Electrocardiographic and morphological cardiac remodeling in competitive female athletes - a scoping review.

AIMS: To quantitatively analyse exercise-induced cardiac remodeling (EICR) data in female athletes. METHODS: This scoping review included from the databases Medline, Embase, and Google Scholar, peer-reviewed original English-language articles on female athlete-populations aged ≥18 years containing data on electrocardiography (ECG), echocardiography or cardiac magnetic resonance (CMR), and excluded athletes with cardiovascular conditions. From the extracted ECG data, we calculated prevalence percentages, and from the imaging data we compared the results with the upper reference limits of the general female population (URL). RESULTS: We included 31 articles comprising 4,896 female athletes, aged mean 22.2±4.6 years. On ECG (n=889), most prevalent findings were increased QRS voltages for LV hypertrophy (LVH, n=97), J-point elevation (JPE, n=108), and T-wave inversion (TWI, n=104). On echocardiography (n=4,644), we found increased mean of means BSA-indexed volumes for the LV 67.3 mL/m2 (95%CI 66.8-67.8; URL=61) and right ventricle (RV) 82.7 mL/m2 (95%CI 79.5-86.0; URL=74), while atrial volumes, septal wall thickness and LV mass were within the upper reference limits of the general population (URL). On CMR (n=309), the mean of means volumes of LA (62.0 mL/m2, 95%CI 58.8-65.2; URL=61), LV (103.4 mL/m2, 95%Ci 101.8-105.0; URL=96), and RV (105.3 mL/m2, 95%CI 103.3-110.6; URL=107.2) were >URL. CONCLUSION: Female athletes demonstrate distinct features of electrical (increased QRS voltages for LVH, JPE and TWI) and morphological EICR (biventricular dilatation). On CMR, LA was borderline dilated. Extensive studies on female athletes are needed to understand sex specific EICR.

Prolonged and repetitive exercise induces changes in the heart, both electrical (as seen on the ECG) and in size and shape (as seen on echocardiography or cardiac magnetic resonance imaging. These changes may include wall thickening and increase in chamber volumes. These changes are well-described in male athletes, but not in female athletes. This review highlights the changes in the hearts of healthy female athletes including electrical signs of increased cardiac muscle mass and of altered electrical reloading, and shape changes that include increases in left and right sided chamber volumes with normal ventricular wall thickness and mass.

Population-based incidence rates of 15 neuromuscular disorders: a nationwide capture-recapture study in the Netherlands.

Most neuromuscular disorders are rare, but as a group they are not. Nevertheless, epidemiological data of specific neuromuscular disorders are scarce, especially on the incidence. We applied a capture-recapture approach to a nationwide hospital-based dataset and a patients association-based dataset to estimate the annual incidence rates for fifteen neuromuscular disorders in the Netherlands. The annual incidence rates per 100,000 population varied from 0.03/100,000 (95% CI 0.00 ‒ 0.06) for glycogenosis type 5 to 0.9/100,000 (95% confidence interval 0.7 ‒ 1.0) for myotonic dystrophy type 1. The summed annual incidence rate of these disorders was 4.1 per 100,000 per population. Nine of the provided incidence rates were previously unavailable, three rates were similar to the rates in the literature, and three rates were generally higher compared to previous findings but with overlapping confidence intervals. This study provides nationwide incidence rates for fifteen neuromuscular disorders predominantly diagnosed in adult life, nine which were previously unavailable. The capture-recapture approach provided estimates of the total number of individuals with neuromuscular disorders. To complete the gaps in the knowledge of disease frequencies, there is a need for estimates from an automated, obligatory data collection system of diagnosed and newly diagnosed patients with neuromuscular disorders.

Living with facioscapulohumeral muscular dystrophy during the first two COVID-19 outbreaks: a repeated patient survey in the Netherlands.

