Ultra-low-dose estradiol and dydrogesterone for treatment of vasomotor symptoms in Europe and China.

OBJECTIVE: Among postmenopausal women, oral, ultra-low-dose continuous combined estradiol (E0.5 mg) plus dydrogesterone (D2.5 mg) reduces vasomotor symptoms (VMS). METHODS: This study was a post hoc analysis of data from two phase 3, double-blind studies. Postmenopausal women were randomized 2:1:2 to receive E0.5 mg/D2.5 mg, E1 mg/D5 mg (not included in this analysis) or placebo for 13 weeks (European study), or randomized 1:1 to receive E0.5 mg/D2.5 mg or placebo for 12 weeks (Chinese study). Endpoints assessed in ethnicity subgroups (European and Chinese) included changes from baseline in number of hot flushes, number of moderate-to-severe hot flushes and Menopause Rating Scale (MRS) score. RESULTS: Overall, 579 women were included in the analysis (E0.5 mg/D2.5 mg, n = 288; placebo, n = 291). European and Chinese women receiving E0.5 mg/D2.5 mg experienced greater reductions from baseline in mean daily number of hot flushes and mean daily number of moderate-to-severe hot flushes at week 4, week 8 and end of treatment versus those receiving placebo. Significant improvements in the 'hot flushes, sweating' MRS item score were reported in both European and Chinese women. CONCLUSION: Oral, ultra-low-dose continuous combined 0.5 mg 17ß-estradiol and 2.5 mg dydrogesterone improved VMS compared with placebo in European and Chinese postmenopausal women, with a positive impact on health-related quality of life.

Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis.

Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.

Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists.

Women undergo important changes in sex hormones throughout their lifetime that can impact cardiovascular disease risk. Whereas the traditional cardiovascular risk factors dominate in older age, there are several female-specific risk factors and inflammatory risk variables that influence a woman's risk at younger and middle age. Hypertensive pregnancy disorders and gestational diabetes are associated with a higher risk in younger women. Menopause transition has an additional adverse effect to ageing that may demand specific attention to ensure optimal cardiovascular risk profile and quality of life. In this position paper, we provide an update of gynaecological and obstetric conditions that interact with cardiovascular risk in women. Practice points for clinical use are given according to the latest standards from various related disciplines (Figure 1).

Effects of tibolone or continuous combined oestradiol and norethisterone acetate on lipids, high-density lipoprotein subfractions and apolipoproteins in postmenopausal women in a two-year, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To compare the effects of (a) tibolone, (b) continuous combined oestrogen plus progestogen and (c) placebo on plasma lipid and lipoprotein markers of cardiovascular risk in healthy postmenopausal women. STUDY DESIGN: Randomized, single-centre, placebo-controlled, double-blind study. PATIENTS: One hundred and one postmenopausal women were randomized (1:1:1) into one of three groups taking daily 2.5 mg tibolone, continuous oral oestradiol-17ß 2 mg plus norethisterone acetate 1 mg daily (E2 /NETA) or placebo. MAIN OUTCOME MEASURES: Fasting serum lipid, lipoprotein and apolipoprotein concentrations measured at baseline and after 6, 12 and 24 months of treatment. RESULTS: Both tibolone and E2 /NETA lowered plasma total cholesterol concentrations relative to placebo. With tibolone, high-density lipoprotein cholesterol (HDL-C) was reduced (-27% at 24 months, P < .001), the greatest effect being in the cholesterol-enriched HDL2 subfraction (-40%, P < .001). Tibolone's effect on HDL concentrations was also apparent in the principal HDL protein component, apolipoprotein AI (-29% at 24 months, P < .001). However, there was no significant effect of tibolone on low-density or very low-density lipoprotein cholesterol (LDL-C and VLDL-C, respectively). By contrast, the greatest reduction in cholesterol with E2 /NETA was in LDL-C (-22% at 24 months, P = .008). E2 /NETA reduced HDL-C to a lesser extent than tibolone (-12% at 24 months, P < .001). Effects on HDL apolipoproteins were similarly diminished relative to tibolone. E2 /NETA had no effect on VLDL-C or on the protein component of LDL, apolipoprotein B. CONCLUSION: Tibolone reduces serum HDL. E2 /NETA reduces LDL cholesterol but not apolipoprotein B, suggesting decreased cholesterol loading of LDL. Any impact these changes may have on CVD risk needs further investigation.

