Phase I interim results of a phase I/II study of the IgG-Fc fusion COVID-19 subunit vaccine, AKS-452

To address the coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recombinant subunit vaccine, AKS-452, is being developed comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain (SP/RBD) antigen and human IgG1 Fc emulsified in the water-in-oil adjuvant, Montanide™ ISA 720. A single-center, open-label, phase I dose-finding and safety study was conducted with 60 healthy adults (18–65 years) receiving one or two doses 28 days apart of 22.5 µg, 45 µg, or 90 µg of AKS-452 (i.e., six cohorts, N = 10 subjects per cohort). Primary endpoints were safety and reactogenicity and secondary endpoints were immunogenicity assessments. No AEs ≥ 3, no SAEs attributable to AKS-452, and no SARS-CoV-2 viral infections occurred during the study. Seroconversion rates of anti-SARS-CoV-2 SP/RBD IgG titers in the 22.5, 45, and 90 µg cohorts at day 28 were 70%, 90%, and 100%, respectively, which all increased to 100% at day 56 (except 89% for the single-dose 22.5 µg cohort). All IgG titers were Th1-isotype skewed and efficiently bound mutant SP/RBD from several SARS-CoV-2 variants with strong neutralization potencies of live virus infection of cells (including alpha and delta variants). The favorable safety and immunogenicity profiles of this phase I study (ClinicalTrials.gov: NCT04681092) support phase II initiation of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain

The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Contains fulltext : 220851.pdf (Publisher’s version ) (Open Access)OBJECTIVES: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score. DESIGN: A cross-sectional study. PARTICIPANTS: 200 women aged >45 with PCOS, and 200 age-matched controls. MEASUREMENTS: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured. RESULTS: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P < .001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P < .001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. CONCLUSIONS: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning long-term risk for CVD

The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Objectives: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score. Design: A cross-sectional study. Participants: 200 women aged >45 with PCOS, and 200 age-matched controls. Measurements: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured. Results: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P <.001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P <.001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. Conclusions: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning lon

Posttraumatic stress symptoms and interpersonal processes in burn survivors and their partners

Background: A burn event can elicit symptoms of posttraumatic stress disorder (PTSD) in survivors and their partners and may impact the way these couple members interact with each other. They may try to protect each other from further emotional distress by avoiding talking about the burn event, but they may also show concern towards each other. Objective: The aim of this study was to investigate bidirectional relationships between survivor’s and partner’s PTSD symptoms and two interpersonal processes: partner-oriented ‘self-regulation’, which is avoidance-oriented, and ‘expressed concern’, which is approach-oriented. Method: In this longitudinal multi-centre study, 119 burn survivors and their partners participated. Measures of PTSD symptoms, self-regulation, and expressed concern were administered in the acute phase following the burns, and follow-ups took place up to 18 months postburn. Intra- and interpersonal effects were examined in a random intercept cross-lagged panel model. Exploratory effects of burn severity were also investigated. Results: Within individuals, survivor’s expressed concern predicted later higher levels of survivor’s PTSD symptoms. In their partners, self-regulation and PTSD symptoms reinforced each other in the early phase postburn. Between the two couple members, partner’s expressed concern predicted later lower levels of survivor’s PTSD symptoms. Exploratory regression analyses showed that burn severity moderated the effect of survivor’s self-regulation on survivor’s PTSD symptoms, indicating that self-regulation was continuously related to higher levels of PTSD symptoms over time within more severely burned survivors, but not in less severely burned survivors. Conclusion: PTSD symptoms and self-regulation reinforced each other in partners and possibly also in more severely burned survivors. Partner’s expressed concern was related to lower levels of survivor’s PTSD symptoms, whereas survivor’s expressed concern was related to higher levels of survivor’s PTSD symptoms. These findings emphasize the importance of screening for and monitoring PTSD symptoms in burn survivors and their partner and of encouraging couple’s self-disclosure

Prevalence and course of posttraumatic stress disorder symptoms in partners of burn survivors

Background: Partners of burn survivors may develop posttraumatic stress disorder (PTSD) symptoms in response to the potential life threatening nature of the burn event and the burn survivor’s medical treatment. Objective: This longitudinal study examined the prevalence, course and potential predictors of partners’ PTSD symptoms up to 18 months post-burn. Methods: Participants were 111 partners of adult burn survivors. In a multi-centre study, PTSD symptoms were assessed with the Impact of Event Scale-Revised during the acute phase and subsequently at 3, 6, 12 and 18 months post-burn. Partners’ appraisal of life threat, anger, guilt and level of rumination were assessed as potential predictors of PTSD symptoms in an exploratory piecewise latent growth model. Results: Acute PTSD symptoms in the clinical range were reported by 30% of the partners, which decreased to 4% at 18 months post-burn. Higher acute PTSD symptoms were related to perceived life threat and higher levels of anger, guilt, and rumination. Over time, mean symptom levels decreased, especially in partners with high levels of acute PTSD symptoms, perceived life threat and rumination. From three months onward, PTSD symptoms decreased less in partners of more severely burned survivors. At 18 months post-burn, higher levels of PTSD symptoms were related to higher acute PTSD symptoms and more severe burns. Conclusions: One in three partners reported clinical levels of acute PTSD symptoms, of which the majority recovered over time. Perceived life threat, feelings of anger and guilt, and rumination may indicate the presence of acute PTSD symptoms, whereas more severe burns predict long-term PTSD symptom levels. The results highlight the need to screen for acute PTSD symptoms and offer psychological help to partners to alleviate acute elevated stress levels if indicated

