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Summary: This study evaluated the yield of routine laboratory examination in a large population of older women in primary care. The prevalence of laboratory abnormalities was low and the clinical consequences in follow-up were limited. There was a weak association of laboratory abnormalities with osteoporosis but no association with vertebral fractures and recent fractures. Purpose: Most osteoporosis guidelines advice routine laboratory examination. We have investigated the yield of laboratory examinations in facture risk evaluation of elderly women in primary care. Methods: We assessed the prevalence of laboratory abnormalities and their association with risk factors for fractures, recent fractures, low bone mineral density (BMD), and prevalent vertebral fracture in 8996 women ≥ 65 years of age participating in a primary care fracture risk screening study. In a sample of 2208 of these participants, we also evaluated the medical consequences in the medical records during a follow-up period of ≥ 1 year. Results: Vitamin D deficiency (< 30 nmol/L) was present in 13% and insufficiency (< 50 nmol/L) in 43% of the study sample. The prevalence of other laboratory abnormalities (ESR, calcium, creatinine, FT4) was 4.6% in women with risk factors for fractures, 6.1% in women with low BMD (T-score ≤ − 2.5), 6.0% after a prevalent vertebral fracture, 5.2% after a recent fracture and 2.6% in the absence of important risk factors for fractures. Laboratory abnormalities other than vitamin D were associated with low BMD (OR 1.4, 95%CI 1.1–1.8) but not with prevalent vertebral fractures nor recent fractures. Low BMD was associated with renal failure (OR 2.0, 95%CI 1.3–3.4), vitamin D insufficiency (OR 1.2, 95%CI 1.0–1.3) and deficiency (OR 1.3, 95%CI 1.1–.5). In the follow-up period, 82% of the laboratory abnormalities did not result in a new diagnosis or treatment reported in the medical records. Conclusions: We identified a low prevalence of laboratory abnormalities in a primary care population of older women and the majority of these findings had no medical consequences. [ABSTRACT FROM AUTHOR]