BACKGROUND: Patients with facioscapulohumeral dystrophy (FSHD) suffer from slowly progressive muscle weakness. Approximately 20% of FSHD patients end up wheelchair-dependent. FSHD patients benefit from physical activity to maintain their muscle strength as much as possible. The impact of the COVID-19 pandemic on the health of FSHD patients was unknown. OBJECTIVE: This study assessed changes in daily care received, perceived psychosocial stress, and worsening of FSHD complaints in 2020. Furthermore, we compared COVID-19 infection incidence and severity of symptoms between FSHD patients and non-FSHD housemates. METHODS: Three online survey rounds were sent out to all adult participants of the Dutch FSHD registry regarding daily care received, perceived psychosocial stress, COVID-19 infection rate, and COVID-19 symptoms severity. They also included COVID-19-related questions regarding the participants' housemates, which served as control group. RESULTS: Participation rate was 210 (61%), 186 (54%), and 205 (59%) for survey 1, 2, and 3, respectively. Care reduction was reported by 42.7%, 40%, and 28.8% of the participants in the respective surveys. Perceived psychosocial stress increased in 44%, 30%, and 40% of the participants. Compared to the 197 non-FSHD housemates, the 213 FSHD patients reported more possibly COVID-19-related symptoms (27% vs. 39%, p = 0.017) of mostly minimal severity (63%). No difference in (possible) COVID-19 infection incidence rates was found (2.0% vs. 2.8%, p = 0.527). CONCLUSIONS: The COVID-19 pandemic negatively impacted care received and increased perceived psychosocial stress in FSHD patients. However, COVID-19 infection incidence in FSHD patients was similar to their non-FSHD housemates.

Long-term cause of death patterns and mode of breast cancer detection in The Netherlands, 2004-2019.

OBJECTIVE: Early detection through mammographic screening and various treatment modalities of cancer may have changed life expectancy and cause-specific mortality of breast cancer patients. We aimed to determine the long-term cause of death patterns in screening-detected patients and clinically diagnosed patients in the Netherlands compared with the general population. METHODS: Using data from the Netherlands Cancer Registry and Statistics Netherlands of around 26,000 women, aged 50-75 at diagnosis and surgically treated for invasive breast cancer in 2004-2008, we compared patients with screening-detected and clinically diagnosed cancer for major causes of death until 2020. The expected number of all-cause and cause-specific deaths was calculated using rates of the general population. RESULTS: During the follow-up period, 4310 women died. The age-standardised all-cause mortality ratio for the screening-detected cancer group was 1.41 (95% confidence interval (95% CI), 1.37-1.46). A higher mortality ratio was observed for patients with clinically detected cancer: 2.27 (95% CI, 2.19-2.34). The observed versus expected breast cancer mortality ratio in the screening-detected patient group was 8.92 (95% CI, 8.45-9.40) and 20.23 (19.38-21.09) in the clinical group. Excess mortality was found for lung cancer in both patient groups, and small elevations for circulatory and respiratory disease in the clinically detected group. CONCLUSION: Our results indicate that for the screening group no other causes of death but breast and lung cancer were prominent compared with the general population. The clinical group showed excess mortality for some other causes of death as well, suggesting a less healthy group compared with the general population.

Quality of athlete screening for high-risk cardiovascular conditions-A systematic review.

