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An abstract of the article "Bazedoxifene in Postmenopausal Women," E.S. Siris, J.A. Simon, I.P. Barton, M.R. McClung and A. Grauer is presented.

Objective: We explored the relationship between the Sleep Hygiene Practices Scale (SHPS) and sleep quality and sleep-related impairment in Black and Latinx adults with type 2 diabetes (T2DM)., Methods: Forty Black and Latinx adults with T2DM participated. Self-reported measures include the Pittsburg Sleep Quality Index (PSQI), Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) measures, and SHPS (domains include sleep schedule and timing, arousal-related behaviors, poor eating/drinking habits prior to sleep, and poor sleep environment)., Results: SHPS Cronbach's alpha coefficients were 0.58 (schedule), 0.78 (arousal), 0.29 (eating), 0.81 (environment) and 0.88 (overall for four domains). SHPS scores correlated with PSQI (Pearson correlation r = 0.67, 95% CI [0.44, 0.81], PROMIS-SD (r = 0.61 [0.36-0.77]), and PROMIS-SRI (r = 0.43, [0.13-0.65]). There remained a significant relationship between sleep hygiene and both sleep quality and sleep-related impairment adjusting for hemoglobin A1c, age, and body mass index in regression models., Conclusions: We observed moderate correlations between sleep quality and sleep-related impairment with sleep hygiene using the SHPS in Black and Latinx adults with T2DM., Competing Interests: None of the authors have a conflict of interest to disclose., (© 2023 Published by Elsevier B.V.)

Study Objectives: Text messaging (TM) may provide an inexpensive and convenient method for self-reported sleep assessment. This pilot study evaluated the feasibility of a TM sleep diary among a racial/ethnic minority population with uncontrolled type 2 diabetes., Methods: A convenience sample of 40 participants with uncontrolled type 2 diabetes was recruited. Participants wore an Actiwatch (Philips Spectrum Plus, Philips Respironics, Murrysville, Pennsylvania) for 7 consecutive days during both wake and sleep intervals and completed a daily TM sleep diary including 10 questions adapted from the Consensus Sleep Diary. The relationships between sleep measures from TMs and actigraphy were explored through Bland-Altman plots and correlations., Results: Of the 40 participants enrolled, 34 were African American and 6 were Latino. The mean age was 52.2 years (standard deviation = 8.2), and the mean hemoglobin A1c was 9.0% (standard deviation = 1.5). All but 1 participant attempted to complete the TM sleep diary. With a maximum of 70 TM replies possible, the median number of responses per participant was 66 (interquartile range = 59.5-69). Actigraphy and TM measures were related for total sleep time (median = 382 vs 393 min, respectively [r = .71; P < .01]), sleep onset latency (median = 31.4 vs 27.5 min [r = .61; P < .01]), time in bed (433.3 vs 489.3 min [r = .74; P < .01]), and sleep efficiency (77% vs 86% [r = .45; P = .005]). The measure of wake after sleep onset was higher from actigraphy than from TM, with a weak relationship between the 2 measures (median 47.9 vs 6.0 min [r = .31; P = .05])., Conclusions: TM is a novel and feasible method for sleep assessment in racial/ethnic minority adults with uncontrolled type 2 diabetes., (© 2021 American Academy of Sleep Medicine.)

Many life-saving drugs are still inaccessible and unaffordable in low- and middle-income countries, particularly in Sub-Saharan Africa. This contributes to poor health outcomes, wider health and socioeconomic inequities, and higher patient spending on healthcare. While resource limitations facing national regulatory authorities (NRAs) contribute to the problem, we believe that (1) fragmented and complex drug regulations, (2) suboptimal enforcement of existing regulations, and (3) poorly designed disincentives for non-compliance play a larger role. These "unintended consequences" that are a direct result of our current regulatory regimes limit competition, keep drug costs high, and lead to shortages and the proliferation of illegitimate and unregistered drugs. While NRAs can gain a lot from increased investment in their work, regulatory harmonization and innovation can arrest and reverse the regulatory failures we still see today and improve medicine access in Africa. Unfortunately, harmonization initiatives in Sub-Saharan Africa have made modest impact and have done so slowly. We encourage greater attention and investment in harmonization and other downstream functions of NRAs. We also urge increased participation of national governments-particularly executive agencies in health and the treasury-and patient advocacy groups in advancing harmonization across the subcontinent., (Copyright © 2019 Barton, Avanceña, Gounden and Anupindi.)