Background: People living with chronic obstructive pulmonary disease (COPD) have an increased risk of experiencing cardiovascular (CV) events, particularly after an exacerbation. Such CV burden is not yet known for incident COPD patients. We examined the risk of severe CV events in incident COPD patients in periods following either moderate and/or severe exacerbations. Methods: Persons aged ≥ 40 years with an incident COPD diagnosis from the PHARMO Data Network were included. Exposed time periods included 1–7, 8–14, 15–30, 31–180 and 181–365 days following an exacerbation. Moderate exacerbations were defined as those managed in outpatient settings; severe exacerbations as those requiring hospitalisation. The outcome was a composite of time to first severe CV event (acute coronary syndrome, heart failure decompensation, cerebral ischaemia, or arrhythmia) or death. Hazard ratios (HR) were estimated for association between each exposed period and outcome. Results: 8020 patients with newly diagnosed COPD were identified. 2234 patients (28%) had ≥ 1 exacerbation, 631 patients (8%) had a non-fatal CV event, and 461 patients (5%) died during a median follow-up of 36 months. The risk of experiencing the composite outcome was increased following a moderate/severe exacerbation as compared to time periods of stable disease [range of HR: from 15.3 (95% confidence interval 11.8–20.0) in days 1–7 to 1.3 (1.0–1.8) in days 181–365]. After a moderate exacerbation, the risk was increased over the first 180 days [HR 2.5 (1.3–4.8) in days 1–7 to 1.6 (1.3–2.1) in days 31–180]. After a severe exacerbation, the risk increased substantially and remained higher over the year following the exacerbation [HR 48.6 (36.9–64.0) in days 1–7 down to 1.6 (1.0–2.6) in days 181–365]. Increase in risk concerned all categories of severe CV events. Conclusions: Among incident COPD patients, we observed a substantial risk increase of severe CV events or all-cause death following either a moderate or severe exacerbation of COPD. Increase in risk was highest in the initial period following an exacerbation. These findings highlight the significant cardiopulmonary burden among people living with COPD even with a new diagnosis. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has had a significant impact on healthcare systems worldwide, including the postponing or canceling of appointments and procedures for type 2 diabetes (T2D) care by general practitioners (GPs) in the Netherlands. The aim of this study was to investigate the impact of the COVID-19 pandemic on primary healthcare use and clinical measurements for people with T2D. Additionally, we aimed to determine if changes were observed among specific risk groups: (1) persons 70 years or older, or below 70 years, (2) patients who were meeting their HbA1c targets and those who were not, and (3) patients with high-risk and non-high-risk T2D. This retrospective cohort study among persons with T2D was conducted using data from the DIAbetes MANagement and Treatment (DIAMANT) data infrastructure, deriving data from electronic medical records of Dutch GPs. The study assessed GP visit counts, and counts and values of clinical measurements, including hemoglobin A1c (HbA1c), body mass index (BMI), low-density lipoprotein (LDL) cholesterol, and systolic blood pressure (SBP). Adjusted negative binomial (NB) regression and generalized estimating equations (GEE) models were used to estimate GP visit counts and population averages of clinical measurements, respectively, comparing 2019 (pre-pandemic) with 2020 (during the pandemic). Changes in specific groups were examined by stratifying outcomes for the aforementioned subgroups. The cohort consisted of 182,048 patients with T2D (47% female, mean age 69 ± 13 years) on 1 March 2019, of which 168,097 persons (92%) still contributed follow-up data in 2020. We observed an increase in total GP visits in 2020, with an adjusted rate ratio (RR) of 1.09 (95% CI 1.08–1.09). The frequency increased for office visits (RR 1.06; 1.06–1.07) and phone calls (RR 1.33; 1.31–1.35) but remained stable for home visits (RR 1.02; 0.99–1.04). On both population and individual levels, HbA1c values increased in 2020 by 1.65 (1.59–1.70) mmol/mol compared to 2019. Observed changes in 2020 for BMI, LDL, and SBP values were also statistically significant but small. Subgroup stratifications showed higher scores of all clinical measurements in younger persons (<70 years), those who met their HbA1c target, and non-high-risk T2D patients than their respective high-risk subgroups. During the first year of the COVID-19 pandemic in the Netherlands, changes in primary healthcare use were observed among persons with T2D, with an increase in GP office visits and phone calls and a decreased number of clinical measurements and GP home visits. HbA1c levels increased among patients with T2D in 2020. Further research is necessary to determine the impact of the COVID-19 pandemic on long-term clinical outcomes and (long-term) T2D complications. [ABSTRACT FROM AUTHOR]

Background: Use of the direct oral anticoagulant rivaroxaban has strongly increased in Europe since its market approval for non-valvular atrial fibrillation in 2011. Patients characteristics of rivaroxaban initiators may have changed over time but this has not been investigated so far. Objective: We aimed to describe time trends of patient baseline characteristics among new rivaroxaban users with non-valvular atrial fibrillation from 2011 to 2016/17 in two European countries. Methods: We used data from Germany (German Pharmacoepidemiological Research Database) and the Netherlands (PHARMO Database Network). We included new rivaroxaban users with (i) a first dispensing between 2011 and 2016/17, (ii) ≥ 2 years of age, and (iii) a diagnosis of non-valvular atrial fibrillation and described their baseline medication and comorbidity prior to starting rivaroxaban stratified by year of inclusion. Results: Overall, 130,652 new rivaroxaban users were included during the study period (Germany: N = 127,743, the Netherlands: N = 2909). The sex ratio and median age remained relatively stable over time. The proportion of patients without prior use of oral anticoagulants before initiation of rivaroxaban increased in both countries between 2011 and 2016/17 (Germany: from 51 to 76%, the Netherlands: from 57 to 85%). In Germany, we observed a relative decrease by 27% in the proportion of new rivaroxaban users with a history of ischemic stroke and by 18% in the proportion with a transient ischemic attack at baseline. No such a pattern was observed in the Netherlands. The proportion of patients with heart failure at baseline showed a three-fold increase in the Netherlands, while there was a relative decrease by 12% in Germany. Conclusions: Patient characteristics of new rivaroxaban users with non-valvular atrial fibrillation changed between 2011 and 2016/17, but changes differed between countries. These patterns have methodological implications. They have to be considered in the interpretation of observational studies comparing effectiveness and safety of oral anticoagulants, especially regarding potential bias due to unmeasured confounding. [ABSTRACT FROM AUTHOR]

