Predictors of new and severe vertebral fractures: results from the HORIZON Pivotal Fracture Trial.

UNLABELLED: We examined prevalent and recent vertebral fractures in 1 year as predictors of new vertebral fractures over subsequent 2 years using data from RCT placebo patients. We found that prevalent and recent vertebral fractures strongly and independently predicted subsequent vertebral fractures including those which were severe. INTRODUCTION: While several studies have shown that prevalent vertebral fractures (pVFx) increase the risk of new vertebral fractures (VFx), the impact of recent vertebral fractures on future fractures is less studied. METHODS: Data from the placebo arm of the HORIZON Pivotal Fracture Trial, an international trial of zoledronic acid in postmenopausal, osteoporotic women between 65 and 85 years, were used. We included the subset of 2677 women with annual spinal radiographs to study the impact of vertebral fractures in year 1 (Y1 VF) on those occurring in years 2 and 3 using morphometric and semiquantitative (SQ) criteria. In addition, a subset of severe VFx was defined using SQ criteria. Logistic regression examined the impact of pVFx and Y1 VF on all incident VFx and on severe incident VFx. RESULTS: Two hundred fourty-five (9.1%) women sustained a new VFx in years 2-3. VFx risk in years 2-3 was 3.9% in those without pVFx or VFy1 and 29.8% in those with both risk factors. Both pVF and VFy1 remained independent predictors for future VF when they were both entered into a logistic regression model (odds ratio (OR) = 3.3; 95% confidence interval (CI), 2.3-4.7; OR = 3.7, 95% CI, 2.3, 5.8, respectively). ORs were similar after adjustment. Of the total number of women, 4.1% had severe VFx. PVFx and Y1 VF were also significant predictors of severe VFx; however, Y1 VF appeared more strongly predictive of severe VFx. CONCLUSIONS: Prevalent and incident vertebral fractures are highly predictive of subsequent new and severe vertebral fractures. Women with both of these risk factors are likely to benefit from anti-osteoporosis treatment.

Treatment of canine osseous tumors with photodynamic therapy: a pilot study.

Photodynamic therapy uses nonthermal coherent light delivered via fiber optic cable to locally activate a photosensitive chemotherapeutic agent that ablates tumor tissue. Owing to the limitations of light penetration, it is unknown whether photodynamic therapy can treat large osseous tumors. We determined whether photodynamic therapy can induce necrosis in large osseous tumors, and if so, to quantify the volume of treated tissue. In a pilot study we treated seven dogs with spontaneous osteosarcomas of the distal radius. Tumors were imaged with MRI before and 48 hours after treatment, and the volumes of hypointense regions were compared. The treated limbs were amputated immediately after imaging at 48 hours and sectioned corresponding to the MR axial images. We identified tumor necrosis histologically; the regions of necrosis corresponded anatomically to hypointense tissue on MRI. The mean volume of necrotic tissue seen on MRI after photodynamic therapy was 21,305 mm(3) compared with a pretreatment volume of 6108 mm(3). These pilot data suggest photodynamic therapy penetrates relatively large canine osseous tumors and may be a useful adjunct for treatment of bone tumors.

Validation of the revised Patient Perception of Migraine Questionnaire (PPMQ-R): measuring satisfaction with acute migraine treatment in clinical trials.

This study was aimed to evaluate in clinical trial settings the psychometric properties of the revised Patient Perception of Migraine Questionnaire (PPMQ-R), a satisfaction measure for acute migraine treatment. The PPMQ-R was administered 24 h post dosing in 1304 migraineurs randomized to two identical Phase 3, single-attack trials. Reliability, concurrent and construct validity and known-groups validity were evaluated using Cronbach's alpha, Pearson correlations and analysis of variance, respectively. PPMQ-R scale and Total scores (Efficacy, Functionality and Ease of use) showed very good internal consistency reliability (alpha 0.84-0.99). Efficacy, Functionality and Total PPMQ-R scores showed large, inverse relationships with migraine pain severity, number of migraine symptoms and work ability (r = -0.62 to -0.75; all P < 0.0001). All scales discriminated among migraine pain severity levels (all P < 0.001). The PPMQ-R has sufficient evidence of validity and reliability for measuring patient satisfaction, an important benchmark of quality and effective care.

Treatment satisfaction and efficacy of the rapid release formulation of sumatriptan 100 mg tablets utilising an early intervention paradigm in patients previously unsatisfied with sumatriptan.

