Vertebral fractures and trabecular microstructure in men with prostate cancer on androgen deprivation therapy

Androgen deprivation therapy (ADT), a treatment for prostate cancer, is associated with bone loss and fractures. Dual‐energy X‐ray absorptiometry (DXA)–measured bone mineral density does not assess vertebral fractures (VF). High‐resolution micro‐magnetic resonance imaging (HR‐MRI) assesses bone microarchitecture and provides structural information. To determine if VF identification increased the diagnosis of osteoporosis beyond DXA and if HR‐MRI demonstrated skeletal deterioration in men with VF, we cross‐sectionally studied 137 men aged ≥ 60 years with nonmetastatic prostate cancer on ADT for ≥ 6 months. Vertebral fracture assessment (VFA) by DXA was confirmed with X‐rays. HR‐MRI of the wrist included bone volume to total volume (BV/TV), surface density (trabecular plates), surface/curve ratio (plates/rods), and erosion index (higher depicts deterioration). VF were found in 37% of men; the majority were unknown. Seven percent of participants were classified as osteoporotic by hip or spine DXA. Thirty‐seven percent of men without osteoporosis by DXA had VF identified, suggesting that 90% of patients with clinical osteoporosis would have been misclassified by DXA alone. By ANOVA comparison across VF grades, the BV/TV, surface density, and spine, hip, and wrist DXA were lower, and erosion index was higher in men with moderate‐severe VF compared with lesser grades (all p < 0.05). By unadjusted ROC analysis, the addition of HR‐MRI to DXA at the spine, hip, and femoral neck added substantially (AUC increased 0.831 to 0.902, p < 0.05) to prediction of moderate‐severe vertebral fracture. HR‐MRI indices were associated with spine, hip, and wrist DXA measures (p < 0.01). Longer duration of ADT was associated with lower BV/TV, surface density, and surface/curve ratio (p < 0.05). ADT for men with prostate cancer is associated with silent VF. DXA alone leads to misclassifications of osteoporosis, which can be avoided by VF assessment. HR‐MRI provides a novel technique to assess deterioration of structural integrity in men with VF and adds micro‐structural information. © 2013 American Society for Bone and Mineral Research     

Cost‐Effectiveness of Osteoporosis Screening Strategies for Men

Osteoporosis affects many men, with significant morbidity and mortality. However, the best osteoporosis screening strategies for men are unknown. We developed an individual‐level state‐transition cost‐effectiveness model with a lifetime time horizon to identify the cost‐effectiveness of different osteoporosis screening strategies for US men involving various screening tests (dual‐energy X‐ray absorptiometry [DXA]; the Osteoporosis Self‐Assessment Tool [OST]; or a fracture risk assessment strategy using age, femoral neck bone mineral density [BMD], and Vertebral Fracture Assessment [VFA]); screening initiation ages (50, 60, 70, or 80 years); and repeat screening intervals (5 years or 10 years). In base‐case analysis, no screening was a less effective option than all other strategies evaluated; furthermore, no screening was more expensive than all strategies that involved screening with DXA or the OST risk assessment instrument, and thus no screening was “dominated” by screening with DXA or OST at all evaluated screening initiation ages and repeat screening intervals. Screening strategies that most frequently appeared as most cost‐effective in base‐case analyses and one‐way sensitivity analyses when assuming willingness‐to‐pay of $50,000/quality‐adjusted life‐year (QALY) or $100,000/QALY included screening initiation at age 50 years with the fracture risk assessment strategy and repeat screening every 10 years; screening initiation at age 50 years with fracture risk assessment and repeat screening every 5 years; and screening initiation at age 50 years with DXA and repeat screening every 5 years. In conclusion, expansion of osteoporosis screening for US men to initiate routine screening at age 50 or 60 years would be expected to be effective and of good value for improving health outcomes. A fracture risk assessment strategy using variables of age, femoral neck BMD, and VFA is likely to be the most effective of the evaluated strategies within accepted cost‐effectiveness parameters. DXA and OST are also reasonable screening options, albeit likely slightly less effective than the evaluated fracture risk assessment strategy. © 2016 American Society for Bone and Mineral Research.     

