Estimating the long-term functional burden of osteoporosis-related fractures.

Although fractures are associated with short-term reductions in functional status, there is limited information on longer-term burden of fracture. This study documents evidence of an association between fractures and significant declines and functional health and activities that persist but attenuate beyond two years. INTRODUCTION: Although fractures are associated with short-term reductions in functional status and may have other short-term effects on healthcare utilization (hospitalization and follow-up care), there is limited information on long-term burden of fracture beyond 12 to 24 months post-fracture. Analysis of the long-term health burden can inform policymakers, health care practitioners, and payers. METHODS: We acquired a data set containing the 1992-2012 Health and Retirement Survey data linked to the same individuals' Medicare claims. Fracture cases (n = 745) were matched to non-fracture controls using propensity scores matching. A regression-adjusted difference-in-difference (DD) approach was used to compare the change in functional status measures from baseline to two post-fracture periods for fracture cases relative to the change over the same time periods for matched controls. Self-reported measures of functional status were examined: limitations to activities of daily living (ADLs), limitations to instrumental activities of daily living (IADLs), a mobility index, a gross motor skills index, a fine motor skills index, and self-reported general health status. RESULTS: Fracture cases reported increases in limitations to ADLs, difficulties with mobility, difficulties with gross motor skills, and difficulties with fine motor skills in each HRS collection period (the survey is administered every 2 years) following the fracture or index date (thus up to two years later) than matched controls (all p values < 0.05). The magnitude of these effects diminished in the second post-fracture wave (two to four years after fracture/index date), but they were still statistically significant. CONCLUSIONS: Results suggest that fractures are associated with significant declines in some measures of functional activities up to two years following the fracture. The effects persist beyond two years but are smaller in magnitude.

Health information quality on the internet in gynecological oncology: a multilingual evaluation.

BACKGROUND: Oncological internet information quality is considered variable, but no comprehensive analysis of gynecological malig- nancies exists. The present authors' objectives were to compare the quality of common malignancy websites and to assess for language or disease differences; and secondly, to perform a quality comparison between medical and layperson terminology. MATERIALS AND METHODS: World Health Organization (WHO) Health on the Net (HON) principles may be applied to websites using an automated toolbar function. Using a search engine (www.Google.com) 8,400 websites were assessed using keywords 'endometrial, 'uterine', 'cervical', 'ovarian', 'vaginal', 'vulvar', plus 'cancer', in English, French, German, and Spanish; repeated for alternate terms e.g. 'cervix', 'womb'. RESULTS: Searches for "vaginal' 'uterine', 'cervical', and 'endometrial' each returned millions of websites. The total percentage of all assessed HON-accredited sites was notably low across all search terms (median 15%; range 3-19%). Significant differences by malignancy type (p < 0.0001), language (p < 0.0001), and tertiles (thirds) of the first 150 websites returned (p < 0.0001). French language had most accredited websites. Using alternate terms demonstrated significant differences (p < 0.001) in accredited websites for most gynecological cancers. CONCLUSIONS: Internet data on gynecological malignancies is overwhelming. Further, a lack of validation of the majority of gynecological oncologic sites should be appreciated with discrepancies in quality and number of websites across diseases, languages, and also between medical and layperson terms. Physicians should encourage and more importantly their professional bodies should participate in the development of informative, ethical, and reliable health websites on the internet and direct patients to them.

Involvement of the endocannabinoid system in attentional modulation of nociceptive behaviour in rats.

BACKGROUND: Distraction is used clinically to relieve and manage pain. It is hypothesized that pain demands attention and that exposure to another attention-demanding stimulus causes withdrawal of attention away from painful stimuli, thereby reducing perceived pain. We have recently developed a rat model that provides an opportunity to investigate the neurobiological mechanisms mediating distraction-induced analgesia, as these mechanisms are, at present, poorly understood. Given the well-described role of the endogenous cannabinoid (endocannabinoid; EC) system in the modulation of pain and attentional processing, the present study investigated its role in distraction-induced antinociception in rats. METHODS: Animals received the CB1 receptor antagonist/inverse agonist, rimonabant or vehicle intraperitoneally, 30 min prior to behavioural evaluation. Formalin-evoked nociceptive behaviour was measured in the presence or absence of a novel-object distractor. Liquid chromatography-tandem mass spectrometry was used to determine the levels of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol (2-AG) in the ventral hippocampus (vHip). RESULTS: Exposure to a novel object distractor significantly reduced formalin-evoked nociceptive behaviour. The novel object-induced reduction in nociceptive behaviour was attenuated by rimonabant. Novel object exposure was also associated with increased tissue levels of anandamide and 2-AG in the vHip. CONCLUSIONS: These data suggest that the reduction in formalin-evoked nociceptive behaviour that occurs as a result of exposure to a novel object may be mediated by engagement of the EC system, in particular in the vHip. The results provide evidence that the EC system may be an important neural substrate subserving attentional modulation of pain.

