We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the ...University College London sample collections with successful genotyping for 372,193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P=1.66 x 10(-7)) and tetraspanin-8 (TSPAN8; P=6.11 x 10(-7)). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P=2.04 x 10(-8), TSPAN8; P=7.57 x 10(-7) and EGFR; P=8.36 x 10(-8)). For replication, we genotyped 304 SNPs in family-based NIMH samples (n=409 trios) and University of Edinburgh case-control samples (n=365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.
Highlights ► Real Time Medication Monitoring provides detailed and accurate data on patients’ medication use. ► SMS reminders sent only if patients forget medication improve adherence to oral ...antidiabetics. ► SMS reminders are appreciated by patients. ► Real Time Medication Monitoring with SMS reminders provide opportunities for other patient groups as well.
Objective
To investigate the safety and effects of a restrictive red blood cell (RBC) transfusion strategy in pediatric cardiac surgery patients.
Design
Randomized controlled trial.
Setting
Pediatric ...ICU in an academic tertiary care center, Leiden University Medical Center, Leiden, The Netherlands.
Patients
One hundred seven patients with non-cyanotic congenital heart defects between 6 weeks and 6 years of age. One hundred three patients underwent corrective surgery on cardiopulmonary bypass.
Interventions
Prior to surgery patients were randomly assigned to one of two groups with specific RBC transfusion thresholds: Hb 10.8 g/dl (6.8 mmol/l) and Hb 8.0 g/dl (5.0 mmol/l).
Measurements
Length of stay in hospital (primary outcome), length of stay in PICU, duration of ventilation (secondary outcome), incidence of adverse events and complications related to randomization (intention to treat analysis).
Results
In the restrictive transfusion group, mean volume of transfused RBC was 186 (±70) ml per patient and in the liberal transfusion group 258 (±87) ml per patient, (95 % CI 40.6–104.6),
p
< 0.001. Length of hospital stay was shorter in patients with a restrictive RBC transfusion strategy: median 8 (IQR 7–11) vs. 9 (IQR 7–14) days,
p
= 0.047. All other outcome measures and incidence of adverse effects were equal in both RBC transfusion groups. Cost of blood products for the liberal transfusion group was 438.35 (±203.39) vs. 316.27 (±189.96) euros (95 % CI 46.61–197.51) per patient in the restrictive transfusion group,
p
= 0.002.
Conclusions
For patients with a non-cyanotic congenital heart defect undergoing elective cardiac surgery, a restrictive RBC transfusion policy (threshold of Hb 8.0 g/dl) during the entire perioperative period is safe, leads to a shorter hospital stay and is less expensive.
Aims
To investigate short‐ and long‐term effects of real‐time monitoring medication use combined with short message service (SMS) reminders for missed doses on refill adherence to oral anti‐diabetic ...medication.
Methods
A randomized controlled trial with two intervention groups and one control group involving 161 participants with Type 2 diabetes with suboptimal adherence. For 6 months, participants in the SMS group (n = 56) were monitored and received SMS reminders if they missed their medication. Participants in the non‐SMS group (n = 48) were only monitored. The control group (n = 57) was not exposed to any intervention. Primary outcome measure was refill adherence to oral anti‐diabetic medication. Multi‐level regression analyses were performed to examine intervention effects on adherence between and within groups after 1 and 2 years of follow‐up.
Results
At baseline, mean refill adherence was comparable between the groups. After 1 year, adherence in the SMS group was significantly higher than in the control group (79.5% vs. 64.5%; P < 0.001) and showed a significant improvement from baseline (+16.3%; P < 0.001). Mean adherence in the non‐SMS group reached 73.1% (+7.3%; P < 0.05), but did not differ from the control group (P = 0.06). After 2 years, the improved adherence in the SMS group persisted and remained significantly higher than in the control group (80.4% vs. 68.4%; P < .01), contrary to the non‐SMS group whose adherence approached baseline level again (65.5%).
Conclusions
This study shows the long‐term effectiveness of real‐time medication monitoring combined with SMS reminders in improving refill adherence. This new reminder system can strengthen the self‐management of people with diabetes.
