General Dutch Population Research Articles

Short-term and long-term increased mortality in elderly patients with burn injury: a national longitudinal cohort study

BackgroundThe population of elderly patients with burn injuries is growing. Insight into long-term mortality rates of elderly after burn injury and predictors affecting outcome is limited. This study aimed to provide this information.MethodsA multicentre observational retrospective cohort study was conducted in all three Dutch burn centres. Patients aged ≥65 years, admitted with burn injuries between 2009 and 2018, were included. Data were retrieved from electronic patient records and the Dutch Burn Repository R3. Mortality rates and standardized mortality ratios (SMRs) were calculated. Multivariable logistic regression was used to assess predictors for in-hospital mortality and mortality after discharge at 1 year and five-year. Survival analysis was used to assess predictors of five-year mortality.ResultsIn total, 682/771 admitted patients were discharged. One-year and five-year mortality rates were 8.1 and 23.4%. The SMRs were 1.9(95%CI 1.5–2.5) and 1.4(95%CI 1.2–1.6), respectively. The SMRs were highest in patients aged 75–80 years at 1 year (SMRs 2.7, 95%CI 1.82–3.87) and five-year in patients aged 65–74 years (SMRs 10.1, 95%CI 7.7–13.0). Independent predictors for mortality at 1 year after discharge were higher age (OR 1.1, 95%CI 1.0–1.1), severe comorbidity, (ASA-score ≥ 3) (OR 4.8, 95%CI 2.3–9.7), and a non-home discharge location (OR 2.0, 95%CI 1.1–3.8). The relative risk of dying up to five-year was increased by age (HR 1.1, 95%CI 1.0–1.1), severe comorbidity (HR 2.3, 95%CI 1.6–3.5), and non-home discharge location (HR 2.1, 95%CI 1.4–3.2).ConclusionLong-term mortality until five-year after burn injury was higher than the age and sex-matched general Dutch population, and predicted by higher age, severe comorbidity, and a non-home discharge destination. Next to pre-injury characteristics, potential long-lasting systemic consequences on biological mechanisms following burn injuries probably play a role in increased mortality. Decreased health status makes patients more prone to burn injuries, leading to early death.

Risk of second primary malignancies in patients with chronic lymphocytic leukemia: a population-based study in the Netherlands, 1989-2019

The longevity of patients with chronic lymphocytic leukemia (CLL) has improved progressively over the past decades, making it essential to understand long-term health outcomes, such as second primary malignancies (SPMs). Therefore, this nationwide, population-based study assessed the risk of SPM development in CLL patients diagnosed during 1989-2019 in the Netherlands compared to the expected number of malignancies in an age-, sex-, and period-matched group from the general Dutch population. In 24,815 CLL patients followed for 162,698.49 person-years, 4369 SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.63 (95% confidence interval [CI] 1.59–1.68). This elevated risk was observed for solid (SIR, 1.67; 95% CI, 1.65–1.75) and hematological SPMs (SIR 1.42; 95% CI, 1.24–1.62). The highest risk for SPMs was noted beyond five years post-diagnosis (SIR, 1.70; 95% CI, 1.62–1.77), for male individuals (SIR, 1.70; 95% CI, 1.64–1.77), and patients aged 18–69 years (SIR, 1.92; 95% CI, 1.79–2.05). The risk of SPMs was higher in CLL patients who received anti-neoplastic therapy (SIR, 2.12; 95% CI, 1.96–2.28), as compared with those who did not (SIR, 1.58; 95% CI, 1.53–1.63). Routine surveillance activities and tailored interventions to counteract the increased morbidity and excess mortality associated with SPMs are essential for improving long-term outcomes in CLL patients.

Low Sodium Intake, Low Protein Intake, and Excess Mortality in an Older Dutch General Population Cohort: Findings in the Prospective Lifelines-MINUTHE Study.

