Onset Of Functional Disability Research Articles

Physical frailty and survival time after the onset of functional disability: Is there a sex difference?

Physical frailty accelerates the timing of both subsequent disability and death; however, evidence regarding the impact of frailty on the period from disability onset to death and sex differences of this impact is lacking. The aim of this study was to examine the relationship among physical frailty, disability, death, and sex differences. This Japanese cohort study included 10,524 community-dwelling people aged ≥65 years. Physical frailty was operationalized by key phenotypes as per Fried's criteria (slowness, weakness, exhaustion, weight loss, and low activity) at baseline. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for disability onset and post-disability survival according to the frailty status. During a 5-year follow-up, the risk of disability onset for pre-frailty (HR: 1.74, 95% CI: 1.51-2.00) and frailty (HR: 3.27, 95% CI: 2.77-3.87) were significantly higher than that for robust people. Furthermore, among participants who developed disabilities within 5 years (n = 1481), the risk of post-disability death for pre-frailty was not different from that for robust (HR: 1.49, 95% CI: 0.99-2.24), but frailty showed a higher risk of post-disability death than did robust people. (HR: 1.75, 95% CI: 1.13-2.72). In the sex-stratified analysis, although the female group showed no association between frailty status and post-disability death (HR: 1.21, 95% CI: 0.63-2.33 in pre-frailty; HR: 1.24, 95% CI: 0.60-2.57 in frailty), the male group showed higher risk of post-disability death in both pre-frailty (HR: 1.74, 95% CI: 1.03-2.96) and frailty (HR: 2.32, 95% CI: 1.32-4.09). Physical frailty shortens the period from disability onset to death. Additionally, the impact of frailty on post-disability death is greater for males than for females. Our findings suggest that physical frailty is an important clinical indicator distinct from disability and that interventions to prevent and address frailty in men need further investigation.

Relationship between functional disability, depression, and social and civic engagement among older European adults: A three wave longitudinal study using SHARE

Abstract Background Studies show that depression has a long-term effect on physical health and functional capabilities. Vice versa, onset of functional disability has a detrimental role in the decline in emotional and mental well-being of older adults. The current study was sought to explore the direction of the association between functional disability and depression, and further examined if social-civic engagement, as a means of coping, moderated the association. Methods Study employed a secondary analysis using data derived from waves 5 (2013), 6 (2015) and 7 (2017) of the Survey of Health, Aging and Retirement in Europe (SHARE). In total, 36 323 older adults aged 65+ at baseline (mean age 74.41 ± 7.09 years; 54.8% women; 83.2% retired) were followed up over a 4-year period. Analysis included GALI (The Global Activity Limitation Indicator), ADLs (Activities of Daily Living), IADLs (Instrumental Activities of Daily Living), EURO-D depression scale, and different types of social/civic activities (voluntary/charity work; educational or training course; sport, social or other kind of club; and political or community-related organization). Covariates included socio-demographic variables. Results Controlling for the effects of covariates, the association between functional disability and depression is reciprocal over time, but depression had a greater impact on functional disability than the reverse at both follow-up points. Different types of social-civic participation appeared to moderate the association between depression and functional disability, but in varied ways. Conclusions Finding suggests that depression is associated with higher odds of functional disability, and impede recovery from the disability. Early behavioural and psychological interventions and social prescribing including social/civic activities can help develop positive resources, coping strategies, and resilience, and thereby, alleviating the vicious cycle linking functional disability and depression.

Parks/sports facilities in local communities and the onset of functional disability among older adults in Japan: The J-shaped spatial spillover effects.