Independent relationships between bone mineral density, regional body fat and insulin sensitivity in white males.

BACKGROUND: Adiposity and insulin sensitivity may affect bone mineral density (BMD), but the confounding effect of weight hinders discrimination of independent associations. We explored whether regional fat masses and insulin sensitivity are independently related to BMD. MATERIALS AND METHODS: Relationships between total and regional body fat, insulin sensitivity and measures of BMD in 8 different regions were evaluated in a cross section of 590 generally healthy, white males, 274 of whom received measurement of insulin sensitivity (Si) using the intravenous glucose tolerance test. Measurements included total, android and gynoid fat and lean body mass and regional BMDs by dual-energy X-ray absorptiometry. Linear regression analyses were combined in a mediation analysis to explore associations with each regional BMD. RESULTS: Weight correlated positively with total fat mass (R2  = 0.67, P < 0.001) and negatively with Si (R2  = 0.14, P < 0.001). Body composition measures were consistently positively related to BMD in all regions except lumbar and thoracic spine. Accounting for body weight rendered negative majority of associations between total and regional fat masses and BMDs. An independent association between android fat and spine BMD was particularly apparent. Si was positively associated with total and limb BMD (P < 0.01) specifically among exercisers. Accounting for Si diminished the associations of total fat (negative) and lean body mass (positive) with total and limb BMD. CONCLUSION: Android fat is independently negatively associated with spine BMD. Among those taking exercise, increased insulin sensitivity is associated with higher limb BMD and may underlie positive associations between lean body mass and BMD.

Effects of gender, age and menopausal status on serum apolipoprotein concentrations.

OBJECTIVE: To undertake a comprehensive evaluation of apolipoprotein risk markers for cardiovascular disease (CVD) according to gender, age and menopausal status. DESIGN: Cross-sectional analysis of independent associations of gender, age and menopause with serum apolipoproteins. PARTICIPANTS: Apparently healthy Caucasian premenopausal (n = 109) and postmenopausal (n = 252) women not taking oral contraceptives or hormone replacement, and Caucasian men (n = 307). MEASUREMENTS: Serum apolipoprotein (apo) B, A-I and A-II concentrations were measured, plus serum total cholesterol, low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), triglycerides, cholesterol in HDL subfractions and the apoB/apoA-I, LDL-C/apoB, HDL-C/apoA-I and HDL-C/apoA-II ratios. Analyses were undertaken with and without standardization for confounding characteristics and in 5-year age ranges. RESULTS: Overall, apoB concentrations were highest in men but in women rose with age and menopause to converge, in the age range of 50-55 years, with concentrations in men. The LDL-C/apoB ratio was generally higher in women than in men. ApoA-I concentrations were highest in postmenopausal women and lowest in men (standardized median (IQR) 144 (130, 158) vs 119 (108, 132) g/l, respectively, P < 0·001). ApoA-II concentrations were also highest in postmenopausal women but were lowest in premenopausal women (40·3 (37·5, 44·5) vs 32·9 (30·5, 35·7) g/l, respectively, P < 0·001). Nevertheless, postmenopausal women had HDL-C/apoA-I and HDL-C/apoA-II ratios approaching the lowest ratios, which were seen in men. CONCLUSIONS: Consistent with adverse effects on CVD risk, male gender, ageing in women and menopause were associated with increased apoB concentrations, and menopause and male gender were associated with a decreased cholesterol content of HDL particles.

Lipoprotein(a) in postmenopausal women: assessment of cardiovascular risk and therapeutic options.