From 2006 to 2014, Supply Chain Management System (SCMS), the global procurement and distribution project for the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), distributed over US$1.6 billion worth of antiretroviral drugs and other health commodities, with over US$263 million purchased from local vendors in 14 countries in sub-Saharan Africa. A simple framework was developed and 39 local suppliers from 4 countries were interviewed between 2013 and 2014 to understand how SCMS local sourcing impacted supplier development. SCMS local suppliers reported new contracts with other businesses (77%), new assets acquired (67%), increased access to capital from local lending institutions (75%), offering more products and services (92%), and ability to negotiate better prices from their principles (80%). Additionally, 70% (n=27) of the businesses hired between 1 and 30 new employees after receiving their first SCMS contract and 15% (n=6) hired between 30 and 100 new employees. This study offers preliminary guidance on how bilateral and multilateral agencies could design effective local sourcing programs to create sustainable local markets for selected pharmaceutical products, laboratory, and transport services., (© Yadav et al.)

During a trip to Cyprus, 27 September-4 October 2015, 4 specimens (3♂ and 1♀) of a Coleophora sp. unknown to the author were collected in the Oreites Forest, above Kouklia, Paphos District (N34 7307149: E32 6366901, altitude 340m). Two males and the one female were dissected. No match in habitus, or for the genitalia of either sex, was found when compared with any of the Coleophora sp. recorded for Cyprus (Fauna Europaea), other than C. arenbergerella about which no information could be found. The author contacted Giorgio Baldizzone, the author of the species, to see whether he could provide any information on C. arenbergerella; he kindly sent a copy of photos he had of the ♂ holotype, informing the author that the species was only known from that male. This allowed the author to confirm that the four specimens were C. arenbergerella, a species given as close to Coleophora kuehenella (Goeze) in Baldizzone (1985). So far this species is only known from Cyprus so may be endemic to the island.

Unlabelled: This posthoc analysis of four trials studied the efficacy of risedronate to reduce fragility fractures in postmenopausal women with osteopenia (i.e., T-scores between -1 and -2.5). Risedronate reduced the fracture risk by 73% (p = 0.023) in this population of women with low femoral neck bone mass and no prevalent vertebral fractures., Introduction: Low bone mass represents an increasing health risk and burden. Half of fragility fractures occur in osteopenic women underscoring the need for treatments reducing fracture risk. This analysis reports the effect of risedronate to reduce fragility fracture risk in osteopenic women without prevalent vertebral fractures., Methods: Postmenopausal women with osteopenia, defined as femoral neck T-score between -1 and -2.5 by DXA and no prevalent vertebral fractures, were identified from four controlled randomized trials (BMD Multinational, BMD North America, VERT Multinational and VERT North America). The risk reduction for fragility fractures in patients receiving 5 mg risedronate daily for 1.5 to 3 years compared to placebo was assessed. An additional sensitivity analysis excluded patients who were osteopenic at the femoral neck but had a BMD lower than -2.5 SD at the lumbar spine., Results: Six hundred and twenty postmenopausal women with osteopenia were included, receiving either placebo (n = 309) or risedronate 5 mg (n = 311). Risedronate reduced the risk of fragility fractures by 73% over 3 years versus placebo (p = 0.023); cumulative fragility fracture incidence was 6.9% in placebo-treated versus 2.2% in risedronate-treated patients. The magnitude of the effect was similar in the sensitivity analysis subset., Conclusion: Risedronate significantly reduced the risk of fragility fractures in postmenopausal women with osteopenia (femoral neck T-score between -1 and -2.5 SD) and no prevalent vertebral fractures.

Introduction: The prevalence of hypoactive sexual desire disorder (HSDD) in menopausal women and the frequency of sexual activity, sexual behavior, and relationship or sexual satisfaction associated with HSDD have not been studied using validated instruments to identify women with HSDD., Aims: To determine: (i) the prevalence of HSDD among women who have undergone hysterectomy and bilateral oophorectomy (surgical menopause) with that of premenopausal or naturally menopausal women; (ii) the relationship between low sexual desire and sexual activity and behavior; and (iii) the relationship between low sexual desire and sexual or partner relationship satisfaction., Methods: Cross-sectional survey of 2,467 European women aged 20-70 years, resident in France, Germany, Italy, and the United Kingdom. Measures were the Profile of Female Sexual Function (PFSF), Personal Distress Scale (PDS), and a sexual activities measure., Outcome Measures: Clinically derived cutoff scores for the desire domain of the PFSF and the PDS were used, sequentially, to classify women as having low sexual desire and to further classify these women with low desire as distressed or nondistressed. Thus, women with HSDD had low sexual desire and were distressed by their low desire. The analysis population included 1,356 women who had current sexual partners and were surgically menopausal, regularly menstruating, or naturally postmenopausal., Results: A greater proportion of surgically menopausal women had low sexual desire compared with premenopausal or naturally menopausal women (odds ratio [OR] = 1.4; confidence interval [CI] = 1.1, 1.9; P = 0.02). Surgically menopausal women were more likely to have HSDD than premenopausal or naturally menopausal women (OR = 2.1; CI = 1.4, 3.4; P = 0.001). Sexual desire scores and sexual arousal, orgasm, and sexual pleasure were highly correlated (P < 0.001), demonstrating that low sexual desire is frequently associated with decreased functioning in other aspects of sexual response. Women with low sexual desire were less likely to engage in sexual activity and more likely to be dissatisfied with their sex life and partner relationship than women with normal desire (P < 0.001)., Conclusions: Surgically menopausal women are at increased risk for HSDD. HSDD is associated with diminished sexual and partner relationship satisfaction and negative emotional states.

