Predictors of non-spine fracture in elderly men: the MrOS study.

We examined determinants of nonvertebral fracture in elderly men from six U.S. communities followed an average of 4.1 years. Six clinical risk factors predicted fracture risk independent of hip BMD: tricyclic antidepressant use, previous fracture, inability to complete a narrow walk trial, falls in previous year, age > or =80 years, and depressed mood. INTRODUCTION: There are few prospective studies of fracture determinants in men. We examined the associations between a comprehensive set of clinical risk factors and risk of nonspine fracture in older men and whether determinants of fracture risk were independent of total hip BMD. MATERIALS AND METHODS: A total of 5995 men > or =65 years of age were recruited from six communities in the Unites States and followed prospectively for an average of 4.1 years. Baseline assessments of demographic, lifestyle, medical history, functional status, anthropometry, and cognitive, visual, and neuromuscular function were assessed by questionnaire or examination. Triannual mailed questionnaires ascertained incident fracture; reported fractures were adjudicated by physicians using medical records and X-ray reports. Proportional hazards models were used to develop multivariable models, selecting variables and controlling for BMD. RESULTS: Of 5876 men, 4.7% (N = 275) reported an incident nonspine fracture during follow-up (11.46/1000 person-years). Tricyclic antidepressant use (hazard ratio [HR], 2.36; 95% CI, 1.25-4.46), history of fracture at or after age 50 (HR, 2.07; 95% CI, 1.62-2.65), inability to complete a narrow walk trial (HR, 1.70; 95% CI, 1.23-2.34), falls in previous year (HR, 1.59; 95% CI, 1.23-2.05), age > or =80 years (HR, 1.33; 95% CI, 1.01-1.76), depressed mood (HR, 1.72; 95% CI, 1.00-2.95), and decreased total hip BMD (HR, 1.53; 95% CI, 1.34-1.74) were independently related to increased risk. Compared with having none (48.0% of men), having three or more of the clinical risk factors (4.9% of men) increased fracture risk 5-fold, independent of BMD. Having three or more risk factors and being in the lowest tertile of BMD was associated with a 15-fold greater risk than having no risk factors and being in the highest BMD tertile. CONCLUSIONS: Several clinical risk factors were independently associated with nonspine fractures in elderly men. The combination of multiple risk factors and low BMD was a very powerful indicator of fracture risk.     

Age and gender interactions on verbal memory performance.

Age and gender effects on verbal episodic memory are well established. However, the possibility of interactions between age and gender has been raised by studies linking estrogen and verbal memory performance, and by research suggesting gender differences in age-related cortical atrophy. We evaluated whether age by gender interactions in verbal memory were present. Subjects within three years of the median age of menopause were excluded from a large cohort of normal subjects, resulting in a younger sample (16-47 years) of 288 men and 285 women, and an older sample (55-89 years) of 201 men and 245 women. All subjects were administered the CVLT-2, a multiple-trial list-learning task. Verbal memory was negatively correlated with age for younger men, older men, and older women, but not for younger women. Multivariate analyses indicated age by gender interactions on memory for the younger group but not the older group. Results indicate that verbal memory declines with age for younger men but not younger women, whereas both older men and older women show age-related declines. These findings are consistent with hypotheses linking estrogen and verbal memory performance, and with imaging data suggesting that age-related hippocampal atrophy is found in younger men but not younger women. The role of estrogen on cognition in normal aging warrants further study.     

Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study

Background  

Genes involved in dopaminergic neurotransmission have been suggested as candidates for involvement in smoking behavior. We hypothesized that alleles associated with reduced dopaminergic neurotransmission would be more common in continuing smokers than among women who quit smoking.     

A preliminary cost effectiveness analysis of an intervention to reduce homelessness among the mentally ill

The Critical Time Intervention Project is a three-year clinical trial which tests a time-limited, supportive intervention to reduce recurrent homelessness among mentally ill men moving from a shelter to the community. Along with a comparison of nights spent homeless and other outcomes, the evaluation of the Critical Time Intervention includes a comparison of the relative costs of the intervention, compared to usual treatment. Such cost effectiveness analyses are difficult to perform and are rarely applied to mental health treatments. This paper presents the general scheme of this analysis and discusses critical issues in the construction and measurement of cost variables. Preliminary results which have implications for the cost analysis are presented.     

The effects of three nebulized osmotic agents in the dry larynx.