INTRODUCTION: Lipoprotein(a) [Lp(a)], a low-density lipoprotein (LDL)-like particle, has been independently associated with increased cardiovascular disease (CVD) risk in various populations, such as postmenopausal women. The purpose of this narrative review is to present current data on the role of Lp(a) in augmenting CVD risk in postmenopausal women and focus on the available therapeutic strategies. METHODS: PubMed was searched for English language publications until November 2015 under the following terms: "therapy" OR "treatment" AND ["lipoprotein (a)" OR "Lp(a)"] AND ("postmenopausal women" OR "menopausal women" OR "menopause"). RESULTS: Only hormone replacement therapy (mainly oral estrogens) and tibolone have been specifically studied in postmenopausal women and can reduce Lp(a) concentrations by up to 44%, although evidence indicating a concomitant reduction in CVD risk associated with Lp(a) is lacking. As alternative treatments for women who cannot, or will not, take hormonal therapies, niacin and the upcoming proprotein convertase subtilisin / kexin type 9 (PCSK-9) inhibitors are effective in reducing Lp(a) concentrations by up to 30%. Statins have minimal or no effect on Lp(a). However, data for these and other promising Lp(a)-lowering therapies including mipomersen, lomitapide, cholesterol-ester-transfer protein inhibitors and eprotirome are derived from studies in the general, mainly high CVD risk, population, and include only subpopulations of postmenopausal women. CONCLUSIONS: Past, present and emerging therapies can reduce Lp(a) concentrations to a varying extent. Overall, it remains to be proven whether the aforementioned reductions in Lp(a) by these therapeutic options are translated into CVD risk reduction in postmenopausal women.

Pioneer microbial communities of the Fimmvörðuháls lava flow, Eyjafjallajökull, Iceland.

Little is understood regarding the phylogeny and metabolic capabilities of the earliest colonists of volcanic rocks, yet these data are essential for understanding how life becomes established in and interacts with the planetary crust, ultimately contributing to critical zone processes and soil formation. Here, we report the use of molecular and culture-dependent methods to determine the composition of pioneer microbial communities colonising the basaltic Fimmvörðuháls lava flow at Eyjafjallajökull, Iceland, formed in 2010. Our data show that 3 to 5 months post eruption, the lava was colonised by a low-diversity microbial community dominated by Betaproteobacteria, primarily taxa related to non-phototrophic diazotrophs such as Herbaspirillum spp. and chemolithotrophs such as Thiobacillus. Although successfully cultured following enrichment, phototrophs were not abundant members of the Fimmvörðuháls communities, as revealed by molecular analysis, and phototrophy is therefore not likely to be a dominant biogeochemical process in these early successional basalt communities. These results contrast with older Icelandic lava of comparable mineralogy, in which phototrophs comprised a significant fraction of microbial communities, and the non-phototrophic community fractions were dominated by Acidobacteria and Actinobacteria.

Nucleosome assembly factors CAF-1 and HIR modulate epigenetic switching frequencies in an H3K56 acetylation-associated manner in Candida albicans.

CAF-1 and HIR are highly conserved histone chaperone protein complexes that function in the assembly of nucleosomes onto chromatin. CAF-1 is characterized as having replication-coupled nucleosome activity, whereas the HIR complex can assemble nucleosomes independent of replication. Histone H3K56 acetylation, controlled by the acetyltransferase Rtt109 and deacetylase Hst3, also plays a significant role in nucleosome assembly. In this study, we generated a set of deletion mutants to genetically characterize pathway-specific and overlapping functions of CAF-1 and HIR in C. albicans. Their roles in epigenetic maintenance of cell type were examined by using the white-opaque switching system in C. albicans. We show that CAF-1 and HIR play conserved roles in UV radiation recovery, repression of histone gene expression, correct chromosome segregation, and stress responses. Unique to C. albicans, the cac2Δ/Δ mutant shows increased sensitivity to the Hst3 inhibitor nicotinamide, while the rtt109Δ/Δ cac2Δ/Δ and hir1Δ/Δ cac2Δ/Δ mutants are resistant to nicotinamide. CAF-1 plays a major role in maintaining cell types, as the cac2Δ/Δ mutant exhibited increased switching frequencies in both directions and switched at a high frequency to opaque in response to nicotinamide. Like the rtt109Δ/Δ mutant, the hir1Δ/Δ cac2Δ/Δ double mutant is defective in maintaining the opaque cell fate and blocks nicotinamide-induced opaque formation, and the defects are suppressed by ectopic expression of the master white-opaque regulator Wor1. Our data suggest an overlapping function of CAF-1 and HIR in epigenetic regulation of cell fate determination in an H3K56 acetylation-associated manner.

An observational case series of dabigatran and rivaroxaban exposures reported to a poison control system.