BACKGROUND: Sudden cardiac death (SCD) is the leading medical cause of death in athletes. To prevent SCD, screening for high-risk cardiovascular conditions (HRCC) is recommended. Screening strategies are based on a limited number of studies and expert consensus. However, evidence and efficacy of athlete HRCC screening is unclear. OBJECTIVE: To determine methodological quality and quality of evidence of athlete screening, and screening efficacy to detect HRCC in a systematic review. METHODS: We performed a systematic search of Medline, Embase, Scopus and Cochrane Library up to June 2021. We included articles containing original data of athlete cardiovascular screening, providing details of screening strategies, test results and HRCC detection. We assessed methodological quality of the included articles by QUADAS-2, quality of evidence of athlete HRCC screening by GRADE, and athlete HRCC screening efficacy by SWiM. RESULTS: Of 2720 citations, we included 33 articles (1991-2018), comprising 82 417 athletes (26.7% elite, 73.4% competitive, 21.7% women, 75.2% aged ≤35). Methodological quality was 'very low' (33 articles), caused by absence of data blinding and inappropriate statistical analysis. Quality of evidence was 'very low' (33 articles), due to observational designs and population heterogeneity. Screening efficacy could not be reliably established. The prevalence of HRCC was 0.43% with false positive rate (FPR) 13.0%. CONCLUSIONS: Methodological quality and quality of evidence on athlete screening are suboptimal. Efficacy could not be reliably established. The prevalence of screen detected HRCC was very low and FPR high. Given the limitations of the evidence, individual recommendations need to be prudent.

Value of routine follow-up in oropharyngeal squamous cell cancer patients treated with curative intent.

BACKGROUND: The major goal of routine follow-up in oropharyngeal squamous cell carcinoma (OPSCC) patients is the asymptomatic detection of new disease in order to improve survival. This study evaluated the effect of routine follow-up on overall survival (OS). METHODS: A retrospective cohort of 307 consecutive OPSCC patients treated with curative intent between 2006 and 2012 was analyzed. The effectiveness of routine follow-up was studied by comparing treatment-intent and OS in patients with asymptomatically versus symptomatically detected new disease. RESULTS: Three- and five-year risks of new disease were 29% (95% CI: 24-34) and 33% (95% CI: 27-39). Of the 81 patients with locoregional recurrence or second primary head and neck cancer, 8 (10%) were detected asymptomatically with no difference in OS with those detected with symptoms. CONCLUSIONS: Asymptomatic detection of new disease during routine visits was not associated with improved OS. The focus of follow-up should be on providing psychosocial care and rehabilitation.

Trends in three major histological subtypes of cutaneous melanoma in the Netherlands between 1989 and 2016.

BACKGROUND: Time trend analysis of cutaneous melanoma (CM) mortality in fair skin populations shows both a gradual decrease and/or an increase. To explain these differences, we analyzed long-term time trends in the incidence of the most common histological subtypes of CM: superficial spreading melanoma (SSM), lentigo maligna melanoma (LMM), and nodular melanoma (NM). METHODS: Using data from the Netherlands Cancer Registry and Statistics Netherlands, the number and rates of cases diagnosed with SSM, LLM, and NM from 1989 to 2016 were analyzed by age, calendar period, and birth cohort of people born in successive periods from 1925 to 1973. RESULTS: Primary CM was diagnosed in 52,000 men and 66,588 women in the study period. The annual age-standardized incidence rate increased three-fold from 14 to 42 per 100,000 person-years. The most common subtype was SSM (50%), followed by LMM (23%) and NM (14%). Age-specific subtype rates showed an upward trend over time for both men and women. Younger birth cohorts had higher rates of SSM and LMM diagnosis than older birth cohorts. This birth cohort pattern was not observed for NM. CONCLUSIONS: We observed a strong increase in the melanoma epidemic curves in the light-skinned Dutch population over the last three decades. This increase is explained by younger generations having higher rates of SSM and LMM than older generations.

Predicting readiness for return to sport and performance after anterior cruciate ligament reconstruction rehabilitation.

