Immune Responses 6 Months After mRNA-1273 COVID-19 Vaccination and the Effect of a Third Vaccination in Patients with Inborn Errors of Immunity

Purpose: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective long-term protection against COVID-19 is therefore of great importance in these patients, but little is known about the decay of the immune response after primary vaccination. We studied the immune responses 6 months after two mRNA-1273 COVID-19 vaccines in 473 IEI patients and subsequently the response to a third mRNA COVID-19 vaccine in 50 patients with common variable immunodeficiency (CVID).Methods: In a prospective multicenter study, 473 IEI patients (including X-linked agammaglobulinemia (XLA) (N = 18), combined immunodeficiency (CID) (N = 22), CVID (N = 203), isolated or undefined antibody deficiencies (N = 204), and phagocyte defects (N = 16)), and 179 controls were included and followed up to 6 months after two doses of the mRNA-1273 COVID-19 vaccine. Additionally, samples were collected from 50 CVID patients who received a third vaccine 6 months after primary vaccination through the national vaccination program. SARS-CoV-2-specific IgG titers, neutralizing antibodies, and T cell responses were assessed.Results: At 6 months after vaccination, the geometric mean antibody titers (GMT) declined in both IEI patients and healthy controls, when compared to GMT 28 days after vaccination. The trajectory of this decline did not differ between controls and most IEI cohorts; however, antibody titers in CID, CVID, and isolated antibody deficiency patients more often dropped to below the responder cut-off compared to controls. Specific T cell responses were still detectable in 77% of controls and 68% of IEI patients at 6 months post vaccination. A third mRNA vaccine resulted in an antibody response in only two out of 30 CVID patients that did not seroconvert after two mRNA vaccines.Conclusion: A similar decline in IgG titers and T cell responses was observed in patients with IEI when compared to healthy controls 6 months after mRNA-1273 COVID-19 vaccination. The limited beneficial benefit of a third mRNA COVID-19 vaccine in previous non-responder CVID patients implicates that other protective strategies are needed for these vulnerable patients.</p

Research Review: Psychological and psychosocial interventions for children and adolescents with depression, anxiety, and post-traumatic stress disorder in low- and middle-income countries - a systematic review and meta-analysis

BackgroundThe incidence of depression, anxiety, and post-traumatic stress disorder (PTSD) among children and adolescents residing in low- and middle-income countries (LMICs) poses a significant public health concern. However, there is variation in the evidence of effective psychological interventions. This meta-analysis aims to provide a complete overview of the current body of evidence in this rapidly evolving field.MethodsWe conducted searches on PubMed, Embase.com, and EBSCO/APA PsycInfo databases up to June 23, 2022, identify randomized controlled trials (RCTs) investigating the effectiveness of psychological interventions in LMICs that targeted children and adolescents with elevated symptoms above a cut-off score for depression, anxiety, and PTSD, comparing a psychological or psychosocial intervention with other control conditions. We conducted random effects meta-analyses for depression, anxiety, and PTSD symptoms. Sensitivity analysis for outliers and high-risk studies, and analyses for the publication bias were carried out. Subgroup analyses investigated how the intervention type, intervention format, the facilitator, study design, and age group of the participant predicted effect sizes.ResultsThirty-one RCTs (6,123 participants) were included. We found a moderate effect of interventions on depression outcomes compared to the control conditions (g = 0.53; 95% CI: 0.06-0.99; NNT = 6.09) with a broad prediction interval (PI) (-1.8 to 2.86). We found a moderate to large effect for interventions on anxiety outcomes (g = 0.88; 95% CI: -0.03 to 1.79; NNT = 3.32) with a broad PI (-3.14 to 4.9). Additionally, a moderate effect was observed on PTSD outcomes (g = 0.54; 95% CI: 0.19-0.9; NNT = 5.86) with a broad PI (-0.64 to 1.72).ConclusionsPsychological and psychosocial interventions aimed at addressing depression, anxiety, and PTSD among children and adolescents in LMICs have demonstrated promising results. However, future studies should consider the variation in evidence and incorporate long-term outcomes to better understand the effectiveness of these interventions

Preoperative screening and prehabilitation strategies prior to ileocolic resection in patients with Crohn’s disease are not incorporated in routine care

Purpose: Recently, recommendations on perioperative care have been published to optimize postoperative outcomes in preoperative patients with inflammatory bowel disease. This study evaluated the current use of preoperative screening and prehabilitation strategies (PS) prior to elective ileocolic resection (ICR) in patients with Crohn’s disease (CD). Methods: Patients with CD who underwent an elective ICR were identified from a Dutch prospective cohort study. Primary endpoint was to evaluate to what extent IBD-relevant PS were applied in patients with CD prior to ICR according to the current recommendations. Results: In total, 109 CD patients were included. Screening of nutritional status was performed in 56% of the patients and revealed malnutrition in 46% of these patients. Of the malnourished patients, 46% was referred to a dietitian. Active smoking and alcohol consumption were reported in 20% and 28%; none of these patients were referred for a cessation program. A preoperative anemia was diagnosed in 61%, and ferritin levels were assessed in 26% of these patients. Iron therapy was started in 25% of the patients with an iron deficiency anemia. Exposure to corticosteroids at time of ICR was reported in 29% and weaned off in 3%. Consultation of a dietitian, psychologist, and physiotherapist was reported in 36%, 7%, and 3%. Physical fitness was assessed in none of the patients. Conclusion: PS are not routinely applied and not individually tailored in the preoperative setting prior to elective ICR in patients with CD. Prior to implementation, future research on the costs and effectiveness of PS on postoperative outcomes and quality of life is necessary.</p