What's new?
The innovative real‐time medication monitoring system evaluated in this study is the first to provide the opportunity to intervene only when patients forget to take their medication.
This study showed that receiving short message service (SMS) reminders only when a dose is missed results in a higher refill adherence, and is the first to demonstrate long‐term effectiveness of electronic reminders on adherence.
The real‐time medication monitoring reminder system can especially provide support for people who have problems taking their medication because of forgetfulness.
This system can also strengthen a person's self‐management, as medication management is an important aspect of self‐management.
A high sedentary time is associated with increased mortality risk. Previous studies indicate that replacement of sedentary time with light- and moderate-to-vigorous physical activity attenuates the ...risk for adverse outcomes and improves cardiovascular risk factors. Patients with cardiovascular disease are more sedentary compared to the general population, while daily time spent sedentary remains high following contemporary cardiac rehabilitation programmes. This clinical trial investigated the effectiveness of a sedentary behaviour intervention as a personalised secondary prevention strategy (SIT LESS) on changes in sedentary time among patients with coronary artery disease participating in cardiac rehabilitation.
Patients were randomised to usual care (n = 104) or SIT LESS (n = 108). Both groups received a comprehensive 12-week centre-based cardiac rehabilitation programme with face-to-face consultations and supervised exercise sessions, whereas SIT LESS participants additionally received a 12-week, nurse-delivered, hybrid behaviour change intervention in combination with a pocket-worn activity tracker connected to a smartphone application to continuously monitor sedentary time. Primary outcome was the change in device-based sedentary time between pre- to post-rehabilitation. Changes in sedentary time characteristics (prevalence of prolonged sedentary bouts and proportion of patients with sedentary time ≥ 9.5 h/day); time spent in light-intensity and moderate-to-vigorous physical activity; step count; quality of life; competencies for self-management; and cardiovascular risk score were assessed as secondary outcomes.
Patients (77% male) were 63 ± 10 years and primarily diagnosed with myocardial infarction (78%). Sedentary time decreased in SIT LESS (- 1.6 - 2.1 to - 1.1 hours/day) and controls (- 1.2 ─1.7 to - 0.8), but between group differences did not reach statistical significance (─0.4 ─1.0 to 0.3) hours/day). The post-rehabilitation proportion of patients with a sedentary time above the upper limit of normal (≥ 9.5 h/day) was significantly lower in SIT LESS versus controls (48% versus 72%, baseline-adjusted odds-ratio 0.4 (0.2-0.8)). No differences were observed in the other predefined secondary outcomes.
Among patients with coronary artery disease participating in cardiac rehabilitation, SIT LESS did not induce significantly greater reductions in sedentary time compared to controls, but delivery was feasible and a reduced odds of a sedentary time ≥ 9.5 h/day was observed.
Netherlands Trial Register: NL9263. Outcomes of the SIT LESS trial: changes in device-based sedentary time from pre-to post-cardiac rehabilitation (control group) and cardiac rehabilitation + SIT LESS (intervention group). SIT LESS reduced the odds of patients having a sedentary time >9.5 hours/day (upper limit of normal), although the absolute decrease in sedentary time did not significantly differ from controls. SIT LESS appears to be feasible, acceptable and potentially beneficial, but a larger cluster randomised trial is warranted to provide a more accurate estimate of its effects on sedentary time and clinical outcomes. CR: cardiac rehabilitation.
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an autosomal dominant inherited disease with incomplete penetrance and variable expression. Causative mutations in genes encoding ...5 desmosomal proteins are found in ≈50% of ARVD/C index patients. Previous genotype-phenotype relation studies involved mainly overt ARVD/C index patients, so follow-up data on relatives are scarce.