BACKGROUND: Determining readiness to return to sport after anterior cruciate ligament (ACL) reconstruction is challenging. OBJECTIVES: To develop models to predict initial (directly after rehabilitation) and sustainable (one year after rehabilitation) return to sport and performance in individuals after ACL reconstruction. METHODS: We conducted a multicentre, prospective cohort study and included 208 participants. Potential predictors - demographics, pain, effusion, knee extension, muscle strength tests, jump tasks and three sport-specific questionnaires - were measured at the end of rehabilitation and 12 months post discharge from rehabilitation. Four prediction models were developed using backward logistic regression. All models were internally validated by bootstrapping. RESULTS: All 4 models shared 3 predictors: the participant's goal to return to their pre-injury level of sport, the participant's psychological readiness and ACL injury on the non-dominant leg. Another predictor for initial return to sport was no knee valgus, and, for sustainable return to sport, the single-leg side hop. Bootstrapping shrinkage factor was between 0.91 and 0.95, therefore the models' properties were similar before and after internal validation. The areas under the curve of the models ranged from 0.74 to 0.86. Nagelkerke's R2 varied from 0.23 to 0.43 and the Hosmer-Lemeshow test results varied from 2.7 (p = 0.95) to 8.2 (p = 0.41). CONCLUSION: Initial and sustainable return to sport and performance after anterior cruciate ligament reconstruction rehabilitation can be easily predicted by the sport goal formulated by the individual, the individual's psychological readiness, and whether the affected leg is the dominant or non-dominant leg.

Geriatric Falls: A Registry-Based Study in the Netherlands.

BACKGROUND: Falls in people 65 years and older evaluated in the emergency department are increasing. Of all unintentional injury-related deaths among older people, 55% are due to falls. The impact of falls, especially concerning Dutch older people with the highest proportion of living independently worldwide, is unclear. OBJECTIVE: To identify the influence of age, gender, health conditions, and type of fall on the severity of injury, hospital length of stay, mortality, and discharge destination. METHODS: A total number of 6,084 patients from a comprehensive regional trauma care system, 65 years and older and hospitalized after a fall, were included. Groups were compared for patient-related factors and multivariable logistic regression analysis to explore the consequences. RESULTS: Mean age was 82 years (SD = 8.3), and 70% were female. Most falls (66.4%) were due to "slipping and tripping" or "falls on the same level," 57.4% had Injury Severity Scores between 9 and 12, and 43.3% were discharged home. Higher age and type of fall increased the likelihood of severe injuries. Men experienced shorter hospital stays than women and were less frequently discharged home. Mortality was higher in males (10.8%) than in females (6.7%) and increased with the American Society of Anesthesiologists scores for preexisting health conditions. CONCLUSION: Advanced age, gender, type of fall, and prior health status play a significant role in the severity of injuries, length of hospital stay, 30-day mortality, and higher discharge destination to care homes in older people hospitalized after a fall.

Quantifying the duration of the preclinical detectable phase in cancer screening: a systematic review.

OBJECTIVES: The aim of this study was to provide an overview of published mathematical estimation approaches to quantify the duration of the preclinical detectable phase (PCDP) using data from cancer screening programs. METHODS: A systematic search of PubMed and Embase was conducted for original studies presenting mathematical approaches using screening data. The studies were categorized by mathematical approach, data source, and assumptions made. Furthermore, estimates of the duration of the PCDP of breast and colorectal cancer were reported per study population. RESULTS: From 689 publications, 34 estimation methods were included. Five distinct types of mathematical estimation approaches were identified: prevalence-to-incidence ratio (n=8), maximum likelihood estimation (n=16), expectation-maximization algorithm (n=1), regression of observed on expected (n=6) and Bayesian Markov-chain Monte Carlo estimation (n=5). Fourteen studies used data from both screened and unscreened populations, whereas 19 studies included only information from a screened population. Estimates of the duration of the PCDP varied between 2 years and 7 years for breast cancer in the Health Insurance Plan study (annual mammography and clinical breast examinations in women aged 40-64 years) and 2 years and 5 years for colorectal cancer in the Calvados study (a guaiac fecal occult blood test in men and women aged 45-74 years). CONCLUSIONS: Different types of mathematical approaches lead to different estimates of the PCDP duration. We advise researchers to use the method that matches the data available, and to use multiple methods for estimation when possible, since no method is perfect.

Trends and projections in the incidence of oesophageal cancer in the Netherlands: An age-period-cohort analysis from 1989 to 2041.

