth and development, women undergo multiple physiological changes during pregnancy. In recent years, several studies contributed to the accumulating evidence about the impact of gestational hyperlipidemia on cardiovascular risk for mother and child. This review aims to provide a comprehensive overview of the current research on lipid profile alterations during pregnancy and its associated (cardiovascular) outcomes for mother and child from a clinical perspective.Recent findings:In a normal pregnancy, total and LDL-cholesterol levels increase by approximately 30-50%, HDL-cholesterol by 20-40%, and triglycerides by 50-100%. In some women, for example, with familial hypercholesterolemia (FH), a more atherogenic lipid profile is observed. Dyslipidemia during pregnancy is found to be associated with adverse (cardiovascular) outcomes for the mother (e.g. preeclampsia, gestational diabetes, metabolic syndrome, unfavorable lipid profile) and for the child (e.g. preterm birth, large for gestational age, preatherosclerotic lesions, unfavorable lipid profile).Summary:The lipid profile of women during pregnancy provides a unique window of opportunity into the potential future cardiovascular risk for mother and child. Better knowledge about adverse outcomes and specific risk groups could lead to better risk assessment and earlier cardiovascular prevention. Future research should investigate implementation of gestational screening possibilities.</p

Clinical consequences of antibody formation, serum concentrations, and HLA-Cw6 status in psoriasis patients on Ustekinumab

Background: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine. Methods: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for >16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or >64 of ustekinumab treatment. Results: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02-3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6-positive and HLA-Cw6-negative patients (P = 0.164). Conclusions: The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged

Improvement in the regulation of the vitamin K antagonist acenocoumarol after a standard initial dose regimen: prospective validation of a prescription model

Background In a retrospective study we have developed a model which determines the dose of acenocoumarol based on the age of the patient and on the first INR obtained after a standard initial loading dose. The group of patients of this study was used as the control group of the present study. Aim The aim of this study was to prospectively validate the model and to assess whether the use of this model improves the quality of the treatment in the 0-2 months study period. Patients and methods In 197 patients the model was evaluated by (1) in the initial phase: comparison of INRs with the control group, after assessing the dose according to the model, and (2) in the 0-2 months period: calculation of the percentage of time spent in the therapeutic target range compared to the control group. Furthermore, the eventual dose was compared to the dose of the model when the INRs were within the therapeutic target range for the first time and on two successive occasions. Results (1) When dosed according to the model, 50% of INRs in the total group were within the therapeutic target range compared to 45% in the control group, and (2) the percentage time spent within this range was 68 in the total group compared to 63 in the control group (P = 0.0013). When the INRs were within the range for the first time and successively twice, the eventual doses were similar to the model in 59 and 50%, respectively. About 20% of the patients did not achieve two successive INRs within the range. Conclusions Using the model the quality of treatment improved. We advice to use a standardized individualized dose regimen at the initiation of vitamin K antagonist treatmen

The optimal intensity of vitamin k antagonists in patients with mechanical heart valves A meta-analysis

AbstractObjectivesThe purpose of this study was to compare two different intensities of vitamin K antagonists (VKA) among patients with mechanical heart valves using meta-analytic techniques.BackgroundPatients with mechanical heart valves are at increased risk for valve thrombosis and systemic embolism, which can be reduced by VKA. The range of optimal intensity of VKA is still a matter of debate.MethodsA computerized search in the PubMed database was made for relevant articles. A meta-analysis was performed of all eligible studies with data on the incidences of thromboembolic and bleeding complications in patients with mechanical heart valve prostheses during different intensities of VKA therapy. The studies were classified into low-intensity VKA therapy (mean target international normalized ratio [INR] of 3.0 or lower) or high-intensity VKA therapy (mean target INR above 3.0).ResultsThirty-five eligible studies were identified, including in total 23,145 patients, who were studied for 108,792 patient-years. For patients with an aortic valve, high intensity resulted in a lower incidence of thromboembolic events (risk ratio [RR] = 0.73, p < 0.0001); however, the incidence of bleeding was increased (RR = 1.23, p < 0.0001). In the mitral valve group, the incidence rate for thromboembolism was lower in the high-intensity group (RR = 0.74, p < 0.0001), without a significantly increased bleeding incidence (RR = 1.08, p = 0.0524). The total number of thromboembolic and bleeding events was decreased in the high-intensity group compared with low-intensity VKA therapy for both aortic and mitral valve prostheses (RR = 0.94 [p = 0.0067] and 0.84 [p < 0.0001]), respectively.ConclusionsThis meta-analysis shows that both aortic and mitral valves will benefit from a treatment strategy with a target INR higher than 3.0

Recombinant human activated protein C resets thrombin generation in patients with severe sepsis – a case control study