The health potential of urban water: Future scenarios on local risks and opportunities

Although cities can be characterised as sources of economic, environmental and social challenges, they can also be part of the solution for healthy and sustainable societies. While most cities are situated close to water, whether inland waterways, lakes, or the sea, these blue spaces are not integrated into urban planning to their full potential and their public health impacts are not always recognised by planning authorities. Furthermore, cities face future challenges regarding climate change, socio-economic developments like tourism, urbanization, and rising social inequalities. The development of healthy blue spaces can support cities in their pursuit of ways to confront these challenges. Interdisciplinary and transdisciplinary analyses of the local impacts of these trends and promising interventions have been scarce to date. This study explores the use of such methodology by presenting experiences related to five European cities: Amsterdam, Barcelona, Plymouth, Tallinn and Thessaloniki, using an interactive and participative approach with local experts and stakeholders. Future scenarios have been developed based on the question: How can blue spaces contribute to a healthier city population, given the long term trends? The results highlight the importance of addressing the local context when seeking sustainable solutions for cities. The future scenarios deliver information that could serve as useful input for local planning processes

Internet-based early intervention to prevent poststraumatic stress disorder in injury patients: Randomized controlled trial.

Background: Posttraumatic stress disorder (PTSD) develops in 10-20% of injury patients. We developed a novel, self-guided Internet-based intervention (called Trauma TIPS) based on techniques from cognitive behavioral therapy (CBT) to prevent the onset of PTSD symptoms. Objective: To determine whether Trauma TIPS is effective in preventing the onset of PTSD symptoms in injury patients. Methods: Adult, level 1 trauma center patients were randomly assigned to receive the fully automated Trauma TIPS Internet intervention (n=151) or to receive no early intervention (n=149). Trauma TIPS consisted of psychoeducation, in vivo exposure, and stress management techniques. Both groups were free to use care as usual (nonprotocolized talks with hospital staff). PTSD symptom severity was assessed at 1, 3, 6, and 12 months post injury with a clinical interview (Clinician-Administered PTSD Scale) by blinded trained interviewers and self-report instrument (Impact of Event Scale-Revised). Secondary outcomes were acute anxiety and arousal (assessed online), self-reported depressive and anxiety symptoms (Hospital Anxiety and Depression Scale), and mental health care utilization. Intervention usage was documented. Results: The mean number of intervention logins was 1.7, SD 2.5, median 1, interquartile range (IQR) 1-2. Thirty-four patients in the intervention group did not log in (22.5%), 63 (41.7%) logged in once, and 54 (35.8%) logged in multiple times (mean 3.6, SD 3.5, median 3, IQR 2-4). On clinician-assessed and self-reported PTSD symptoms, both the intervention and control group showed a significant decrease over time (P<.001) without significant differences in trend. PTSD at 12 months was diagnosed in 4.7% of controls and 4.4% of intervention group patients. There were no group differences on anxiety or depressive symptoms over time. Post hoc analyses using latent growth mixture modeling showed a significant decrease in PTSD symptoms in a subgroup of patients with severe initial symptoms (n=20) (P<.001). Conclusions: Our results do not support the efficacy of the Trauma TIPS Internet-based early intervention in the prevention of PTSD symptoms for an unselected population of injury patients. Moreover, uptake was relatively low since one-fifth of individuals did not log in to the intervention. Future research should therefore focus on innovative strategies to increase intervention usage, for example, adding gameplay, embedding it in a blended care context, and targeting high-risk individuals who are more likely to benefit from the intervention

The health potential of urban water: Future scenarios on local risks and opportunities

This is the final version. Available on open access from Elsevier via the DOI in this recordAlthough cities can be characterised as sources of economic, environmental and social challenges, they can also be part of the solution for healthy and sustainable societies. While most cities are situated close to water, whether inland waterways, lakes, or the sea, these blue spaces are not integrated into urban planning to their full potential and their public health impacts are not always recognised by planning authorities. Furthermore, cities face future challenges regarding climate change, socio-economic developments like tourism, urbanization, and rising social inequalities. The development of healthy blue spaces can support cities in their pursuit of ways to confront these challenges. Interdisciplinary and transdisciplinary analyses of the local impacts of these trends and promising interventions have been scarce to date. This study explores the use of such methodology by presenting experiences related to five European cities: Amsterdam, Barcelona, Plymouth, Tallinn and Thessaloniki, using an interactive and participative approach with local experts and stakeholders. Future scenarios have been developed based on the question: How can blue spaces contribute to a healthier city population, given the long term trends? The results highlight the importance of addressing the local context when seeking sustainable solutions for cities. The future scenarios deliver information that could serve as useful input for local planning processes.European Union Horizon 202

