Accuracy of patient-reported height loss and risk factors for height loss among postmenopausal women

Background

Since loss of height may indicate vertebral fracture, the accuracy of the information on height is relevant for clinical practice. We undertook this study to compare reported and measured loss of height among post-menopausal women in a primary care setting. We also analyzed the determinants of this height loss.

Methods

In an observational study conducted between December 2007 and May 2008, we asked 1779 randomly selected general practitioners to recruit the first five female patients who were more than 60 years of age, regardless of the reason for the consultation. Using a questionnaire, physicians collected data on demographic and clinical variables, history of osteoporosis and current anti-osteoporotic treatment. We used three assessments of height: tallest height in early adulthood recalled by the patient, estimated current height reported by the patient at the visit and current measured height. We defined loss of height as the difference between the patient’s tallest recalled height and her current measured height.

Results

A total of 8610 patients were included in the analysis; the mean age was 70.9 (standard deviation [SD] 7.2) years. The mean loss of height was 4.5 cm. The mean current reported height was 2.1 (SD 2.5) cm lower than the tallest recalled height and 2.4 (SD 2.6) cm lower than the measured current height. The best predictors of a loss of height of 3 cm or more were age (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.08–1.10), previous vertebral fracture (OR 1.49, 95% CI 1.16–1.91), previous nonvertebral fracture (OR 1.26, 95% CI 1.06–1.51), thoracic kyphosis (OR 2.07, 95% CI 1.69–2.55), scoliosis (OR 1.35, 95% CI 1.12–1.63), back pain (OR 1.22, 95% CI 1.07–1.39) and osteoporosis (OR 1.39, 95% CI 1.20–1.60).

Interpretation

Our study showed that the patients’ estimated current height was not correct, with a mean difference of −2.5 cm from the current measured height. The mean height loss was 4.5 cm. Previous vertebral fracture and thoracic kyphosis were strong determinants of the height loss.Loss of height is common with advancing age.^1,2 Causes include changes in curvature of the spine, narrowing of intervertebral discs and vertebral fractures. Height loss is associated with back pain and thoracic hyperkyphosis.^3,4 Two-thirds of adults have back pain at any time. Controversies exist about the need for radiographs of the spine: Does the benefit of detecting treatable disorders of the spine such as vertebral fracture outweigh the harm of unnecessary radiographs? Loss of height is usually recorded as one of the clinical signs to help identify postmenopausal women with vertebral fractures.⁵ The use of this parameter to decide whether radiography is needed depends on the threshold for height loss associated with a strong risk of vertebral fracture. The thresholds useful in clinical practice to detect prevalent vertebral fracture range from 3 cm to 6 cm,^6–9 with the risk of prevalent fracture increasing with the magnitude of the height loss. Thus, the accuracy of the information on height is relevant for clinical practice.We conducted this study to compare reported and measured loss of height in a large population of women more than 60 years old in a primary care setting and to analyze the determinants of this height loss.     

Diversification and Distribution of Ruminant Chlamydia abortus Clones Assessed by MLST and MLVA

Chlamydia abortus, an obligate intracellular bacterium, is the most common infectious cause of abortion in small ruminants worldwide and has zoonotic potential. We applied multilocus sequence typing (MLST) together with multiple-locus variable-number tandem repeat analysis (MLVA) to genotype 94 ruminant C. abortus strains, field isolates and samples collected from 1950 to 2011 in diverse geographic locations, with the aim of delineating C. abortus lineages and clones. MLST revealed the previously identified sequence types (STs) ST19, ST25, ST29 and ST30, plus ST86, a recently-assigned type on the Chlamydiales MLST website and ST87, a novel type harbouring the hemN_21 allele, whereas MLVA recognized seven types (MT1 to MT7). Minimum-spanning-tree analysis suggested that all STs but one (ST30) belonged to a single clonal complex, possibly reflecting the short evolutionary timescale over which the predicted ancestor (ST19) has diversified into three single-locus variants (ST86, ST87 and ST29) and further, through ST86 diversification, into one double-locus variant (ST25). ST descendants have probably arisen through a point mutation evolution mode. Interestingly, MLVA showed that in the ST19 population there was a greater genetic diversity than in other STs, most of which exhibited the same MT over time and geographical distribution. However, the evolutionary pathways of C. abortus STs seem to be diverse across geographic distances with individual STs restricted to particular geographic locations. The ST30 singleton clone displaying geographic specificity and represented by the Greek strains LLG and POS was effectively distinguished from the clonal complex lineage, supporting the notion that possibly two separate host adaptations and hence independent bottlenecks of C. abortus have occurred through time. The combination of MLST and MLVA assays provides an additional level of C. abortus discrimination and may prove useful for the investigation and surveillance of emergent C. abortus clonal populations.     