The aim of this study was to examine the effects of risedronate (5 mg/daily) in patients identified solely on the basis of a prior fragility fracture, without BMD as an inclusion criterion. A total of 1,802 patients were examined from the VERT-NA and VERT-MN clinical trials. Lateral radiographs (T4 to L4) were obtained at baseline and annually; incident fractures were evaluated using quantitative and semiquantitative methods at the central facility. BMD was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry. Secondary analyses evaluated vertebral fracture efficacy in patient subgroups categorized according to the presence of risk factors for osteoporosis at baseline (age, femoral neck BMD, lumbar spine BMD, more severe BMD, height, weight, body mass index, prevalent nonvertebral fracture status, smoking, and bone turnover marker levels). Over 3 years, risedronate reduced the risk of new vertebral fractures by 44% (95% CI, 28% to 56%) compared with placebo. In patients subgrouped according to the presence or absence of putative risk factors, the efficacy of risedronate was comparable across all groups (all treatment-by-non BMD subgroup interactions p > or =0.210). Adjustment for age, baseline BMD, and prevalent vertebral fractures on fracture risk gave results similar to the unadjusted analysis. In patients taking placebo, the incidence of new vertebral fracture was higher in several of the high-risk categories (elderly, T-score < or = -2.5 SD). In conclusion, the findings of this study suggest that risedronate is effective in patients identified solely on the basis of a prior fragility fracture and that the efficacy of risedronate in the reduction of vertebral fractures is largely independent of the presence of clinical risk factors for osteoporotic fracture.

The laminarity of high-current multi-MeV proton beams produced by irradiating thin metallic foils with ultraintense lasers has been measured. For proton energies >10 MeV, the transverse and longitudinal emittance are, respectively, <0.004 mm mrad and <10(-4) eV s, i.e., at least 100-fold and may be as much as 10(4)-fold better than conventional accelerator beams. The fast acceleration being electrostatic from an initially cold surface, only collisions with the accelerating fast electrons appear to limit the beam laminarity. The ion beam source size is measured to be <15 microm (FWHM) for proton energies >10 MeV.

Unlabelled: It is unclear whether the antifracture efficacy of bisphosphonates depends on pretreatment bone turnover. We analyzed the risedronate phase III clinical programs using the urinary excretion of deoxypyridinoline (uDPD) as an index of pretreatment bone resorption rates. Risedronate reduced incident vertebral fractures in women with postmenopausal osteoporosis independent from pretreatment bone resorption., Introduction: Earlier studies on postmenopausal osteoporosis have suggested that the therapeutic efficacy of antiresorptive therapies might be influenced by pretreatment bone turnover. Because all of these studies have used bone mineral density (BMD) as the primary endpoint, it remains unclear whether this association holds true for incident fractures., Materials and Methods: This study aims to answer this question in a post hoc analysis of a subset of the risedronate phase III clinical programs, using the urinary excretion of deoxypyridinoline (uDPD) as an index of pretreatment bone resorption (PBR). A total of 1593 women with postmenopausal osteoporosis that had baseline uDPD values and paired spinal radiographs available were pooled, in similar proportions, from the risedronate multinational and North American VERT, and from the risedronate HIP trials. Patients from treatment and placebo groups were stratified by the uDPD premenopausal normative median. The four resulting groups were balanced for age, years since menopause, body mass index, baseline femoral neck BMD, and number of prevalent fractures, but baseline lumbar spine BMD was significantly higher in patients with low PBR rates., Results: In all groups, the proportion of patients with new vertebral fractures was higher in patients with baseline uDPD levels above the normative median. The incidence of vertebral fracture was significantly lower in groups assigned to risedronate compared with placebo. This effect was independent of PBR: in patients with high PBR, the relative risk (RR) of vertebral fracture after 1 year of risedronate was 0.28 (p = 0.03 compared with controls, absolute risk reduction 7.1%). In patients with low PBR, the RR of fracture after 1 year was 0.33 (p < 0.001, absolute risk reduction 4%). After 3 years, the RR of fracture was 0.52 (p = 0.042, absolute risk reduction 8.3%) in patients with high PBR, and 0.54 (p = 0.002, absolute risk reduction 7.1%) in patients with low PBR. Results were similar after adjusting for age, baseline lumbar spine BMD, and prevalent fractures. The number needed to treat to avoid one vertebral fracture at 12 months was 15 in the group of patients with high PBR and 25 in patients with low PBR. Risedronate significantly increased lumbar spine BMD. During the first year of treatment, women with high PBR gained lumbar spine BMD at a faster rate than patients with low PBR. Treatment-by-PBR status interactions were not significantly different over time., Conclusion: The efficacy of risedronate to reduce incident vertebral fractures in women with postmenopausal osteoporosis is largely independent of pretreatment bone resorption rates.