OBJECTIVE: Characterize clinical presentations and outcomes of dabigatran and rivaroxaban exposures reported to a poison control system. METHODS: Data for cases of dabigatran and rivaroxaban exposures called into the California Poison Control System from January 2011 to July 2013 were collected. Data collected included patient demographics, type of exposure, medication, dosage, vital signs, laboratory values, interventions, outcomes, and disposition. Exclusion criteria included confirmed nonexposures or miscoded cases. RESULTS: A total of 56 cases were identified, with 7 excluded, leaving 37 dabigatran and 12 rivaroxaban cases. Children age 12 years or less accounted for 5 dabigatran and 2 rivaroxaban cases. Bleeding was reported in 15 dabigatran cases. There were 4 cases of acute self-harm overdose with dabigatran ranging from 1800 to 3900 mg. Mild bleeding was reported in only one of these overdose cases. There were 2 fatal hemorrhages in dabigatran cases, both in chronic therapeutic dosing. Bleeding was reported in 5 rivaroxaban cases, all in patients with chronic exposure; no deaths were reported. There were no adverse outcomes in pediatric patients. Coagulation parameters did not correlate well with bleeding. CONCLUSIONS: In our series, the greatest risk of adverse events was in patients chronically taking these agents, irrespective of excess dosing. Acute self-harm ingestions and accidental pediatric ingestions had few adverse effects, although massive overdose can lead to abnormal coagulation studies. It does not appear that single low-dose ingestions of either medication will lead to clinically significant bleeding. It may be possible to manage some pediatric exposures and most accidental ingestions with observation.

Cardiovascular health and the menopause, metabolic health.

Estrogen depletion following menopause predisposes to increased risk of cardiovascular disease (CVD), mainly due to ischemic heart disease. This is mostly evident in cases with premature menopause. The pathophysiological basis for this atherosclerotic process is the accumulation of several risk factors, such as abdominal obesity, atherogenic dyslipidemia, insulin resistance and arterial hypertension. The presence of vasomotor symptoms may further augment this risk, especially in women younger than 60 years. Menopausal hormone therapy (MHT) exerts many beneficial effects on lipid profile and glucose homeostasis as well as direct arterial effects, and may reduce CVD risk if initiated promptly (i.e.,<60 years or within ten years of the final menstrual period). Transdermal estradiol and micronized progesterone or dydrogesterone are the safest regimens in terms of venous thromboembolic events (VTE) and breast cancer risk. In any case, an individualized approach, taking into account the patient's total CVD, VTE and breast cancer risk, is recommended.

Effects of tibolone or continuous combined oestradiol/norethisterone acetate on glucose and insulin metabolism.

OBJECTIVE: To determine the effects of tibolone or oestradiol (E(2) )/norethisterone acetate (NETA) hormone replacement therapy on glucose and insulin metabolism in postmenopausal women. DESIGN: Single-centre double-blind placebo-controlled randomized clinical trial. SUBJECTS/METHODS: We randomized 105 healthy postmenopausal women to tibolone 2·5 mg daily, continuous combined oral E(2) 2 mg/NETA 1 mg daily or placebo over a 2-year study. We performed intravenous glucose tolerance tests (IVGTT) with measurements of plasma glucose, insulin and C-peptide concentrations and the IVGTT glucose elimination rate, k. Mathematical modelling was performed to determine measures of insulin sensitivity, S(i) , pancreatic insulin secretion and hepatic and plasma insulin elimination. RESULTS: Tibolone decreased S(i) to 53-63% and k to 72-79% of baseline values but increased IVGTT phase 2 C-peptide concentrations 1·6-1·8-fold and pancreatic insulin secretion 2·2-2·4-fold, so overall IVGTT glucose concentrations were unaffected. Similar, but for k, significantly smaller changes in insulin and C-peptide secretion were seen with E(2) /NETA, also with no effect on overall IVGTT glucose concentrations. CONCLUSIONS: Tibolone reduces insulin sensitivity. Healthy postmenopausal women seem able to compensate for this and maintain normal postload glucose concentrations, but it may not be advisable to prescribe tibolone to women with, or at increased risk for, diabetes.

Outcomes and complications following spinous process fixation: a single-center analysis of 192 cases.