AIMS: To evaluate treatment satisfaction, efficacy and functional ability of the rapid release formulation of sumatriptan 100 mg tablets (sumatriptan RT 100 mg) in an early intervention paradigm in patients who were dissatisfied with low-dose sumatriptan and not completely satisfied with their current migraine regimen. METHODS: Experienced migraineurs who reported a mild migraine pain phase, dissatisfaction with the previous sumatriptan treatment and some dissatisfaction with their current treatment regimen had no experience with sumatriptan at the 100 mg dose were enrolled in an open-label, single group study. Subjects were instructed to treat four migraine attacks within 30 min of the onset of mild pain. Treatment satisfaction was measured with the Patient Perception of Migraine Questionnaire Revised version (PPMQ-R) questionnaire. RESULTS: More than half of the subjects were either very satisfied or satisfied with the efficacy of early intervention sumatriptan RT 100 mg after each attack and at the follow-up study visit. The mean total PPMQ-R score was 75.2 out of 100. Between 63% and 73% of subjects were pain-free within 4 h of dosing. Between 79% and 90% of subjects reported an ability to function normally within 4 h of taking the study medication. CONCLUSION: Subjects who were previously unsatisfied with lower doses of sumatriptan and less than very satisfied with their current treatment regimen were more likely to be satisfied or very satisfied with sumatriptan RT 100 mg in an early intervention paradigm. Results were consistent across four migraine attacks and at a follow-up visit. The treatment satisfaction results corresponded with positive results on efficacy measures and a functional status measure.

Placement of iliosacral screws using 3D image-guided (O-Arm) technology and Stealth Navigation: comparison with traditional fluoroscopy.

AIMS: We compared the accuracy, operating time and radiation exposure of the introduction of iliosacral screws using O-arm/Stealth Navigation and standard fluoroscopy. MATERIALS AND METHODS: Iliosacral screws were introduced percutaneously into the first sacral body (S1) of ten human cadavers, four men and six women. The mean age was 77 years (58 to 85). Screws were introduced using a standard technique into the left side of S1 using C-Arm fluoroscopy and then into the right side using O-Arm/Stealth Navigation. The radiation was measured on the surgeon by dosimeters placed under a lead thyroid shield and apron, on a finger, a hat and on the cadavers. RESULTS: There were no neuroforaminal breaches in either group. The set-up time for the O-Arm was significantly longer than for the C-Arm, while total time for placement of the screws was significantly shorter for the O-Arm than for the C-Arm (p = 0.001). The mean absorbed radiation dose during fluoroscopy was 1063 mRad (432.5 mRad to 4150 mRad). No radiation was detected on the surgeon during fluoroscopy, or when he left the room during the use of the O-Arm. The mean radiation detected on the cadavers was significantly higher in the O-Arm group (2710 mRem standard deviation (sd) 1922) than during fluoroscopy (11.9 mRem sd 14.8) (p < 0.01). CONCLUSION: O-Arm/Stealth Navigation allows for faster percutaneous placement of iliosacral screws in a radiation-free environment for surgeons, albeit with the same accuracy and significantly more radiation exposure to cadavers, when compared with standard fluoroscopy. TAKE HOME MESSAGE: Placement of iliosacral screws with O-Arm/Stealth Navigation can be performed safely and effectively. Cite this article: Bone Joint J 2016;98-B:696-702.

The causes and consequences of genetic variation in dengue virus.

Despite the fact that dengue is one of the most prevalent viral infections of humans, the mechanisms responsible for its pathogenesis remain uncertain. Evolutionary studies of dengue virus have revealed that its genetic diversity is increasing. This, coupled with evidence that viral strains could naturally differ in virulence, suggests that in the future we might be exposed to viruses with an expanded range of pathogenic properties.

Photodynamic therapy for the treatment of vertebral metastases in a rat model of human breast carcinoma.

