[Show abstract][Hide abstract] ABSTRACT: Objective:
To investigate the efficacy of 3-D printed bone models as a tool to facilitate initiation of bisphosphonate treatment among individuals who were newly diagnosed with osteoporosis.
58 participants with estimated fracture risk above that at which guidelines recommend pharmacological intervention were randomised to receive either a standard physician interview or an interview augmented by the presentation of 3-D bone models.
Main outcome measures:
Participants' beliefs about osteoporosis and bisphosphonate treatment, initiation of bisphosphonate therapy assessed at two months using self-report and pharmacy dispensing data.
Individuals in the 3-D bone model intervention condition were more emotionally affected by osteoporosis immediately after the interview (p = .04) and reported a greater understanding of osteoporosis at follow-up (p = .04), than the control group. While a greater proportion of the intervention group initiated an oral bisphosphonate regimen (alendronate) (52%) in comparison to the control group (21%), the overall initiation of medication for osteoporosis, including infusion (zoledronate), did not differ significantly (intervention group 62%, control group 45%, p=0.19).
The presentation of 3-D bone models during a medical consultation can modify cognitive and emotional representations relevant to treatment initiation among people with osteoporosis, and might facilitate commencement of bisphosphonate treatment.
Psychology & Health 10/2015; DOI:10.1080/08870446.2015.1112389 · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Systematic reviews of randomized, controlled trials (RCTs) are considered the highest level of evidence to inform clinical practice. Meta-analyses of large RCTs of calcium and/or vitamin D supplements completed in the last 15 years provide strong evidence for clinical recommendations. These meta-analyses with data for > 50 000 older adults reported that calcium with or without vitamin D has only weak, inconsistent effects on fracture, and that vitamin D without calcium has no effect on fracture. Only one RCT of co-administered calcium and vitamin D in frail, institutionalized, elderly women with low dietary calcium intake and vitamin D levels showed significant reductions in fracture risk. These RCTs have also reported previously unrecognized adverse events of calcium supplements including kidney stones, myocardial infarction, hypercalcemia, and hospitalization with acute gastrointestinal symptoms. The small risk of these important adverse effects, together with the moderate risk of minor side-effects such as constipation, probably outweighs any benefits of calcium supplements on fracture. These data suggest the role for calcium and vitamin D supplements in osteoporosis management is very limited. Neither calcium nor vitamin D supplements should be recommended for fracture prevention in community-dwelling adults, although vitamin D should be considered for prevention of osteomalacia in at-risk individuals.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Branding medication with a known pharmaceutical company name or product name bestows on the drug an added assurance of authenticity and effectiveness compared to a generic preparation. This study examined the impact of brand name and generic labeling on medication effectiveness and side effects.
87 undergraduate students with frequent headaches took part in the study. Using a within-subjects counterbalanced design, each participant took tablets labeled either as brand name "Nurofen" or "Generic Ibuprofen" to treat each of 4 headaches. In reality, half of the tablets were placebos, and half were active ibuprofen (400 mg). Participants recorded their headache pain on a verbal descriptor and visual analogue scale prior to taking the tablets, and again 1 hour afterward. Medication side effects were also reported.
Pain reduction following the use of brand name labeled tablets was similar in active ibuprofen or a placebo. However, if the tablets had a generic label, placebo tablets were significantly less effective compared to active ibuprofen. Fewer side effects were attributed to placebo tablets with brand name labeling compared to the same placebo tablets with a generic label.
Branding of a tablet appears to have conferred a treatment benefit in the absence of an active ingredient, while generic labeled tablets were substantially less effective if they contained no active ingredient. Branding is also associated with reduced attribution of side effects to placebo tablets. Future interventions to improve perceptions of generics may have utility in improving treatment outcomes from generic drugs. (PsycINFO Database Record
Health Psychology 10/2015; DOI:10.1037/hea0000282 · 3.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Observational studies (OS) and randomized controlled trials (RCTs) often report discordant results. In the Women's Health Initiative Calcium and Vitamin D (WHI CaD) RCT, women were randomly assigned to CaD or placebo, but were permitted to use personal calcium and vitamin D supplements, creating a unique opportunity to compare results from randomized and observational analyses within the same study.