Spinous process fixation (SPF) is presented as less invasive than pedicle screws. There has been little quantitative data to support this assertion, and "minimally invasive" has not been well defined in spine surgery. Length of stay (LOS) and blood loss (BL) were chosen as surrogate measures of "minimally invasive." A chart review was conducted on 192 lumbar fusion patients (374 levels). A backward-selection multiple-linear-regression was performed to determine what variables contribute to LOS and estimated blood loss (EBL). A logistic regression controlling for age and number of levels on complication rates was also performed. Number of levels with supplementary screw fixation (SSF) was significantly associated with LOS (p = 0.003). Controlling for number of surgical levels, LOS increased by 0.30 days (95% CI: 0.02-0.58) for each level with SSF. For each additional level including SSF, BL increases by 25.31 cc (95% CI: 3.50-47.12, p = 0.023). Interbody fusion increases blood loss by 68.16 cc (95% CI: 17.18-119.13, p = .009). For each additional level with SSF, odds of perioperative complications increase by OR = 2.34 (95% CI: 1.35-4.05). Long-term complications were not affected by instrumentation. LOS and BL are increased in patients with SSF vs. SPF only. Odds of perioperative complications are increased in patients with SSF relative to those treated with SPF alone.

Coalitional capacities and environmental strategies to prevent underage drinking.

Coalitions are the most common platform for implementing community-level environmental strategies (ES), such as media, policy, or enforcement for substance use prevention. The current study examines the associations between two types of coalition capacity (general and innovation-specific) and ES implementation efforts and outputs within 14 intervention communities over a three-year period. Efforts refer to the amount of energy exerted to implement an ES while outputs refer to the materials produced through these efforts. Quantitative measures of capacity were provided by coalition key informants and expert-raters. Additionally, Training and Technical Assistance (TTA) provided proactively to improve the implementation of ES was also examined. Greater general capacity, as rated by a coalition informant, was associated with more ES policy effort. Both expert-rated general and innovation-specific capacity, however, were associated with greater ES outputs. Study results also found that community coalitions that endorsed weaker mobilization, structure and task leadership, (measures of general capacity), utilized more TTA compared to those who perceived their coalition as having greater capacity. Moreover, communities that utilized more TTA resources reported a greater number of successful policy changes. The study supports the need to consider both general and innovation-specific capacity for ES implementation and offers promising preliminary findings regarding the role of TTA for improving coalitions' capacity to facilitate policy change.

Rheumatoid Arthritis-Linked Artificial Joint Infections Leading to Amputations.

Rheumatoid arthritis (RA) is a common autoimmune condition that can rarely cause more serious complications, such as permanent joint damage or infection, and may pose a significant additional risk during certain routine procedures. One major consequence of RA is that it can lead to serious and permanent joint damage requiring arthroplasty. Additionally, RA is a known cause of infection, with orthopedic prosthetic joint infections (PJIs) being documented. We explore one such serious case of a patient with long-term RA and a left knee joint replacement who presented to the emergency room with a serious PJI. History revealed that he repeatedly was affected by infections and had an extensive and severe clinical course, including nine revision surgeries. After a physical examination, imaging was performed, which further supported the diagnosis of joint infection. Considering the extensive number of attempts to salvage the joint, clinicians decided an above-knee amputation was necessary. This case highlights the fact that RA both increases the need for orthopedic arthroplasties and the risk of complications from these procedures, complicating clinical decision-making for physicians. Additionally, this patient had other underlying medical conditions and social habits that may have contributed to his severe clinical course, and we hope to explore these, discuss possible methods of modifying them, and assist clinicians in not only better treating similar patients but also emphasizing the importance of further developing standardized predictive algorithms and scoring tools.

Researcher Views of Barriers to Clinical and Translational Research in a Statewide Program.

The Tracking and Evaluation Core of Rhode Island Advance-CTR conducted an online needs assessment survey at the program's inception in 2016 and again in 2021. Now dealing with well-established support systems provided by the grant, we were particularly interested in how the perceived needs of the research community in Rhode Island might have changed over five years. Specifically, what barriers have been reduced or eliminated and which have persisted or increased? How do those barriers vary by demographic status and what implications do those differences have for the CTR? An online survey was completed by 199 researchers, who reported the extent to which they perceived the lack of access to a range of research supports as a barrier to conducting research at their institution. Overall, researchers indicated statistically significant changes from 2016 to 2021 such that a lack of pilot project funding and proposal development support had decreased as barriers, while space for research, and advice on commercial development, had increased. Statistically significant differences in the salience of particular barriers by some demographic variables were also noted and the results of this study suggest Centers for Clinical and Translational Research can have salutary effects on the research paradigm within their partnering institutions in a relatively short time.