The feasibility and efficacy of photodynamic therapy (PDT) for the treatment of vertebral metastases using a minimally invasive surgical technique adapted from vertebroplasty was evaluated in a rodent model. Initial validation included photosensitizer (benzoporphyrin-derivative monoacid-ring A) drug uptake studies and in vitro confirmation of PDT efficacy. Intracardiac injection of human MT-1 breast cancer cells was performed in athymic rats. In 63 rats that developed vertebral metastases 21 days post-inoculation, single treatment of PDT was performed using a parapedicular approach placing an optical fiber adjacent to targeted vertebrae. Two milligrams per kilogram of photosensitizer drug was administered intravenously followed by 150 mW of 690 nm light illumination at varying drug-light intervals and light energies. Histologic and immunohistochemical analysis was performed assessing treatment effect. Local tumor viability and growth was quantified by bioluminescence imaging pre and 48 h post-treatment. PDT demonstrated an ablative effect on vertebral metastases (light energies 25-150 J). The effect varied in proportion to light energy with the greatest anti-tumor effect observed at 150 J using a 3 h drug-light interval. 9/22 rodents in the 3 h drug-light interval developed hindlimb paralysis following treatment, consistent with drug uptake studies demonstrating an increase in spinal cord uptake 3h following drug administration. The observations of paralysis following treatment highlight the importance of closely defining the therapeutic window of treatment in safety and efficacy.

Photodynamic therapy for the treatment of metastatic lesions in bone: studies in rat and porcine models.

This study represents the first reported use of photodynamic therapy (PDT) for metastatic bone lesions and specifically, as a treatment for spinal metastases. A model of bone metastasis in rat confirmed the efficacy of benzoporphyrin derivative-monoacid-mediated PDT for treating lesions within the spine and appendicular bone. Fluorimetry confirmed the selective accumulation of drug into the tumor(s) at 3 h post-injection. 48 h post-light delivery into the vertebral body of the rat spine loss of bioluminescent signal and histological analyses of sectioned spine confirmed MT-1 tumor cell kill in vivo as previously confirmed in vitro using an established cell viability assay. Porcine vertebrae provided a model comparable to that of human for light propagation and PDT response. Histological examination of vertebrae 48 h post-PDT revealed a necrotic radius of 0.6 cm with an average fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident up to 2 cm out from the treatment fiber. Results support the application of PDT to the treatment of primary or metastatic lesions within bone.

Volume CT with a flat-panel detector on a mobile, isocentric C-arm: pre-clinical investigation in guidance of minimally invasive surgery.

A mobile isocentric C-arm (Siemens PowerMobil) has been modified in our laboratory to include a large area flat-panel detector (in place of the x-ray image intensifier), providing multi-mode fluoroscopy and cone-beam computed tomography (CT) imaging capability. This platform represents a promising technology for minimally invasive, image-guided surgical procedures where precision in the placement of interventional tools with respect to bony and soft-tissue structures is critical. The image quality and performance in surgical guidance was investigated in pre-clinical evaluation in image-guided spinal surgery. The control, acquisition, and reconstruction system are described. The reproducibility of geometric calibration, essential to achieving high three-dimensional (3D) image quality, is tested over extended time scales (7 months) and across a broad range in C-arm angulation (up to 45 degrees), quantifying the effect of improper calibration on spatial resolution, soft-tissue visibility, and image artifacts. Phantom studies were performed to investigate the precision of 3D localization (viz., fiber optic probes within a vertebral body) and effect of lateral projection truncation (limited field of view) on soft-tissue detectability in image reconstructions. Pre-clinical investigation was undertaken in a specific spinal procedure (photodynamic therapy of spinal metastases) in five animal subjects (pigs). In each procedure, placement of fiber optic catheters in two vertebrae (L1 and L2) was guided by fluoroscopy and cone-beam CT. Experience across five procedures is reported, focusing on 3D image quality, the effects of respiratory motion, limited field of view, reconstruction filter, and imaging dose. Overall, the intraoperative cone-beam CT images were sufficient for guidance of needles and catheters with respect to bony anatomy and improved surgical performance and confidence through 3D visualization and verification of transpedicular trajectories and tool placement. Future investigation includes improvement in image quality, particularly regarding x-ray scatter, motion artifacts and field of view, and integration with optical tracking and navigation systems.

Measurement of 6-MV X-ray surface dose when topical agents are applied prior to external beam irradiation.

PURPOSE: Radiation therapy patients are typically warned not to apply lotions, deodorants, or powders to the skin within the treatment area because of the possible increase in surface dose due primarily to a bolus effect. This study investigates the effect of 15 products, with and without high atomic number components, on surface dose. METHODS AND MATERIALS: A Markus-type parallel plate ionization chamber in a polystyrene phantom was used to measure surface doses for normal applications of the products for a small (5 x 5-cm2) and a large (25 x 25-cm2) field size. RESULTS: The greatest surface dose increase for any product was 5.4% (21.8-27.2%) of the d(max) dose for the small field and 1.0% (43.6-44.6%) for the large field. Products with high-atomic-number components did not increase the surface dose relative to radiation therapy specialty products. CONCLUSION: No large increase in surface dose was detected with a normal application of the products. However, the possibility exists that an increase in skin reaction may occur owing to chemical irritants in the applied product.