INTRODUCTION: Recombinant human activated protein C (rhAPC) is the first drug for which a reduction of mortality in severe sepsis has been demonstrated. However, the mechanism by which this reduction in mortality is achieved is still not clearly defined. The aim of the present study was to evaluate the dynamics of the anticoagulant, anti-inflammatory and pro-fibrinolytic action of rhAPC in patients with severe sepsis, by comparing rhAPC-treated patients with case controls. METHODS: In this prospectively designed multicenter case control study, 12 patients who were participating in the ENHANCE study, an open-label study of rhAPC in severe sepsis, were treated intravenously with rhAPC at a constant rate of 24 μg/kg/h for a total of 96 h. Twelve controls with severe sepsis matching the inclusion criteria received standard therapy. The treatment was started within 48 h after the onset of organ failure. Blood samples were taken before the start of the infusion and at 4, 8, 24, 48, 96 and 168 h, for determination of parameters of coagulation and inflammation. RESULTS: Sepsis-induced thrombin generation as measured by thrombin-antithrombin complexes and prothrombin fragment F1+2, was reset by rhAPC within the first 8 h of infusion. The administration of rhAPC did not influence parameters of fibrinolysis and inflammation. There was no difference in outcome or occurrence of serious adverse events between the treatment group and the control group. CONCLUSION: Sepsis-induced thrombin generation in severely septic patients is reset by rhAPC within the first 8 h of infusion without influencing parameters of fibrinolysis and inflammation

Effectiveness of interventions to prevent pre-frailty and frailty progression in older adults:a systematic review

OBJECTIVE: To summarize the best available evidence regarding the effectiveness of interventions for preventing frailty progression in older adults. INTRODUCTION: Frailty is an age-related state of decreased physiological reserves characterized by an increased risk of poor clinical outcomes. Evidence supporting the malleability of frailty, its prevention and treatment, has been presented. INCLUSION CRITERIA: The review considered studies on older adults aged 65 and over, explicitly identified as pre-frail or frail, who had been undergoing interventions focusing on the prevention of frailty progression. Participants selected on the basis of specific illness or with a terminal diagnosis were excluded. The comparator was usual care, alternative therapeutic interventions or no intervention. The primary outcome was frailty. Secondary outcomes included: (i) cognition, quality of life, activities of daily living, caregiver burden, functional capacity, depression and other mental health-related outcomes, self-perceived health and social engagement; (ii) drugs and prescriptions, analytical parameters, adverse outcomes and comorbidities; (iii) costs, and/or costs relative to benefits and/or savings associated with implementing the interventions for frailty. Experimental study designs, cost effectiveness, cost benefit, cost minimization and cost utility studies were considered for inclusion. METHODS: Databases for published and unpublished studies, available in English, Portuguese, Spanish, Italian and Dutch, from January 2001 to November 2015, were searched. Critical appraisal was conducted using standardized instruments from the Joanna Briggs Institute. Data was extracted using the standardized tools designed for quantitative and economic studies. Data was presented in a narrative form due to the heterogeneity of included studies. RESULTS: Twenty-one studies, all randomized controlled trials, with a total of 5275 older adults and describing 33 interventions, met the criteria for inclusion. Economic analyses were conducted in two studies. Physical exercise programs were shown to be generally effective for reducing or postponing frailty but only when conducted in groups. Favorable effects on frailty indicators were also observed after the interventions, based on physical exercise with supplementation, supplementation alone, cognitive training and combined treatment. Group meetings and home visits were not found to be universally effective. Lack of efficacy was evidenced for physical exercise performed individually or delivered one-to-one, hormone supplementation and problem solving therapy. Individually tailored management programs for clinical conditions had inconsistent effects on frailty prevalence. Economic studies demonstrated that this type of intervention, as compared to usual care, provided better value for money, particularly for very frail community-dwelling participants, and had favorable effects in some of the frailty-related outcomes in inpatient and outpatient management, without increasing costs. CONCLUSIONS: This review found mixed results regarding the effectiveness of frailty interventions. However, there is clear evidence on the usefulness of such interventions in carefully chosen evidence-based circumstances, both for frailty itself and for secondary outcomes, supporting clinical investment of resources in frailty intervention. Further research is required to reinforce current evidence and examine the impact of the initial level of frailty on the benefits of different interventions. There is also a need for economic evaluation of frailty interventions

Outcome of intracranial bleeding managed with prothrombin complex concentrate in patients on direct factor Xa inhibitors or vitamin K antagonists

