Psychologic Distress and Quality of Life After ICU Treatment for Coronavirus Disease 2019: A Multicenter, Observational Cohort Study.

To quantify short- and long-term psychologic distress, that is, symptoms of posttraumatic stress disorder, anxiety, and depression, and the health-related quality of life in coronavirus disease 2019 ICU survivors. DESIGN: A prospective, observational cohort study. SETTING: Postcoronavirus disease 2019 clinics of three hospitals in Rotterdam, the Netherlands. PATIENTS: Adult patients admitted for coronavirus disease 2019 to the ICU, who visited the postcoronavirus disease 2019 follow-up clinic. MEASURES AND MAIN RESULTS: The primary outcomes were psychologic distress and overall and mental health-related quality of life, assessed using the Impact of Event Scale-Revised, Hospital Anxiety and Depression Scale, Short-Form 36, and European Quality of Life 5D, 6 weeks, 3 months, and 6 months post hospital discharge. Second, we compared 3-month psychologic and mental health-related quality of life outcomes with a historical critical illness survivor cohort and overall and mental health-related quality of life with the Dutch population. We included 118 patients with a median age of 61 years (95% range, 36-77 yr) of whom 79 (68%) were male. At 6 weeks, 13 patients (23%) reported psychologic distress, copresence of probable psychiatric disorders was common, and no decline in psychologic distress was observed throughout follow-up. Coronavirus disease 2019 patients tend to suffer less from posttraumatic stress disorder and reported less severe symptoms of anxiety (Hospital Anxiety and Depression Scale Anxiety Score: 3 [0-17] vs 5 [0-16]; estimated mean difference 2.3 [95% CI, 0.0-4.7]; p = 0.05) and depression (Hospital Anxiety and Depression Scale Depression Score: 3 [0-15] vs 5 [0-16]; estimated mean difference 2.4 [95% CI, 0.1-2.4]; p = 0.04) than the historical critical illness cohort. Overall and mental health-related quality of life increased over time. Coronavirus disease 2019 ICU survivors reported better mental health-related quality of life than our historical cohort, but overall and mental health-related quality of life was still poorer than the Dutch population. CONCLUSIONS: Psychologic distress was common in coronavirus disease 2019 ICU survivors and remained similar until 6 months after hospital discharge. Health-related quality of life increased over time and was higher than in a historical cohort, but was lower than in the Dutch population. Our findings highlight that coronavirus disease 2019 ICU survivors should be monitored after ICU treatment to detect possible psychologic distress.

Effect of intensive care unit-specific virtual reality (ICU-VR) to improve psychological well-being and quality of life in COVID-19 ICU survivors: a study protocol for a multicentre, randomized controlled trial.

BACKGROUND: The SARS-CoV-2 outbreak has resulted in a tremendous increase in hospital and intensive care unit (ICU) admissions all over the world. Patients with severe coronavirus disease 2019 (COVID-19) warranting ICU treatment usually have prolonged mechanical ventilation and are expected to be prone to develop psychological impairments, such as post-traumatic stress disorder (PTSD), anxiety and depression, which negatively impact quality of life. To date, no effective treatment strategy is available. In the current trial, we aim to assess the effect of an ICU-specific virtual reality (ICU-VR) intervention on psychological well-being and quality of life after COVID-19 ICU treatment. METHODS: In this multicentre, randomized controlled trial, we aim to examine whether COVID-19-specific ICU-VR, offered 3 months after hospital discharge, improves psychological well-being and quality of life. Secondary objectives are, firstly, to examine the intra-group changes in psychological well-being and quality of life and the inter-group differences in psychological well-being and quality of life during follow-up, up to 12 months after hospital discharge, and secondly, to examine patients' satisfaction with and rating of ICU care and aftercare and patients' perspectives on ICU-VR. Eighty adult patients treated for COVID-19 in the mixed-surgical ICUs of four hospitals in Rotterdam, the Netherlands, will be included and randomized (1:1) to either early or late ICU-VR between June 29 and December 31, 2020. Patients randomized to early ICU-VR will receive the ICU-VR intervention during an outpatient clinic visit 3 months after hospital discharge, whereas patients randomized to late ICU-VR will receive ICU-VR 6 months after hospital discharge. Primary outcomes of this study are psychological well-being, assessed using the Impact of Event Scale-Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS), and quality of life, assessed using the European Quality of Life 5 Dimensions (EQ-5D) and RAND-36 questionnaires, up to 6 months after hospital discharge. DISCUSSION: Currently, an effective treatment for psychological sequelae after ICU treatment for specific illnesses is unavailable. Results from this study will provide insight whether virtual reality is a modality that can be used in ICU aftercare to improve psychological well-being and quality of life, or satisfaction, after ICU treatment for specific illnesses such as COVID-19. TRIAL REGISTRATION: This trial has been retrospectively registered on the Netherlands Trial Register on August 14, 2020 ( NL8835 ).