A filtration method for improving film dosimetry in photon radiation therapy.

Successful radiotherapy requires accurate dosimetry for treatment verification. Existing dosimeters such as ion chambers, TLD, and diodes have drawbacks such as relatively long measurement time and poor spatial resolution. These disadvantages become serious problems for dynamic-wedged beams. Thus the clinical use of dynamic wedges requires an improved dosimetry method. X-ray film may serve this purpose. However, x-ray film is not clinically accepted as a dosimeter for photon beams, because it overresponds to photons with energies below about 400 keV. This paper presents and develops a method which was initially proposed by Burch to improve the dose response of x-ray film in a phantom. The method is based on placing high-atomic number foils next to the film. The foils are used as filters to preferentially remove low-energy photons. The optimal film and filter configuration in a phantom was determined using a mathematical scheme derived in this study and a Monte Carlo technique (ITS code). The optimal configuration thus determined is as follows: the filter-to-film distance of 6 mm and the filter thickness of 0.15 mm for percent depth-dose measurement; the distance of 1 cm and the thickness of 0.25 mm for off-axis (dose) ratio measurement. The configuration was then tested with photon beams from a 4 MV linac. The test result indicates that the in-phantom dose distribution based on the optimal configuration agrees well with those measured by ion chambers.

A new approach to film dosimetry for high energy photon beams: lateral scatter filtering.

A method of film dosimetry for high energy photon beams is proposed which reduces the required film calibration exposures to a set of films obtained for a small radiation field size and shallow depth (6 cm x 6 cm at 5 cm depth). It involves modification of a compression type polystyrene film phantom to include thin lead foils parallel to the vertical film plane at approximately 1 cm from both sides of the film emulsion. The foils act as high atomic number filters which remove low energy Compton scatter photons that otherwise would cause the film sensitivity to change with field size and depth. The proposed method is best described as "lateral scatter filtering." To validate the proposed method, central axis depth doses and isodose curves for a 4 MV photon beam were determined from films exposed within the modified phantom and the results compared with ionization chamber measurements. When no lateral filtering was used, for field sizes of 6 cm x 6 cm and 25 cm x 25 cm, this comparison demonstrated up to a 65% difference between film and ionization chamber central axis depth dose measurements. When using the lateral scatter filtering technique, less than a 4% difference was observed for these field sizes.

A new approach to film dosimetry for high-energy photon beams using organic plastic scintillators.

This study is concerned with dose measurement of photon beams, both dynamic and static, by using x-ray film. As discussed in our last study (Burch et al 1997, Yeo et al 1997), x-ray film, as an integrating dosimeter, can be an ideal candidate if the over-response problem to low-energy photons (energies below 400 keV) is solved. In summary, the problem of the over-response can be explained as follows. Because the mass energy absorption coefficient of x-ray film increases as photon energy decreases, softening of the photon spectra with depth in a phantom makes the extent of film over-response a function of phantom depth (Burch et al 1997, Yeo et al 1997). Film dosimetry is based upon (a) calibration of the film response (i.e. optical density) at some specific depth in a phantom and (b) conversion of the film density which can cover whole depths in a phantom to dose by using the calibration curve. In megavoltage dosimetry, this normally causes over-response in doses at depths greater than the calibration depth.

Measurement of density variations in tablets using X-ray computed tomography.

In this paper the application of X-ray computed tomography (CT) to measure the material density distribution in pharmaceutical tablets is discussed. X-ray CT is a non-destructive inspection technique which provides cross-sectional images in different planes through a component. The CT image values provide information on the local X-ray attenuation coefficients. For a particular material and X-ray energy, X-ray attenuation is approximately proportional to material density. Determination of quantitative density distributions requires consideration of non-linear instrumental effects including scatter and "beam hardening". Density maps in tablets manufactured under controlled conditions are presented. The results are discussed with reference to the local properties of the material within the tablet and the tablet design features.

Generation of dose calculation data tables using cubic spline interpolation.