Several studies have found a U-shaped association between sodium intake and mortality. The increased mortality risk of low sodium intake has raised debates and hampers widespread acceptance of public health campaigns and dietary guidelines on reducing sodium intake. Whether the excess risk can be attributed to low sodium intake alone or concomitant inadequate intake of other relevant nutrients is unknown. We investigated whether concomitant low protein intake could explain the lower part of the U-shaped association of sodium intake with all-cause mortality. We included 1603 individuals aged between 60 and 75 years old from the gender- and socioeconomic status-balanced prospective Lifelines-MINUTHE cohort study. Using multivariable Cox regression analyses, we investigated the association of sodium intake (24 h urinary sodium excretion) with all-cause mortality, including the interaction with protein intake calculated from the Maroni formula. Mean intakes of sodium and protein were 3.9 ± 1.6 g/day and 1.1 ± 0.3 g/kg/day, respectively. After a median follow-up of 8.9 years, 125 individuals (7.8%) had died. The proportion of participants with insufficient protein intake (<0.8 g/kg/day) was inversely related to sodium intake (i.e., 23.3% in Q1 versus 2.8% in Q4, p < 0.001). We found an increased risk for mortality in both the highest quartile (Q4, >4.7 g/day; hazard ratio (HR) 1.74 (95% confidence interval (CI) 1.03-2.95)) and the lowest two quartiles of sodium intake (Q1, 0.7-2.8 g/day; 2.05 (1.16-3.62); p = 0.01 and Q2, 2.8-3.6 g/day; 1.85 (1.08-3.20); p = 0.03), compared with the third quartile of sodium intake (Q3, 3.6-4.7 g/day). This U-shaped association was significantly modified by protein intake (Pinteraction = 0.006), with the increased mortality risk of low sodium intake being reversed to the lowest mortality risk with concomitant high protein intake. In contrast, the increased mortality risk of low sodium intake was magnified by concomitant low protein intake. We found that a higher protein intake counteracts the increased mortality risk observed in subjects with a low sodium intake. In contrast, a joint low intake of sodium and protein is associated with an increased mortality risk, allegedly due to poor nutritional status. These findings support the guidelines that advocate a lower sodium intake, while highlighting the importance of recognizing overall nutritional status among older adults.

Limited Health Literacy and Its Associated Health Outcomes Among Adults With at Least 2 Atopic Diseases

Health literacy (HL) is essential for patients with multiple atopic diseases to improve their health, given the complexity of their disease and treatment regimens. To estimate the proportion of adults with multiple atopic diseases (at least 2 of atopic dermatitis, asthma, allergic rhinitis, and food allergy) in the Dutch general population and to evaluate the prevalence of limited HL, and its association with socioeconomic status (SES), lifestyle factors, and health-related quality of life (HR-QoL) in this patient population. This cross-sectional study was conducted within the Lifelines Cohort Study via sending an add-on digital questionnaire, including (among others) questions on atopic dermatitis, to all adult participants (n= 135,950) between February and May 2020. Data on asthma, allergic rhinitis, lifestyle factors, HR-QoL, and SES were extracted from baseline assessment between 2006 and 2013. Functional, communicative, and critical HL were measured by validated items from Chew and the Dutch Functional Communicative and Critical Health Literacy questionnaires between 2012 and 2016. Food allergy was measured by the Food Allergy Questionnaire between 2014 and2016. In total, 11.8% of the overall study population reported ever having multiple atopic diseases; of those, 23.6% reported having limited functional HL, with a higher prevalence among those with a low SES. Limited functional HL showed positive associations with smoking, obesity, chronic stress, a low diet quality, and decreased HR-QoL among subjects with multiple atopic diseases. We identified an HL deficit, and its association with a low SES and poor health outcomes among patients with multiple atopic diseases. Further research is warranted to utilize a more extensive assessment to measure HL and include more health outcomes, such as treatment adherence and disease control.

Testing the mood brightening hypothesis: Hedonic benefits of physical, outdoor, and social activities in people with anxiety, depression or both

BackgroundThe mood brightening hypothesis postulates that people with depressive symptoms report more positive affect (PA) and less negative affect (NA) than healthy controls after rewarding daily life activities. Whether mood brightening also occurs in people with anxiety symptoms remains unclear. This study examined effects of physical activity, being outdoors, and social activity on PA and NA across different levels of depression and anxiety symptoms in the general Dutch population. MethodsParticipants completed an electronic diary on their smartphone, thrice daily over 30 days, to assess activities and affect (n = 430; 22,086 assessments). We compared five groups based on their scores on the Depression, Anxiety and Stress Scales: asymptomatic participants, participants with mild symptoms of depression and/or anxiety, depression symptoms, anxiety symptoms, and comorbid depression and anxiety symptoms. Multilevel linear regression models with interaction terms were used to compare the association between activities and affect in these five groups. ResultsAll activities were associated with increased PA and reduced NA in all groups. We found a mood brightening effect in participants with depression, as physical activity and being outdoors were associated with reduced NA. Participants with depression had increased PA and reduced NA when in social company compared to asymptomatic participants. No mood brightening effects were observed in participants with anxiety or comorbid depression and anxiety. LimitationsOur sample included mainly women and highly educated subjects, which may limit the generalizability of our findings. ConclusionMood brightening is specific to depression, and typically stronger when in social company.