One hundred forty-nine ARVD/C index patients (111 male patients; age, 49±13 years) according to 2010 Task Force criteria and 302 relatives from 93 families (282 asymptomatic; 135 male patients; age, 44±13 years) were clinically and genetically characterized. DNA analysis comprised sequencing of plakophilin-2 (PKP2), desmocollin-2, desmoglein-2, desmoplakin, and plakoglobin and multiplex ligation-dependent probe amplification to identify large deletions in PKP2. Pathogenic mutations were found in 87 index patients (58%), mainly truncating PKP2 mutations, including 3 cases with multiple mutations. Multiplex ligation-dependent probe amplification revealed 3 PKP2 exon deletions. ARVD/C was diagnosed in 31% of initially asymptomatic mutation-carrying relatives and 5% of initially asymptomatic relatives of index patients without mutation. Prolonged terminal activation duration was observed more than negative T waves in V(1) to V(3), especially in mutation-carrying relatives <20 years of age. In 45% of screened families, ≥1 affected relatives were identified (90% with mutations).
Pathogenic desmosomal gene mutations, mainly truncating PKP2 mutations, underlie ARVD/C in the majority (58%) of Dutch index patients and even 90% of familial cases. Additional multiplex ligation-dependent probe amplification analysis contributed to discovering pathogenic mutations underlying ARVD/C. Discovering pathogenic mutations in index patients enables those relatives who have a 6-fold increased risk of ARVD/C diagnosis to be identified. Prolonged terminal activation duration seems to be a first sign of ARVD/C in young asymptomatic relatives.
Background
Data on chronic pain after kidney donation are sparse. The aim of this study was to assess the incidence of chronic pain after hand‐assisted laparoscopic nephrectomy.
Methods
Living kidney ...donors who donated between 2011 and 2017 at the University Medical Centre Groningen were included. All patients underwent hand‐assisted laparoscopic donor nephrectomy. Postdonation pain and movement disabilities were assessed using the Carolinas Comfort Scale (CCS) and a visual analogue scale (VAS). The prevalence, severity of pain and the need for analgesics were reported.
Results
Some 333 living kidney donors with a mean age of 56 years were included. At a median of 19 (i.q.r. 10–33) months after donation, 82 donors (24·6 per cent) had a CCS score above 0, of which 58 (71 per cent) had a CCS score of at least 2 and 57 (70 per cent) reported movement limitations. Some 110 donors (33·0 per cent) had a VAS score of more than 0. Complaints mainly occurred during bending over (12·3 per cent) and exercising (12·4 per cent). Thirty‐two donors (9·7 per cent) required analgesics during follow‐up between donation and the time of measurement, and six of 82 (7 per cent) reported chronic inguinal pain. In multivariable analysis, donor age (odds ratio (OR) 0·97, 95 per cent c.i. 0·95 to 0·99; P = 0·020) and length of hospital stay (OR 1·21, 1·01 to 1·51; P = 0·041) were independently associated with chronic pain.
Conclusion
One‐quarter of donors experienced chronic postdonation pain or discomfort, most of which was bothersome. Younger donors and those with a longer postoperative hospital stay had more symptoms.
Living donor nephrectomy is associated with chronic pain in 25 per cent of donors. Complaints occur during bending over and exercising. Younger donors and donors with a longer hospital stay had more complaints.
Significant in a quarter of patients
Background
Coronavirus disease 2019 (COVID-19) lockdown restrictions may impact lifestyle and therefore also physical (in)activity patterns in patients with cardiovascular disease (CVD). This study ...aimed to evaluate the effect of lockdown on physical activity and sedentary behaviour.
Methods
A total of 1565 Dutch CVD patients participated in this prospective cohort study, in which we compared physical activity and sedentary behaviour before and during the COVID-19 lockdown period. Baseline measures were assessed in 2018 and data on follow-up measures were collected between 17 and 24 April 2020 (5 weeks after the introduction of COVID-19 lockdown restrictions). Validated questionnaires were used to assess physical activity and sedentary behaviour.
