Impact of physical activity on activity of daily living in moderate to severe dementia: a critical review

The objectives of this study were to describe the different modalities of physical activity programs designed for moderate to severe dementia and to identify their impact on functional independence in activities of daily living (ADL). A critical review of randomized controlled trials related to the impact of physical activity programs in moderately to severely demented persons on ADL performance and meta-analysis of the identified studies were performed. Among the 303 identified articles, five responded to the selection criteria. Four out of the five studies demonstrated limited methodological quality. In one high-quality study, physical activity programs significantly delayed deterioration of ADL performance. The program components and ADL assessment tools vary widely across studies. Although the proposed treatments have not proven their efficiency in improving the ADL status of the patients, they were able to limit the decline in ADL functioning. Future research is warranted in order to identify clinically relevant modalities for physical activity programs for people with moderate to severe dementia.

Continuous monitoring and quantification of multiple parameters of daily physical activity in ambulatory Duchenne muscular dystrophy patients.

Multiple motor function and strength assessment tools exist for the evaluation of neuromuscular diseases, but most do not directly assess functional ability in the patients' daily physical activity in their home environment. In this study our aim was to assess: 1) the feasibility and accuracy of physical activity monitoring during two days in a home environment of five DMD patients using a non-commercialized monitor containing a 3D accelerometer and a gyroscope, 2) if a difference in the physical activity parameters could be measured before and one month after starting prednisolone. We reliably quantified the time spend sitting, standing, lying, walking, the number of steps taken, the cadence, the number of walking episodes and their duration as well as how these were distributed over the day. Parameters possibly reflecting endurance, such as the duration of the walking episodes or the succession of two or three walking episodes lasting more than 30 s were the most improved after prednisolone treatment. This degree of detailed determination of physical activity in a home environment has not been previously reported in neuromuscular disorders to our knowledge and some of the reported parameters are potential new outcome measures in clinical trials.

Estimating dominant upper-limb segments during daily activity.

A new method of evaluation for functional assessment of the shoulder during daily activity is presented. An ambulatory system using inertial sensors attached on the humerus was used to differentiate a dominant from a non-dominant shoulder. The method was tested on 31 healthy volunteers with no shoulder pathology while carrying the system during 8h of their daily life. Shoulder mobility based on the angular velocities and the accelerations of the humerus were calculated and compared every 5s for both sides. Our data showed that the dominant arm of the able bodied participants was more active than the non-dominant arm for standing (+20% for the right handed, +15% for the left handed) and sitting (+24% for the right handed, +32% for the left handed) posture, while for the walking periods the use of the right and left side was almost identical. The proposed method could be used to objectively quantify upper-limb usage during activities of daily living in various shoulder disorders.

Sex differences in lipid and glucose kinetics after ingestion of an acute oral fructose load.

The increase in VLDL TAG concentration after ingestion of a high-fructose diet is more pronounced in men than in pre-menopausal women. We hypothesised that this may be due to a lower fructose-induced stimulation of de novo lipogenesis (DNL) in pre-menopausal women. To evaluate this hypothesis, nine healthy male and nine healthy female subjects were studied after ingestion of oral loads of fructose enriched with 13C6 fructose. Incorporation of 13C into breath CO2, plasma glucose and plasma VLDL palmitate was monitored to evaluate total fructose oxidation, gluconeogenesis and hepatic DNL, respectively. Substrate oxidation was assessed by indirect calorimetry. After 13C fructose ingestion, 44.0 (sd 3.2)% of labelled carbons were recovered in plasma glucose in males v. 41.9 (sd 2.3)% in females (NS), and 42.9 (sd 3.7)% of labelled carbons were recovered in breath CO2 in males v. 43.0 (sd 4.5)% in females (NS), indicating similar gluconeogenesis from fructose and total fructose oxidation in males and females. The area under the curve for 13C VLDL palmitate tracer-to-tracee ratio was four times lower in females (P < 0.05), indicating a lower DNL. Furthermore, lipid oxidation was significantly suppressed in males (by 16.4 (sd 5.2), P < 0.05), but it was not suppressed in females ( -1.3 (sd 4.7)%). These results support the hypothesis that females may be protected against fructose-induced hypertriglyceridaemia because of a lower stimulation of DNL and a lower suppression of lipid oxidation.

Current cardiovascular risk management patterns with special focus on lipid lowering in daily practice in Switzerland.