Regulation of white and opaque cell-type formation in Candida albicans by Rtt109 and Hst3.

How different cell types with the same genotype are formed and heritability maintained is a fundamental question in biology. We utilized white-opaque switching in Candida albicans as a system to study mechanisms of cell-type formation and maintenance. Each cell type has tractable characters, which are maintained over many cell divisions. Cell-type specification is under the control of interlocking transcriptional feedback loops, with Wor1 being the master regulator of the opaque cell type. Here we show that deletion of RTT109, encoding the acetyltransferase for histone H3K56, impairs stochastic and environmentally stimulated white-opaque switching. Ectopic expression of WOR1 mostly bypasses the requirement for RTT109, but opaque cells lacking RTT109 cannot be maintained. We have also discovered that nicotinamide induces opaque cell formation, and this activity of nicotinamide requires RTT109. Reducing the copy number of HST3, which encodes the H3K56 deacetylase, also leads to increased opaque formation. We further show that the Hst3 level is downregulated in the presence of genotoxins and ectopic expression of HST3 blocks genotoxin induced switching. This finding links genotoxin induced switching to Hst3 regulation. Together, these findings suggest RTT109 and HST3 genes play an important role in the regulation of white-opaque switching in C. albicans.

Recommendations on the management of fragility fracture risk in women younger than 70 years.

The risk for fragility fracture represents a problem of enormous magnitude. It is estimated that only a small fraction of women with this risk take the benefit of preventive measures. The relationship between estrogen and bone mass is well known as they are the other factors related to the risk for fracture. There are precise diagnostic methods, including a tool to diagnose the risk for fracture. Yet there continues to be an under-diagnosis, with the unrecoverable delay in instituting preventive measures. Women under the age of 70 years, being much more numerous than those older, and having risk factors, are a group in which it is essential to avoid that first fragility fracture. Today it is usual not to differentiate between the treatment and the prevention of osteoporosis since the common aim is to prevent fragility fractures. Included in this are women with osteoporosis or with low bone mass and increased risk for fracture, for whom risk factors play a primary role. There is clearly controversy over the type of treatment and its duration, especially given the possible adverse effects of long-term use. This justifies the concept of sequential treatment, even more so in women under the age of 70, since they presumably will need treatment for many years. Bone metabolism is age-dependent. In postmenopausal women under 70 years of age, the increase in bone resorption is clearly predominant, related to a sharp drop in estrogens. Thus a logical treatment is the prevention of fragility fractures by hormone replacement therapy (HRT) and, in asymptomatic women, selective estradiol receptor modulators (SERMs). Afterwards, there is a period of greater resorption, albeit less intense but continuous, when one could utilise anti-resorptive treatments such as bisphosphonates or denosumab or a dual agent like strontium ranelate. Bone formation treatment, such as parathyroid hormone (PTH), in women under 70 years will be uncommon. That is because it should be used in cases where the formation is greatly diminished and there is a high risk for fracture, something found in much older women.

Use of monetary and nonmonetary incentives to increase response rates among African Americans in the Wisconsin Pregnancy Risk Assessment Monitoring System.

From 2009 to 2010, an experiment was conducted to increase response rates among African American mothers in the Wisconsin Pregnancy Risk Assessment Monitoring System (PRAMS). Sample members were randomly assigned to groups that received a prepaid, cash incentive of $5 (n = 219); a coupon for diapers valued at $6 (n = 210); or no incentive (n = 209). Incentives were included with the questionnaire, which was mailed to respondents. We examined the effects of the incentives on several outcomes, including response rates, cost effectiveness, survey response distributions, and item nonresponse. Response rates were significantly higher for the cash group than for the coupon (42.5 vs. 32.4%, P < .05) or no incentive group (42.5 vs. 30.1%, P < .01); the coupon and no incentive groups performed similarly. While absolute costs were the highest for the cash group, the cost per completed survey was the lowest. The incentives had limited effects on response distributions for specific survey questions. Although respondents completing the survey by mail in the cash and coupon groups exhibited a trend toward being less likely to have missing data, the effect was not significant. Compared to a coupon or no incentive, a small cash incentive significantly improved response rates and was cost effective among African American respondents in Wisconsin PRAMS. Incentives had only limited effects, however, on survey response distributions, and no significant effects on item nonresponse.