We examined the associations between parks/sports facilities in local communities and the onset of functional disability among Japanese older adults. We further investigated the spatial spillover effects of parks/sports facilities in 1st-, 2nd-, and 3rd-degree neighboring communities. Data on the onset of functional disability, including date of onset, sex, age, and address (school district) of all older adults aged 65 years and older living in Kobe City were obtained from the public long-term care insurance database (163,348 men [190,831 person-year] and 200,443 women [230,464 person-year]). Multilevel proportional hazard regression analyses showed that the number of parks and sports facilities were negatively associated with the onset of functional disability among men. In particular, these associations were stronger for the adjacent district than for individuals' living districts. Our results imply that involving multiple neighboring communities as the intervention unit is effective when utilizing community built environments for long-term care prevention in men.

Risk Factors of Long-Term Care Insurance Certification in Japan: A Scoping Review.

This study aimed to review evidence on future long-term care associated with pre-existing factors among community-dwelling Japanese older adults. We systematically searched cohort and nested case–control studies published between 2000 and 2019 that assessed long-term care certification using the PubMed, CINAHL, and EMBASE databases. The relationship between long-term care insurance information and risk factors was investigated. The protocol was registered with the Open Science Framework. We extracted 91 studies for synthesis, including 84 prospective cohort studies, 1 retrospective cohort study, and 6 nested case–control studies. Certification for long-term care was classified into two endpoints: onset of functional disability and dementia. There were 72 studies that used long-term care certification as a proxy for functional disability, and 22 used long-term care information to indicate the onset of dementia. Common risk factors related to functional disability were physical function, frailty, and oral condition. Motor function and nutritional status were common risk factors for dementia. We found consistent associations between premorbid risk factors and functional disability and dementia. The accumulation of evidence on the incidence of long-term care and associated factors can aid the development of preventive measures. Future studies should aim to integrate this evidence.

Assessing Health Care Use Trajectories After the Onset of Functional Disability: Application of a Group-Based Trajectory Model.

While older adults with activity limitations have high levels of health care use, we do not know how this varies over time. We aimed to assess trajectories of Emergency Department (ED) use and hospitalization after the onset of receipt of help with self-care or mobility. We used the 2011-2017 National Health Aging Trends Study (NHATS) linked to Medicare claims to identify a cohort of older adults who began to receive help with self-care or mobility in the past year. Primary outcome was the quarterly rates of ED use and/or hospitalization over the 24 months following the onset of receiving help. We fit a Group-Based Trajectory Model to identify the trajectories of ED use or hospitalization and assessed the association of characteristics preceding and concurrent to the onset of help with trajectory group membership. Among 1,687 NHATS respondents newly receiving help with self-care/mobility, health care use escalated and then immediately fell. We found distinct trajectories of ED use and hospitalization: delayed rise (13.5%), falling (26.2%), and persistent (60.4%). Trajectory group membership was predicted by clinical, economic, and regional characteristics; and the individuals in each group differed in terms of concurrent new illnesses and degree of disability. While activity limitations are a strong predictor of health care use among older adults, trajectories of health care use are heterogeneous. Along with clinical characteristics, potentially modifiable household and regional factors shaped health care trajectories, indicating that addressing these factors could potentially shift health care use patterns.

Does laughing with others lower the risk of functional disability among older Japanese adults? The JAGES prospective cohort study

While laughter is evoked mainly in social contexts, the potential link between laughter in daily life and health benefits is unclear. This study aimed to examine the association between laughter in daily life and the onset of functional disability among older adults in Japan. Data were obtained from a 6-year follow-up cohort of 12,571 participants (46.1% male) in the Japan Gerontological Evaluation Study, aged ≥65 years, who could independently perform daily activities. We evaluated their laughter in daily life from three perspectives: the types of situations in which people laugh, the number of situations in which people laugh with others, and the persons with whom people laugh. Using the Cox proportional hazards model, the risk of functional disability was estimated. A total of 1420 functional disabilities were observed during follow-up. After adjusting for potential confounders, participants who laughed with others (e.g., during conversations with friends) were at a reduced risk of functional disability (hazard ratio, 0.77; 95% confidence interval, 0.65–0.92) than those who laughed alone (e.g., during watching television). Similarly, the number of situations to laugh with others was inversely associated with the risk of functional disability (Ptrend < 0.001). Laughing in a conversation with friends reduced the risk of functional disability by approximately 30% compared to laughing alone. Overall, laughing with others was associated with a reduced risk of functional disability. Having more situations to laugh with others or at least the situation to laugh with friends might contribute to reducing the risk of functional disability later in life.

