Folic acid and vitamin B12 play key roles in one-carbon metabolism. Disruption of one-carbon metabolism may be involved in the risk of cancer. Our aim was to assess the long-term effect of ...supplementation with both folic acid and vitamin B12 on the incidence of overall cancer and on colorectal cancer in the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial.
Long-term follow-up of B-PROOF trial participants (
= 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 μg) and vitamin B12 (500 μg) versus placebo on fracture incidence. Information on cancer incidence was obtained from the Netherlands cancer registry (Integraal Kankercentrum Nederland), using the International Statistical Classification of Disease (ICD-10) codes C00-C97 for all cancers (except C44 for skin cancer), and C18-C20 for colorectal cancer.
Allocation to B vitamins was associated with a higher risk of overall cancer 171 (13.6%) vs. 143 (11.3%); HR 1.25; 95% confidence interval (CI), 1.00-1.53,
= 0.05. B vitamins were significantly associated with a higher risk of colorectal cancer 43(3.4%) vs. 25(2.0%); HR 1.77; 95% CI, 1.08-2.90,
= 0.02.
Folic acid and vitamin B12 supplementation was associated with an increased risk of colorectal cancer.
Our findings suggest that folic acid and vitamin B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin B12 are needed to evaluate whether folic acid and vitamin B12 supplementation should be limited to patients with a known indication, such as a proven deficiency.
Summary
Hyperkyphosis, an increased kyphosis angle of the thoracic spine, was associated with a higher fall incidence in the oldest quartile of a large prospective cohort of community-dwelling older ...adults. Hyperkyphosis could serve as an indicator of an increased fall risk as well as a treatable condition.
Introduction
Hyperkyphosis is frequently found in adults aged 65 years and older and may be associated with falls. We aimed to investigate prospectively in community-dwelling older adults whether hyperkyphosis or change in the kyphosis angle is associated with fall incidence.
Methods.
Community-dwelling older adults (
n
= 1220, mean age 72.9 ± 5.7 years) reported falls weekly over 2 years. We measured thoracic kyphosis through the Cobb angle between the fourth and 12th thoracic vertebra on DXA-based vertebral fracture assessments and defined hyperkyphosis as a Cobb angle ≥ 50°. The change in the Cobb angle during follow-up was dichotomized (< 5 or ≥ 5°). Through multifactorial regression analysis, we investigated the association between the kyphosis angle and falls.
Results
Hyperkyphosis was present in 15% of the participants. During follow-up, 48% of the participants fell at least once. In the total study population, hyperkyphosis was not associated with the number of falls (adjusted IRR 1.12, 95% CI 0.91–1.39). We observed effect modification by age (
p
= 0.002). In the oldest quartile, aged 77 years and older, hyperkyphosis was prospectively associated with a higher number of falls (adjusted IRR 1.67, 95% CI 1.14–2.45). Change in the kyphosis angle was not associated with fall incidence.
Conclusions
Hyperkyphosis was associated with a higher fall incidence in the oldest quartile of a large prospective cohort of community-dwelling older adults. Because hyperkyphosis is a partially reversible condition, we recommend investigating whether hyperkyphosis is one of the causes of falls and whether a decrease in the kyphosis angle may contribute to fall prevention.
Purpose
Higher folate and vitamin-B12 have been linked to lower risk of overweight. However, whether this is a causal effect of these B-vitamins on obesity risk remains unclear and evidence in older ...individuals is scarce. This study aimed to assess the role of B-vitamin supplementation and levels on body composition in older individuals.
Methods
A double-blind, randomized controlled trial in 2919 participants aged ≥ 65 years with elevated homocysteine levels. The intervention comprised a 2-year supplementation with a combination of folic acid (400 µg) and vitamin B12 (500 µg), or with placebo. Serum folate, vitamin-B12, active vitamin-B12 (HoloTC), methylmalonic acid (MMA), and anthropometrics were measured at baseline and after 2 years of follow-up. Dietary intake of folate and vitamin-B12 was measured at baseline in a subsample (
n
= 603) using a validated food-frequency questionnaire. Fat mass index (FMI) and fat-free mass index (FFMI) were assessed with Dual Energy X-ray absorptiometry (DXA).