Results
Moderate-to-vigorous physical activities increased from 1.6 (0.9, 2.8) to 2.0 (1.0, 3.5) h/day median (interquartile range) (
p
< 0.001) during the COVID-19 lockdown, mainly due to an increase in time spent walking and doing odd jobs. In contrast, time spent exercising significantly declined 1.0 (0.0, 2.3) to 0.0 (0.0, 0.6) h/week, whereas sedentary time increased from 7.8 (6.1, 10.4) to 8.9 (6.8, 11.4) h/day (
p
< 0.001). The absolute increase in physical activity was 13 (−36, 81) min/day, whereas sedentary behaviour increased by 55 (−72, 186) min/day.
Conclusion
Despite a small increase in physical activities, the larger increase in sedentary time induced a net reduction in habitual physical activity levels in Dutch CVD patients during the first-wave COVID-19 lockdown. Since a more inactive lifestyle is strongly associated with disease progression and mortality, we encourage CVD patients and their caregivers to explore novel solutions to increase physical activity levels and reduce sedentary time during (and beyond) the COVID-19 pandemic.
Background: For the second time a plan to monitor public health and health inequalities in the Netherlands through general practice was put into action: the Second National Survey of General Practice ...(DNSGP-2, 2001). The first aim of this paper is to describe the general design of DNSGP-2. Secondly, to describe self assessed health inequalities in the Netherlands. Thirdly, to present differences in prevalence of chronic conditions by educational attainment using both self-assessed health and medical records of GPs. Finally, inequalities in 1987 (DNSGP-1) and 2001 will be compared. Methods: Data were collected from 96 (1987) and 104 (2001) general practices. The data include background information on patients collected via a census, approximately 12 000 health interview surveys per time point and more than one million recorded contacts of patients with their GPs in both years. The method of statistical analysis is logistic regression. Results: The analyses shows that the lower educated have significantly higher odds of feeling unhealthy and having chronic conditions in 2001. Diabetes and myocardial infarction (GP data) showed the largest difference in prevalence between educational groups (OR 2.5 and 2.4, self-reported data). The way the data is collected (self-assessment versus GP registration) hardly affects the magnitude of the educational differences in the prevalence of chronic conditions. The pattern of health inequalities across chronic conditions in 1987 and 2001 hardly differs. Diabetes doubled in prevalence and health inequalities were not significant in 1987, but compared to the other conditions were largest in 2001 (OR 1.1 versus 2.5). Conclusion: Health inequalities were shown to be substantial in 2001 and persistent over time. Socio-economic differences were shown to be similar using self-assessed health data and GP data. Hence, a person's educational attainment did not appear to play a part in presenting health problems to the GP.
Key points Socio-economic differences showed to be similar using self-assessed health data and GP data. Educational attainment plays no part in presenting health problems to the GP in the Netherlands. Between 1987 and 2001 diabetes doubled in prevelance and shows large educational differences.
BACKGROUND: Greater insight into the effectiveness of usual dietetic care will contribute to the ongoing development of dietetic services. The present study examined the change in body mass index ...(BMI) in overweight patients after dietetic treatment in primary care, the sources of variability and factors associated with BMI change. METHODS: This population‐based observational study was based on data from a Dutch registration network of dietitians in primary health care. Data were derived from electronic medical records concerning 3960 overweight adult patients (BMI ≥ 25 kg m⁻²) who received usual care from 32 registered dietitians between 2006 and 2012. Multilevel linear regression analyses were conducted. RESULTS: Patients’ BMI significantly (P < 0.001) decreased by 0.94 kg m⁻² on average during treatment. An additional reduction of 0.8 kg m⁻² was observed in patients treated for longer than 6 months. BMI decreased by 0.06 kg m⁻² for each additional unit in initial BMI above 31.6. Most (97%) variability in BMI change was attributed to patients and 3% to dietitians. Part of the variance between patients (11%) and dietitians (30%) was explained by patient sociodemographic characteristics, nutrition‐related health aspects, initial body weight and treatment duration. CONCLUSIONS: Dietetic treatment in primary care lowers BMI in overweight patients. Patients’ change in BMI was rather similar between dietitians. Greater BMI reductions were observed in those with a high initial BMI and those treated for at least 6 months. Future research is necessary to study the long‐term effects of weight loss after treatment by primary healthcare dietitians, especially because many patients drop out of treatment prematurely.
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