Quality of life of muscle-invasive bladder cancer patients after brachytherapy-based treatment: A cross-sectional study.

To determine the quality of life (QoL) of patients with muscle-invasive bladder cancer (MIBC) who underwent bladder-sparing treatment with high-dose-rate brachytherapy, and compare their QoL with an age-matched general Dutch population. We conducted a single-center, prospective, descriptive cross-sectional study. MIBC patients who underwent brachytherapy-based bladder sparing treatment in Arnhem, The Netherlands from January 2016 to June 2021, were requested to complete the following questionnaires: European Organization for Research and Treatment of Cancer (EORTC) generic (QLQ-C30), bladder cancer-specific (QLQ-BLM30), and expanded prostate cancer index composite bowel (EPIC-50). Mean scores were calculated and compared with general Dutch population. The mean global health status/QoL score of the treated patients was 80.6. High scores were noted in the functional scales, including physical (86.8), role (85.6), emotional (88.6), cognitive (88.3), and social functioning (88.9), while the main reported complains were related to fatigue (21.9) and urinary symptoms (25.1). Compared to the general Dutch population, significant differences were visible in global health status/QoL (80.6 vs. 75.7), pain (9.0 vs. 17.8), insomnia (23.3 vs. 15.2), and constipation (13.3 vs. 6.8). However, in no case did the mean score differ by more than ten points, which was considered clinically relevant. With a mean global health status/QoL score of 80.6, the patients after brachytherapy-based bladder sparing treatment have a good QoL. We found no clinically relevant difference in QoL comparing with an age-matched general Dutch population. The outcome strengthens the idea that this treatment option should be discussed with all patients eligible for brachytherapy-based treatment.

COVID-19 Incidence and Disease Course Among Patients at an Allergy Department.

Since the coronavirus pandemic in 2020, there is not much reported about the disease course of COVID-19 in patients with allergic diseases. The aim of this study was to investigate the cumulative incidence and severity of COVID-19 among patients from the allergy department compared with the general Dutch population and people from their household. We conducted a comparative longitudinal cohort study. In this study patients of the allergy department were included with their household members as a control group. Data from the beginning of the pandemic were systematically obtained through questionnaires by telephonic interviews and retrieved from electronic patient files between October 15, 2020 and January 29, 2021. Main outcomes were confirmed SARS-CoV-2 infection, disease duration, hospitalization, intensive care admission, and mortality. Questions regarding applied social distancing measures were inventoried as well. Three hundred and eighty nine patients (median age 39.1 (18.7-84.7) years, 69.9% female) and 441 household members (median age 42.0 (18.0-91.5), 44.1% female) were included. The cumulative COVID-19 incidence in patients was higher compared with the general population (10.5% vs 5.6%, P < .001). In total, 41 (10.5%) patients attending the allergy clinic compared to 38 (8.6%) household members were infected with SARS-CoV-2 (P = .407). Median disease duration was 11.0 (0.0-61.0) days in patients compared to 10.5(1.0-232.0) days in household members (P = .996). The cumulative COVID-19 incidence in patients from the allergy cohort was higher compared with the general Dutch population, but similar compared with household members. There was no difference in symptoms, disease duration, or hospitalization rate between the allergy cohort and their household members.

Alcohol use as a predictor of the course of major depressive disorder: a prospective population-based study.