Results
Cross-sectional analyses showed that a 1 nmol/L higher serum folate was associated with a 0.021 kg/m
2
lower BMI (95% CI − 0.039; − 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m
2
higher FMI (95% CI 0.262; 1.647), and higher MMA (per μgmol/L) was associated with a 1.108 kg/m
2
lower FMI (95% CI − 1.899; − 0.316). However, random allocation of B-vitamins did not have a significant effect on changes in BMI, FMI or FFMI during 2 years of intervention.
Conclusions
Although observational data suggested that folate and vitamin B12 status are associated with body composition, random allocation of a supplement with both B-vitamins combined versus placebo did not confirm an effect on BMI or body composition.
Aims
To investigate the association between use of β‐blockers and β‐blocker characteristics – selectivity, lipid solubility, intrinsic sympathetic activity (ISA) and CYP2D6 enzyme metabolism – and ...fall risk.
Methods
Data from two prospective studies were used, including community‐dwelling individuals, n = 7662 (the Rotterdam Study) and 2407 (B‐PROOF), all aged ≥55 years. Fall incidents were recorded prospectively. Time‐varying β‐blocker use was determined using pharmacy dispensing records. Cox proportional hazard models adjusted for age and sex were applied to determine the association between β‐blocker use, their characteristics – selectivity, lipid solubility, ISA and CYP2D6 enzyme metabolism – and fall risk. The results of the studies were combined using meta‐analyses.
Results
In total 2917 participants encountered a fall during a total follow‐up time of 89 529 years. Meta‐analysis indicated no association between use of any β‐blocker, compared to nonuse, and fall risk, hazard ratio (HR) = 0.97 95% confidence interval (CI) 0.88–1.06. Use of a selective β‐blocker was also not associated with fall risk, HR = 0.92 (95%CI 0.83–1.01). Use of a nonselective β‐blocker was associated with an increased fall risk, HR = 1.22 (95%CI 1.01–1.48). Other β‐blocker characteristics including lipid solubility and CYP2D6 enzyme metabolism were not associated with fall risk.
Conclusion
Our study suggests that use of a nonselective β‐blocker, contrary to selective β‐blockers, is associated with an increased fall risk in an older population. In clinical practice, β‐blockers have been shown effective for a variety of cardiovascular indications. However, fall risk should be considered when prescribing a β‐blocker in this age group, and the pros and cons for β‐blocker classes should be taken into consideration.
Background: Elevated plasma homocysteine concentrations are a risk factor for osteoporotic fractures. Lowering homocysteine with combined vitamin B-12 and folic acid supplementation may reduce ...fracture risk.Objective: This study B-vitamins for the PRevention Of Osteoporotic Fractures (B-PROOF) aimed to determine whether vitamin B-12 and folic acid supplementation reduces osteoporotic fracture incidence in hyperhomocysteinemic elderly individuals.Design: This was a double-blind, randomized, placebo-controlled trial in 2919 participants aged ≥65 y with elevated homocysteine concentrations (12–50 μmol/L). Participants were assigned to receive daily 500 μg vitamin B-12 plus 400 μg folic acid or placebo supplementation for 2 y. Both intervention and placebo tablets also contained 600 IU vitamin D3. The primary endpoint was time to first osteoporotic fracture. Exploratory prespecified subgroup analyses were performed in men and women and in individuals younger than and older than age 80 y. Data were analyzed according to intention-to-treat and per-protocol principles.Results: Osteoporotic fractures occurred in 61 persons (4.2%) in the intervention group and 75 persons (5.1%) in the placebo group. Osteoporotic fracture risk was not significantly different between groups in the intention-to-treat analyses (HR: 0.84; 95% CI: 0.58, 1.21) or per-protocol analyses (HR: 0.81; 95% CI: 0.54, 1.21). For persons aged >80 y, in per-protocol analyses, osteoporotic fracture risk was lower in the intervention group than in the placebo group (HR: 0.27; 95% CI: 0.10, 0.74). The total number of adverse events (including mortality) did not differ between groups. However, 63 and 42 participants in the intervention and placebo groups, respectively, reported incident cancer (HR: 1.56; 95% CI: 1.04, 2.31).Conclusions: These data show that combined vitamin B-12 and folic acid supplementation had no effect on osteoporotic fracture incidence in this elderly population. Exploratory subgroup analyses suggest a beneficial effect on osteoporotic fracture prevention in compliant persons aged >80 y. However, treatment was also associated with increased incidence of cancer, although the study was not designed for assessing cancer outcomes. Therefore, vitamin B-12 plus folic acid supplementation cannot be recommended at present for fracture prevention in elderly people. The B-PROOF study was registered with the Netherlands Trial Register (trialregister.nl) as NTR1333 and at clinicaltrials.gov as NCT00696414.