Presentation of endogenous acetylcholine receptor antigen to a specific CD4+ T-cell line by a transfected B-cell line.

Currently, the limited supply and stability of some human autoantigens pose formidable difficulties in characterizing patients' T cells specific for them; recombinant preparations may contain bacterial contaminants, and synthetic peptides have arbitrarily chosen start and stop points. In order to provide a stable antigen source with naturally processed epitopes, a full-length acetylcholine receptor (AChR) alpha subunit construct was transfected into B-lymphoblastoid cell lines (B-LCL). Expression was much easier to detect at the mRNA level than the protein level. Nevertheless, this transfectant also stimulated a T-cell line that recognized the alpha 149-156 region in the context of HLA-DR4 at high sensitivity. The responses were specific both for the antigen transfected and for the presenting HLA-DR allele. This study thus confirms the potential of autologous B-LCL expressing natural epitopes in the context of HLA class II molecules for characterizing established T-cell lines, and perhaps also for initiating new ones.

Attitudes to oral feeding following caesarean section.

In order to evaluate postoperative nutrition in women who have undergone Caesarean section, we conducted a national survey. Questionnaires were sent to 100 randomly selected obstetric units in the UK, and were completed and returned by senior midwives. We found that that only 21.5% of units had a departmental policy concerning feeding after Caesarean section. Midwives decided when women could eat and drink in the majority of obstetric units (78.5%), often without the help of guidelines. The period of postoperative starvation was found to vary greatly, from < 1 h in some units to > 24 h in others. We suggest that all obstetric units should produce guidelines in order to rationalise postoperative feeding for women following Caesarean section.

The patient-at-risk team: identifying and managing seriously ill ward patients.

A 'patient-at-risk team', established to allow the early identification of seriously ill patients on hospital wards, made 69 assessments on 63 patients over 6 months. Predefined physiological criteria were not able to reliably predict which patients would be admitted to the intensive care unit. The incidence of cardiopulmonary resuscitation before intensive care admission was 3.6% for patients seen by the team and 30.4% for those not seen (p < 0.005). Of admissions seen by the team, 25% died on the intensive care unit compared with 45% of those not seen (not significant, p = 0.07). Among those not seen by the team, mortality was 40% for those who did not require resuscitation and 57% for those who did (not significant). Many critically ill ward patients had abnormal physiological values before intensive care unit admission. Identification of critically ill patients on the ward and early advice and active management are likely to prevent the need for cardiopulmonary resuscitation and to improve outcome.

Use of Epstein-Barr virus-based vectors for expression of thyroid auto-antigens in human B-lymphoblastoid cell lines.

The TSH-receptor (TSH-R) and thyroid peroxidase (TPO) are targets of autoantibody production in the autoimmune thyroid disease, Graves' disease, and are also likely to be the target of T-cell responses. To facilitate the analysis of T-cell responses we have investigated a system that allows expression of these autoantigens as recombinant proteins in autologous cells. Human B-lymphoblastoid cell lines (B-LCL), which are known to present antigen to autologous T cells, were transfected with constructs directing the expression of human TSH-R and TPO. The constructs utilized an expression vector replicating under the control of EBV-derived sequences that is maintained episomally in transfected cells. Both proteins were shown to be expressed by transfected B-LCL and present on the cell surface. Such transfected B-LCL could be used for the derivation, screening and characterization of autologous T-cell clones against thyroid autoantigens.

CL22 - a novel cationic peptide for efficient transfection of mammalian cells.

Condensing peptide-DNA complexes have great potential as nonviral agents for gene delivery. To date, however, such complexes have given transfection activities greatly inferior to adenovirus and somewhat inferior to cationic lipid-DNA complexes, even for cell lines and primary cells in vitro. We report here the identification of a novel condensing peptide, CL22, which forms DNA complexes that efficiently transfect many cell lines, as well as primary dendritic and endothelial cells. We report studies with sequence and structure variants that define some properties of the peptide that contribute to efficient transfection. We demonstrate that the superior transfection activity of CL22 compared with other DNA condensing peptides is conferred at a step after uptake of the complexes into cells. We show that CL22-DNA complexes have transfection activity that is at least equivalent to the best available nonviral agents.