Trends in functional disability and cognitive impairment among the older adult in China up to 2060: estimates from a dynamic multi-state population model

BackgroundAvailable evidence suggests that cognitive impairment (CI), which leads to deficits in episodic memory, executive functions, visual attention, and language, is associated with difficulties in the capacity to perform activities of daily living. Hence any forecast of the future prevalence of functional disability should account for the likely impact of cognitive impairment on the onset of functional disability. Thus, this research aims to address this gap in literature by projecting the number of older adults in China with functional disability and cognitive impairment while accounting for the impact of cognitive impairment on the onset of functional disability.MethodsWe developed and validated a dynamic multi-state population model which simulates the population of China and tracks the transition of Chinese older adults (65 years and older) from 2010 to 2060, to and from six health states—(i) active older adults without cognitive impairment, (ii) active older adults with cognitive impairment, (iii) older adults with 1 to 2 ADL limitations, (iv) older adults with cognitive impairment and 1 to 2 ADL limitations, (v) older adults with 3 or more ADL limitations, and (vi) older adults with cognitive impairment and 3 or more ADL limitations.ResultsFrom 2015 to 2060, the number of older adults 65 years and older in China is projected to increase, of which the number with impairment (herein referred to as individuals with cognitive impairment and/or activity of daily living limitations) is projected to increase more than fourfold from 17·9 million (17·8–18·0) million in 2015 to 96·2 (95·3–97·1) million by 2060. Among the older adults with impairment, those with ADL limitations only is projected to increase from 3·7 million (3·6–3·7 million) in 2015 to 23·9 million (23·4–24·6 million) by 2060, with an estimated annual increase of 12·2% (12·1–12·3); while that for cognitive impairment only is estimated to increase from 11·4 million (11·3–11·5 million) in 2015 to 47·8 million (47·5–48·2 million) by 2060—this representing an annual growth of 7·07% (7·05–7·09).ConclusionOur findings suggest there will be an increase in demand for intermediate and long-term care services among the older adults with functional disability and cognitive impairment.

Social isolation, loneliness and functional disability in Chinese older women and men: a longitudinal study.

This study investigated whether loneliness or social isolation is associated with the onset of functional disability over 4years among Chinese older populations. This study used data from the China Health and Retirement Longitudinal Study (CHARLS). Functional status was assessed by activities of daily living (ADL) and instrumental activities of daily living (IADL). Analyses were conducted with data from two waves (2011 and 2015) and were restricted to those respondents aged 50 and older and free of functional disability at baseline [n = 5,154, mean age (SD) = 60.72 (7.51); male, 52.3%]. Social isolation, loneliness and covariates were measured at baseline. Follow-up measures of new-onset ADL and IADL disability were obtained 4years later. We stratified the sample by gender, and then used binary logistic regressions to evaluate the associations between baseline isolation, loneliness and new-onset ADL and IADL disability. For women, baseline social isolation was significantly associated with new-onset ADL (OR = 1.18, 95% CI = 1.07-1.30) and IADL (OR = 1.11, 95% CI = 1.01-1.21) disability; no significant association between loneliness and ADL or IADL disability was found. For men, neither social isolation nor loneliness was found to be significantly associated with ADL or IADL disability. This longitudinal study found that social isolation, rather than loneliness, was significantly associated with functional disability over 4years among women (but not men) in China. These findings expand our knowledge about the association between social relationships and functional status among non-Western populations.

Bathing Frequency and Onset of Functional Disability Among Japanese Older Adults: A Prospective 3-Year Cohort Study From the JAGES.