•45% of this Dutch older population had serum 25(OH)D concentrations <50nmol/L.•Only 6% of the participants with a vitamin D deficiency used vitamin D supplements.•Sun habits are still an important ...determinant of 25(OH)D status in older adults.•35% of the variation in serum 25(OH)D was explained by the determinants under study.
The prevalence of vitamin D deficiency among seniors is high. Whereas sun exposure, vitamin D intake, genes, demographics, and lifestyle have been identified as being important determinants of vitamin D status, the impact of these factors is expected to differ across populations. To improve current prevention and treatment strategies, this study aimed to explore the main determinants of vitamin D status and its relative importance in a population of community-dwelling Dutch older adults.
Serum 25-hydroxyvitamin D (25(OH)D) was measured in 2857 adults aged ≥65 years. Sun exposure was assessed with a structured questionnaire (n=1012), vitamin D intake using a Food Frequency Questionnaire (n=596), and data on genetic variation that may affect 25(OH)D status was obtained for 4 genes, DHCR7 (rs12785878), CYP2R1 (rs10741657), GC (rs2282679), and CYP24A1 (rs6013897) (n=2530).
Serum 25(OH)D concentrations <50nmol/L were observed in 45% of the population; only 6% of these participants used vitamin D supplements. Sun exposure (being outside daily during summer: 66±25nmol/L vs not being outside daily during summer: 58±27nmol/L, P=0.02) and vitamin D intake (per unit μg/day during winter/spring: 3.1±0.75nmol/L, P<0.0001) were associated with higher 25(OH)D concentrations. Major allele carriers of SNPs related to DHCR7, CYP24A1, and GC, as well as CYP2R1 minor allele carriers had the highest 25(OH)D concentrations. Together, sun (R2=0.29), vitamin D intake (R2=0.24), and genes (R2=0.28) explained 35% (R2=0.35) of the variation in 25(OH)D concentrations during summer/autumn period, when adjusted for age, sex, BMI, education, alcohol consumption, smoking, physical activity, and self-rated health status (n=185).
The investigated determinants explained 35% of 25(OH)D status. Of the three main determinants under study, sun exposure still appeared to be an important determinant of serum 25(OH)D in older individuals, closely followed by genes, and vitamin D intake. Given the low frequency of vitamin D supplement use in this population, promoting supplement use may be an inexpensive, easy, and effective strategy to fight vitamin D deficiency.
ObjectivesThe objective is to develop a pragmatic framework, based on value-based healthcare principles, to monitor health outcomes per unit costs on an institutional level. Subsequently, we ...investigated the association between health outcomes and healthcare utilisation costs.DesignThis is a retrospective cohort study.SettingA teaching hospital in Rotterdam, The Netherlands.ParticipantsThe study was performed in two use cases. The bariatric population contained 856 patients of which 639 were diagnosed with morbid obesity body mass index (BMI) <45 and 217 were diagnosed with morbid obesity BMI ≥45. The breast cancer population contained 663 patients of which 455 received a lumpectomy and 208 a mastectomy.Primary and secondary outcome measuresThe quality cost indicator (QCI) was the primary measures and was defined asQCI = (resulting outcome * 100)/average total costs (per thousand Euros)where average total costs entail all healthcare utilisation costs with regard to the treatment of the primary diagnosis and follow-up care. Resulting outcome is the number of patients achieving textbook outcome (passing all health outcome indicators) divided by the total number of patients included in the care path.ResultsThe breast cancer and bariatric population had the highest resulting outcome values in 2020 Q4, 0.93 and 0.73, respectively. The average total costs of the bariatric population remained stable (avg, €8833.55, min €8494.32, max €9164.26). The breast cancer population showed higher variance in costs (avg, €12 735.31 min €12 188.83, max €13 695.58). QCI values of both populations showed similar variance (0.3 and 0.8). Failing health outcome indicators was significantly related to higher hospital-based costs of care in both populations (p <0.01).ConclusionsThe QCI framework is effective for monitoring changes in average total costs and relevant health outcomes on an institutional level. Health outcomes are associated with hospital-based costs of care.