Background: There may be a considerable gap between LDL cholesterol (LDL-C) and blood pressure (BP) goal values recommended by the guidelines and results achieved in daily practice. Design Prospective cross-sectional survey of cardiovascular disease risk profiles and management with focus on lipid lowering and BP lowering in clinical practice. Methods: In phase 1, the cardiovascular risk of patients with known lipid profile visiting their general practitioner was anonymously assessed in accordance to the PROCAM-score. In phase 2, high-risk patients who did not achieve LDL-C goal less than 2.6 mmol/l in phase 1 could be further documented. Results: Six hundred thirty-five general practitioners collected the data of 23 892 patients with known lipid profile. Forty percent were high-risk patients (diabetes mellitus or coronary heart disease or PROCAM-score >20%), compared with 27% estimated by the physicians. Goal attainment rate was almost double for BP than for LDL-C in high-risk patients (62 vs. 37%). Both goals were attained by 25%. LDL-C values in phase 1 and 2 were available for 3097 high-risk patients not at LDL-C goal in phase 1; 32% of patients achieved LDL-C goal of less than 2.6 mmol/l after a mean of 17 weeks. The most successful strategies for LDL-C reduction were implemented in only 22% of the high-risk patients. Conclusion: Although patients at high cardiovascular risk were treated more intensively than low or medium risk patients, the majority remained insufficiently controlled, which is an incentive for intensified medical education. Adequate implementation of Swiss and International guidelines would expectedly contribute to improved achievement of LDL-C and BP goal values in daily practice.

Daily energy expenditure in free-living conditions in obese and non-obese children: comparison of doubly labelled water (2H2(18)O) method and heart-rate monitoring.

OBJECTIVE: To compare the heart-rate monitoring with the doubly labelled water (2H2(18)O) method to estimate total daily energy expenditure in obese and non-obese children. DESIGN: Cross sectional study of obese and normal weight children. SUBJECTS: 13 prepubertal children: six obese (4M, 2F, 9.1 +/- 1.5 years, 47.3 +/- 9.7 kg) and seven non-obese (3M, 4F, 9.3 +/- 0.6 years, 31.8 +/- 3.2 kg). MEASUREMENTS: Total daily energy expenditure was assessed by means of the doubly labelled water method (TEEDLW) and of heart-rate monitoring (TEEHR). RESULTS: TEEHR was significantly (P < 0.05) higher than TEEDLW in obese children (9.47 +/- 0.84 MJ/d vs 8.99 +/- 0.63 MJ/d) whereas it was not different in non-obese children (8.43 +/- 2.02 MJ/d vs 8.42 +/- 2.30 MJ/d, P = NS). The difference of TEE assessed by HR monitoring in the obese group averaged 6.2 +/- 4.7%. At the individual level, the degree of agreement (difference between TEEHR and TEEDLW +/- 2s.d.) was low both in obese (-0.36, 1.32 MJ/d) and in non-obese children (-1.30, 1.34 MJ/d). At the group level, the agreement between the two methods was good in nonobese children (95% c.i. for the bias:-0.59, 0.63 MJ/d) but not in obese children (0.04, 0.92 MJ/d). Duration of sleep and energy expenditure during resting and physical activity were not significantly different in the two groups. Patterns of heart-rate (or derived energy expenditure) during the day-time were similar in obese and non-obese children. CONCLUSION: The HR monitoring technique provides an estimation of TEE close to that assessed by the DLW method in non-obese prepubertal children. In comparison with DLW, the HR monitoring method yields a greater TEE value in obese children.

Blood-Borne Circadian Signal Stimulates Daily Oscillations in Actin Dynamics and SRF Activity.

In peripheral tissues circadian gene expression can be driven either by local oscillators or by cyclic systemic cues controlled by the master clock in the brain's suprachiasmatic nucleus. In the latter case, systemic signals can activate immediate early transcription factors (IETFs) and thereby control rhythmic transcription. In order to identify IETFs induced by diurnal blood-borne signals, we developed an unbiased experimental strategy, dubbed Synthetic TAndem Repeat PROMoter (STAR-PROM) screening. This technique relies on the observation that most transcription factor binding sites exist at a relatively high frequency in random DNA sequences. Using STAR-PROM we identified serum response factor (SRF) as an IETF responding to oscillating signaling proteins present in human and rodent sera. Our data suggest that in mouse liver SRF is regulated via dramatic diurnal changes of actin dynamics, leading to the rhythmic translocation of the SRF coactivator Myocardin-related transcription factor-B (MRTF-B) into the nucleus.