In Western populations, the incidence of oesophageal squamous cell carcinoma (OSCC) has been declining, whereas the incidence of oesophageal adenocarcinoma (OAC) has been increasing. Our study examines temporal trends in the incidence of oesophageal cancer in the Netherlands between 1989 and 2016, in addition to predicting future trends through 2041. Data from the Netherlands Cancer Registry and Statistics Netherlands were collected to obtain incidence trends of OSCC and OAC for the period 1989 to 2016. Age-period-cohort (APC) modelling was used to estimate the contribution of age, calendar period and birth cohort on the observed incidence trends. To predict the future numbers of new cases of both OSCC and OAC from 2017 to 2041, log-linear APC models were fitted to the trends of 1989 to 2016. The age-standardised incidence rates of OSCC have decreased slightly for men and increased slightly for women. In contrast, a marked increase in the incidence of OAC was observed, ranging from 2.8 per 100 000 persons in 1989 to 10.1 in 2016. This increase in OAC incidence was more prominent in men, and it will result in an increased risk of OAC for successive generations. Future projections indicate that the incidence of OAC will further increase to 13.1 per 100 000 persons in 2037 to 2041, meaning that there will be 13 259 cases of OAC in 2037 to 2041, as compared to 9386 diagnoses in 2017 to 2021. The changing epidemiologic trends in oesophageal cancer in the Netherlands should be reflected in the development of prevention, early detection and treatment strategies.

Immediate Bystander Cardiopulmonary Resuscitation to Sudden Cardiac Arrest During Sports is Associated with Improved Survival-a Video Analysis.

BACKGROUND: Sudden cardiac arrest (SCA) during sports can be the first symptom of yet undetected cardiovascular conditions. Immediate chest compressions and early defibrillation offer SCA victims the best chance of survival, which requires prompt bystander cardiopulmonary resuscitation (CPR). AIMS: To determine the effect of rapid bystander CPR to SCA during sports by searching for and analyzing videos of these SCA/SCD events from the internet. METHODS: We searched images.google.com , video.google.com , and YouTube.com , and included any camera-witnessed non-traumatic SCA during sports. The rapidity of starting bystander chest compressions and defibrillation was classified as < 3, 3-5, or > 5 min. RESULTS: We identified and included 29 victims of average age 27.6 ± 8.5 years. Twenty-eight were males, 23 performed at an elite level, and 18 participated in soccer. Bystander CPR < 3 min (7/29) or 3-5 min (1/29) and defibrillation < 3 min was associated with 100% survival. Not performing chest compressions and defibrillation was associated with death (14/29), and > 5 min delay of intervention with worse outcome (death 4/29, severe neurologic dysfunction 1/29). CONCLUSIONS: Analysis of internet videos showed that immediate bystander CPR to non-traumatic SCA during sports was associated with improved survival. This suggests that immediate chest compressions and early defibrillation are crucially important in SCA during sport, as they are in other settings. Optimal use of both will most likely result in survival. Most videos showing recent events did not show an improvement in the proportion of athletes who received early resuscitation, suggesting that the problem of cardiac arrest during sports activity is poorly recognized.

Second primary tumours after squamous cell carcinoma of the oral cavity.

INTRODUCTION: The aim of this study was to determine the incidence, location and timing of second primary tumours (SPT) after diagnosis of oral squamous cell carcinoma (OSCC) and relate the risk of SPT to that after head and neck squamous cell carcinoma (HNSCC) and the risks of those tumours in the general population in order to assess the need for a separate follow-up programme for OSCC patients and to aid development of an evidence-based and individualized follow-up programme for OSCC patients. MATERIALS AND METHODS: All patients diagnosed with OSCC or HNSCC in the Netherlands in 1991-2015 were selected from the Netherlands Cancer Registry. Cumulative incidence rates and Standardized Incidence Ratios (SIR) were calculated. Analyses were stratified by incidence period and age at primary diagnosis of the index tumour, follow-up time, and site of the SPT. RESULTS: We included 11263 patients with OSCC from a population of 34244 patients with HNSCC, of which the median follow-up time was 4.0 years. OSCC SPT develop in different patterns and at different locations than after HNSCC. The 5-year risk of SPT and SIR (95% confidence intervals) were respectively 0.13 (0.13-0.14) and 3.0 (2.9-3.1) for OSCC. The risk of a SPT was continuous over follow-up time and calendar period but decreased with an increasing age at diagnosis of the index tumour up to the age of 75 and there were differences in sites of SPT. CONCLUSION: A specific follow-up protocol for OSCC is needed, which can be individualized on the basis of, among others, age.