Background
Symptoms of apathy are common in older persons. Negative effects on physical performance and fall risk are plausible, considering the pathophysiology of apathy. However, literature is ...scarce.
Aim
To longitudinally assess the association between apathy and (1) decline of physical performance and (2) the number of falls in older community-dwelling persons.
Methods
The ‘B vitamins for the PRevention Of Osteoporotic Fractures’ study provided data on 2919 older persons over a period of 2 years. Apathy was assessed using the Geriatric Depression Scale 3. A physical performance score (PPS) was calculated using three performance tests. Falls were registered prospectively. We calculated adjusted odds ratios (ORs), Incidence Rate Ratios (IRRs), and their 95% confidence intervals. Effect modification by age and gender was investigated. We also investigated mediation by baseline PPS for the association between apathy and the number of falls.
Results
Apathy and decline of PPS were independently associated. After stratification, the effect only remained in men. Age was an effect modifier; higher ORs for decreasing age. Apathy was also independently associated with the number of falls. After stratification, women had higher IRRs than men. Age modified the association in the opposite direction: higher IRRs for increasing age. Baseline PPS was a mediator in the association.
Conclusion
The impact of apathy on physical performance and fall incidents varied with age and gender. Potentially, in older individuals with apathy, fall risk is preceded by a decline in physical performance. In clinical practice, identifying apathy in older persons might be useful to target mobility preserving interventions.
We investigated prospectively among community-dwelling older adults aged 65 years and over whether a larger kyphosis angle is associated with poorer physical performance (balance, muscle strength or ...both), and whether this association is unidirectional.
ale and female participants performed a multicomponent physical performance test with subscores for gait, muscle strength and balance at baseline and after 2 years. Hand grip strength was also measured at baseline and at follow-up. The Cobb angle was measured on DXA-based Vertebral Fracture Assessments, made at the baseline and follow-up visit. Through linear and logistic regression analysis, we investigated the association between the kyphosis angle and physical performance and vice versa. We stratified for sex, and tested for effect modification by age and study center.
The mean kyphosis angle was 37° and 15% of the participants (n=1220, mean age 72.9±5.7 years) had hyperkyphosis (Cobb angle ≥50°). A larger kyphosis angle at baseline was independently associated with a poorer total physical performance score in women of the oldest quartile (≥77 years) in both the cross-sectional and longitudinal analyses (baseline B-0.32, 95%CI -0.56--0.08; follow-up B 0.32, 95%CI -0.55--0.10). There was no association between physical performance at baseline and kyphosis progression.
A larger kyphosis angle is independently associated with a poorer physical performance at baseline and over time, and the direction of this association is unidirectional. These results emphasize the importance of early detection and treatment of hyperkyphosis to prevent further worsening of the kyphosis angle, thereby potentially preserving physical performance.
BackgroundKnowledge about patient characteristics predicting treatment dropout for post-traumatic stress disorder (PTSD) is scarce, whereas more understanding about this topic may give direction to ...address this important issue. MethodData were obtained from a randomized controlled trial in which a phase-based treatment condition (Eye Movement Desensitization and Reprocessing EMDR therapy preceded by Skills Training in Affect and Interpersonal Regulation STAIR; n = 57) was compared with a direct trauma-focused treatment (EMDR therapy only; n = 64) in people with a PTSD due to childhood abuse. All pre-treatment variables included in the trial were examined as possible predictors for dropout using machine learning techniques. ResultsFor the dropout prediction, a model was developed using Elastic Net Regularization. The ENR model correctly predicted dropout in 81.6% of all individuals. Males, with a low education level, suicidal thoughts, problems in emotion regulation, high levels of general psychopathology and not using benzodiazepine medication at screening proved to have higher scores on dropout. ConclusionOur results provide directions for the development of future programs in addition to PTSD treatment or for the adaptation of current treatments, aiming to reduce treatment dropout among patients with PTSD due to childhood abuse.
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