Studying sex and gender differences in pain and analgesia: a consensus report

In September 2006, members of the Sex, Gender and Pain Special Interest Group of the International Association for the Study of Pain met to discuss the following: (1) what is known about sex and gender differences in pain and analgesia; (2) what are the "best practice" guidelines for pain research with respect to sex and gender; and (3) what are the crucial questions to address in the near future? The resulting consensus presented herein includes input from basic science, clinical and psychosocial pain researchers, as well as from recognized experts in sexual differentiation and reproductive endocrinology. We intend this document to serve as a utilitarian and thought-provoking guide for future research on sex and gender differences in pain and analgesia, both for those currently working in this field as well as those still wondering, "Do I really need to study females?"     

Temporal summation of pain characterizes women but not men with temporomandibular disorders

AIMS: To examine differences in temporal summation of mechanically evoked pain between women and men suffering from chronic pain associated with temporomandibular disorders (TMD), as well as between male TMD patients and healthy controls. METHODS: Series of 10 repetitive, mildly noxious mechanical stimuli were applied to the fingers of 27 female TMD patients, 16 male TMD patients, and 20 healthy men. The subjects rated the pain intensity caused by the 1st, 5th, and 10th stimulus in the series. Pain ratings were analyzed by 3-way repeated-measures analysis of variance. RESULTS: Pain ratings increased significantly with stimulus repetition for the female TMD patients (P < .001). Women with TMD exhibited significantly greater temporal summation of pain than TMD men (P < .001). Neither the healthy men nor the male TMD patients exhibited significant increases in pain perception with repetitive stimulation. In the female TMD patient group, perceptual pain magnitudes were higher with an interstimulus interval of 2 seconds rather than 10 seconds (P < .005). CONCLUSION: These findings suggest that central nociceptive processing upregulation is likely to contribute to TMD pain for women but is not a factor for     

The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells

In this study, we explored whether thrombopoietin (Tpo) has a direct in vitro effect on the proliferation and differentiation of long-term repopulating hematopoietic stem cells (LTR-HSC). We previously reported a cell separation method that uses the fluorescence-activated cell sorter selection of low Hoescht 33342/low Rhodamine 123 (low Ho/low Rh) fluorescence cell fractions that are highly enriched for LTR-HSC and can reconstitute lethally irradiated recipients with fewer than 20 cells. Low Ho/low Rh cells clone with high proliferative potential in vitro in the presence of stem cell factor (SCF) + interleukin-3 (IL-3) + IL-6 (90% to 100% HPP-CFC). Tpo alone did not induce proliferation of these low Ho/low Rh cells. However, in combination with SCF or IL-3, Tpo had several synergistic effects on cell proliferation. When Tpo was added to single growth factors (either SCF or IL-3 or the combination of both), the time required for the first cell division of low Ho/low Rh cells was significantly shortened and their cloning efficiency increased substantially. Moreover, the subsequent clonal expansion at the early time points of culture was significantly augmented by Tpo. Low Ho/low Rh cells, when assayed in agar directly after sorting, did not form megakaryocyte colonies in any growth condition tested. Several days of culture in the presence of multiple cytokines were required to obtain colony-forming units-megakaryocyte (CFU-Mk). In contrast, more differentiated, low Ho/high Rh cells, previously shown to contain short- term repopulating hematopoietic stem cells (STR-HSC), were able to form megakaryocyte colonies in agar when cultured in Tpo alone directly after sorting. These data establish that Tpo acts directly on primitive hematopoietic stem cells selected using the Ho/Rh method, but this effect is dependent on the presence of pluripotent cytokines. These cells subsequently differentiate into CFU-Mk, which are capable of responding to Tpo alone. Together with the results of previous reports of its effects on erythroid progenitors, these results suggest that the effects of Tpo on hematopoiesis are greater than initially anticipated.     

Calcium/calmodulin-dependent protein kinase II and potassium channel subunit eag similarly affect plasticity in Drosophila.