BackgroundWhile bathing styles vary among countries, most Japanese people prefer tub bathing to showers and saunas. However, few studies have examined the relationship between tub bathing and health outcomes. Accordingly, in this prospective cohort study, we investigated the association between tub bathing frequency and the onset of functional disability among older people in Japan.MethodsWe used data from the Japan Gerontological Evaluation Study (JAGES). The baseline survey was conducted from August 2010 through January 2012 and enrolled 13,786 community-dwelling older people (6,482 men and 7,304 women) independent in activities of daily living. During a 3-year observation period, the onset of functional disability, identified by new certification for need of Long-Term Care Insurance, was recorded. Tub bathing frequencies in summer and winter at baseline were divided into three groups: low frequency (0–2 times/week), moderate frequency (3–6 times/week), and high frequency (≥7 times/week). We estimated the risks of functional disability in each group using a multivariate Cox proportional hazards model.ResultsFunctional disability was observed in a total of 1,203 cases (8.7%). Compared with the low-frequency group and after adjustment for 14 potential confounders, the hazard ratios of the moderate- and high-frequency groups were 0.91 (95% confidence interval [CI], 0.75–1.10) and 0.72 (95% CI, 0.60–0.85) for summer and 0.90 (95% CI, 0.76–1.07) and 0.71 (95% CI, 0.60–0.84) for winter.ConclusionHigh tub bathing frequency is associated with lower onset of functional disability. Therefore, tub bathing might be beneficial for older people’s health.

Community social capital and the onset of functional disability among older adults in Japan: a multilevel longitudinal study using Japan Gerontological Evaluation Study (JAGES) data

ObjectiveThe present study examined the association between community social capital and the onset of functional disability among older Japanese people by using validated indicators of social capital and a prospective...

Depressive Symptoms and Onset of Functional Disability Over 2 Years: A Prospective Cohort Study.

This prospective cohort study examined the relationship between depressive symptoms and onset of functional disability over 2 years among US Chinese older adults, a rapidly growing minority older adult population. This study used survey data from 2713 Chinese older adults who completed both baseline (2011-2013) and follow-up (2013-2015) interviews of the Population Study of Chinese Elderly in Chicago. Depressive symptoms were assessed at baseline by the nine-item Patient Health Questionnaire. Functional disability was measured by three validated scales, Katz Index of Independence in Activities of Daily Living (ADLs), the Lawton Instrumental Activities of Daily Living (IADLs) scale, and the Rosow and Breslau mobility scale. Multivariate logistic regression was conducted to examine the relationship between baseline depressive symptoms and the development of functional disability (ADLs, IADLs, mobility) at 2-year follow-up while adjusting for covariates. Of the 2713 participants, 5.2% experienced ADL disability onset, 35.6% experienced IADL disability onset, and 23.3% experienced mobility disability onset over 2 years. After adjusting for covariates, the odds of ADL disability onset (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 1.02-1.11), IADL disability onset (OR = 1.05; 95% CI = 1.01-1.09), and mobility disability onset (OR = 1.05; 95% CI = 1.01-1.09) were consistently higher in US Chinese older adults with higher levels of depressive symptoms than their less-depressed counterparts. Other significant risk factors included older age and more chronic physical conditions. Study findings underscore a significant relationship between depressive symptoms and onset of functional disability. Screening and, subsequently, treating depressive symptoms have the potential to reduce disability among US Chinese older adults. Culturally relevant depressive symptom screening may help identify Chinese older adults who are at greater risks for the development of functional disability. J Am Geriatr Soc 67:S538-S544, 2019.

Fear of Falling Predicts Incidence of Functional Disability 2 Years Later: A Perspective From an International Cohort Study.