PURPOSE: This investigation examined the effects of nebulized hypertonic saline, isotonic saline (IS), and sterile (hypotonic) water on phonation threshold pressure (PTP) and self-perceived phonatory effort (PPE) following a surface laryngeal dehydration challenge. METHOD: In a double-blind, randomized experimental trial, 60 vocally healthy women (n = 15 per group) underwent a laryngeal desiccation challenge involving oral breathing for 15 min using medical-grade dry air (RH<1%). Three of the four groups then received nebulized isotonic saline (0.9% NaCl), hypertonic saline (7% NaCl), or sterile (hypotonic) water, respectively; the 4th group served as a nontreatment control. PTP and PPE were estimated for high-pitched productions at baseline, immediately postdesiccation, and at 5, 20, 35, and 50 min postnebulization. RESULTS: PTP increased significantly for all groups following the desiccation challenge. PTP values were, on average, 0.5 cm H(2)O greater immediately postdesiccation versus baseline. In contrast, PTP values did not change significantly following the administration of nebulized treatments, although a temporary trend toward a reduction in PTP was observed for the IS group. Unexpectedly, PPE ratings decreased significantly after the desiccation challenge. In general, PPE ratings were poorly correlated with PTP measures. CONCLUSION: A laryngeal desiccation challenge (i.e., temporary exposure to extremely low relative humidity while breathing transorally) significantly increased PTP. Although interesting trends emerged, none of the nebulized treatments significantly enhanced recovery from the negative effects of desiccation on PTP. In light of very low correlations between PTP and PPE, serious questions are raised regarding presumed associations between these measures.     

A comparison of the sniff magnitude test and the University of Pennsylvania Smell Identification Test in children and nonnative English speakers

The sniff magnitude test (SMT) is a reliable and rapid clinical test of olfactory function that is minimally dependent on cognitive and linguistic abilities. In this study, we compared performance on the SMT and University of Pennsylvania Smell Identification Test (UPSIT) in samples of children and nonnative English speakers. Previous research has shown that these populations perform poorly on the UPSIT as compared with young, healthy U.S. adults. Such performance differences may reflect variations in memory/cognition and language/culture rather than olfactory abilities. The UPSIT scores of children and of Indian and Chinese graduate students were found to be lower than those of young U.S. adults. By contrast, these groups did not perform more poorly than U.S. adults did on the SMT. The results are consistent with findings from our studies, with the elderly showing that performance on the UPSIT, but not the SMT, is significantly correlated with measures of memory, language and other cognitive abilities. The findings highlight the utility of the SMT when evaluating the olfactory ability of the very young, older adults and people with diverse linguistic and cultural backgrounds.     

Genetic damage detected in CD-1 mouse pups exposed perinatally to 3'-azido-3'-deoxythymidine or dideoxyinosine via maternal dosing, nursing, and direct gavage: II. Effects of the individual agents compared to combination treatment

We previously reported extraordinary increases in micronucleated erythrocytes in CD-1 mouse pups exposed to 3'-azido-3'-deoxythymidine (AZT) and dideoxyinosine (ddI; 50/250, 75/375, 150/750 mg/kg/day AZT/ddI) by gavage throughout gestation and lactation, followed by direct pup dosing beginning postnatal day (PND) 4 (Bishop et al. [2004]: Environ Mol Mutagen 43: 3-9). That study was conducted to explore the potential for genetic damage in newborns exposed perinatally to antiretrovirals in order to reduce maternal-infant transmission of HIV-1. Because dramatic increases in frequencies of micronucleated erythrocytes were seen in exposed pups, additional studies were conducted to clarify the relative contribution of each drug to the observed damage. Pregnant CD-1 mice were administered AZT (50, 75, 150 mg/kg/day) or ddI (250, 375, 750 mg/kg/day) by gavage twice daily in equal fractions beginning prior to mating and continuing throughout gestation and lactation. Direct pup dosing (same regimens) began on PND 4. Peripheral blood erythrocytes of male pups were screened for micronuclei on PNDs 1, 4, 8, and 21. Significant increases in micronucleated erythrocytes were observed in pups and dams exposed to AZT at all doses and sampling times. The highest micronucleus levels were observed in pups on PND 8 after the initiation of direct dosing. In contrast, effects seen in pups and dams treated with ddI were minimal. These results demonstrate that AZT, a component of many anti-HIV combination therapies, induces chromosomal damage in perinatally exposed neonatal mice. Comparison of micronucleated cell frequencies induced by AZT alone or in combination with ddI suggests that ddI potentiates AZT-induced chromosomal damage following direct exposure.