Prevention of nonvertebral fractures, which account for a substantial proportion of osteoporotic fractures, is an important goal of osteoporosis treatment. Risedronate, a pyridinyl bisphosphonate, significantly reduces clinical vertebral fracture incidence within 6 months. To determine the effect of risedronate on osteoporosis-related nonvertebral fractures, data from four large, randomized, double-blind, placebo-controlled, Phase III studies were pooled and analyzed. The population analyzed consisted of postmenopausal women, with and without vertebral fractures, who had low bone mineral density (lumbar spine T-score <-2.5). Patients received placebo (N = 608) or risedronate 5 mg daily (N = 564) for 1 to 3 years. At baseline, 58% had at least one prevalent vertebral fracture, and the mean lumbar spine T-score was -3.4. Among placebo-treated patients, the presence of prevalent vertebral fractures did not increase the risk of incident nonvertebral fractures overall, although fractures of the humerus and hip and pelvis were more common in patients who had prevalent vertebral fractures than in those who did not. Risedronate 5 mg significantly reduced the incidence of nonvertebral fractures within 6 months compared with control. After 1 year, nonvertebral fracture incidence was reduced by 74% compared with control ( P = 0.001), and after 3 years, the incidence was reduced by 59% ( P = 0.002). The results indicate that risedronate significantly reduces the incidence of osteoporosis-related nonvertebral fractures within 6 months.

Objective: To evaluate predictors of vertebral fractures, including a threshold for bone mineral density (BMD), in patients receiving oral glucocorticoids (GCs)., Methods: Data were obtained from 2 randomized clinical trials (prevention and treatment trials of risedronate) using similar methods, but different inclusion criteria were applied with regard to prior exposure to GCs. Predictors of vertebral fracture in the placebo group were identified using Cox regression with forward selection. The BMD threshold analysis involved a comparison of the 1-year fracture risk in postmenopausal women receiving placebo in the GC trials with that in postmenopausal women not taking GCs in 3 other trials., Results: The study population comprised 306 patients with baseline and 1-year followup data on vertebral fractures (111 receiving placebo and 195 receiving risedronate). In the placebo group, the statistically significant predictors of incident fracture were the baseline lumbar spine BMD (for each 1-point decrease in T score, relative risk [RR] 1.85, 95% confidence interval [95% CI] 1.06-3.21) and the daily GC dose (for each 10-mg dose increase, RR 1.62, 95% CI 1.11-2.36). In the BMD threshold analysis, compared with nonusers of GCs, patients receiving GCs were younger, had a higher BMD at baseline, and had fewer prevalent fractures; nevertheless, the risk of fracture was higher in the GC users compared with nonusers (adjusted RR 5.67, 95% CI 2.57-12.54). The increased risk of fracture was observed in GC users regardless of whether osteoporosis was present., Conclusion: The daily, but not cumulative, GC dose was found to be a strong predictor of vertebral fracture in patients receiving GCs. At similar levels of BMD, postmenopausal women taking GCs, as compared with nonusers of GCs, had considerably higher risks of fracture.

Changes in the level of biochemical markers of bone resorption with risedronate treatment for osteoporosis were examined as a surrogate for the decrease in fracture risk. Greater decreases in bone resorption markers were associated with greater decreases in vertebral (and nonvertebral) fractures. Antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density. Early decreases in bone resorption may also play a role. We tested this hypothesis by measuring two bone resorption markers, the C-telopeptide of type I collagen (CTX) and the N-telopeptide of type I collagen (NTX), in osteoporotic patients in risedronate vertebral fracture trials. We studied 693 women with at least one vertebral deformity (mean age, 69 +/- 7 years) who received calcium (and vitamin D if required) and placebo or risedronate 5 mg daily for 3 years. The reductions in urinary CTX (median, 60%) and NTX (51%) at 3-6 months with risedronate therapy were significantly associated (p < 0.05) with the reduction in vertebral fracture risk (75% over 1 year and 50% over 3 years). The changes in both CTX and NTX accounted for approximately one-half (CTX, 55%; NTX, 49%) of risedronate's effect in reducing the risk of vertebral fractures in the first year and approximately two-thirds (CTX, 67%; NTX, 66%) over 3 years compared with placebo. The changes in CTX and NTX accounted for 77% and 54%, respectively, of risedronate's effect in reducing the risk of nonvertebral fractures over 3 years compared with placebo. The relationships between vertebral fracture risk and changes from baseline in CTX and NTX were not linear (p < 0.05). There was little further improvement in fracture benefit below a decrease of 55-60% for CTX and 35-40% for NTX. The decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk. There may be a level of bone resorption reduction below which there is no further fracture benefit.