There are indications that problematic alcohol use may negatively impact the course of major depressive disorder (MDD). However, most studies on alcohol use and adverse MDD outcomes are conducted amongst MDD populations with (severe) alcohol use disorder in psychiatric treatment settings. Therefore, it remains unclear whether these results can be generalised to the general population. In light of this, we examined the longitudinal relationship between alcohol use and MDD persistence after a 3-year follow-up amongst people with MDD from the general population. Data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a psychiatric epidemiological prospective study comprising four waves amongst the adult Dutch general population (n = 6.646). The study sample (n = 642) consisted of those with 12-month MDD who participated at the follow-up wave. The outcome was 12-month MDD persistence after the 3-year follow-up, which was assessed via the Composite International Diagnostic Interview version 3.0. Weekly alcohol consumption was operationalised as non-drinking (0 drinks), low-risk drinking (⩽7 drinks; reference), at-risk drinking (women 8-13 drinks, men 8-20 drinks) and high-risk drinking (women ⩾14, men ⩾21 drinks). We performed univariate and multiple logistic regression analyses, which were adjusted for various socio-demographic and health-related factors. The majority (67.4%) of the MDD sample were female, while the mean age was 47.1 years. Amongst these, 23.8% were non-drinkers, 52.0% were low-risk drinkers and 14.3% and 9.4% were at-risk and high-risk drinkers, respectively. Around one-quarter of the sample (23.6%) met the criteria for a persistent MDD after 3-year follow-up. No statistically significant association was found between alcohol use and MDD persistence, either for the crude model or the adjusted models. In comparison to low-risk drinking, the full adjusted model showed no statistically significant associations between MDD persistence and non-drinking (odds ratio (OR) = 1.15, p = 0.620), at-risk drinking (OR = 1.25, p = 0.423), or high-risk drinking (OR = 0.74, p = 0.501). Contrary to our expectations, our findings showed that alcohol use was not a predictor of MDD persistence after 3-year follow-up amongst people with MDD from the general population.

Late Effects in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation for Nonmalignant Diseases: Proxy- and Patient-Reported Outcomes

Survival rates in pediatric hematopoietic stem cell transplantation (HSCT) for nonmalignant diseases have improved due to advances in conditioning regimens, donor selection, and prophylaxis and treatment of infections and graft-versus-host disease. Insight into the long-term patient-reported outcomes (PROs) after pediatric HSCT for nonmalignant disease is lacking but essential for optimal shared decision making, counseling, and quality of care. The purpose of this research was to determine long-term patient-reported outcomes in allogeneic pediatric HSCT for nonmalignant diseases and to compare these results with Dutch reference data. This single-center cohort study evaluated PROs (PedsQL 4.0, PROMIS item banks), self- or proxy-reported, among patients at ≥2 years after pediatric allogeneic HSCT for nonmalignant disease. Mean scores were compared with those of the Dutch general population. Of 171 eligible patients, 119 participated, for a 70% response rate. The median patient age was 15.8 years (range, 2 to 49 years), and the median duration of follow-up was 8.7 years (range, 2 to 34 years). Indications for HSCT included inborn errors of immunity (n=41), hemoglobinopathies (n=37), and bone marrow failure (n=41). Compared with reference data, significantly lower scores were found in adolescents (age 13 to 17 years) on the Total, Physical Health, and School Functioning PedsQL subscales. Significantly more Sleep Disturbance was reported in children (age 8 to 18 years). On the other hand, significantly better scores were seen on PROMIS Fatigue (age 5 to 7 years) and Pain Interference (age 8 to 18 years) and, in adults (age 19 to 30 years), on Depressive Symptoms and Sleep Disturbance. This study showed better or comparable very long-term PROs in patients after pediatric HSCT for nonmalignant diseases compared with the reference population. Children and adolescents seem to be the most affected, indicating the need for supportive care to prevent impaired quality of life and, more importantly, to amplify their long-term well-being.

Daily life and psychosocial functioning of adults with congenital heart disease: a 40–53 years after surgery follow-up study

IntroductionNowadays, more than 90% of patients with congenital heart disease (CHD) reach adulthood. However, knowledge about their psychosocial functioning is limited.MethodsLongitudinal cohort study of patients (n = 204, mean age: 50 years, 46.1% female) who were operated during childhood (< 15 years) between 1968 and 1980 for one of the following diagnoses: atrial septal defect, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot or transposition of the great arteries. Psychosocial functioning was measured every 10 years, using standardized and validated questionnaires. Results were compared with the general Dutch population and over time.ResultsAfter a median follow-up of 45 [40–53] years adults with CHD had a significantly lower educational level, occupation level and employment rate, but better health-related quality of life and emotional functioning compared with normative data. Patients with moderate/severe defects reported significantly more self-perceived physical restrictions and lack of physical strength due to their CHD. Compared to 2011, in 2021 patients considered their CHD as more severe and they felt more often disadvantaged.ConclusionsOverall, despite a lower education, occupation level and employment rate, our sample of patients with CHD had a positive perception of their life and their psychosocial functioning was even better than the norm. Although the quality of life was very good, their view on their disease was more pessimistic than 10 years ago, especially for patients with moderate/severe CHD.Graphic abstract