Trends and projections in cutaneous melanoma death in the Netherlands from 1950 to 2045.

ABSTRACT: Child sun protection has recently been linked to the future disappearance of fatal melanoma in adults in successive generations. In the Netherlands, however, mortality rates from melanoma have increased gradually from the 1950s, with some indication of stabilisation since 2010, which may be compatible with a birth cohort effect by sun-protective measures and screening. To study the trajectories ahead a trend analysis was applied. Numbers of people with cutaneous melanoma as underlying cause of death from 1950 to 2018 and population data were derived from Statistics Netherlands. A graphical approach was used to explore trends in mortality by age, calendar period, and cohorts born in the successive periods of 1889 to 1979. Age-period-cohort modelling outcomes and population forecasts provided projections of mortality until 2045. Based on 24,151 cases of melanoma death (13,256 men, 10,895 women), age-standardised mortality rates were similar from 1950 to 1989 for both genders, and increased thereafter more in men. The age-curve patterns changed gradually towards higher death rates at older age, implying the existence of a birth cohort effect. The age-period-cohort models showed an increase in melanoma mortality rates in successive generations. For women, the birth cohort effect plateaued for generations born since the mid-1980s. The projected total mortality number was predicted to rise in the next 3 decades.It is concluded that a small future decline of mortality in younger generations can be expected in the Netherlands, but mortality is still rising for the total population.

Correlates of Total and domain-specific Sedentary behavior: a cross-sectional study in Dutch adults.

BACKGROUND: Sedentary behavior (SB) is associated with increased risks of detrimental health outcomes. Few studies have explored correlates of SB in physically active individuals. Furthermore, SB correlates may depend on settings of SB, such as occupation, transportation and leisure time sitting. This study aims to identify subject-, lifestyle- and health-related correlates for total SB and different SB domains: transportation, occupation, and leisure time. METHODS: Dutch participants were recruited between June, 2015 and December, 2016. Participant characteristics (i.e. age, sex, weight, height, marital status, education level, employment), lifestyle (sleep, smoking, alcohol consumption, physical activity) and medical history were collected via an online questionnaire. SB was assessed using the Sedentary Behavior Questionnaire and estimated for 9 different activities during weekdays and weekend days. Logistic regression was used to calculate odds ratios and 95% confidence intervals for the association between correlates and SB. Total SB was dichotomized at > 8 h/day and > 10 h/day, and being sedentary during transportation, occupation and leisure time at the 75th percentile (60 min/day, 275 min/day and 410 min/day, respectively). RESULTS: In total, 8471 participants (median age 55, 55% men) were included of whom 86% met the physical activity guidelines. Median SB was 9.1 h/day (Q25 6.3-Q75 12.0) during weekdays and 7.4 h/day (Q25 5.5-Q75 9.5) during weekend days. SB was most prevalent during leisure time (5.3 h/day; Q25 3.9-Q75 6.8), followed by occupation (2 h/day; Q25 0.1-Q75 4.6) and transportation (0.5 h/day; Q25 0.2-Q75 1.0). Younger age, male sex, being unmarried, higher education, employment and higher BMI were significantly related to higher levels of total SB. Younger age, male sex, employment, and higher BMI increased the odds for high SB volumes during occupation and transportation. Higher education, being unmarried and smoking status were positively associated with high volumes of occupational SB only, whereas older age, being unmarried, unemployment, higher BMI and poor health were positively linked to leisure time SB. CONCLUSIONS: SB is highly prevalent in physically active individuals, with SB during leisure time as the most important contributor. Correlates for high volumes of SB vary substantially across SB domains, emphasizing the difficulty to target this unhealthy lifestyle.