Persons with diabetes mellitus may have an increased risk of severe illness or death from COVID-19 compared to persons without diabetes. Prior studies indicate that immune response and thus vaccine effectiveness might be lower in persons with diabetes. We aimed to systematically review the effectiveness of COVID-19 vaccines in adults with diabetes. Pubmed, Embase, Web of Science and Cochrane Library were searched for studies that evaluated the effectiveness of COVID-19 vaccines in adults with diabetes, published before 4 March 2022. Risk of bias in the included studies was evaluated using the ROBINS-I tool. At least two reviewers conducted the study selection, data extraction, and risk of bias assessment independently. After screening of 2196 studies, a total of 17 articles were included. Six different COVID-19 vaccines (Ad5-nCoV-S, AZD1222, BNT162b2, CoronaVac, JNJ-78436735, and mRNA-1273) were included in the synthesis. Vaccine effectiveness was reported for SARS-CoV-2 infection, symptomatic COVID-19, hospitalization, and death, and ranged from 24 to 96% in persons with diabetes, and from 33 to 97% in total study populations; effectiveness was generally lower for persons with diabetes. Odds ratios for breakthrough infection or severe COVID-19 ranged from 1.03 to 2.41 in vaccinated persons with diabetes compared to persons without diabetes. Even though the included studies were very heterogeneous, results from the synthesis indicate that effectiveness of COVID-19 vaccines might be lower in persons with diabetes. More research is needed on the comparison of vaccine effectiveness between persons with and without diabetes, and the effectiveness of repeat COVID-19 vaccinations. [ABSTRACT FROM AUTHOR]

Background: We investigated prospectively among community-dwelling older adults aged 65 years and older whether a larger kyphosis angle is associated with poorer physical performance (balance, muscle strength, or both), and whether this association is unidirectional.Methods: Male 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.Results: The mean kyphosis angle was 37° and 15% of the participants (n = 1 220, 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% confidence interval [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.Conclusion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Adherence to osteoporosis treatment is crucial for good treatment effects. However, adherence has been shown to be poor and a substantial part of the patients don’t even initiate treatment. This study aimed to gain insight into the considerations of both osteoporosis patients and general practitioners (GP) concerning intentional non-initiation of bisphosphonate treatment. Methods: Osteoporosis patients and GPs were recruited from the SALT Osteoporosis Study and a transmural fracture liaison service, both carried out in the Netherlands. Using questionnaires, we identified non-starters and starters of bisphosphonate treatment. Semi-structured interviews were conducted to gain a detailed overview of all considerations until saturation of the data was reached. Starters were asked to reflect on the considerations that were brought forward by the non-starters. Interviews were open coded and the codes were classified into main themes and subthemes using an inductive approach. Results: 16 non-starters, 10 starters, and 13 GPs were interviewed. We identified three main themes: insufficient medical advice, attitudes towards medication use including concerns about side effects, and disease awareness. From patients’ as well as GPs’ perspective, insufficient or ambiguous information from the GP influenced the decision of the non-starters to not start bisphosphonates. In contrast, starters were either properly informed, or they collected information themselves. Patients’ aversion towards medication, fear of side effects, and a low risk perception also contributed to not starting the medication, whereas starters were aware of their fracture risk and were confident of the outcome of the treatment. Concerns about osteoporosis treatment and its side effects were also expressed by several GPs. Some GPs appeared to have a limited understanding of the current osteoporosis guidelines and the indications for treatment. Conclusions: Many reasons we found for not starting bisphosphonate treatment were related to the patients or the GPs themselves being insufficiently informed. Attitudes of the GPs were shown to play a role in the decision of patients not to start treatment. Interventions need to be developed that are aimed at GPs, and at education of patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin Bi2 supplementation with participants who did not. Methods: Participants of the B-PROOF study (n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B12, or a placebo. After two years of intervention, T1-weighted magnetic resonance imaging (MRI) scans were made in a random subsample (n = 218) to obtain grey and white matter volume, and total brain volume (TBV). Plasma homocysteine, serum folate, vitamin B12, holotranscobalamin, and methylmalonic acid concentrations were measured. Results: Multiple linear regression analyses showed inverse associations between plasma homocysteine with TBV (β = -0.91, 95% CI -1.85-0.03; p = 0.06) and between serum folate and TBV (β = -0.20, 95% CI -0.38, -0.02; p = 0.03). No significant associations were observed for serum vitamin B12 and holotranscobalamin. Fully adjusted ANCOVA models showed that the group that received B-vitamins had a lower TBV (adjusted mean 1064,95% CI 1058-1069 mL) than the non-supplemented group (1072, 95% CI 1067-1078 mL, p = 0.03). Conclusions: Results were contradictory, with higher Hcy levels associated with lower TBV, but also with higher folate levels associated with lower TBV. In addition, the lack of a baseline measurement withholds us from giving recommendations on whether folic acid and vitamin B12 supplementation will be beneficial above and beyond normal dietary intake for brain health. [ABSTRACT FROM AUTHOR]

Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing vitamin B12 and folic acid may reduce depressive symptoms and improve health-related quality of life (HR-QoL) in older adults. This study aimed to test this hypothesis in a randomized controlled trial. Participants (N = 2919, ≥65 years, Hcy concentrations ≥12 µmol/L) received either 500 µg vitamin B12 and 400 µg folic acid daily or placebo for two years. Both tablets contained 15 µg vitamin D3. Depressive symptoms were measured with the Geriatric Depression Scale-15 (GDS-15). HR-QoL was assessed with the SF-12 Mental and Physical component summary scores and the EQ-5D Index score and Visual Analogue Scale. Differences in two-year change scores were analyzed with Analysis of Covariance (ANCOVA). Hcy concentrations decreased more in the intervention group, but two-year change scores of the GDS-15 and three of four HR-QoL measures did not differ between groups. The EQ-5D Index score declined less in the intervention group than in the placebo group (mean change 0.00 vs. -0.02, p = 0.004). In conclusion, two-year supplementation with vitamin B12 and folic acid in older adults with hyperhomocysteinemia showed that lowering Hcy concentrations does not reduce depressive symptoms, but it may have a small positive effect on HR-QoL. [ABSTRACT FROM AUTHOR]

B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study. This study was conducted within the framework of the B-PROOF trial, which included 2919 hyperhomocysteinemic elderly individuals, who received daily vitamin B12 (500 μg) and folic acid (400 μg) or placebo for 2 years. Using an electrochemiluminescence platform, we measured intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), serum amyloid A (SAA), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at baseline and follow-up in a subsample of 522 participants (271 intervention group; 251 placebo). Treatment effects were analyzed with ANCOVA. The participants had a mean age of 72 years, and 55% of them were male. At the 2-year follow-up, B-vitamins did not change the ICAM-1 (+36% change in the intervention group versus +32% change in the placebo group; p = 0.72), VCAM-1 (+27% vs +25%; p = 0.39), VEGF (–1% vs +4%; p = 0.40), SAA (+34% vs +38%; p = 0.85) or CRP levels (+26% vs +36%; p = 0.70) as compared to placebo. In conclusion, in elderly patients with hyperhomocysteinemia, vitamin B12 and folic acid are unlikely to influence either endothelial function or low-grade systemic inflammation. ClinicalTrials.gov Identifier: NCT00696514 [ABSTRACT FROM AUTHOR]

Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged ≥65 years with elevated plasma homocysteine concentrations [12-50 µmol/L (n = 2919)] were randomly assigned to daily supplementation of 500 µg vitamin B12, 400 µg folic acid, and 600 IU vitamin D3, or to placebo with 600 IU vitamin D3. Physical performance (range 0-12) and handgrip strength (kg) were measured at baseline and after 2 years. Falls were reported prospectively on a research calendar. Intention-to-treat (primary) and per-protocol (secondary) analyses were performed. Physical performance level and handgrip strength significantly decreased during the follow-up period, but this decline did not differ between groups. Moreover, time to first fall was not significantly different (HR: 1.0, 95% CI 0.9-1.2). Secondary analyses on a per-protocol base identified an interaction effect with age on physical performance. In addition, the treatment was associated with higher follow-up scores on the walking test (cumulative OR: 1.3, 95% CI 1.1-1.5). Two-year supplementation of vitamin B12 and folic acid was neither effective in reducing the age-related decline in physical performance and handgrip strength, nor in the prevention of falling in elderly persons. Despite the overall null-effect, the results provide indications for a positive effect of the intervention on gait, as well as on physical performance among compliant persons >80 years. These effects should be further tested in future studies. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine whether functional septorhinoplasty provides improvement of the nasal passage in validated patient-reported outcome measures (PROMs) for adults with an anatomical obstruction of the nasal valve. All patients with an anatomical obstruction of the nasal valve area due to nasal valve pathology and/or septal deviations in this area were included.Methods: A systematic PubMed, Embase and Cochrane Library search was performed to identify relevant articles. The articles were critically appraised and ranked according to validity and relevance.Results: Sixteen articles met our inclusion criteria, and after critical appraisal, 10 were eligible for further analysis. In 9 studies, the Nose Obstruction Symptom Evaluation (NOSE) score improved from 35 to 60 points. In 1 study, the Sino-Nasal Outcome Test (SNOT-22) improved 3.5 points.Conclusion: The results suggest that there is a significant improvement of the validated PROMs after functional septorhinoplasty in the first postoperative year. We recommend that adults with nasal breathing problems due to an anatomical problem of the nasal valve area should consider undergoing functional septorhinoplasty. [ABSTRACT FROM AUTHOR]

High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged ≥65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p < 0.01) and SOS did not change in either treatment arm. No statistically significant differences between the intervention and placebo group were present for FN-BMD (p = 0.24), LS-BMD (p = 0.16), SOS (p = 0.67), and BUA (p = 0.96). However, exploratory subgroup analyses revealed a small positive effect of the intervention on BUA at follow-up among compliant persons >80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement. [ABSTRACT FROM AUTHOR]

Background: several studies have been pointing towards a non-linear relationship between serum 25(OH)D and cardiovascular disease. Next to vitamin D deficiency, also higher levels of 25(OH)D have been reported to be associated with increased cardiovascular risk. We aimed to investigate the nature of the relationship between serum 25(OH)D and measures of arterial stiffness and arteriosclerosis in an elderly population.Design: cross-sectional.Setting/subjects: a subgroup of the B-PROOF study was included to determine associations between serum 25(OH)D and arterial stiffness and atherosclerosis (n = 567, 57% male, age 72.6 ± 5.6 years, mean serum 25(OH)D 54.6 ± 24.1 nmol/l).Methods: carotid intima media thickness (IMT) was assessed using ultrasonography and pulse wave velocity (PWV) was determined with applanation tonometry. Associations were tested using multivariable restricted cubic spline functions and stratified linear regression analysis.Results: the associations between serum 25(OH)D and carotid IMT or PWV were non-linear. Spline functions demonstrated a difference between 25(OH)D deficient and sufficient individuals. In serum 25(OH)D sufficient participants (≥50 nmol/l; n = 287), a positive association with IMT and serum 25(OH)D was present (β 1.24; 95%CI [0.002; 2.473]). PWV levels were slightly lower in vitamin D deficient individuals, but the association with 25(OH)D was not significant.Conclusion: our study demonstrates that associations of serum 25(OH)D and PWV and IMT in an elderly population are not linear. In particular from serum 25(OH)D levels of 50 nmol/l and up, there is a slight increase of IMT with increasing 25(OH)D levels. [ABSTRACT FROM AUTHOR]