The ADENO study: ADenomyosis and its Effect on Neonatal and Obstetric outcomes: a retrospective population-based study

Adenomyosis is a benign gynecologic condition arising from the uterine junctional zone. Recent studies suggest a relationship between adenomyosis and adverse obstetrical outcomes, but evidence remains conflicting. There is no large-scale study investigating obstetrical outcomes in women with adenomyosis using the gold standard of histopathologic diagnosis. This study aimed to investigate the prevalence of adverse obstetrical and neonatal outcomes in women with histopathologic adenomyosis and that of the general (Dutch) population. This retrospective population-based study used 2 Dutch national databases (Perined, the perinatal registry, and the nationwide pathology databank [Pathologisch Anatomisch Landelijk Geautomiseerd Archief], from 1995 to 2018) to compare obstetrical outcomes in women before histopathologic adenomyosis diagnosis to the general Dutch population without registered histopathologic adenomyosis. The adjusted odds ratios (95% confidence interval) were calculated for adverse obstetrical outcomes. The outcomes were adjusted for maternal age, parity, ethnicity, year of registered birth, induction of labor, hypertensive disorders in previous pregnancies, multiple gestation, and low socioeconomic status. The pregnancy outcomes of 7925 women with histopathologic adenomyosis were compared with that of 4,615,803 women without registered adenomyosis. When adjusted for confounders, women with adenomyosis had adjusted odds ratios of 1.37 (95% confidence interval, 1.25-1.50) for hypertensive disorders, 1.37 (95% confidence interval, 1.25-1.51) for preeclampsia, 1.15 (95% confidence interval, 1.07-1.25) for small-for-gestational-age infants, 1.54 (95% confidence interval, 1.41-1.68) for emergency cesarean delivery, 1.24 (95% confidence interval, 1.12-1.37) for failure to progress, 1.29 (95% confidence interval, 1.10-1.48) for placental retention, and 1.23 (95% confidence interval, 1.10-1.38) for postpartum hemorrhage. No increased risk of HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, placental abruption, or operative vaginal delivery or need for oxytocin stimulation was found. Women with a histopathologic diagnosis of adenomyosis showed an increased prevalence of hypertensive disorders of pregnancy and small-for-gestational-age infants, failure to progress in labor, and placental retention compared with the general population in previous pregnancies. This suggests that uterine (contractile) function in labor and during pregnancy is impaired in women with adenomyosis.

Prevalence and Impact of COVID-19 among Severe COPD Patients post Bronchoscopic Lung Volume Reduction Treatment with Endobronchial Valves

Background: The COVID-19 pandemic has a great impact on numberless aspects of our society. In our bronchoscopic lung volume reduction interventional program, we work with severe COPD patients on a daily basis. Objectives: We were interested in the prevalence and outcome of COVID-19, impact of the pandemic on daily life, and the vaccination coverage in our severe COPD patients who have been treated with one-way endobronchial valves. Method: A questionnaire, which consisted of questions related to the infection rate, treatment, and outcome of COVID-19 infections; feelings of anxiety related to the pandemic; adherence to preventive measures; and willingness to be vaccinated; was sent to our patients in June 2021. Results: The questionnaire was sent to 215 patients, and the response rate was 100%. The vaccination rate was 97% in our surveyed population. The majority of patients (63%) indicated that they were quite or very anxious to get infected with COVID-19. Twenty-five (11.5%) patients were diagnosed with COVID-19, with none of these patients having been vaccinated at the time of infection. The infection rate reported in this study is comparable to that of the general Dutch population. However, the hospital admission rate and mortality rates are higher. Conclusions: Our results show that the SARS-CoV-2 infection rate in severe COPD patients treated with endobronchial valves was comparable with the general population; however, the hospital admission and mortality rates were worse.

Exposure to Thioguanine During 117 Pregnancies in Women With Inflammatory Bowel Disease.