Independent risk factors for fracture include advanced age, preexisting fractures, and low bone mineral density. Rised-ronate has been shown in several large trials to be safe and effective for patients with osteoporosis, but its effects in populations at high risk are not well characterized. To determine the effect of risedronate on vertebral fracture in high-risk subjects, we pooled data from two randomized, double-blind studies [Vertebral Efficacy with Risedronate Therapy (VERT) Multinational (VERT-MN) and VERT-North America (VERT-NA)] in 3684 postmenopausal osteoporotic women treated with placebo or risedronate 2.5 or 5 mg/d and analyzed fracture risk in subgroups of subjects at high risk for fracture due to greater age or more prevalent fractures (vs. median for overall study population), or lower bone mineral density (T-score, -2.5 or less). Fractures were diagnosed by quantitative and semiquantitative assessment of radiographs at baseline and 1 yr. In the overall population, treatment for 1 yr with risedronate 5 mg/d reduced the risk of new vertebral fractures by 62% vs. control (relative risk, 0.38; 95% confidence interval, 0.25, 0.56; P < 0.001) and of multiple new vertebral fractures by 90% vs. control (relative risk, 0.10; 95% confidence interval, 0.04, 0.26; P < 0.001). Consistent risk reductions were observed at 1 yr in the risedronate-treated high-risk subgroups. Significant reduction in fracture risk after 1 yr is an important benefit in patients at high risk for fracture because, without treatment, these patients are likely to sustain new fractures in the near term.

The effects of 3 years of oral risedronate treatment on bone quality and remodeling were assessed in women with postmenopausal osteoporosis. Transiliac bone biopsies were obtained at baseline and after treatment with placebo or risedronate 5 mg/day in 55 women (placebo, n = 27; risedronate 5 mg, n = 28); these pairs of samples allowed comparison of treatment effects vs. both baseline values and between treatment groups. A further 15 women (placebo, n = 6; risedronate 5 mg, n = 9) had measurements from a posttreatment biopsy, but not from a baseline biopsy. Samples were examined for qualitative changes (e.g., osteomalacia, peritrabecular fibrosis, and woven bone); no histological abnormalities were found to be associated with treatment. Among women with both baseline and posttreatment biopsies, risedronate-treated women experienced a moderate and expected reduction from baseline in bone turnover, which was reflected in mean decreases in mineralizing surface of 58% and in activation frequency of 47%. Histomorphometrical parameters indicated that bone formation rate decreased significantly from baseline with risedronate treatment, reflecting a decrease in bone turnover; bone mineralization was normal following treatment. Basic multicellular unit (BMU) balance tended to improve in the risedronate-treated women, whereas it tended to worsen in the placebo-treated women, although these changes were not statistically significant. There were no significant changes in structural parameters with treatment. The effects of 3 years of risedronate treatment on bone histology and histomorphometry reflect the antiresorptive mechanism of action, and are consistent with the antifracture efficacy and favorable bone safety profile demonstrated in large clinical trials.

Following a 52-wk randomized controlled trial of intermittent cyclic etidronate therapy in patients using corticosteroids, we performed a 52-wk open-label trial of calcium alone in 114 corticosteroid-treated patients to determine whether the beneficial effect of etidronate is maintained after the drug is discontinued. All patients were given 500 mg/d of elemental calcium. Sixty-one and 53 patients made up the former placebo and etidronate groups, respectively. A total of 89 (98%) of patients in the former placebo and etidronate groups remained on corticosteroids throughout the second year. The mean (SE) percentage change in bone mineral density of the lumbar spine, femoral neck, and trochanter were compared between groups. The difference between groups in mean percentage change from baseline (wk 0, initiation of etidronate or placebo therapy) in the bone density of the lumbar spine, femoral neck, and trochanter, following 104 wk, was 3.8 (0.9), 3.0 (1.1), and 4.3 (1.1), respectively (p < 0.05, all sites), in favor of the former etidronate group. While not significant, the former placebo group demonstrated a slightly larger rate of decline in bone density over the second year than the former etidronate group at all three sites. Following the discontinuation of etidronate therapy, there was no accelerated bone loss and there was evidence of a residual protective effect in both the lumbar spine and femoral neck for up to 1 yr posttreatment.

The aim of this work is to define the basis for design guidelines that will minimise the risk of exposure from airborne organisms in hospital isolation rooms. This research employs an algorithm that combines an understanding of the interaction between the room airflow and the ultra violet (UV) system. The airflow in such a room is complex and therefore cannot easily be accounted for by existing design guidance. The main findings were firstly, the mean lifetime of the ventilated particles does not reduce in proportion with increasing ventilation rate. Secondly, an increase in the ventilation rate reduces the effectiveness of ultra violet germicidal irradiation (UVGI) with only a limited increase in the number of particles that are ventilated. Finally, there is a social benefit attached to this project from the point of view of helping people who are vulnerable as well as reducing their risk of being exposed to possible tuberculosis infection. The significance of these findings is to provide the engineer and the architect with an essential tool to ensure good design practice. It is also important to ensure that the methodology can be applicable to most isolation room uses.