Staying cool in a changing landscape: the influence of maximum daily ambient temperature on grizzly bear habitat selection

To fulfill their needs, animals are constantly making trade-offs among limiting factors. Although there is growing evidence about the impact of ambient temperature on habitat selection in mammals, the role of environmental conditions and thermoregulation on apex predators is poorly understood. Our objective was to investigate the influence of ambient temperature on habitat selection patterns of grizzly bears in the managed landscape of Alberta, Canada. Grizzly bear habitat selection followed a daily and seasonal pattern that was influenced by ambient temperature, with adult males showing stronger responses than females to warm temperatures. Cutblocks aged 0–20 years provided an abundance of forage but were on average 6 °C warmer than mature conifer stands and 21- to 40-year-old cutblocks. When ambient temperatures increased, the relative change (odds ratio) in the probability of selection for 0- to 20-year-old cutblocks decreased during the hottest part of the day and increased during cooler periods, especially for males. Concurrently, the probability of selection for 21- to 40-year-old cutblocks increased on warmer days. Following plant phenology, the odds of selecting 0- to 20-year-old cutblocks also increased from early to late summer while the odds of selecting 21- to 40-year-old cutblocks decreased. Our results demonstrate that ambient temperatures, and therefore thermal requirements, play a significant role in habitat selection patterns and behaviour of grizzly bears. In a changing climate, large mammals may increasingly need to adjust spatial and temporal selection patterns in response to thermal constraints.     

Cyan fluorescent protein carries a constitutive mutation that prevents its dimerization

The tendency of GFP-like fluorescent proteins to dimerize in vitro is a permanent concern as it may lead to artifacts in FRET imaging applications. However, we have found recently that CFP and YFP (the couple of GFP variants mostly used in FRET studies) show no trace of association in the cytosol of living cells up to millimolar concentrations. In this study, we investigated the oligomerization properties of purified CFP, by fluorescence anisotropy and sedimentation velocity. Surprisingly, we found that CFP has a much weaker homoaffinity than other fluorescent proteins (K(d) ≥ 3 × 10(-3) M), and that this is due to the constitutive N146I mutation, originally introduced into CFP to improve its brightness.     

In vivo and in vitro analyses of toxic mutants of HET-s: FTIR antiparallel signature correlates with amyloid toxicity

The folding and interactions of amyloid proteins are at the heart of the debate as to how these proteins may or may not become toxic to their host. Although little is known about this issue, the structure seems to be clearly involved with effects on molecular events. To understand how an amyloid may be toxic, we previously generated a yeast toxic amyloid (mutant 8) from the nontoxic HET-s_(218-289) prion domain of Podospora anserina. Here, we performed a comprehensive structure-toxicity study by mutating individually each of the 10 mutations found in mutant 8. The study of the library of new mutants generated allowed us to establish a clear link between Fourier transform infrared antiparallel signature and amyloid toxicity. All of the mutants that form parallel β-sheets are not toxic. Double mutations may be sufficient to shift a parallel structure to antiparallel amyloids, which are toxic to yeast. Our findings also suggest that the toxicity of antiparallel structured mutants may be linked to interaction with membranes.     

Anti-cetuximab IgE ELISA for identification of patients at a high risk of cetuximab-induced anaphylaxis

Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, has proven effective in the treatment of metastatic colorectal cancer and squamous cell carcinoma of the head and neck. However, a high incidence of immediate hypersensitivity reactions (HSR) to cetuximab after the first infusion has been observed. We have developed a test for identification of patients likely to show treatment-related HSR to cetuximab. An enzyme-linked immunosorbent assay (ELISA) for detecting anti-cetuximab IgEs was developed and tested on serum samples collected from cancer patients before start of cetuximab treatment, and from healthy blood donors. Similar levels of anti-cetuximab IgE were detected in pre-treatment patient sera (24/92, 26.1%) and sera from healthy blood donors (33/117, 28.2%). HSR were observed in 14 out of the 92 patients (15.2%), and 8 of these (57.1%) were grade 3–4. Anti-cetuximab IgEs were detected in 7/8 of the patients (87.5%) with severe HSRs as compared with 14/78 patients (17.9%) with no HSR (p = 0.0002). Predictive value of the anti-cetuximab IgE test for HSR events of grades 3–4 was calculated using Receiver Operating Characteristics analysis. With a cut-off value of 29 arbitrary units for the anti-cetuximab IgE, the ELISA test showed a sensitivity of 87.5%, specificity of 82.1%, positive predictive value of 33.3% and negative predictive value of 98.5%. Anti-cetuximab IgE ELISA detection could be a valuable tool to help the physician anticipate an anaphylaxis episode following cetuximab infusion and opt for a suitable alternative treatment.Key words: anti-cetuximab antibodies, ELISA, hypersensitivity, therapeutic monoclonal antibody, ROC     

Bisphosphonated fluoroquinolone esters as osteotropic prodrugs for the prevention of osteomyelitis

Osteomyelitis is a difficult to treat bacterial infection of the bone. Delivering antibacterial agents to the bone may overcome the difficulties in treating this illness by effectively concentrating the antibiotic at the site of infection and by limiting the toxicity that may result from systemic exposure to the large doses conventionally used. Using bisphosphonates as osteophilic functional groups, different forms of fluoroquinolone esters were synthesized and evaluated for their ability to bind bone and to release the parent antibacterial agent. Bisphosphonated glycolamide fluoroquinolone esters were found to present a profile consistent with effective and rapid bone binding and efficient release of the active drug moiety. They were assessed for their ability to prevent bone infection in vivo and were found to be effective when the free fluoroquinolones were not.