Safety of thioguanine in pregnant patients with inflammatory bowel disease [IBD] is sparsely recorded. This study was aimed to document the safety of thioguanine during pregnancy and birth. In this multicentre case series, IBD patients treated with thioguanine during pregnancy were included. Data regarding disease and medication history, pregnancy course, obstetric complications, and neonatal outcomes were collected. Data on 117 thioguanine-exposed pregnancies in 99 women were collected. Most [78%] had Crohn's disease and the mean age at delivery was 31 years. In 18 pregnancies [15%], IBD flared. Obstetric and infectious complications were seen in 15% [n = 17] and 7% [n = 8] of pregnancies, respectively. Ten pregnancies [8.5%] resulted in a first trimester miscarriage, one in a stillbirth at 22 weeks of gestational age and one in an induced abortion due to trisomy 21. In total, 109 neonates were born from 101 singleton pregnancies and four twin pregnancies. One child was born with a congenital abnormality [cleft palate]. In the singleton pregnancies, 10 children were born prematurely and 10 were born small for gestational age. Screening for myelosuppresion was performed in 16 neonates [14.7%]; two had anaemia in umbilical cord blood. All outcomes were comparable to either the general Dutch population or to data from three Dutch cohort studies on the use of conventional thiopurines in pregnant IBD patients. In this large case series, the use of thioguanine during pregnancy is not associated in excess with adverse maternal or neonatal outcomes.

Pelvic floor physical therapy in the treatment of chronic anal fissure (PAF trial): quality of life outcome.

Chronic anal fissure is one of the most common anorectal diseases and is associated with reduced quality of life. The aim of this study was to investigate the effects of pelvic floor physical therapy on quality of life in patients with chronic anal fissure using the Short-Form 36 Health Survey (RAND-36). Adult patients, with chronic anal fissure and concomitant pelvic floor dysfunction, such as dyssynergia and increased pelvic floor muscle tone, were recruited at the Proctos Clinic in the Netherlands, between December 2018 and July 2021 and randomly assigned to an intervention group, receiving 8weeks of pelvic floor physical therapy or assigned to a control group receiving postponed pelvic floor physical therapy (PAF trial). Quality of life and pain ratings were outcomes of the study and were measured at 8- and 20-week follow-up. One hundred patients (50 women and 50 men, median age 44.6years [range 19-68years]), completed the RAND-36 questionnaire and visual analog (VAS) pain scale score at admission. A significant improvement was found at 20-week follow-up in all domains of the RAND-36; physical functioning, pain, health change (p < 0.001); physical role, vitality, general health, social functioning, emotional role, mental health (p < 0.05). VAS pain was significantly reduced at 8weeks (mean estimated difference 1.98; 95% CI 1.55-2.42, p < 0.001) and remained significant at 20-week follow-up (p < 0.001). The difference between the groups as regards change in the mean pain intensity scores at 8weeks was 2.48 (95% CI -3.20 to -1.75; p < 0.001). Compared to the reference values of the general Dutch population, the patients in our study with a chronic anal fissure and pelvic floor dysfunction reported an impaired quality of life in 8 of 9 domains of the RAND-36. After treatment, significant lower scores were found in 2 out of 9 domains. The results of this study provide evidence that treatment by pelvic floor physical therapy improves quality of life and reduces pain, making it an important tool in management of chronic anal fissure and concomitant pelvic floor dysfunction.

Mortality in Pedigrees with Acute Intermittent Porphyria.

High mortality rates have been reported in historical cohorts of acute intermittent porphyria (AIP) patients. The mortality associated with (hydroxymethylbilane synthase) HMBS variant heterozygosity is unknown. This study estimates all-cause mortality in pedigrees with HMBS gene variants that cause AIP. We collected data on the lifespan of individuals in Dutch AIP pedigrees and performed analyses using the family tree mortality ratio method. This gave us standardized mortality ratios for these pedigrees compared to the Dutch general population as a primary outcome. Between 1810 and 2017, the overall mortality in these pedigrees was identical to that of the general Dutch population: (SMR 1.01, p = 0.441). However, compared with the general population the SMR was significantly higher in women aged 45−64 years (SMR 1.99, p = 0.00003), which was based on excess mortality between 1915 and 1964 (SMR 1.94, p < 0.00002). In men aged 70−74 years, the SMR was 1.55 (p = 0.0021), based on excess mortality that occurred between 1925 and 1964 (SMR 1.92, p = 0000000003). Overall, mortality from HMBS variant heterozygosity was not increased compared with the general population. Severe excess mortality occurred in young women and old men between 1915 and 1964. Heterozygotes reached a normal lifespan during the past half-century, in parallel with disease awareness and the prevention of new attacks through family counselling.