We describe the advantages of using diffractive (Fresnel) lenses on thin membranes over conventional optics for, among others, future space telescope projects. Fabrication methods are presented for lenses on two types of freestanding membrane up to 50 cm in size. The first is a Fresnel lens etched into a thin (380-microm) glass sheet, and the second is an approximately 50-microm-thick polymer membrane containing a Fresnel lens made by replication process from a specially made fused-silica master. We show optical performance analysis of all the lenses that are fabricated, including a diffraction-limited Airy spot from a 20-m- focal-length membrane lens in a diffractive telescope system.

Context: Vertebral fractures significantly increase lifetime risk of future fractures, but risk of further vertebral fractures in the period immediately following a vertebral fracture has not been evaluated., Objective: To determine the incidence of further vertebral fracture in the year following a vertebral fracture., Design and Setting: Analysis of data from 4 large 3-year osteoporosis treatment trials conducted at 373 study centers in North America, Europe, Australia, and New Zealand from November 1993 to April 1998., Subjects: Postmenopausal women who had been randomized to a placebo group and for whom vertebral fracture status was known at entry (n = 2725)., Main Outcome Measure: Occurrence of radiographically identified vertebral fracture during the year following an incident vertebral fracture., Results: Subjects were a mean age of 74 years and had a mean of 28 years since menopause. The cumulative incidence of new vertebral fractures in the first year was 6.6%. Presence of 1 or more vertebral fractures at baseline increased risk of sustaining a vertebral fracture by 5-fold during the initial year of the study compared with the incidence in subjects without prevalent vertebral fractures at baseline (relative risk [RR], 5.1; 95% confidence interval [CI], 3.1-8.4; P<.001). Among the 381 participants who developed an incident vertebral fracture, the incidence of a new vertebral fracture in the subsequent year was 19.2% (95% CI, 13.6%-24.8%). This risk was also increased in the presence of prevalent vertebral fractures (RR, 9.3; 95% CI, 1.2-71.6; P =.03)., Conclusion: Our data indicate that women who develop a vertebral fracture are at substantial risk for additional fracture within the next year.

Men and women (n = 518) receiving moderate-to-high doses of corticosteroids were enrolled in two studies with similar protocols and randomly assigned to receive either placebo or risedronate (2.5 or 5 mg) for 1 year. All patients received daily calcium supplementation (500-1000 mg), and most also received supplemental vitamin D (400 IU). The primary endpoint was the difference between the placebo and active groups in lumbar spine bone mineral density (BMD) at 1 year; changes in BMD at other sites, biochemical markers of bone turnover, and the incidence of vertebral fractures were also assessed. In the overall population, the mean (SE) lumbar spine BMD increased 1.9 +/- 0.38% from baseline in the risedronate 5 mg group (P < 0.001) and decreased 1.0 +/- 0.4% in the placebo group (P = 0. 005). BMD at the femoral neck, trochanter, and distal radius increased or was maintained with risedronate 5 mg treatment, but decreased in the placebo group. Midshaft radius BMD did not change significantly in either treatment group. The difference in BMD between the risedronate 5 mg and placebo groups was significant at all skeletal sites (P < 0.05) except the midshaft radius at 1 year. The 2.5 mg dose also had a positive effect on BMD, although of a lesser magnitude than that seen with risedronate 5 mg. A significant reduction of 70% in vertebral fracture risk was observed in the risedronate 5 mg group compared with the placebo group (P = 0.01). Risedronate was efficacious in both men and women, irrespective of underlying disease and duration of corticosteroid therapy, and had a favorable safety profile, with a similar incidence of upper gastrointestinal adverse events in the placebo and active treatment groups. Daily treatment with risedronate 5 mg significantly increases BMD and decreases vertebral fracture risk in patients receiving moderate-to-high doses of corticosteroid therapy.

A diffractive Alvarez lens is demonstrated that consists of two separate phase plates, each having complementary 16-level surface-relief profiles that contain cubic phase delays. Translation of these two components in the plane of the phase plates is shown to produce a variable astigmatic focus. Both spherical and cylindrical phase profiles are demonstrated with good accuracy, and the discrete surface-relief features are shown to cause less than lambda/10 wave-front aberration in the transmitted wave front over a 40 mm x 80 mm region.