Heritability of blood pressure traits and the genetic contribution to blood pressure variance explained by four blood-pressure-related genes.

OBJECTIVE: To study the heritability of four blood pressure traits and the proportion of variance explained by four blood-pressure-related genes. METHODS: All participants are members of an extended pedigree from a Dutch genetically isolated population. Heritability and genetic correlations of systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure were assessed using a variance components approach (SOLAR). Polymorphisms of the alpha-adducin (ADD1), angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R) and G protein beta3 (GNB3) genes were typed. RESULTS: Heritability estimates were significant for all four blood pressure traits, ranging between 0.24 and 0.37. Genetic correlations between systolic blood pressure, diastolic blood pressure and mean arterial pressure were high (0.93-0.98), and those between pulse pressure and diastolic blood pressure were low (0.05). The ADD1 polymorphism explained 0.3% of the variance of pulse pressure (P = 0.07), and the polymorphism of GNB3 explained 0.4% of the variance of systolic blood pressure (P = 0.02), 0.2% of mean arterial pressure (P = 0.05) and 0.3% of pulse pressure (P = 0.06). CONCLUSION: Genetic factors contribute to a substantial proportion of blood pressure variance. In this study, the effect of polymorphisms of ADD1, AGT, AT1R and GNB3 explained a very small proportion of the heritability of blood pressure traits. As new genes associated with blood pressure are localized in the future, their effect on blood pressure variance should be calculated.

Heritabilities, apolipoprotein E, and effects of inbreeding on plasma lipids in a genetically isolated population: the Erasmus Rucphen Family Study.

Despite considerable progress in unravelling the genetic basis of dyslipidemias, most findings are based on families with extreme phenotypes. We studied lipid levels in an extended pedigree ascertained irrespective of phenotype from the population of a recent genetic isolate in the Netherlands. Heritabilities of plasma lipid measures were examined; this analysis also included estimates of the proportion of variance attributable to ApoE genotype. The association between inbreeding and lipids was also considered, as a substantial fraction of the population had known inbreeding. A total of 868 individuals from this pedigree, containing more than 60,000 people over 15 generations, were investigated in this study. Laboratory analysis of these subjects included the determination of fasting plasma lipids. ApoE epsilon2/3/4 status was ascertained using TaqMan assays. Heritabilities for plasma lipids were estimated with adjustments for multiple covariates using SOLAR. Heritabilities for total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides (TG), TC/HDL ratio, and TG/HDL ratio were found to be 0.35, 0.56, 0.30, 0.24, 0.49, and 0.39, respectively. The addition of ApoE genotype in the model significantly decreased these estimates (Deltah(2) = -0.030, -0.004, -0.054, and -0.006 for TC, HDL, LDL, and TG). In a further analysis, TC and LDL were positively associated with the extent of inbreeding (p (trend) = 0.02 and p (trend) = 0.05, respectively). These data provide estimates of lipid heritability unbiased due to selection and suggest that this population represents a good opportunity to localize novel genes influencing plasma lipid levels.

Mortality in patients with hypertension on angiotensin-I converting enzyme (ACE)-inhibitor treatment is influenced by the ACE insertion/deletion polymorphism.