Time patterns of recurrence and second primary tumors in a large cohort of patients treated for oral cavity cancer.

INTRODUCTION: Routine follow-up after curative treatment of patients with oral squamous cell carcinoma (OSCC) is common practice considering the high risk of second primaries and recurrences (ie second events). Current guidelines advocate a follow-up period of at least 5 years. The recommendations are not evidence-based and benefits are unclear. This is even more so for follow-up after a second event. To facilitate the development of an evidence- and personalized follow-up program for OSCC, we investigated the course of time until the second and subsequent events and studied the risk factors related to these events. MATERIALS AND METHODS: We retrospectively studied 594 OSCC patients treated with curative intent at the Head and Neck Cancer Unit of the Radboud University Medical Centre from 2000 to 2012. Risk of recurrence was calculated addressing death from intercurrent diseases as competing event. RESULTS: The 1-, 5- and 10-year cumulative risks of a second event were 17% (95% CI:14%;20%), 30% (95% CI:26%;33%), and 37% (95% CI:32%;41%). Almost all locoregional recurrences occurred in the first 2 years after treatment. The incidence of second primary tumors was relatively stable over the years. The time pattern of presentation of third events was similar. DISCUSSION: Our findings support a follow-up time of 2 years after curative treatment for OSCC. Based on the risk of recurrence there is no indication for a different follow-up protocol after first and second events. After 2 years, follow-up should be tailored to the individual needs of patients for supportive care, and monitoring of late side-effects of treatment.

Cardiovascular risk in 159 934 frequent blood donors while addressing the healthy donor effect.

OBJECTIVE: To investigate whether regular blood donation decreases cardiovascular risk. METHODS: All 159 934 Dutch whole-blood donors with an active donation career of at least 10 years were categorised into sex-specific donation tertiles based on the number of donations during this 10-year qualification period. Cardiovascular endpoints were based on hospital discharge diagnoses and death certificates from Dutch Hospital Data and Statistics Netherlands and occurring after the 10-year qualification period. Cox regression was used to estimate the age-adjusted and starting year-adjusted hazard rate ratio (HRR). RESULTS: Female high-frequency blood donors had a reduced cardiovascular morbidity (HRR=0.91, 95% CI 0.85 to 0.98) compared with low-frequency blood donors. No effect was observed in men (HRR=1.00, 95% CI 0.95 to 1.05). To rule out a residual healthy donor effect (HDE), additional sensitivity analyses using a 5-year qualification period were conducted. The results supported the absence of a residual HDE. CONCLUSIONS: This study showed a protective effect of long-term, high-frequency blood donation against cardiovascular disease. This effect was only observed in women and not in men.

Assessment of medication use during pregnancy by Web-based questionnaires, pharmacy records and serum screening.

OBJECTIVE: To compare assessment of early pregnancy medication exposure using three methods of data collection. METHODS: Serum samples were obtained from 752 women participating in the PRegnancy and Infant DEvelopment (PRIDE) Study before gestational week 17. For 52 women using medication at the date of blood sampling according to Web-based questionnaires or pharmacy records, we analysed serum samples using untargeted liquid chromatography time-of-flight spectrometry. RESULTS: Medication was detected in 18 serum samples (35%). Medications taken orally for chronic conditions reported in the questionnaire were detected in serum and vice versa. Pharmacy records did not identify additional exposed women, but missed exposure in 5 women mainly due to unavailability. We observed substantial discordance between the three methods for inhaled medication, dermatological preparations, and medications for short-term use, which went often undetected in serum. CONCLUSIONS: It remains challenging to assess medication use in large-scale studies as no 'gold standard' is currently available.