Intracranial hemorrhage (ICH) is the most feared complication of anticoagulation with a high mortality and morbidity. Before registration of a specific reversal agent for factor Xa inhibitors (FXa-I), international guidelines recommended prothrombin complex concentrate (PCC), which also is the specific reversal agent for vitamin K antagonists (VKA). In two contemporary cohorts, we compared clinical outcomes between patients with FXa-I and VKA related ICH treated with PCC between 2014 and 2018. Primary outcome was effective hemostasis after 24 h, according to the International Society of Thrombosis and Hemostasis definition. Safety outcomes were defined as venous and arterial thromboembolic complications and death within 30 days. Thirty-six patients with FXa-I-ICH and 39 patients with VKA-ICH were available for analysis. Baseline characteristics were comparable between both groups, except for time from start of symptoms to presentation at the hospital. In the FXa-I-ICH cohort, 24 (73%) patients achieved effective hemostasis compared to 23 (62%) patients in the VKA-ICH cohort (crude odds ratio [OR] 1.62 [95%CI 0.59–4.48], adjusted OR 1.45 [95%CI 0.44–4.83]). Eight (24%) patients with FXa-I-ICH deceased compared to 17 (45%) patients with VKA-ICH (crude OR 0.38 [95%CI 0.14–1.24], adjusted OR 0.41 [95%CI 0.12–1.24]). In this observational cohort study, the outcome of ICH managed with PCC was similar in patients with FXa-I-ICH and in patients with VKA-ICH

Measurement of physical quantities in upper-limb tele-rehabilitation

A total of 50 patients (affected by traumatic brain injury, stroke or multiple sclerosis) were treated for one month using a rehabilitation protocol. Rehabilitation could be monitored using a Portable Unit (PU) which could be installed in a patient's home allowing the measurement of kinetic and kinematic variables during exercise. In a preliminary analysis, the variables related to four rehabilitation exercises were examined for two patients at baseline and at the end of the one-month treatment. The exercises involved movement of checkers, a pencil, a jar and a key. The results suggest that, even if the overall duration of exercise execution is an important aspect of the rehabilitation process, other variables acquired by the PU might deliver useful information for assessing the patient's status. In order to integrate such variables into the assessment process, further studies are needed to investigate their eventual correlation with traditional rehabilitation scales and variables

FOCUS : frailty management optimisation through EIPAHA commitments and utilisation of stakeholders’ input – an innovative European project in elderly care

The goal of FOCUS, which stands for Frailty Management Optimization through EIPAHA Commitments and Utilization of Stakeholders’ Input, is to reduce the burden of frailty in Europe. The partners are working on advancing knowledge of frailty detection, assessment, and management, including biological, clinical, cognitive and psychosocial markers, in order to change the paradigm of frailty care from acute intervention to prevention. FOCUS partners are working on ways to integrate the best available evidence from frailty-related screening tools, epidemiological and interventional studies into the care of frail people and their quality of life. Frail citizens in Italy, Poland and the UK and their caregivers are being called to express their views and their experiences with treatments and interventions aimed at improving quality of life. The FOCUS Consortium is developing pathways to leverage the knowledge available and to put it in the service of frail citizens. In order to reach out to the broadest audience possible, the FOCUS Platform for Knowledge Exchange and the platform for Scaling Up are being developed with the collaboration of stakeholders. The FOCUS project is a development of the work being done by the European Innovation Partnership on Active and Healthy Ageing (EIPAHA), which aims to increase the average healthy lifespan in Europe by 2020 while fostering sustainability of health/social care systems and innovation in Europe. The knowledge and tools developed by the FOCUS project, with input from stakeholders, will be deployed to all EIPAHA participants dealing with frail older citizens to support activities and optimize performance

Pregnancy outcomes in women with Budd-Chiari syndrome or portal vein thrombosis A multicentre retrospective cohort study

OBJECTIVE: To evaluate current practice and outcomes of pregnancy in women previously diagnosed with Budd-Chiari syndrome and/or portal vein thrombosis, with and without concomitant portal hypertension. DESIGN AND SETTING: Multicentre retrospective cohort study between 2008-2021. POPULATION: Women who conceived in the predefined period after the diagnosis of Budd-Chiari syndrome and/or portal vein thrombosis. METHODS AND MAIN OUTCOME MEASURES: We collected data on diagnosis and clinical features. The primary outcomes were maternal mortality and live birth rate. Secondary outcomes included maternal, neonatal and obstetric complications. RESULTS: Forty-five women (12 Budd-Chiari syndrome, 33 portal vein thrombosis; 76 pregnancies) were included. Underlying prothrombotic disorders were present in 23 of 45 women (51%). Thirty-eight women (84%) received low-molecular-weight heparin during pregnancy. Of 45 first pregnancies, 11 (24%) ended in pregnancy loss and 34 (76%) resulted in live birth of which 27 at term age (79% of live births and 60% of pregnancies). No maternal deaths were observed, one woman developed pulmonary embolism during pregnancy and two women (4%) had variceal bleeding requiring intervention. CONCLUSIONS: The high number of term live births (79%) and lower than expected risk of pregnancy-related maternal and neonatal morbidity in our cohort suggest that Budd-Chiari syndrome and/or portal vein thrombosis should not be considered as an absolute contra-indication for pregnancy. Individualized, nuanced counselling and a multidisciplinary pregnancy surveillance approach are essential in this patient population