BACKGROUND: The response to angiotensin-I converting enzyme (ACE)-inhibitor therapy is highly variable. Residual ACE activity during treatment, potentially modified by the ACE insertion/deletion (I/D) polymorphism, may explain part of this variability. We studied the possible interaction between ACE-inhibitor therapy in patients with hypertension and the ACE I/D polymorphism in incident heart failure and death. METHODS: We studied 3365 hypertensive participants of the population-based Rotterdam Study, without heart failure at baseline for whom ACE-genotyping was successful. Incident heart failure was defined according to established criteria. In addition, total and cardiovascular mortality were studied as endpoints. A Cox regression model with use of ACE-inhibitors defined as time-dependent covariates was used for data-analysis. Interaction was tested in this model assuming an allele-effect relationship. RESULTS: Although we could not demonstrate a beneficial effect of ACE-inhibitors, there was significant interaction between the ACE I/D polymorphism (II-ID-DD) and ACE-inhibitor use in the prediction of total and cardiovascular mortality. Mortality risk associated with treatment increased with the number of D alleles present; e.g. for total mortality in the II genotype group: RR=0.95 (95% CI 0.63-1.45), in the ID genotype group: RR=1.08 (95% CI 0.84-1.38) and in the DD genotype group: RR=1.61 (95% CI 1.18-2.18). No statistically significant interaction was found for incident heart failure. CONCLUSION: The results of our study suggest a relative resistance to ACE-inhibitor therapy in subjects with hypertension and the DD genotype compared to the II genotype, with the ID genotype in an intermediate position.

Angiotensin converting enzyme insertion/deletion polymorphism and the risk of heart failure in hypertensive subjects.

AIMS: Cardiac angiotensin-I converting enzyme (ACE) activity is influenced by the ACE I/D polymorphism. Evidence suggests that the DD-genotype may be a risk factor for cardiac hypertrophy and heart failure, especially in hypertensive subjects. We assessed the relation between the ACE I/D polymorphism and the risk of incident heart failure in normotensive and hypertensive subjects. METHODS AND RESULTS: We investigated 4264 normotensive and 2174 hypertensive participants of the Rotterdam Study, a population based prospective cohort study. All subjects were available for follow-up from 1990 until 2000. Incidence rates (IR) of heart failure in normotensive subjects were the same over all genotype strata (10 per 1000 person-years). In hypertensive subjects, the IR increased with the number of D-alleles present (II: IR=13, ID: IR=18 and DD: IR=20 per 1000 person-years). Hypertensive subjects carrying the II-genotype did not have an increased risk of heart failure compared to normotensive II subjects. However, hypertensive subjects carrying one or two copies of the D-allele did have a significantly increased risk of heart failure (ID: RR: 1.4 (1.1-1.9) and DD: RR: 1.5 (1.2-2.1)). CONCLUSION: Our findings suggest that the ACE I/D polymorphism may play a modifying role in the development of heart failure in hypertensive subjects.

Genetic polymorphisms and heart failure.

Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism. Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system. Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study gene-gene interactions and gene-environment interactions.

Smoking-dependent effects of the angiotensin-converting enzyme gene insertion/deletion polymorphism on blood pressure.

BACKGROUND: Studies on the role of the angiotensin-converting enzyme (ACE) gene in the development of hypertension have yielded conflicting results. Recent studies suggested that this gene might have smoking-dependent effects on the development of cardiovascular disease. OBJECTIVE: To study the relationship between the ACE insertion/deletion (I/D) polymorphism, blood pressure and risk of hypertension in current, former and non-smokers in a population-based cohort. METHODS: We included 2412 non-smokers, 2794 former smokers and 1508 current smokers, all participants in the Rotterdam Study. In each group, we assessed the relationship between the ACE I/D polymorphism, systolic (SBP) and diastolic (DBP) blood pressures and risk of hypertension. Mean blood pressures and prevalence of hypertension were compared between carriers and non-carriers of the D allele. All analyses were adjusted for age, sex, body mass index, diabetes mellitus, high-density lipoprotein cholesterol, total cholesterol and use of antihypertensive medication. RESULTS: In non-smokers and former smokers, blood pressure and the risk of hypertension did not differ significantly between genotypes. In smokers, we found a significant increase in SBP in DD carriers (139.6 +/- 22.8 mmHg) compared with II carriers (136.0 +/- 22.7 mmHg) (P = 0.04). No effect of ACE genotype was observed for DBP. The risk of hypertension was significantly increased in smokers who carried one [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0 to 1.9; P = 0.05] or two (OR 1.5, 95% CI 1.1 to 2.2; P = 0.02) copies of the D allele. CONCLUSIONS: The D allele of the ACE polymorphism is associated with a significantly increased SBP and risk of hypertension in smokers. Our study underlines the importance of gene-environment interactions in the study of candidate genes for hypertension.