To study the extent to which fear of falling (FOF) is associated with the onset of functional disability over a 2-year period in older adults using self-reported and performance-based measures. In 2012, 1,601 participants (aged 65-74 years) were recruited from four sites: Kingston and Saint-Hyacinthe, Canada; Manizales, Colombia; and Natal, Brazil. They were re-assessed in 2014. We quantified FOF using the Fall Efficacy Scale-International (FES-I; range: 16-64). Functional disability measures were (i) self-reported incident mobility disability, defined as difficulty climbing a flight of stairs or walking 400 m and (ii) incident poor physical performance, defined as a score <9 on the Short Physical Performance Battery. In the Poisson regression analysis, we included only those participants without functional disability at baseline to calculate incident risk ratios in 2014. 1,355 participants completed the 2014 assessment, of which 917 and 1,078 had no mobility disability and poor physical performance at baseline, respectively. In 2014, 131 (14.3%), and 166 (15.4%) participants reported incident mobility disability and poor physical performance, respectively. After adjusting for age, sex, socioeconomic, and health covariates, a one-point increase in FES-I at baseline was significantly associated with a 4% increase in the risk of reporting incident mobility disability (95% CI: 1.02-1.05) and a 3% increase in the risk of developing poor physical performance at follow up in the overall sample (95%CI: 1.01-1.05). FOF is associated with a higher risk of incident mobility disability and poor physical performance in a cohort of older adults. It is increasingly important to study FOF's effect on functional disability and to take necessary measures to prevent the transition to end-stage disability.

Likelihood that expectations of informal care will be met at onset of caregiving need: a retrospective study of older adults in the USA

BackgroundAgeing adults are likely to expect informal caregiving assistance from a friend or family member, reflecting the reality that most long-term care (LTC) is provided by family and friends. The...

Dental Status and Compression of Life Expectancy with Disability

This study examined whether the number of teeth contributes to the compression of morbidity, measured as a shortening of life expectancy with disability, an extension of healthy life expectancy, and overall life expectancy. A prospective cohort study was conducted. A self-reported baseline survey was given to 126,438 community-dwelling older people aged ≥65 y in Japan in 2010, and 85,161 (67.4%) responded. The onset of functional disability and all-cause mortality were followed up for 1,374 d (follow-up rate = 96.1%). A sex-stratified illness-death model was applied to estimate the adjusted hazard ratios (HRs) for 3 health transitions (healthy to dead, healthy to disabled, and disabled to dead). Absolute differences in life expectancy, healthy life expectancy, and life expectancy with disability according to the number of teeth were also estimated. Age, denture use, socioeconomic status, health status, and health behavior were adjusted. Compared with the edentulous participants, participants with ≥20 teeth had lower risks of transitioning from healthy to dead (adjusted HR, 0.58 [95% confidence interval (CI), 0.50–0.68] for men and 0.70 [95% CI, 0.57–0.85] for women) and from healthy to disabled (adjusted HR, 0.52 [95% CI, 0.44–0.61] for men and 0.58 [95% CI, 0.49–0.68] for women). They also transitioned from disabled to dead earlier (adjusted HR, 1.26 [95% CI, 0.99–1.60] for men and 2.42 [95% CI, 1.72–3.38] for women). Among the participants aged ≥85 y, those with ≥20 teeth had a longer life expectancy (men: +57 d; women: +15 d) and healthy life expectancy (men: +92 d; women: +70 d) and a shorter life expectancy with disability (men: –35 d; women: –55 d) compared with the edentulous participants. Similar associations were observed among the younger participants and those with 1 to 9 or 10 to 19 teeth. The presence of remaining teeth was associated with a significant compression of morbidity: older Japanese adults’ life expectancy with disability was compressed by 35 to 55 d within the follow-up of 1,374 d.

Abstract P298: Associations Between Time-varying Physical Activity and Physical Performance Measures in Postmenopausal Women: the Women’s Health Initiative

Introduction: Maintaining regular physical activity (PA) may delay the onset of functional disability and preserve mobility later in life. Whereas many population-based studies have reported the prospective relationship of initial PA levels to later-life functional status, few studies have examined the longitudinal relationships between changes in PA to changes in physical functioning. This study examined associations between changes in PA and changes in standard physical performance measures (PPM) over 6-years in older women. Methods: Recreational PA was reported using the WHI questionnaire; gait speed, timed chair stand, and grip strength were assessed in clinic using standardized protocols. Exposures were assessed at baseline, years 1, 3 and 6 of the Women’s Health Initiative Clinical Trials (n=5092 women; mean age = 69.8 y). Mixed effects linear regression models were used to evaluate the association between time-varying PA and change in each PPM. Potential interactions between time-varying PA and race and age (&lt;70 y; ≥70 y) were also tested. Results: At baseline, 23.0% women were categorized as sedentary (SED; &lt;100 MET-min/wk), 30.4% as light PA level (100- &lt;500 MET-min/wk), 27.5% as moderate (500- &lt;1200 MET-min/wk); and 19.1% as high PA (≥ 1200 MET-min/wk). Significant, dose-response associations between PA and improvements in all PPMs were observed over the 6 y follow-up after adjusting for demographic, lifestyle, and clinical factors. Compared to SED, women in the high PA groups showed better grip strength (0.48 kg higher; P &lt;0.01), more chair stands (0.35 more; P &lt;0.001), and faster gait speeds (0.06 m/s faster ; P &lt;0.001). Older women (≥70 y) benefited more from higher levels of PA than the younger women (P interaction for age =0.014), as reflected by their greater increase in chair stands ( P &lt;0.001); however, interactions between PA and race were not significant. Conclusions: These findings provide evidence that, in post-menopausal women, maintaining higher PA levels over time is associated with benefits in lower extremity function, as compared to being sedentary. These data are consistent with the view that regular PA plays an important role in maintaining functional status during aging, particularly in older women.

Social participation and the onset of functional disability by socioeconomic status and activity type: The JAGES cohort study

The impact of social participation on older adults' health may differ by individual socioeconomic status (SES). Consequently, we examined SES effect modification on the associations between types of social activity participation and incident functional disability. Cohort data from the 2003 Japan Gerontological Evaluation Study (JAGES) was utilized. This included individuals who were aged 65 or older and functionally independent at baseline. Analysis was carried out on 12,991 respondents after acquisition of information about their long-term care (LTC) status in Japan. Incident functional disability was defined based on medical certification and LTC information was obtained from municipal insurance databases. Cox proportional hazard regression was conducted for analysis. Results indicated that participants in a sport (hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.51, 0.85) or hobby group (HR: 0.69; 95% CI: 0.55, 0.87), or who had a group facilitator role (HR: 0.82; 95% CI: 0.66, 1.02) were less likely to be disabled. While men with 13 or more years of education were less likely to become disabled if they held facilitator roles, this association was weak among men with 0–5years of education (HR of interaction term between 0 and 5years of education and facilitator role dummy variable=3.95; 95% CI: 1.30, 12.05). In conclusion, the association between group participation and smaller risk of the functional disability was stronger among highly educated older adults. Intervention programs promoting social participation should consider participants' socioeconomic backgrounds.

Criteria for social isolation based on associations with health indicators among older people. A 10-year follow-up of the Aichi Gerontological Evaluation Study

No clear evidence for a cut-off point for social isolation has been established so far. The purpose of this study was to evaluate the criteria for social isolation based on associations with objective health outcomes in a 10-year follow-up study. We performed a prospective study of functionally independent residents aged 65 years or older who lived in six municipalities as part of the Aichi Gerontological Evaluation Study (response rate: 50.4%) that began in 2003. Data on the onset of functional disability, dementia, and death were obtained from municipal databases of the public long-term care insurance system. A total of 12,085 participants were followed up for up to 10 years. We used frequencies of face-to-face and non-face-to-face contact with non-resident children, relatives and friends, or neighbors as indicators of social isolation. The overall frequency of contact with others was categorized from "less than once a month" to "frequently, every day." Cox's proportional hazard model revealed that, after controlling for sex, age, education level, marital status, equivalent household income, need for medical care, self-recognition of forgetfulness, and residential area, the hazard ratios for functional disability (over long-term care level 2), dementia, and premature death increase in those with contact frequency of "less than once a month" were 1.37 (95% confidence interval [CI]: 1.16-1.61), 1.45 (95% CI: 1.21-1.74), and 1.34 (95% CI: 1.16-1.55), respectively. The "from once a month to once a week" frequency was also associated with these health indicators, although the "more than once a week" frequency was not significantly associated with any measured outcome. The prevalence of "less than once a month" contact was 7.4% (men=10.2%, women=4.7%), and this was 15.8% (men=21.2%, women=10.6%) when including those with "less than once a week" contact. These findings suggest that "less than once a week" or "less than once a month" contact with non-cohabitant others are valid operational definitions of social isolation that are closely associated with premature death and other health indicators.

Does social capital affect the incidence of functional disability in older Japanese? A prospective population-based cohort study

BackgroundRecent increases in numbers of older people have been accompanied by increases in those with functional disability. No study has examined the association between community social capital and the onset...

Avian Muscular Dystrophy: Muscle Ultrastructure and Histochemistry Following Isaxonine Treatment

Due to many similar properties, including high serum creatine phosphokinase (CPK) levels and histological signs of muscle degeneration, inherited muscular dystrophy of the chicken has been used for over 20 years as a model for hereditary muscular dystrophy in humans. Line 413 dystrophic chickens were selected for this drug study because they are homozygous for muscular dystrophy (disease appears with 100% incidence), they have a characteristic elevation in CPK activity, they have extensive signs of muscle autolysis, and they demonstrate a reproducible and measurable onset of functional disability in a flip-test procedure. Since the earliest detectable clinical sign of the disease is the inability of the dystrophic bird to right itself from the supine position, any therapeutic agent which can delay the onset of this condition is usually considered beneficial therapy. In this study we investigated the drug, Isaxonine (N-isopropyl amino pyrimidine phosphate) which has been shown to have a nerve growth-promoting action. Dystrophic chickens (413) were injected daily with Isaxonine (50mg/kg weight) from day 3 exc ovo to day 40 and compared to normal controls (412) and non-injected dystrophics. In addition to the flip test, we measured the effect of this drug on serum CPK levels and muscle histology and ultrastructure. The results of these experiments indicate that 14., 20 and 40 day Isaxonine injected dystrophic animals are greatly improved compared to non-injected dystrophic animals. For example, Figure 1 is an electron micrograph of pectoralis skeletal muscle from a 20-day-old normal chicken injected daily with Isaxonine (CPK 560mU/ml plasma, Flip 25) showing normal ultrastructure. Figure 2 is an electron micrograph of pectoralis skeletal muscle from a 20-day-old uninjected dystrophic chicken (CPK 1370mU/ml plasma, Flip 2) illustrating extensive ultrastructural deterioration. Figure 3 is a representative micrograph of pectoralis skeletal muscle from a 20-day-old dystrophic chicken injected daily with Isaxonine (CPK 840mU/ml plasma, Flip 13). Note that the ultra-structural morphology appears more similar to the normal than to the dystrophic animals. Figure 4 is an electron micrograph of pectoralis skeletal muscle from a 20-day-old dystrophic chicken injected every other day with Isaxonine (CPK 1218mU/ml plasma, Flip 3). The ultrastructure of this treatment group more closely resembles the dystrophic rather than the normal control muscle. As is apparent in these figures and confirmed with light microscopic histologic sections of similar tissue, the daily injected animals appear to have greatly improved muscle ultrastructure compared to the dystrophic or every-other-day injected animals. Even though the mode of action of Isaxonine is unknown at present, it does appear that it must be injected daily to have therapeutic value and that cessation of drug administration results in the dystrophic phenotype reappearing. Finally, in another dystrophic strain of chickens (304), we have found Isaxonine to be beneficial, as measured by a 50% reduction in serum CPK levels after 20 days of drug administration.