Background: The periodontal status of 41 medically healthy adults with untreated chronic periodontitis was monitored before and after scaling and root planing (SRP)., Methods: During a 6-month pretreatment phase, clinical measurements, digital subtraction radiography (DSR) analysis of alveolar bone, and measurement of gingival crevicular fluid (GCF) prostaglandin E2 (PGE2) levels were undertaken. SRP was provided during a 1-month treatment phase. Clinical, radiographic, and biochemical analyses were repeated in a 6-month post-treatment healing period., Results: Pretreatment: no clinically significant changes in mean plaque indices (PI), probing depths (PD), bleeding on probing (BOP), or relative clinical attachment levels (CAL) were detected (P>0.05). DSR revealed small but statistically significant bone height (0.04 mm) and mass (0.97 mg) loss (P<0.001). GCF PGE2 levels gradually increased from 38.8 ng/ml at month 1 to 79.4 ng/ml at month 6. Post-treatment: statistically and clinically significant reductions were observed in mean PI, BOP, and PD (P<0.05). A statistically significant reduction in CAL was noted (P<0.05). The trend towards progressive bone loss was halted and reversed, and a statistically significant decrease in GCF PGE2 concentrations was detected (P<0.001). Smokers, non-smokers, and ex-smokers did not differ significantly in PI, BOP, CAL, radiographic, or biochemical parameters at any time. Mean PD was significantly greater in current smokers than in non- and ex-smokers (P<0.005). PD reduced comparably in all 3 smoking subgroups following treatment (P<0.01)., Conclusions: Conventional clinical measurements failed to identify disease progression over a 6-month period. Significant improvements were observed in clinical parameters after SRP, and a trend towards progressive bone loss was halted and reversed. Regular and frequent maintenance visits are important following treatment to maintain improvements in clinical parameters. Smokers had deeper probing depths than non- and ex-smokers, but pockets were reduced significantly and comparably in all 3 smoking subgroups following efficacious treatment.

The prevention and treatment of glucocorticoid-induced osteoporosis is a major concern for rheumatologists since inflammatory joint disease is among the most common reasons for long-term glucocorticoid therapy. We used a randomized placebo-controlled design to evaluate the efficacy of one-year cyclical etidronate therapy in preventing bone loss in 83 glucocorticoid-treated patients with rheumatoid arthritis, polymyalgia rheumatica, or giant cell arteritis. Glucocorticoid treatment duration was shorter than three months, and the starting dose was greater than 7.5 mg of prednisone-equivalent per day. Etidronate was given according to the standard cyclical schedule, i.e. 400 mg/d for periods of 14 days separated by 76-day intervals during which patients took 500 mg of supplemental calcium per day. The primary evaluation criterion was the change in lumbar spine bone mineral density after one year of etidronate therapy. Bone mineral density decreased by 1.94 +/- 0.61% in the placebo group and increased by 0.86 +/- 0.6% in the etidronate group, yielding a between-group difference of 2.8 +/- 0.86% (P = 0.002). The difference was largest in postmenopausal women (3.38 +/- 1.11%; P = 0.004). At the femoral neck, there was a smaller bone mineral density decrease in the etidronate than in the placebo group, but the difference (1.11 +/- 1.13%) was not statistically significant. The most common side effects were gastrointestinal symptoms and showed no difference between the two groups. Four fractures (including one vertebral fracture) occurred in the placebo group versus two (including one vertebral) in the etidronate group. Etidronate prevents glucocorticoid-induced lumbar spine bone loss in patients with rheumatoid arthritis, polymyalgia rheumatica, or giant cell arteritis.

The effects of a magnesium monoperoxyphthalate (MMPP) mouth-rinse, with or without sodium lauryl sulphate (SLS), and an MMPP dentifrice, on salivary counts of bacterial flora and yeasts, and on supragingival plaque scores were investigated in 131 healthy oral candida carriers over a 9 week double blind study. There were no changes in the salivary counts of bacteria studied (anaerobes, streptococci, fusobacteria, Actinomyces, Viellonella) in the test or placebo groups. A significant increase in salivary candida counts was seen in subjects using an MMPP rinse and dentifrice compared with placebo subjects and this phenomenon was not influenced by the presence of SLS. A significant reduction in plaque was seen in subjects using an MMPP rinse and dentifrice compared with placebo subjects. Frank candidosis was observed in only 2 subjects (1 in the placebo rinse group and 1 in the MMPP dentifrice group) but erythematous lesions, with subjective reports of soreness, dryness or burning sensation, were recorded and observed more frequently in the experimental groups than in the placebos, especially in those also using SLS. The substantial plaque reduction achieved with MMPP in the absence of tooth staining but with the increase in salivary Candida counts suggests that further studies of MMPP are warranted.