WHI CaD was a 7-year RCT of 1g calcium/400IU vitamin D daily in 36,282 post-menopausal women. We assessed the effects of CaD on cardiovascular events, death, cancer and fracture in a randomized design- comparing CaD with placebo in 43% of women not using personal calcium or vitamin D supplements- and in a observational design- comparing women in the placebo group (44%) using personal calcium and vitamin D supplements with non-users. Incidence was assessed using Cox proportional hazards models, and results from the two study designs deemed concordant if the absolute difference in hazard ratios was ≤0.15. We also compared results from WHI CaD to those from the WHI Observational Study(WHI OS), which used similar methodology for analyses and recruited from the same population.
In WHI CaD, for myocardial infarction and stroke, results of unadjusted and 6/8 covariate-controlled observational analyses (age-adjusted, multivariate-adjusted, propensity-adjusted, propensity-matched) were not concordant with the randomized design results. For death, hip and total fracture, colorectal and total cancer, unadjusted and covariate-controlled observational results were concordant with randomized results. For breast cancer, unadjusted and age-adjusted observational results were concordant with randomized results, but only 1/3 other covariate-controlled observational results were concordant with randomized results. Multivariate-adjusted results from WHI OS were concordant with randomized WHI CaD results for only 4/8 endpoints.
Results of randomized analyses in WHI CaD were concordant with observational analyses for 5/8 endpoints in WHI CaD and 4/8 endpoints in WHI OS.
PLoS ONE 10/2015; 10(10):e0139975. DOI:10.1371/journal.pone.0139975 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective To determine whether increasing calcium intake from dietary sources affects bone mineral density (BMD) and, if so, whether the effects are similar to those of calcium supplements. Design Random effects meta-analysis of randomised controlled trials. Data sources Ovid Medline, Embase, Pubmed, and references from relevant systematic reviews. Initial searches were undertaken in July 2013 and updated in September 2014. Eligibility criteria for selecting studies Randomised controlled trials of dietary sources of calcium or calcium supplements (with or without vitamin D) in participants aged over 50 with BMD at the lumbar spine, total hip, femoral neck, total body, or forearm as an outcome. Results We identified 59 eligible randomised controlled trials: 15 studied dietary sources of calcium (n=1533) and 51 studied calcium supplements (n=12 257). Increasing calcium intake from dietary sources increased BMD by 0.6-1.0% at the total hip and total body at one year and by 0.7-1.8% at these sites and the lumbar spine and femoral neck at two years. There was no effect on BMD in the forearm. Calcium supplements increased BMD by 0.7-1.8% at all five skeletal sites at one, two, and over two and a half years, but the size of the increase in BMD at later time points was similar to the increase at one year. Increases in BMD were similar in trials of dietary sources of calcium and calcium supplements (except at the forearm), in trials of calcium monotherapy versus co-administered calcium and vitamin D, in trials with calcium doses of ≥1000 versus 500 mg/day, and in trials where the baseline dietary calcium intake was
[Show abstract][Hide abstract] ABSTRACT: Aims/hypothesis
Thiazolidinediones (TZDs) are associated with an increased risk of fracture but the mechanism is unclear. We sought to determine the effect of TZDs on bone mineral density (BMD) and bone turnover markers.
PubMed, EMBASE and Cochrane CENTRAL databases were searched from inception until January 2015 for randomised controlled trials comparing TZDs with metformin, sulfonylureas or placebo, and those reporting changes in BMD and/or bone turnover markers. The primary outcome was percentage change in BMD from baseline and results were pooled with random effects meta-analyses.
In all, 18 trials were included in the primary analyses and another two were included in the sensitivity analyses (n = 3,743, 50% women, mean age 56 years, median trial duration 48 weeks). TZDs decreased BMD at the lumbar spine (difference −1.1% [95% CI −1.6, −0.7]; p
[Show abstract][Hide abstract] ABSTRACT: Overlapping meta-analyses on the same topic are now very common, and discordant results often occur. To explore why discordant results arise, we examined a common topic for overlapping meta-analyses- vitamin D supplements and fracture.