Posttraumatic stress symptoms and interpersonal processes in burn survivors and their partners

Background: A burn event can elicit symptoms of posttraumatic stress disorder (PTSD) in survivors and their partners and may impact the way these couple members interact with each other. They may try to protect each other from further emotional distress by avoiding talking about the burn event, but they may also show concern towards each other. Objective: The aim of this study was to investigate bidirectional relationships between survivor’s and partner’s PTSD symptoms and two interpersonal processes: partner-oriented ‘self-regulation’, which is avoidance-oriented, and ‘expressed concern’, which is approach-oriented. Method: In this longitudinal multi-centre study, 119 burn survivors and their partners participated. Measures of PTSD symptoms, self-regulation, and expressed concern were administered in the acute phase following the burns, and follow-ups took place up to 18 months postburn. Intra- and interpersonal effects were examined in a random intercept cross-lagged panel model. Exploratory effects of burn severity were also investigated. Results: Within individuals, survivor’s expressed concern predicted later higher levels of survivor’s PTSD symptoms. In their partners, self-regulation and PTSD symptoms reinforced each other in the early phase postburn. Between the two couple members, partner’s expressed concern predicted later lower levels of survivor’s PTSD symptoms. Exploratory regression analyses showed that burn severity moderated the effect of survivor’s self-regulation on survivor’s PTSD symptoms, indicating that self-regulation was continuously related to higher levels of PTSD symptoms over time within more severely burned survivors, but not in less severely burned survivors. Conclusion: PTSD symptoms and self-regulation reinforced each other in partners and possibly also in more severely burned survivors. Partner’s expressed concern was related to lower levels of survivor’s PTSD symptoms, whereas survivor’s expressed concern was related to higher levels of survivor’s PTSD symptoms. These findings emphasize the importance of screening for and monitoring PTSD symptoms in burn survivors and their partner and of encouraging couple’s self-disclosure. PTSD symptoms in burn survivors and their partners are related to both avoidance- and approach-oriented interpersonal processes.In partners, higher levels of self-regulation were bidirectionally related to higher levels of posttraumatic stress symptoms.Concern expressed by partners may mitigate posttraumatic stress symptoms in burn survivors. PTSD symptoms in burn survivors and their partners are related to both avoidance- and approach-oriented interpersonal processes. In partners, higher levels of self-regulation were bidirectionally related to higher levels of posttraumatic stress symptoms. Concern expressed by partners may mitigate posttraumatic stress symptoms in burn survivors.</p

Zorg door de huisarts. Nivel Zorgregistraties eerste lijn: jaarcijfers 2017 en trendcijfers 2011-2017

Kernpunten ● Dit rapport bevat cijfers over het zorggebruik van 1,7 miljoen patiënten, ingeschreven bij ongeveer 420 huisartsenpraktijken. ● 78% van de ingeschreven patiënten had in 2017 één of meer gedeclareerde contacten met de huisarts ● Patiënten hadden in 2017 gemiddeld 4,4 keer contact met de huisartsenpraktijk. Voor kinderen in de leeftijdscategorie 5-17 jaar werden gemiddeld de minste contacten per jaar gedeclareerd, namelijk 2,3; in de oudste leeftijdscategorie (85 jaar en ouder) waren dat er het meest, namelijk gemiddeld 13,3. ● Het totaal aantal gedeclareerde contacten is in 2017 heel licht gedaald ten opzichte van vorig jaar. Het aantal lange consulten en telefonische consulten is daarentegen duidelijk toegenomen in de afgelopen vijf jaar. ● Zo’n 16% van de patiënten in de huisartsenpraktijk krijgt tenminste één keer per jaar een maagzuurremmer voorgeschreven. Dit is daarmee, net als in eerdere jaren, het meest voorgeschreven geneesmiddel bij de huisarts in 2017. ● De dalende trend in het percentage patiënten dat een antibioticum kreeg voorgeschreven (17,7%) zet verder door. ● In 2017 waren er 303 verwijzingen per 1.000 ingeschreven patiënten naar een medisch specialist. De meeste tweedelijns verwijzingen gingen naar het specialisme oogheelkunde (32 per 1000 patiënten), gevolgd door orthopedie, KNO-heelkunde en dermatologie. (aut. ref.