Predictive Value of DXA Appendicular Lean Mass for Incident Fractures,Falls, and Mortality,Independent of Prior Falls,FRAX, and BMD: Findings from the Women's Health Initiative (WHI)

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX^®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height²) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height² (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height² was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height² and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height², depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height² and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Pregnancy: The effect of dose of mifepristone and gestation on the efficacy of medical abortion with mifepristone and misoprostol

Although it has been demonstrated that a combination of mifepristoneand a prostaglandin is an effective method of inducing abortionin early pregnancy, the optimum dose of the antigestogen isunknown. Women (n = 220) requesting abortion in early pregnancy(63 days amenorrhoea) were randomized to receive a single doseof either 600 or 200 mg mifepristone followed 48 h later bya single dose of 600 µg misoprostol by mouth. The percentageof women who had a complete abortion (93.6% confidence interval90.4–95.5%) was identical in the two groups. There wasno significant difference in the number of women who passedthe fetus within 4 h of receiving the prostaglandin (64 versus74%), the days of bleeding (14.6 ± 1.1 versus 15.3 ±0.9) nor in the onset of the next period (39.7 ± 1.3versus 36.7 ± 1.3) respectively between the groups receiving200 or 600 mg mifepristone. However, the complete abortion ratewas significantly higher in women 49 days compared to women50–63 days amenorrhoea (97.5 versus 89.1% respectively;P < 0.02). There was no difference in any of the other parametersat different weeks of gestation. We conclude: (i) that the recommendeddose of mifepristone could be reduced from 600 to 200 mg withoutloss of clinical efficacy, (ii) that the combination of mifepristoneand 600 µg misoprostol is a highly effective alternativeto vacuum aspiration for inducing abortion in women < 50days amenorrhoea and (iii) at gestation >56 days, this combinationmay result in too many incomplete abortions to be clinicallyacceptable.     

Effects of priming duration on retention over the first 1 1/2 years of life

Exposing individuals to an isolated component (a prime) of a prior event alleviates its forgetting. Two experiments with 120 human infants between 3 and 18 months of age determined the minimum duration of a prime that can reactivate a forgotten memory and how long the reactivated memory persists. Infants learned an operant task, forgot it, were exposed to the prime, and later were tested for renewed retention. In Experiment 1, the minimum duration of an effective prime decreased logarithmically with age, but was always longer than the duration of a mere glance. In Experiment 2, the reactivated memory was forgotten twice as fast after a minimum-duration prime as after a full-length one, irrespective of priming delay and infant age. These data reveal that the minimum effective prime duration psychophysically equates the accessibility of forgotten memories. We conclude that priming is perceptually based with effects that are organized on a ratio (log) scale.     

Mental retardation in ten-year-old children in relation to their mothers' employment during pregnancy

We conducted a case-control study to examine relationships between potential risk factors in women's prenatal occupational histories and subsequent mental retardation in their 10-year-old children. Children with mental retardation (intelligence quotient less than 71) were identified from special education records maintained by the public school systems in the metropolitan Atlanta area and from records of various medical and social service agencies serving children with special needs. Control children were chosen from the rosters of 10-year-olds who were enrolled in regular education classes in the local public school systems. To obtain occupational histories, sociodemographic data, and other information, we interviewed 352 natural mothers (67%) of 525 case children and 408 natural mothers (64%) of 636 control children. We computed odds ratios for each of 25 selected occupation, industry, and agent categories controlling for maternal education, birth order, and race. Most comparisons yielded odds ratios that were not indicative of unusual risks, but we did find lower than expected risks among children of teachers and health-care professionals. We also found a strong, positive association between mental retardation and maternal employment in the textile and apparel industries. The findings are useful for planning the direction of future studies of childhood cognitive ability to focus on specific parental occupations or industries. © 1993 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Community Care for People with Chronic Conditions: An Analysis of Nine Studies of Health and Social Service Utilization in Ontario

A series of studies conducted in the same region found that programmatic, community-based health and social service interventions have a positive impact on client well-being. These proactive interventions, designed to address the full range of health and social needs, were usually provided at the same–or even lower–costs as uncoordinated, illness-focused care. The results of this series suggest that across-the-board health care reduction, atleast in a system of national health insurance, will produce poorer results, at higher cost, for people with chronic conditions living in the community. Policy planners need more research that concentrates on comparisons of outcomes between and within different models of health and social service delivery. The studies should be designed to help them determine who benefits from different serviceconfigurations carried out within a range of policy environments at various costs.     

Matrix Metalloproteinase Inhibitors: Applications in Oncology

Matrix metalloproteinases (MMP) are a group of zinc dependentenzymes which include the interstitial collagenases, stromelysins,gelatinases and membrane-type metalloproteinases. They are involvedin the remodelling and turnover of the extracellular matrixproteins. They play a role in wound healing and the pathogenesis ofarthritis. In malignancies they play a role in tumor invasion,metastasis and angiogenesis. A number of synthetic matrixmetalloproteinase inhibitors (MMPIs) have been developed forclinical use. In preclinical tumor models they have shown promisingactivity in achievinginhibition of MMPs and reducing tumor growth and metastatic spread.Some have also shown additive or synergistic effects with cytotoxicagents. Phase I and II studies in human subjects have defined themain side effects of these agents as beingmusculoskeletal pains or arthralgias. As they are cytostatic agentsrather than cytotoxic in activity conventional measurements ofradiological response for assessment are not applicable in trials.Biological activity has been demonstrated in certain cancers by theeffects on levels of tumor markers as surrogate markers of tumorresponse and also by a fibrotic stromal reaction seen in tumortissue. Newer agents have been developed withselective inhibition of certain MMPs in an attempt to reduce theside effects. A number of phase III human clinical trialsevaluating MMPs are being carried out at present but onlyone has been formally reported so far. This study suggested thatmarimastat had no survival advantage when compared to chemotherapywith gemcitabine in advanced pancreatic carcinoma. Current trialsare assessing efficacy of MMPIs in maintenance of remission afterother modalities of therapy or in combination with cytotoxicagents. MMPs have also been demonstrated to play an important rolein the articular cartilage destruction seen in both rheumatoidarthritis and osteoarthritis. The use of MMPIs in both exvivoand in vivomodels have shown promising resultsand trials are in process to assess their potential role in thecontrol of articular destruction. The true therapeutic role ofMMPIs await the results of these randomized studies.     

A comparison of the effects of vasopressin and oxytocin with amphetamine and chlordiazepoxide on passive avoidance behaviour in rats

On the basis of results obtained from passive avoidance studies, we have argued that the neuropeptide vasopressin could act on arousal, rather than memory processes in rats (Sahgal et al. 1982). In this report, we examine the effects of substances that are known to increase (d-amphetamine) or decrease (chlordiazepoxide) behavioural arousal, and compare the data with those obtained after vasopressin or oxytocin treatment. All four substances yielded broadly similar bimodal results (although the oxytocin data failed to reach significance). We argue for an arousal interpretation which suggests that performance and arousal are related in an inverted-U manner. The data also indicate that care must be taken in selecting appropriate statistical tests.