We identified 24 meta-analyses of vitamin D (with or without calcium) and fracture in a PubMed search in October 2013, and analysed a sample of 7 meta-analyses in the highest ranking general medicine journals. We used the AMSTAR tool to assess the quality of the meta-analyses, and compared their methodologies, analytic techniques and results. Applying the AMSTAR tool suggested the meta-analyses were generally of high quality. Despite this, there were important differences in trial selection, data extraction, and analytical methods that were only apparent after detailed assessment. 25 trials were included in at least one meta-analysis. Four meta-analyses included all eligible trials according to the stated inclusion and exclusion criteria, but the other 3 meta-analyses "missed" between 3 and 8 trials, and 2 meta-analyses included apparently ineligible trials. The relative risks used for individual trials differed between meta-analyses for total fracture in 10 of 15 trials, and for hip fracture in 6 of 12 trials, because of different outcome definitions and analytic approaches. The majority of differences (11/16) led to more favourable estimates of vitamin D efficacy compared to estimates derived from unadjusted intention-to-treat analyses using all randomised participants. The conclusions of the meta-analyses were discordant, ranging from strong statements that vitamin D prevents fractures to equally strong statements that vitamin D without calcium does not prevent fractures.
Substantial differences in trial selection, outcome definition and analytic methods between overlapping meta-analyses led to discordant estimates of the efficacy of vitamin D for fracture prevention. Strategies for conducting and reporting overlapping meta-analyses are required, to improve their accuracy and transparency.
PLoS ONE 12/2014; 9(12):e115934. DOI:10.1371/journal.pone.0115934 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
This study investigated the impact of the social modeling of side effects following placebo medication ingestion on the nocebo and placebo effect. It also investigated whether medication branding (brand or generic labeling) moderated social modeling effects.
Eighty-two university students took part in the study which was purportedly investigating the impact of fast-acting beta-blocker medications (actually placebos) on preexamination anxiety. After taking the medication, participants were randomized to either witness a female confederate report experiencing side effects or no side effects after taking the same medication. Differences in symptom reporting, blood pressure, heart rate, and anxiety were assessed between the social modeling of side effects and no modeling groups.
Seeing a female confederate report side effects reduced the placebo effect in systolic (p = .009) and diastolic blood pressure (p = .033). Seeing a female confederate report side effects also increased both total reported symptoms (mean [SE] 7.35 [.54] vs. 5.16 [0.53] p = .005) and symptoms attributed to the medication (5.27 [0.60] vs. 3.04 [0.59] p = .01), although the effect on symptoms was only seen in female participants. Females who saw the confederate report side effects reported approximately twice the number of symptoms as those in the no modeling group. Social modeling did not affect heart rate or anxiety. Medication branding did not influence placebo or nocebo outcomes.
The social modeling of symptoms can substantially reduce or eliminate the placebo effect. Viewing a female confederate display symptoms after taking the same medication increases symptom reporting in females. (PsycINFO Database Record
Health Psychology 12/2014; 34(8). DOI:10.1037/hea0000199 · 3.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Type 2 diabetes mellitus (T2DM) is a common chronic disease that may be associated with an increased risk of fracture. Evidence that thiazolidinediones (TZDs) increase fracture risk in women with T2DM has focused attention on the skeletal effects of treatments for diabetes. Only scant, low-quality evidence is available for non-TZD diabetes medications and bone health, but it suggests that there are no clinically important effects.
Current Osteoporosis Reports 11/2014; 13(1). DOI:10.1007/s11914-014-0250-z
[Show abstract][Hide abstract] ABSTRACT: Background
The role of observational studies in informing clinical practice is debated, and high profile examples of discrepancies between the results of observational studies and randomised controlled trials (RCTs) have intensified that debate. We systematically reviewed findings from the Nurses’ Health Study (NHS), one of the longest and largest observational studies, to assess the number and strength of the associations reported and to determine if they have been confirmed in RCTs.
We reviewed NHS publication abstracts from 1978–2012, extracted information on associations tested, and graded the strength of the reported effect sizes. We searched PubMed for RCTs or systematic reviews for 3 health outcomes commonly reported in NHS publications: breast cancer, ischaemic heart disease (IHD) and osteoporosis. NHS results were compared with RCT results and deemed concordant when the difference in effect sizes between studies was ≤0.15.