Background: several studies have been pointing towards a non-linear relationship between serum 25(OH)D and cardiovascular disease. Next to vitamin D deficiency, also higher levels of 25(OH)D have been reported to be associated with increased cardiovascular risk. We aimed to investigate the nature of the relationship between serum 25(OH)D and measures of arterial stiffness and arteriosclerosis in an elderly population.Design: cross-sectional.Setting/subjects: a subgroup of the B-PROOF study was included to determine associations between serum 25(OH)D and arterial stiffness and atherosclerosis (n = 567, 57% male, age 72.6 ± 5.6 years, mean serum 25(OH)D 54.6 ± 24.1 nmol/l).Methods: carotid intima media thickness (IMT) was assessed using ultrasonography and pulse wave velocity (PWV) was determined with applanation tonometry. Associations were tested using multivariable restricted cubic spline functions and stratified linear regression analysis.Results: the associations between serum 25(OH)D and carotid IMT or PWV were non-linear. Spline functions demonstrated a difference between 25(OH)D deficient and sufficient individuals. In serum 25(OH)D sufficient participants (≥50 nmol/l; n = 287), a positive association with IMT and serum 25(OH)D was present (β 1.24; 95%CI [0.002; 2.473]). PWV levels were slightly lower in vitamin D deficient individuals, but the association with 25(OH)D was not significant.Conclusion: our study demonstrates that associations of serum 25(OH)D and PWV and IMT in an elderly population are not linear. In particular from serum 25(OH)D levels of 50 nmol/l and up, there is a slight increase of IMT with increasing 25(OH)D levels. [ABSTRACT FROM PUBLISHER]

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 >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. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis The aim of this study was to ascertain the most reliable objective measurement for the assessment of nasal patency by investigating the relationship between peak nasal inspiratory flow, peak oral inspiratory flow, and the nasal patency index in relation to the patient's subjective perception regarding nasal obstruction. Study Design Prospective cohort study. Methods This study included 131 volunteers of both genders, aged 18 years or older, with or without nasal symptoms, who were able to give informed consent, completed the study protocol, and could speak and write Dutch fluently. Peak nasal inspiratory flow and peak oral inspiratory flow were performed and nasal patency index was computed. The results were evaluated and compared with the subjective perception of nasal passage, using the validated Nasal Obstruction Symptom Evaluation scale and visual analog scale for nasal passage. Results Our study showed that peak nasal inspiratory flow, nasal patency index and nasal patency visual analog scale correlate with the Nasal Obstruction Symptom Evaluation scale in contrast to peak oral inspiratory flow. Peak nasal inspiratory flow and nasal patency index also showed significant association with the Nasal Obstruction Symptom Evaluation scale after adjustment for confounders. Conclusions Peak nasal inspiratory flow is the most reliable method for the assessment of nasal patency. It is quick, inexpensive, and easy to perform, and correlates significantly with the subjective feeling of nasal obstruction. There is no clinical need to measure peak oral inspiratory flow or to calculate the nasal patency index in the evaluation of nasal patency. Level of Evidence 4 Laryngoscope, 124:2665-2669, 2014 [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a major health problem, and the economic burden is expected to rise due to an increase in life expectancy throughout the world. Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12 and folate status are associated with an increased fracture risk. As vitamin B12 and folate intake and status play a large role in homocysteine metabolism, it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration.Methods/design: The B-PROOF (B-Vitamins for the PRevention Of Osteoporotic Fractures) study is a randomized double-blind placebo-controlled trial. The intervention comprises a period of two years, and includes 2919 subjects, aged 65 years and older, independently living or institutionalized, with an elevated homocysteine concentration (≥ 12 μmol/L). One group receives daily a tablet with 500 μg vitamin B12 and 400 μg folic acid and the other group receives a placebo tablet. In both tablets 15 μg (600 IU) vitamin D is included. The primary outcome of the study is osteoporotic fractures. Measurements are performed at baseline and after two years and cover bone health i.e. bone mineral density and bone turnover markers, physical performance and physical activity including falls, nutritional intake and status, cognitive function, depression, genetics and quality of life. This large multi-center project is carried out by a consortium from the Erasmus MC (Rotterdam, the Netherlands), VUmc (Amsterdam, the Netherlands) and Wageningen University, (Wageningen, the Netherlands), the latter acting as coordinator.Discussion: To our best knowledge, the B-PROOF study is the first intervention study in which the effect of vitamin B12 and folic acid supplementation on osteoporotic fractures is studied in a general elderly population. We expect the first longitudinal results of the B-PROOF intervention in the second semester of 2013. The results of this intervention will provide evidence on the efficacy of vitamin B12 and folate supplementation in the prevention of osteoporotic fractures.Trial Registration: The B-PROOF study is registered with the Netherlands Trial (NTR NTR1333) and with ClinicalTrials.gov (NCT00696514). [ABSTRACT FROM AUTHOR]