Projected costs of dementia and quality adjusted life years lost between 2020‐2050: a population‐based microsimulation study

AbstractBackgroundThe total cost of dementia has passed the $1 trillion mark in 2018 and dementia was the sixth most burdensome disease in 2016, causing an immense loss of quality adjusted life years (QALYs). Due to population ageing, costs and burden will further increase. We have quantified the expected future increase in costs and QALYs lost due to dementia.MethodWe used the microsimulation model MISCAN‐Dementia to simulate the life history and development of dementia of 10 million individuals. MISCAN‐Dementia synthesizes population‐based Rotterdam Study data with changes in demographics between birth cohorts from the early 1900s onwards. We assumed cost (from a societal perspective) and disutility values for patients and caregivers by dementia severity stage (MCI, mild, moderate, severe) and setting (home, institution). We determined costs and QALYs lost from 2020‐2050 for three different dementia risk trend scenarios: 1) stable age‐specific incidence, 2) linear decline by 13% per decade, 3) nonlinear declines averaging 13% per decade.ResultWe estimated total costs of dementia in 2020 at 13 billion euros and QALYs lost at 90,000 years for the general Dutch population, irrespective of the trend scenario. Assuming a stable age‐specific incidence resulted in costs of 29 billion euros and 207,000 QALYs lost in the year 2050, corresponding to a 124% increase compared to 2020. In contrast, the linearly declining trend resulted in 19 billion euros (95%CI: 15‐24) and 135,000 QALYs lost (95%CI: 106,000‐169,000) in 2050, translating into a 53% increase compared to 2020. Over the time horizon, costs and QALYs lost are roughly similar between dementia stages, although people spend more time with less severe disease (50% mild, 30% moderate, and 20% severe dementia). Similarly, costs of institutionalized care (30% of life years spent with dementia) are roughly equal to the costs while living at home (70% of life years spent with dementia).ConclusionBy 2050, the annual costs of dementia will increase to 19‐29 billion euros and dementia will cause 135,000‐207,000 QALYs lost per year. These projections highlight the need for policymakers and health care systems to prepare for an increase in the burden of dementia.

Automated mobile virtual reality cognitive behavior therapy for aviophobia in a natural setting: a randomized controlled trial.

Access to evidence-based psychological treatment is a challenge worldwide. We assessed the effectiveness of a fully automated aviophobia smartphone app treatment delivered in combination with a $5 virtual reality (VR) viewer. In total, 153 participants from the Dutch general population with aviophobia symptoms and smartphone access were randomized in a single-blind randomized controlled trial to either an automated VR cognitive behavior therapy (VR-CBT) app treatment condition (n = 77) or a wait-list control condition (n = 76). The VR-CBT app was delivered over a 6-week period in the participants' natural environment. Online self-report assessments were completed at baseline, post-treatment, at 3-month and at 12-month follow-up. The primary outcome measure was the Flight Anxiety Situations Questionnaire (FAS). Analyses were based on intent-to-treat. A significant reduction of aviophobia symptoms at post-test for the VR-CBT app compared with the control condition [p < 0.001; d = 0. 98 (95% CI 0.65-1.32)] was demonstrated. The dropout rate was 21%. Results were maintained at 3-month follow-up [within-group d = 1.14 (95% CI 0.46-1.81)] and at 12-month follow-up [within-group d = 1.12 (95% CI 0.46-1.79)]. Six participants reported adverse effects of cyber sickness symptoms. This study is the first to show that fully automated mobile VR-CBT therapy delivered in a natural setting can maintain long-term effectiveness in reducing aviophobia symptoms. In doing so, it offers an accessible and scalable evidence-based treatment solution that can be applied globally at a fraction of the cost of current treatment alternatives.

284 A genome-wide association study of hand eczema in the Dutch general population

Genetic effects play a role in hand eczema (HE), according to population-based twin and candidate gene studies. However, the genetic factors responsible for HE are not fully understood. Therefore, the aim of this study was to identify and characterize genetic loci associated with HE in Lifelines, a Dutch general population-based prospective cohort and biobank study. The primary analysis consisted of 2.789 cases with self-reported HE and 12.316 healthy controls without self-reported HE, eczema, atopic dermatitis (AD) and/or contact allergy.

Growth charts for Marfan syndrome in the Netherlands and analysis of genotype-phenotype relationships.