Similar defects in both synaptic transmission and associative learning are produced in Drosophila melanogaster by inhibition of calcium/calmodulin-dependent protein kinase II and mutations in the potassium channel subunit gene eag. These behavioral and synaptic defects are not simply additive in animals carrying both an eag mutation and a transgene for a protein kinase inhibitor, raising the possibility that the phenotypes share a common pathway. At the molecular level, a portion of the putative cytoplasmic domain of Eag is a substrate of calcium/calmodulin-dependent protein kinase II. These similarities in behavior and synaptic physiology, the genetic interaction, and the in vitro biochemical interaction of the two molecules suggest that an important component of neural and behavioral plasticity may be mediated by modulation of Eag function by calcium/calmodulin-dependent protein kinase II.     

Performance of risk assessment instruments for predicting osteoporotic fracture risk: a systematic review

Summary

We systematically reviewed the literature on the performance of osteoporosis absolute fracture risk assessment instruments. Relatively few studies have evaluated the calibration of instruments in populations separate from their development cohorts, and findings are mixed. Many studies had methodological limitations making susceptibility to bias a concern.

Introduction

The aim of this study was to systematically review the literature on the performance of osteoporosis clinical fracture risk assessment instruments for predicting absolute fracture risk, or calibration, in populations other than their derivation cohorts.

Methods

We performed a systematic review, and MEDLINE, Embase, Cochrane Library, and multiple other literature sources were searched. Inclusion and exclusion criteria were applied and data extracted, including information about study participants, study design, potential sources of bias, and predicted and observed fracture probabilities.

Results

A total of 19,949 unique records were identified for review. Fourteen studies met inclusion criteria. There was substantial heterogeneity among included studies. Six studies assessed the WHO’s Fracture Risk Assessment (FRAX) instrument in five separate cohorts, and a variety of risk assessment instruments were evaluated in the remainder of the studies. Approximately half found good instrument calibration, with observed fracture probabilities being close to predicted probabilities for different risk categories. Studies that assessed the calibration of FRAX found mixed performance in different populations. A similar proportion of studies that evaluated simple risk assessment instruments (≤5 variables) found good calibration when compared with studies that assessed complex instruments (>5 variables). Many studies had methodological features making them susceptible to bias.

Conclusions

Few studies have evaluated the performance or calibration of osteoporosis fracture risk assessment instruments in populations separate from their development cohorts. Findings are mixed, and many studies had methodological limitations making susceptibility to bias a possibility, raising concerns about use of these tools outside of the original derivation cohorts. Further studies are needed to assess the calibration of instruments in different populations prior to widespread use.     

Placebo effect in burning mouth syndrome: a systematic review

Placebo controls play a critical role in the evaluation of any pharmacotherapy. This review surveys the placebo arm in 12 randomized controlled trials (RCTs) investigating burning mouth syndrome (BMS) and documents a positive placebo response in 6 of them. On average, treatment with placebos produced a response that was 72% as large as the response to active drugs. The lack of homogeneity in the use of placebos adds to the difficulty in comparing results and aggregating data. Future RCTs investigating BMS would benefit from larger sample sizes, adequate follow‐up periods, and use of a standard placebo.     

Novel HPV types present in oral papillomatous lesions from patients with HIV infection

Patients infected with the human immunodeficiency virus (HIV) often develop multiple papillomatous lesions of the oral cavity. In the present study, a total of 67 biopsies from benign oral lesions were analyzed for the presence of human papillomavirus (HPV) DNA using Southern-blot hybridization in combination with a polymerase chain reaction designed to detect all known HPV types, as well as unidentified types. These samples, collected at random from a high-risk population, were subsequently divided into 57 biopsies originating from patients with confirmed HIV infection and 10 biopsies from patients with unknown HIV status. Each sample was amplified with 7 different combinations of degenerate primers. All amplified products were sequenced. HPV DNA sequences were detected in 67% (45/67) of the samples. HPV 7 (19%) and HPV 32 (28%) were the predominant HPV types. HPV 32 was present in 2/4 fibromas tested. Two new HPV types, HPV 72 and HPV 73, were identified in oral warts with atypia. The complete genomes of these viruses were cloned and sequenced. Other HPV types detected were HPV 2a, HPV 6b, HPV 13, HPV 16, HPV 18, HPV 55, HPV 59 and HPV 69. © 1996 Wiley-Liss, Inc.