These studies sought to develop and validate an occlusal site-specific plaque index to be used to measure plaque removal by brushing or chewing gum. The index divides the occlusal surfaces into imaginary zones from which scores are apportioned on a 0-4 basis dependent on the perceived % plaque coverage of each zone. Examiner calibration was conducted over 2 studies assessing inter-examiner reproducibility and intra-examiner repeatibility, respectively. Study 1 involved 2 examiners who recorded scores from the same 3 groups of subjects who had suspended tooth cleaning for 4 days. Analyses for inter-examiner reproducibility showed no significant mean differences between examiners or no significant differences between variances of the 2 examiners scores. Study 2 involved the same 2 examiners individually scoring 3 groups of subjects 2 x (approximately 60 min apart) for occlusal plaque. Analysis for intra-examiner repeatability showed no significant mean differences between the 2 scorings of each examiner. Furthermore, there were no significant differences between the variances of each examiner's scores except for 1 examiner in the repeatability exercise for the 1st group of subjects. Study 3 involved groups of subjects at 2 separate clinical sites (Bristol, England and Berne, Switzerland) being scored for occlusal plaque before and after toothbrushing with water or after no toothbrushing. Data from individual examiners and examiners combined revealed a significant reduction in occlusal plaque with brushing compared to no brushing. Study 4 was the same as study 3 but occlusal plaque was scored before and after chewing gum or not chewing gum. The Bristol examiner recorded a significant reduction in plaque by chewing gum compared to not chewing gum but the Berne examiner did not. The latter may have resulted from a considerable disparity in the number of evaluable occlusal surfaces between the two study sites. The index could be employed as part of the overall assessment or oral hygiene or used in clinical trials to study mechanical and chemical plaque control agents.

We report what we believe to be the first applications of numerical optimization algorithms to the design of diffractive elements that customize the fundamental mode profile of a laser system. Standard design techniques treat these elements as specific phase-conjugation devices, which leads to performance loss when they are quantized to permit fabrication. Numerical optimization can account for quantization of the element to increase the effective performance. Also, it is shown that allowing a slight increase in the intrinsic loss of the cavity can substantially increase the fidelity of the fundamental mode of the customized cavity. The good discrimination qualities of the mode-selection elements are shown to be unaffected by this process.

Space-invariant, multilevel, diffractive phase elements are designed for large-scale pattern-formation tasks. The importance of the design algorithm and the phase-encoding geometry of the diffractive element is discussed with regard to the performance of both on- and off-axis reconstruction, notably for pixelated gratings. A new phase-encoding scheme is presented that results in an increase of the diffraction efficiency for the off-axis case.

We report on the design and fabrication of novel diffractive phase elements that reconstruct distinct intensity patterns in the far-field on illumination with two specific wavelengths. The elements contain deep surface-relief structures that represent phase-delays of greater than 2p radians. The design process incorporates a modified version of the iterative Fourier transform algorithm. A 16 phase-level element for dual wavelength (blue and red) operation, with high diffraction efficiency, is demonstrated experimentally.

Haemofiltration and its variants are simple procedures which allow the management of patients with renal failure in intensive therapy units without the need for continual support from renal specialists. In order for non-renal specialists to manage the practical aspects of these treatments logically, safely and successfully it is important to understand the basic principles involved.

The decline in the use of acute peritoneal dialysis which has followed the recent advances in extracorporeal renal replacement therapy has left many clinicians unfamiliar with an invaluable therapeutic tool. This article is a timely reminder of both the underlying theory and the practical aspects of this technique.

Two hundred and fifty consecutive patients with acute renal failure treated by continuous haemofiltration on one intensive care unit (ICU) were studied prospectively to investigate the possibility of predicting outcome at the time of referral. Logistic regression analysis was used to identify important prognostic factors and the regression coefficients were used to weight a scoring system for the severity of illness of patients with acute renal failure. Overall survival was 53% with improvement over the course of the study. Multivariate analysis showed that outcome was related to age, need for artificial ventilation, use of inotropes, urine volume, serum bilirubin, arterial base deficit and serum creatinine. The scoring system based on the first five of these variables had a specificity of predicting death of 67% and a sensitivity of 76%.

Twelve patients with renal failure and type A lactic acidosis were treated with haemofiltration during a 30-month period. The first three patients received only lactate-buffered replacement fluid and rapidly succumbed despite the infusion of large quantities of sodium bicarbonate. Bicarbonate-buffered replacement fluid was used for the remaining nine patients, of whom three survived. Haemofiltration with bicarbonate-buffered replacement fluid is an effective method of replacing renal function for this group of critically-ill patients.

In a recent paper W. B. Grant ["Water Vapor Absorption Coefficients in the 8-13-microm Spectral Region: a Critical Review," Appl. Opt. 29, 451-462 (1990)] reviewed experimental measurements of the water vapor continuum absorption coefficients in the 8-13-microm spectral region. In comparing three different groundbased techniques he concluded that the absorption coefficients used in the HITRAN and LOWTRAN-7 codes are in reasonable agreement with the measurements. These coefficients are approximately 20% lower than those used in the LOWTRAN-6 code. A fourth method of experimentally determining the water vapor absorption coefficients is described which suggests an opposite result. A comparison between sets of satellite measured infrared radiances and ship measurements of sea surface temperature using a model of infrared transmission through the atmosphere gives coefficients that are 20-40% larger than those used in LOWTRAN-6. Agreement between the four different measurement techniques is only posible if a much stronger negative temperature dependence of the continuum absorption coefficients is adopted. This results in significant increases in the coefficients at temperatures below 270 K.