In order to calculate treatment machine settings for a teletherapy machine (e.g., time or monitor units), tables are usually used for variables such as output factor, TMR, percent depth dose. The tables are often generated from data collected at a few points. A linear interpolation is usually used to generate values between the measured points. This can introduce errors as great as 2% between the calculated and actual data points. Using a mathematical software package a computer can generate smooth, accurate curves that agree with measured values to within a few tenths of a percent. This method is not an averaging type of procedure by which a certain function is chosen and parameters are adjusted to force the function to fit the data as closely as possible, but rather is a procedure that fits curves exactly through the measured data points.

Verification of optical distance indicator accuracy.

The purpose of the optical distance indicator, or rangefinder, is to set the patient at a certain distance from the radiotherapy source when using either fixed SSD or an isocentric technique. If the distance that is set is not accurate, then the tumor dose calculated using this distance is also incorrect. Unfortunately, an ODI that is not properly aligned may show an accurate reading on a flat surface and may give an inaccurate reading on a sloped surface.

Collaboration, facilities and communities in day care services for older people.

Collaborative working in care for older people is often seen as a desirable goal. However, there can be problems with this approach. This paper reports on a single blind randomized controlled trial which was carried out to compare outcomes of rehabilitation in two settings: a day hospital and social services day centres augmented by visiting therapists. The subjects were 105 older patients. Principal outcome measures were the Barthel Index, Philadelphia Geriatric Centre Morale Scale and the Caregiver Strain Index. Two aspects of the trial are examined here. Firstly, we investigated whether trial patients were more disabled than regular day centre attendees. Levels of health and well being amongst trial patients were compared with those of a random sample of 20 regular attendees from both of the participating day centres and an additional voluntary sector day centre. Secondly, key staff from the different settings were interviewed to assess how well the day centre model had worked in practice. Trial patients were significantly more disabled than regular day centre attendees according to the Barthel Index (P < 0.001), but this difference was no longer significant after three months of treatment. The day centre model had several problems, principally discharge policy, acceptability, facilities and attitudes of staff and regular attendees. Positive aspects of the day centre model, as well as successful rehabilitation, included shared skills, knowledge and resources. This paper suggests that collaborative working in day centres requires multipurpose facilities. If health staff maintain a permanent presence, benefits can include improved joint working, easier access to health care and the use of rehabilitative therapy as a preventative strategy. Day care settings can be analyzed as representing different types of communities. Allowing older users a greater degree of choice in facilities may increase the acceptability of care.

Comparison of expected and evidenced baccalaureate degree competencies.

The defining of beginning competencies for the baccalaureate degree in nursing education has been an issue over the past decade. Many researchers have attempted to investigate the performance of graduates of the basic nursing preparation programs. At present, there is little that links education to practice. The purposes of this study were to validate whether the competencies of graduates of baccalaureate degree nursing programs were as expected by nursing service administrators, and whether the expected competencies were evidenced in the work setting. A two-part questionnaire was administered to 142 directors of nursing in health-care settings in Mississippi. The research project requested an evaluation of the baccalaureate competency statement from two perspectives. On a five-point Likert scale, administrators were asked to evaluate if the competency should be expected of a baccalaureate graduate. The administrators then evaluated to what extent the competency statement was evidenced. Analysis of the data was done using descriptive statistics. A mean for each competency was calculated for expected and evidenced responses. A difference of 30% between the expected and evidenced responses was deemed to be significant. Conclusions were drawn and recommendations for further study made.

Consciousness: how does it relate to health?

The purpose of this article is to clarify the concept consciousness as it relates to human health and invite nurses to examine a variety of perspectives on the concept that may influence practice, education, and research. A review of American nursing, medical, psychological, and philosophical literature reveals a considerable range of theories that seem to connect, forming a broad foundation for further study. Initial analysis of the concept yields a working definition that consciousness is the fundamental and thoroughly pervasive implicit field of all existence, both seen and unseen. Additionally, the North American Nursing Diagnosis Association human response patterns were found to provide a useful set of empirical referents. Further exploration and testing of these referents may stimulate important insights into the fundamental domains of nursing.

Management of status asthmaticus.

Status asthmaticus is a medical emergency that requires careful evaluation and aggressive therapy. The mainstay of medical therapy is frequent administration of beta-agonist inhalations, combined with early corticosteroid use. Intravenous magnesium can be used as an adjunctive measure. If available, nebulized ipratropium bromide can be added to the regimen if side effects or poor response occurs to maximal dosages of beta-agonists. Nonconventional therapies should be considered only if conventional treatment fails. Signs and symptoms of deteriorating airflow and respiratory muscle fatigue should determine the need for mechanical ventilation. If mechanical ventilation is required, controlled hypoventilation may be best.