2007 associations between health outcomes and independent variables were reported in 1053 abstracts. 58.0% (1165/2007) were statistically significant, and 22.2% (445/2007) were neutral (no association). Among the statistically significant results that reported a numeric odds ratio (OR) or relative risk (RR), 70.5% (706/1002) reported a weak association (OR/RR 0.5–2.0), 24.5% (246/1002) a moderate association (OR/RR 0.25–0.5 or 2.0–4.0) and 5.0% (50/1002) a strong association (OR/RR ≤0.25 or ≥4.0). 19 associations reported in NHS publications for breast cancer, IHD and osteoporosis have been tested in RCTs, and the concordance between NHS and RCT results was low (≤25%).
NHS publications contain a large number of analyses, the majority of which reported statistically significant but weak associations. Few of these associations have been tested in RCTs, and where they have, the agreement between NHS results and RCTs is poor.
PLoS ONE 10/2014; 9(10):e110403. DOI:10.1371/journal.pone.0110403 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
Recently, the European Medicines Agency reported that strontium ranelate increases myocardial infarction risk in postmenopausal women, 8.5 years after it was registered for use in osteoporosis. Unreported serious adverse events in clinical trials for other pharmaceuticals have been described in recent years. We assessed reporting of adverse events and fracture efficacy of strontium.
We compared data on adverse effects (myocardial infarction, venous thromboembolism and pulmonary embolism) and fracture efficacy of strontium in publicly available regulatory documents with data in publications retrieved from searching PubMed.
We identified 5 regulatory documents and 9 primary publications of 7 randomised, placebo-controlled trials of strontium that reported relevant data. We identified several areas of concern in these reports: the increased risk of myocardial infarction with strontium was not identified in a pivotal phase 3 clinical trial despite specific regulatory review of cardiovascular events; data on myocardial infarction were not included in any primary publication; increased risks of venous thromboembolism and pulmonary embolism with strontium were not reported in either of the phase 3 clinical trials; data on venous thromboembolism were reported in only 5 of 9 primary publications, data on pulmonary embolism in only 2 of 9 primary publications, and either was discussed in <50% of subsequent review articles. There were differences in participant numbers, fracture cases and venous thromboembolism cases between regulatory documents and primary publications. Based on all available data from primary publications and regulatory documents, the number of fractures prevented by strontium use is similar to the number of extra cases of venous thromboembolism, pulmonary embolism and myocardial infarction caused by strontium use.
The risks of strontium use are similar to the benefits. Full disclosure of the clinical trial data and regulatory documents would allow clinicians and their patients to decide whether use of the drug is worthwhile.
BMJ Open 10/2014; 4(10):e005787. DOI:10.1136/bmjopen-2014-005787 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bone density has been followed up for 20 months following completion of a trial which compared calcium 1,200 mg/day with placebo, in normal older men. Following cessation of calcium supplements, there is a small residual benefit in total body bone density, but not at the hip or spine. Calcium supplements, or supplements of calcium-rich foods, have a positive effect on bone mineral density (BMD). However, it is uncertain whether there are any residual benefits of calcium on BMD following cessation of supplementation. In a previously published study, 323 healthy men were randomized to receive elemental calcium 600 mg/day (n = 108), calcium 1,200 mg/day (n = 108), or placebo (n = 107) over 2 years. Consenting men from the placebo and calcium 1,200 mg/day groups (85 and 87, respectively) were followed over the next 1-2 years (mean 20 months), off trial medication. In the core trial, BMD increased at all sites by 1.0-1.5 % at 2 years in the group receiving calcium 1,200 mg/day, compared to the group receiving placebo. In post-trial follow-up, the calcium group has some residual benefit at the total body (0.41 % above placebo; P = 0.04) but there was no significant between-group differences at other sites. Following cessation of calcium supplements in healthy men, there is a small residual benefit in total body BMD, but not at the hip or spine. This is unlikely to confer a clinically significant dividend in terms of ongoing fracture prevention.
Osteoporosis International 09/2014; 26(1). DOI:10.1007/s00198-014-2896-x · 4.17 Impact Factor