Genotype-Guided Thiopurine Dosing Does not Lead to Additional Costs in Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Decreased thiopurine S-methyltransferase [TPMT] enzyme activity increases the risk of haematological adverse drug reactions [ADRs] in patients treated with thiopurines. Clinical studies have shown that in patients with inflammatory bowel disease [IBD], pharmacogenetic TPMT-guided thiopurine treatment reduces this risk of ADRs. The aim of this study was to investigate whether this intervention impacts on healthcare costs and/or quality of life. METHODS: An a priori defined cost-effectiveness analysis was conducted in the Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory bowel disease Clinics [TOPIC] trial, a randomized controlled trial performed in 30 Dutch hospitals. Patients diagnosed with IBD [age ≥18 years] were randomly assigned to the intervention [i.e. pre-treatment genotyping] or control group. Total costs in terms of volumes of care, and effects in quality-adjusted life years [QALYs], based on EuroQol-5D3L utility scores, were measured for 20 weeks. Mean incremental cost savings and QALYs with confidence intervals were calculated using non-parametric bootstrapping with 1000 replications. RESULTS: The intervention group consisted of 381 patients and the control group 347 patients. The mean incremental cost savings were €52 per patient [95% percentiles -682, 569]. Mean incremental QALYs were 0.001 [95% percentiles -0.009, 0.010]. Sensitivity analysis showed that the results were robust for potential change in costs of screening, costs of biologicals and costs associated with productivity loss. CONCLUSIONS: Genotype-guided thiopurine treatment in IBD patients reduced the risk of ADRs among patients carrying a TPMT variant, without increasing overall healthcare costs and resulting in comparable quality of life, as compared to standard treatment.

Risk factors for incidentally detected and symptomatic angiodysplasias: a case-control study with the general population as reference.

BACKGROUND: There is no literature on risk factors for incidentally found angiodysplasias. In clinical practice, endoscopists may defer treatment owing to uncertainty about a causal role of any found angiodysplasia and overt or occult bleeding. The objective is to identify risk factors that distinguish incidental angiodysplasias from angiodysplasias that are the cause of symptomatic bleeding. PARTICIPANTS AND METHODS: A case-control study was conducted to compare angiodysplasia groups and a random sample from the general population. Patients with angiodysplasia were diagnosed between 2010 and 2015. Controls were from a 2005 population survey. Determinants were demographics, past medical history, lifestyle, medication and angiodysplasia characteristics. Multivariable logistic regression analyses were performed to identify independent risk factors. RESULTS: A total of 270 (59% men, mean age 65 years) patients with angiodysplasia and 5594 (46% men, mean age 58 years) controls were included in this study. Independent risk factors for incidental angiodysplasias are male sex [odds ratio (OR): 1.6; 95% confidence interval (CI): 1.02-2.6], thyroid dysfunction (OR: 4.1; 95% CI: 2.0-8.4), autoimmune disease (OR: 2.3; 95% CI: 1.2-4.1), chronic obstructive pulmonary disease (OR: 1.8; 95% CI: 1.0-3.2), and blood thinners (OR: 2.8; 95% CI: 1.6-4.8). Besides angiodysplasia characteristics, factors independently associated with symptomatic angiodysplasias are increased age (OR: 1.7/10 years age band; 95% CI: 1.3-2.5), valvular heart disease (OR: 10.4; 95% CI: 1.6-69.2), diabetes mellitus (OR: 2.6; 95% CI: 1.03-6.7) and hyperlipidemia (OR: 3.7; 95% CI: 1.1-12.1). CONCLUSION: The risk factor profile for incidental angiodysplasias differs from symptomatic angiodysplasias and is more profound for the latter. This knowledge could help endoscopists in the decision-making process to treat an endoscopically detected angiodysplasia.