To optimize care for children with Marfan syndrome (MFS) in the Netherlands, Dutch MFS growth charts were constructed. Additionally, we aimed to investigate the effect of FBN1 variant type (haploinsufficiency [HI]/dominant negative [DN]) on growth, and compare MFS-related height increase across populations. Height and weight data of individuals with MFS aged 0-21 years were retrospectively collected. Generalized Additive Models for Location, Scale and Shape (GAMLSS) was used for growth chart modeling. To investigate genotype-phenotype relationships, FBN1 variant type was included as an independent variable in height-for-age and BMI-for-age models. MFS-related height increase was compared with that of previous MFS growth studies from the United States, Korea, and France. Height and weight data of 389 individuals with MFS were included (210 males). Height-for-age, BMI-for-age, and weight-for-height charts reflected the tall and slender MFS habitus throughout childhood. Mean increase in height of individuals with MFS compared with the general Dutch population was significantly lower than in the other three MFS populations compared to their reference populations. FBN1-HI variants were associated with taller height in both sexes, and decreased BMI in females (p-values <0.05). This Dutch MFS growth study broadens the notion that genetic background and MFS variant type (HI/DN) influence tall and slender stature in MFS.

Quality of Life and Personal Life Goals of Adult Sickle Cell Disease Patients after Curative Allogeneic Stem Cell Transplantation: A Mixed Methods Study

Introduction: Sickle cell disease (SCD) is associated with poor quality of life (QoL) and early mortality. In the Netherlands, allogeneic hematopoietic stem cell transplantation (HSCT) as curative treatment option for adult SCD patients was first introduced in 2018. A thorough understanding of the impact of undergoing HSCT on QoL is essential for health care professionals to be able to meet the needs of this patient population. Aim: To explore the perspectives of adult SCD patients on the impact of curative HSCT on physical, mental, and social health. Methods: Adult SCD patients who underwent HSCT at the Amsterdam UMC ≥ 1 year ago were eligible for this study. A mixed methods approach consisting of an exploratory qualitative design and a questionnaire component was used. All patients participated in a semi-structured interview on their experienced QoL and personal life goals. Interviews were audio recorded, transcribed, and coded using MAXQDA® software. Results were analyzed using Thematic Analysis. Additionally, participants completed a Patient Reported Outcome Measurement Information System (PROMIS®) questionnaire measuring 9 item banks on physical, mental, and social health at the time of the interview. Results of the PROMIS® questionnaires (T-scores) were related to reference T-scores of the general Dutch population using descriptive statistics (IBM SPSS statistics 28.0). Results: Ten SCD patients with a median age of 29.5 years (range 19-49) participated in the study between October 2021 and May 2022. The median time since HSCT was 2.7 years ranging from 1 to 3.5 years. Mean T-scores of all participants fell within normal limits for all 9 PROMIS® item banks, as compared to the Dutch general population (Table 1). However, T-scores varied between patients. Two patients with serious avascular bone necrosis (AVN), developed prior to HSCT, scored mild, moderate, or severe on ≥7 of 9 item banks. Another patient scored mild or moderate on all 3 mental health item banks. These differences between patients, as well as a general satisfaction with their current QoL despite having experienced physical and psychosocial difficulties were reflected in the outcome of the interviews. Eight central themes emerged from the Thematic Analysis: (1) pain, (2) physical wellbeing, (3) mental wellbeing, (4) perspective, (5) counseling/guidance, (6) education and work, (7) family and friends, and (8) activities and participation. These themes were categorized in mental, physical, and social health, following the PROMIS framework, and subsequently described based on four phases: before HSCT, HSCT - 1st year post transplantation, current situation, and future expectations. Most patients reported to experience improved physical, mental, and social health after HSCT and being able to set and achieve personal life goals. However, many participants also described an (ongoing) mental impact of having had SCD their whole life even after curation by HSCT. They expressed a clear need for psychological counseling before, during, and after HSCT. Furthermore, persistence of pain due to AVN had a negative influence on the perceived physical health of some patients. Several patients experienced a discrepancy between their expectations of HSCT and the outcome; either above- or below-expected. Conclusion: QoL of adult SCD patients who underwent curative HSCT seemed generally comparable to the Dutch general population; patients reported to experience improved QoL, and the ability to pursue personal life goals. However, the physical, mental, and social impact after curation can be extensive, ranging from positive to negative and differed between patients. Patients expressed a need for psychological support before, during, and after HSCT. Moreover, irreversible SCD-related organ damage can negatively influence the QoL of transplant recipients and patient expectations should be actively discussed by health care professionals before HSCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal