Physical activity does not alter prolactin levels in post-menopausal women: results from a dose-response randomized controlled trial

Background

Increased circulating levels of prolactin have been associated with increased risk of both in situ and invasive breast cancer. We investigated whether or not physical activity had a dose–response effect in lowering plasma levels of prolactin in postmenopausal women.

Methods

Four hundred previously inactive but healthy postmenopausal women aged 50–74 years of age were randomized to 150 or 300 min per week of aerobic physical activity in a year-long intervention. Prolactin was measured from fasting samples with a custom-plex multiplex assay.

Results

A high compared to moderate volume of physical activity did not reduce plasma prolactin levels in intention-to-treat (Treatment Effect Ratio (TER) 1.00, 95% Confidence Interval (CI) 0.95 – 1.06) or per-protocol analyses (TER 1.02, 95% CI 0.93 – 1.13).

Conclusions

It is unlikely that changes in prolactin levels mediate the reduced risk of breast cancer development in post-menopausal women associated with increased levels of physical activity.

Trial registration

clinicaltrials.gov identifier: NCT01435005.

     

Association between handgrip strength,walking, age-related illnesses and cognitive status in a sample of Portuguese centenarians

Background

Centenarians are a growing population in Europe and present significant variability in motor and cognitive functions. The aim of our study was to characterize health status, as well as cognitive and motor functions in a group of Portuguese centenarians. In addition, our study also aimed at analyzing the relationship between cognitive functions and the burden of diseases affecting the elderly.

Methods

Fifty-two centenarians were evaluated using the Mini-Mental State Examination, short version. Walking-related parameters (velocity and time spent in the 3 m walk test), grip strength and number of age-related illnesses were also measured. The relationship between cognitive scores and time spent in the three metre walk test, velocity, grip strength and number of diseases was analysed.

Results

Cognitive scores showed a positive correlation with both handgrip strength and time spent in the three metre walk. In contrast, no association was found between cognitive scores and the presence/absence of disease, walking velocity or number of diseases present.

Conclusions

These results suggest that in centenarians, cognitive functions may be related with motor functions.

     

Study of the association between gait variability and physical activity

Background

Gait variability can be considered an indirect measure of gait stability, in particular regarding temporal or spatial variability assessment. Physical activity, such as walking, is advised for the elderly and can be improved by gait stability. The aim of this study was to investigate the associations between gait stability and physical activity in women of different age ranges.

Methods

Forty-two healthy women of different age ranges (18-40 yrs. and 65-75 yrs.) were recruited in the study. To assess physical activity, the subjects wore a multi-sensor activity monitor for a whole week, inferring the time spent in moderate to vigorous physical activity (MVPA). MVPA were analysed in bouts of at least 10 subsequent minutes (MVPA_bouts) and in overall minutes (MVPA_tot). A kinematic analysis was performed with an optoelectronic system to calculate gait variability - expressed as standard deviation (SD) and coefficient of variability (CV) of step width, stride length, stance and swing time (during treadmill walking at different speeds).

Results

Elderly women, with high walking speed (5 km/h), and moderate step width variability (CV = 8–27%), met the recommended levels of physical activity (MVPA_tot and MVPA_bouts). Furthermore, gait variability, adjusted for age and number of falls, was significantly and negatively associated with MVPA_tot only at 3.5 km/h, and with MVPA_bouts only at 4 km/h.

Conclusions

In a population of healthy elderly women, gait variability was significantly and negatively associated with the level of physical activity. Healthy elderly women, with moderate gait variability (step width variability), and high preferred walking speed, seem to be able to meet the recommended levels of physical activity.

     

Perceptions of physical activity among elderly residents and professionals in assisted living facilities

Background

Physical activity is often described as being important for people of all ages, but what different people mean when they talk about physical activity is unclear.

Method

A phenomenographic method was used to analyze how 13 older people and 17 professionals answer the question, “If I say physical activity, what does the concept mean to you?” as part of semi-structured interviews conducted in four assisted living facilities in two different municipalities.

Results

We identified a number of different perceptions of physical activity, with the older people and professionals having different responses. Elderly and professionals alike, define physical activity as a requirement for life and as an opportunity to maintain the body although they define the concepts in different ways. Elderly define the concept as a way to create meaning and the professionals have the attitude that the concept means everyday activities.

Conclusion

The concept of physical activity may be defined in many different ways. This study has shown that elderly and professionals do not define physical activity in the same way. Therefore, professionals need to be aware of these differences when talking with elderly about individual needs in everyday life.

     

Implementing Cognitive Behavioral Intervention for Trauma in Schools (CBITS) with Latino Youth

Objective

Many Latino youth are often unable to access mental health services and support following exposure to traumatic and stressful events. This study assesses the benefits and effectiveness of utilizing Cognitive Behavioral Intervention for Trauma in Schools (CBITS), a school based intervention, with Spanish speaking, Latino youth residing in New Orleans, Louisiana, in effort to address presenting symptoms of trauma and depression.

Method

Twenty three children and adolescents ages 10 to 14, in fifth, sixth and seventh grades, presenting with symptoms of trauma and depression, participated in a 10 week program of CBITS which was primarily conducted in Spanish.

Results

Children who participated in CBITS reported significantly fewer symptoms of trauma and depression following the intervention; however, no differences were noted between genders. Significant differences were observed between older boys and girls (12–14), as they were more likely to report higher levels of exposure to trauma than younger boys and girls (10–11). The effect sizes for the intervention were large.

Conclusions

Findings of this study suggest that CBITS is a practical and effective school based intervention available to mental health providers as a resource to be used with Spanish speaking, Latino youth who have been exposed to different forms of stress and trauma.

     

Self- vs proxy-reported mobility using the mobility assessment tool-short form in elderly preoperative patients

Background

Mobility is fundamental to maintenance of an independent lifestyle and can predict clinical outcomes after health events among older individuals. However, certain clinical situations do not accommodate physical or self-assessments. This investigation examines whether proxy-reported assessments of function using the Mobility Assessment Tool-short (MAT-sf) form is a reliable alternative.

Methods

Sixty-six older persons (≥ age 70) and their proxies were enrolled. Proxies rated patients’ mobility using the MAT-sf as did the patients.

Results

The mean age of patients was 78.4 yr. (±6.2); 44% were female and 86% were white. Spouses made up 55% of the proxies, while 39% were children/in-laws. The correlation coefficient between patient and proxy MAT-sf scores was 0.81 (p?<?0.01); a comparison of the slope of the regression line relating patient- and proxy-reported MAT-sf to a line of identity showed disagreement (p?<?0.01), with proxy reports underreporting patient responses by 8.3% in lower mobility patients. The intra-class correlation characterizing agreement between repeated proxy reports 0.81.

Conclusion

Proxy reports of mobility in older patients have good reliability. However, in patients with poor mobility, the proxies tend to report a lower mobility than the patients.

     

Perceptions of Long-Term Community Adaptation of Delinquent Young Adults Who Graduated from Children’s Residential Mental Health Treatment

Purpose

This article presents results from one part of a longitudinal study into the post-discharge community adaptation of youth involved in residential mental health treatment. The focus is on young adults interviewed in Phase 3 of the research who have been identified as experiencing delinquent behaviour in their communities which brings them into contact with the law. This research is unique as young adult graduates of residential treatment were interviewed and they describe in detail how they are currently functioning in their lives.

Method

Qualitative interviews were completed with a convenience sample of 59 young adults between 18 and 25 years of age who had accessed children’s residential mental health treatment up to 10 years prior to data collection.

Results

The results demonstrate that delinquent behaviour post-discharge from residential treatment is a real concern and, for a sub-set of young adults, relates to negative outcomes in multiple domains of living, such as substance abuse, personal well-being, education and employment, and social networks and relationships.

Conclusions

The results indicate there is a need to improve long term community adaptation for this group, and that improving community living outcomes is much more a function of ongoing support and caring than short-term treatment and cure.

     

How an aging society affects the economic costs of inactivity in Germany: empirical evidence and projections

Background

Aging societies represent a major challenge for health care systems all over the world. As older people tend to be more physically inactive, economic costs of inactivity are likely to increase notably. The present study aims to investigate this relationship between an aging society and economic costs of inactivity using the example of Germany.

Methods

Using data from the German Socio-Economic Panel, this study applied the comparative risk assessment method developed by the WHO to estimate the direct costs of inactivity for the period 2001–2013 differentiated by gender-specific age-groups (15–29; 30–44; 45–64; 65+). Based on population statistics predicting the aging of the German population for the years 2014–2060, this research projects the development of future costs of inactivity and potential effects of interventions promoting physical activity among the German population.

Results

The results reveal an increase in the level of physical activity during the observed period (2001–2013) which compensated the negative effect of aging and resulted in a decline of inactivity costs. The projections for the years 2014–2060 indicate a constant increase in direct per capita costs until 2060 because of an aging society. Scenarios indicating how a short-term reduction of physical inactivity impacts costs of inactivity reveal the crucial role of the oldest age-group in this context.

Conclusion

The findings indicate that the aging of the German population demands further actions and initiatives to promote physical activity, especially for the oldest age-group.

     

Influence of a home-based exercise program on the urine pH in elderly female subjects: a secondary analysis of a randomized controlled trial

Background

A low urine pH is a characteristic metabolic feature of metabolic syndrome and type 2 diabetes. The purpose of the current study was to investigate the effects of a 12-week home-based bench step exercise on the urine pH status of elderly female subjects.

Methods

The current study is a secondary analysis of a randomized controlled trial (RCT) in which 59 postmenopausal female subjects were randomized to either the exercise group (n?=?29) or the control group (n?=?30). The subjects in the exercise group were instructed to perform home-based exercises using a bench step at the anaerobic threshold (AT), with a goal of performing ≥140 min/week at home for 12 weeks. The subjects in the control group were instructed to not change their normal lifestyle. Urine was collected after overnight fasting, and the urine pH was measured using a urinary test strip. The inter-group-differences at baseline and the pre-post changes within groups were assessed using the Mann-Whitney U test and Wilcoxon’s signed-rank test, respectively. Additionally, the difference in the post-intervention urine pH levels of the two groups, adjusted for the pre-intervention values (the estimated effect size) and the precision (95% confidence intervals) were investigated using an analysis of covariance.

Results

The pre-post comparison of the urine pH data using Wilcoxon’s signed-rank test showed a significant increase in the urine pH levels of the exercise group (p?<?0.05); there was no significant change in the urine pH levels of the control group. However, the estimated effect size (0.15) was small and the confidence interval straddled 0 (?0.25–0.55).

Conclusions

Based on the results of the current secondary analysis of an RCT, we could not clearly conclude that exercise has a beneficial effect on the urine pH. Further well-designed RCTs should be conducted to determine whether aerobic exercise is truly able to ameliorate urine acidification.

Trial registration

The study was retrospectively registered in the University Hospital Medical Information Network (UMIN) as “Effect of step exercise on aerobic fitness and progression of atherosclerosis in the elderly” under the registration number UMIN 000026743 (the date of registration: March 28, 2017).

     

Barriers and facilitators to adherence to group exercise in institutionalized older people living with dementia: a systematic review

Objectives

Research suggests targeted exercise is important for people living with dementia, especially those living in residential care. The aim of this review was to collect and synthesize evidence on the known barriers and facilitators to adherence to group exercise of institutionalized older people living with dementia.

Methods

We searched all available electronic databases. Additionally, we searched trial registries (clinicaltrial.gov, and WHO ICTRP) for ongoing studies. We searched for and included papers from January 1990 until September 2017 in any language. We included randomized, non-randomized trials. Studies were not eligible if participants were either healthy older people or people suffering from dementia but not living in an institution. Studies were also excluded if they were not focused on barriers and facilitators to adherence to group exercise.

Results

Using narrative analysis, we identified the following themes for barriers: bio-medical reasons and mental wellbeing and physical ability, relationships dynamics, and socioeconomic reasons. The facilitators were grouped under the following thematic frames: bio-medical benefits and benefits related to physical ability, feelings and emotions and confidence improvements, therapist and group relationships dynamics and activity related reasons.

Conclusions

We conclude that institutionalized older people living with dementia, even those who are physically frail, incontinent and/or have mild dementia can demonstrate certain level of exercise adherence, and therefore can respond positively to exercise programs. Tailored, individually-adjusted and supported physical activity, led by a knowledgeable, engaging and well communicating therapist/facilitator improves the adherence to group exercise interventions of institutionalized older people living with dementia.

     

Effects of 12 weeks of Nordic Walking and XCO Walking training on the endurance capacity of older adults

Background

Several studies have already examined the positive effects of various forms of endurance training in patient groups and in healthy adults up to 60 years old. The aim of this study was to analyse the effects of Nordic Walking (NW) and XCO Walking (XCO) training on endurance capacity in healthy older adults, aged 60 years and older.

Methods

Twenty-three older participants (mean age: 69.9 ± 5.4 years) were randomly assigned to either the NW group or the XCO group. All participants were measured before and after the 12 weeks of endurance training (2 sessions/week) to examine oxygen uptake (VO₂) and energy consumption during an outdoor field test. In addition, heart rates were recorded and lactate samples were collected.

Results

NW mainly demonstrated some significant (p < 0.05) decreases in heart rate, lactate concentration at lower to moderate walking speeds, whereas XCO Walking revealed significant (p < 0.05) decreases in lactate concentration and VO₂ at low to higher walking speeds.

Conclusions

NW as well as XCO training increase the efficiency of the cardio-vascular system in older subjects. Both training approaches are suitable options for endurance training, which may serve to counteract age- and inactivity-related decreases in cardio-vascular functioning as well as aid in maintaining overall performance in older adults.

     

Does the diurnal cycle of cortisol explain the relationship between physical performance and cognitive function in older adults?

Background

Regular physical activity is a promising strategy to treat and prevent cognitive decline. The mechanisms that mediate these benefits are not fully clear but physical activity is thought to attenuate the harmful effects of chronic psychological stress and hypercortisolism on cognition. However, the circadian pattern of cortisol secretion is complex and it is not known which aspects are most closely associated with increased cognitive function and better physical performance. This is the first study to simultaneously measure cognitive function, the diurnal cycle of salivary cortisol and physical performance in older adults, without cognitive impairment (n?=?30) and with amnestic Mild Cognitive Impairment (aMCI) (n?=?30).

Results

Regression analysis showed that better cognitive function was associated with better physical performance. A greater variance in cortisol levels across the day from morning to evening was associated with better cognitive function and physical performance.

Conclusions

The results support the idea that a more dynamic cortisol secretion pattern is associated with better cognitive function and physical performance even in the presence of cognitive impairment, but our results could not confirm a mediating role in this relationship.

     

Development of low-volume,high-intensity,aerobic-type interval training for elderly Japanese men: a feasibility study

Background

The purposes of this study were to identify 1) the feasibility of a novel exercise protocol (elderly Japanese male version of high-intensity interval aerobic training: EJ-HIAT) and 2) its preliminary data (%V?O_2peak, rating of perceived exertion) in comparison with traditional moderate-intensity continuous aerobic training (MICT).

Results

Twenty-one sedentary elderly men, aged 60–69 years, performed two exercise protocols: EJ-HIAT, consisting of 3 sets of 2?3-min cycling at 75?85%V?O_2peak with 1??2-min active rests at 50%V?O_2peak between sets, and MICT, consisting of 40-min cycling at 65%V?O_2peak. The completion rate, defined as the rate of participants who 1) did not demand withdrawal, 2) were not interrupted by the tester, and 3) did not change the workload during either exercise protocol, of EJ-HIAT was similar to that of MICT (EJ-HIAT: 100%, MICT: 95.2%). Maximal perceived exertion ratings assessed by Borg scale were also similar between EJ-HIAT and MICT. However, objectively measured maximal intensity assessed by %V?O_2peak was higher for EJ-HIAT than for MICT (EJ-HIAT: 86.0 ± 5.6%, MICT: 67.1 ± 6.4%).

Conclusion

These results suggested that EJ-HIAT has good feasibility and perceived exertion similar to MICT despite having higher objectively measured intensity than MICT. An intervention aimed as identifying the effects of EJ-HIAT on exercise tolerance should be performed in the future.

Trial registration

UMIN000021185 (February 26, 2016).

     

Prospective analysis of time out-of-home and objectively measured walking duration during a week in a large cohort of older adults

Background

Physical activity is considered an effective measure to promote health in older people. There is evidence that the number of outdoor trips increases physical activity by increasing walking duration. The objective of this study was to analyse the relationship between daily time out-of-home and walking duration. Furthermore, predictors for walking duration and time out-of-home were evaluated.

Methods

Walking duration was measured prospectively over a 1 week period by a body-fixed sensor and the time out-of-home was assessed by a questionnaire at the same days. Seven thousand, two hundred and forty-three days from 1289 older people (mean age 75.4 years) with both sensor-based measures and completed questionnaires were included in the analyses. To account for several observation days per participant multilevel regression analyses were applied. Analyses were stratified according to the time out-of-home (more or less than 100 min/day).

Results

In the group with less than 100 min out-of-home, each additional minute out-of-home added 20 s to overall walking duration. If the time exceeded 100 min the additional increase of walking duration was only moderate or weak. Leaving the home once added 40 min of walking, the following trips 15 to 20 min. Increasing age, lower gait speed, comorbidities, low temperature, rain and specific week days (Sunday) decreased both the time out-of-home and walking duration. Other variables like gender (female), isolation or living with a spouse reduced the time out-of-home without affecting walking duration.

Conclusions

Being out-of-home increases daily walking duration. The association is strongest if the time out-of-home is 100 min or less.

     

Validity of the microsoft kinect system in assessment of compensatory stepping behavior during standing and treadmill walking

Background

Rapid compensatory stepping plays an important role in preventing falls when balance is lost; however, these responses cannot be accurately quantified in the clinic. The Microsoft Kinect? system provides real-time anatomical landmark position data in three dimensions (3D), which may bridge this gap.

Methods

Compensatory stepping reactions were evoked in 8 young adults by a sudden platform horizontal motion on which the subject stood or walked on a treadmill. The movements were recorded with both a 3D-APAS motion capture and Microsoft Kinect? systems. The outcome measures consisted of compensatory step times (milliseconds) and length (centimeters). The average values of two standing and walking trials for Microsoft Kinect? and the 3D-APAS systems were compared using t-test, Pearson’s correlation, Altman-bland plots, and the average difference of root mean square error (RMSE) of joint position.

Results

The Microsoft Kinect? had high correlations for the compensatory step times (r?=?0.75–0.78, p?=?0.04) during standing and moderate correlations for walking (r?=?0.53–0.63, p?=?0.05). The step length, however had a very high correlations for both standing and walking (r?>?0.97, p?=?0.01). The RMSE showed acceptable differences during the perturbation trials with smallest relative error in anterior-posterior direction (2-3%) and the highest in the vertical direction (11–13%). No systematic bias were evident in the Bland and Altman graphs.

Conclusions

The Microsoft Kinect? system provides comparable data to a video-based 3D motion analysis system when assessing step length and less accurate but still clinically acceptable for step times during balance recovery when balance is lost and fall is initiated.

     

Whole-body vibration training improves balance control and sit-to-stand performance among middle-aged and older adults: a pilot randomized controlled trial

Background

Aging is associated with decreased balance, which increases falling risk. The objective of the current study was to determine the feasibility and effects of whole-body vibration (WBV) training on knee extensor muscle power, limits of stability, and sit-to-stand performance among community-dwelling middle-aged and older adults in the United States.

Methods

A randomized pilot study with participant blinding was conducted. Feasibility outcomes included recruitment and compliance rate. Twenty-nine community-dwelling older adults were randomly assigned to perform body-weight exercises with either an individualized vibration frequency and amplitude, a fixed vibration frequency and amplitude, or no vibration. Isokinetic knee extensor power, limits of stability, and sit-to-stand tests were conducted before beginning the exercises (baseline) and after 8 weeks of training.

Results

With a favorable recruitment rate (58%) and compliance rates (attrition 9%; adherence 85%), the intervention was deemed feasible. The limits of stability endpoint excursion score for the individualized frequency–amplitude group was increased by 8.8 (12.9%; P = 0.025) after training, and that group’s maximum excursion score was increased by 9.2 (11.5%; P = 0.006) after training. The average weight transfer time score was significantly decreased by 0.2 s in the fixed group. The participants in the individualized group demonstrated a significant increase (3.2%) in weight rising index score after 8 weeks of WBV training.

Conclusions

WBV training is feasible for use with elderly people, and this study achieved good recruitment and compliance. The present paper suggests that 8 weeks of WBV training improves limits of stability and sit-to-stand performance. Future studies must determine whether WBV training improves other factors that affect posture control.

Trial registration

This study was registered at the Texas Woman’s University Institutional Review Board [TWU IRB 17632] on the 3rd of November 2014.

     

Assessment of recovery in older patients hospitalized with different diagnoses and functional levels,evaluated with and without geriatric assessment

Background

The objective of the present study was to investigate 1) the role of different admission diagnoses and 2) the degree of functional loss, on the rate of recovery of older patients after acute hospitalization. Furthermore, to compare the predictive value of simple assessments that can be carried out in a hospital lacking geriatric service, with assessments including geriatric screening tests.

Methods

Prospective, observational cohort study, including 961community dwelling patients aged?≥?70 years, transferred from medical, cardiac, pulmonary and orthopedic acute hospital departments to intermediate care in nursing home. Functional assessment with Barthel index (BI) was performed at admission to the nursing home and further geriatric assessment tests was performed during the first week. Logistic regression models with and without geriatric assessment were compared concerning the patients having 1) slow recovery (nursing home stay up to 2 months before return home) or, 2) poor recovery (dead or still in nursing home at 2 months).

Results

Slow recovery was independently associated with a diagnosis of non-vertebral fracture, BI subgroups 50–79 and <50, and, in the model including geriatric assessment, also with cognitive impairment. Poor recovery was more complex, and independently associated both with BI?<?50, receiving home care before admission, higher age, admission with a non-vertebral fracture, and in the geriatric assessment model, cognitive impairment.

Conclusions

Geriatric assessment is optimal for determining the recovery potential of older patients after acute hospitalization. As some hospitals lack geriatric services and ability to perform geriatric screening tests, a simpler assessment based on admission diagnoses and ADL function (BI), gives good information regarding the possible rehabilitation time and possibility to return home.

     

The FARSEEING real-world fall repository: a large-scale collaborative database to collect and share sensor signals from real-world falls

Background

Real-world fall events objectively measured by body-worn sensors can improve the understanding of fall events in older people. However, these events are rare and hence challenging to capture. Therefore, the FARSEEING (FAll Repository for the design of Smart and sElf-adaptive Environments prolonging Independent livinG) consortium and associated partners started to build up a meta-database of real-world falls.

Results

Between January 2012 and December 2015 more than 300 real-world fall events have been recorded. This is currently the largest collection of real-world fall data recorded with inertial sensors. A signal processing and fall verification procedure has been developed and applied to the data. Since the end of 2015, 208 verified real-world fall events are available for analyses. The fall events have been recorded within several studies, with different methods, and in different populations. All sensor signals include at least accelerometer measurements and 58 % additionally include gyroscope and magnetometer measurements. The collection of data is ongoing and open to further partners contributing with fall signals. The FARSEEING consortium also aims to share the collected real-world falls data with other researchers on request.

Conclusions

The FARSEEING meta-database will help to improve the understanding of falls and enable new approaches in fall risk assessment, fall prevention, and fall detection in both aging and disease.

     

Evaluation of hip abductor and adductor strength in the elderly: a reliability study

Background

In elderly individuals an increased muscle strength contributes to the diminution of the falls risk and associated adverse events. An increasing interest in lateral control exists due to the fatal consequences of postero-lateral falls. Therefore a proper assessment of frontal plane hip muscle strength in elderly is important but remains challenging.Therefore we aimed to investigate the feasibility and repeatability of a hip abductor and adductor maximum voluntary isometric strength (MVIS) and rate of force generation (RFG) test in elderly. This represents an initial step in the development process of a new and clinically relevant test that could lead to more specific treatment protocols for this population.

Methods

In this measurement focused study hip abduction (ABD) and adduction (ADD) MVIS and RFG were tested twice within one to three hours with a dynamometer fixed to a custom made frame in a geriatric population including fallers and non-fallers. Intraclass correlation coefficient (ICC_agreement), standard error of measurement (SEM), and smallest detectable difference (SDD) were determined.

Results

All recruited persons (N?=?76; mean age (SD) 80.46 (7.05) years old) completed the tests. The average time needed to complete the strength tests was 10.58 min. (1.56) per muscle group. The reliability of the hip ABD and ADD was high with ICC’s_agreement ranging from 0.83 to 0.97. The SDD varied between 18.1 and 81.8% depending on the muscle group and type of strength that was evaluated.

Conclusion

Hip abductor and adductor strength measures in older person are feasible and reliable. However, the significance of moderate changes in these measurements may be limited by the large SDD and SEM. Therefore, physical therapist should be careful when using this measure for assessing the progress of an individual person in a daily clinical use.