Immunogenicity of an additional mRNA-1273 SARS-CoV-2 vaccination in people with HIV with hyporesponse after primary vaccination

Background:The COVIH study is a prospective coronavirus disease 2019 (COVID-19) vaccination study in 1154 people with HIV (PWH), of whom 14% showed reduced antibody levels after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders. Methods: The primary end point was the increase in antibodies 28 days after additional mRNA-1273 vaccination. Secondary end points included neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity. Results:Of the 66 participants, 40 previously received 2 doses ChAdOx1-S, 22 received 2 doses BNT162b2, and 4 received a single dose Ad26.COV2.S. The median age was 63 years (interquartile range [IQR], 60–66), 86% were male, and median CD4 + T-cell count was 650/μL (IQR, 423–941). The mean S1-specific antibody level increased from 35 binding antibody units (BAU)/ mL (95% confidence interval [CI], 24–46) to 4317 BAU/mL (95% CI, 3275–5360) (P &lt; .0001). Of all participants, 97% showed an adequate response and the 45 antibody-negative participants all seroconverted. A significant increase in the proportion of PWH with ancestral S-specific CD4 + T cells (P = .04) and S-specific B cells (P = .02) was observed. Conclusions:An additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination.</p

Spontaneous Haemoperitoneum in Pregnancy: Nationwide Surveillance and Delphi Audit System

OBJECTIVE: To evaluate the incidence, diagnostic management strategies and clinical outcomes of women with spontaneous haemoperitoneum in pregnancy (SHiP) and reassess the definition of SHiP. DESIGN: A population-based cohort study using the Netherlands Obstetric Surveillance System (NethOSS). SETTING: Nationwide, the Netherlands. POPULATION: All pregnant women between April 2016 and April 2018. METHODS: This is a case study of SHiP using the monthly registry reports of NethOSS. Complete anonymised case files were obtained. A newly introduced online Delphi audit system (DAS) was used to evaluate each case, to make recommendations on improving the management of SHiP and to propose a new definition of SHiP. MAIN OUTCOME MEASURES: Incidence and outcomes, lessons learned about clinical management and the critical appraisal of the current definition of SHiP. RESULTS: In total, 24 cases were reported. After a Delphi procedure, 14 cases were classified as SHiP. The nationwide incidence was 4.9 per 100 000 births. Endometriosis and conceiving after artificial reproductive techniques were identified as risk factors. No maternal and three perinatal deaths occurred. Based on the DAS, adequate imaging of free intra-abdominal fluid, and identifying and treating women with signs of hypovolemic shock could improve the early detection and management of SHiP. A revised definition of SHiP was proposed, excluding the need for surgical or radiological intervention. CONCLUSIONS: SHiP is a rare and easily misdiagnosed condition that is associated with high perinatal mortality. To improve care, better awareness among healthcare workers is needed. The DAS is a sufficient tool to audit maternal morbidity and mortality

Early Steroid Withdrawal Compared With Standard Immunosuppression in Kidney Transplantation - Interim Analysis of the Amsterdam-Leiden-Groningen Randomized Controlled Trial

BACKGROUND: The optimal immunosuppressive regimen in kidney transplant recipients, delivering maximum efficacy with minimal toxicity, is unknown. METHODS: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in 305 kidney transplant recipients, in which 2 immunosuppression minimization strategies-one consisting of early steroid withdrawal, the other of tacrolimus minimization 6 months after transplantation-were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. The primary endpoint was kidney function. Secondary endpoints included death, primary nonfunction, graft failure, rejection, discontinuation of study medication, and a combined endpoint of treatment failure. An interim analysis was scheduled at 6 months, that is, just before tacrolimus minimization. RESULTS: This interim analysis revealed no significant differences in Modification of Diet in Renal Disease between the early steroid withdrawal group and the standard immunosuppression groups (43.2 mL/min per 1.73 m2 vs 45.0 mL/min per 1.73 m2, P = 0.408). There were also no significant differences in the secondary endpoints of death (1.0% vs 1.5%; P = 0.737), primary nonfunction (4.1% vs 1.5%, P = 0.159), graft failure (3.1% vs 1.5%, P = 0.370), rejection (18.6% vs 13.6%, P = 0.289), and discontinuation of study medication (19.6% vs 12.6%, P = 0.348). Treatment failure, defined as a composite endpoint of these individual secondary endpoints, was more common in the early steroid withdrawal group (P = 0.027), but this group had fewer serious adverse events and a more favorable cardiovascular risk profile. CONCLUSIONS: Based on these interim results, early steroid withdrawal is a safe short-term immunosuppressive strategy. Long-term outcomes, including a comparison with tacrolimus minimization after 6 months, will be reported in the final 2-year analysis