Cannabis use and other predictors of the onset of daily cigarette use in young men: what matters most? Results from a longitudinal study.

BACKGROUND: According to the gateway hypothesis, tobacco use is a gateway of cannabis use. However, there is increasing evidence that cannabis use also predicts the progression of tobacco use (reverse gateway hypothesis). Unfortunately, the importance of cannabis use compared to other predictors of tobacco use is less clear. The aim of this study was to examine which variables, in addition to cannabis use, best predict the onset of daily cigarette smoking in young men. METHODS: A total of 5,590 young Swiss men (mean age = 19.4 years, SD = 1.2) provided data on their substance use, socio-demographic background, religion, health, social context, and personality at baseline and after 18 months. We modelled the predictors of progression to daily cigarette smoking using logistic regression analyses (n = 4,230). RESULTS: In the multivariate overall model, use of cannabis remained among the strongest predictors for the onset of daily cigarette use. Daily cigarette use was also predicted by a lifetime use of at least 50 cigarettes, occasional cigarette use, educational level, religious affiliation, parental situation, peers with psychiatric problems, and sociability. CONCLUSIONS: Our results highlight the relevance of cannabis use compared to other potential predictors of the progression of tobacco use and thereby support the reverse gateway hypothesis.

Alteration and recovery of arm usage in daily activities after rotator cuff surgery.

BACKGROUND: The objective measurement of dominant/nondominant arm use proportion in daily life may provide relevant information on healthy and pathologic arm behavior. This prospective case-control study explored the potential of such measurements as indicators of upper limb functional recovery after rotator cuff surgery. METHODS: Data on dominant/nondominant arm usage were acquired with body-worn sensors for 7 hours. The postsurgical arm usage of 21 patients was collected at 3, 6, and 12 months after rotator cuff surgery in the sitting, walking, and standing postures and compared with a reference established with 41 healthy subjects. The results were calculated for the dominant and nondominant surgical side subgroups at all stages. The correlations with clinical scores were calculated. RESULTS: Healthy right-handed and left-handed dominant arm usage was 60.2% (±6.3%) and 53.4% (±6.6%), respectively. Differences in use of the dominant side were significant between the right- and left-handed subgroups for sitting (P = .014) and standing (P = .009) but not for walking (P = .328). The patient group showed a significant underuse of 10.7% (±8.9%) at 3 months after surgery (P < .001). The patients recovered normal arm usage within 12 months, regardless of surgical side. The arm underuse measurement was weakly related to function and pain scores. CONCLUSION: This study provided new information on arm recovery after rotator cuff surgery using an innovative measurement method. It highlighted that objective arm underuse measurement is a valuable indicator of upper limb postsurgical outcome that captures a complementary feature to clinical scores.

Daily activity patterns of 2316 men and women from five countries differing in socioeconomic development.

Daily rhythmicity in the locomotor activity of laboratory animals has been studied in great detail for many decades, but the daily pattern of locomotor activity has not received as much attention in humans. We collected waist-worn accelerometer data from more than 2000 individuals from five countries differing in socioeconomic development and conducted a detailed analysis of human locomotor activity. Body mass index (BMI) was computed from height and weight. Individual activity records lasting 7 days were subjected to cosinor analysis to determine the parameters of the daily activity rhythm: mesor (mean level), amplitude (half the range of excursion), acrophase (time of the peak) and robustness (rhythm strength). The activity records of all individual participants exhibited statistically significant 24-h rhythmicity, with activity increasing noticeably a few hours after sunrise and dropping off around the time of sunset, with a peak at 1:42 pm on average. The acrophase of the daily rhythm was comparable in men and women in each country but varied by as much as 3 h from country to country. Quantification of the socioeconomic stages of the five countries yielded suggestive evidence that more developed countries have more obese residents, who are less active, and who are active later in the day than residents from less developed countries. These results provide a detailed characterization of the daily activity pattern of individual human beings and reveal similarities and differences among people from five countries differing in socioeconomic development.

Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study.

BACKGROUND: The primary analysis of the FLAMINGO study at 48 weeks showed that patients taking dolutegravir once daily had a significantly higher virological response rate than did those taking ritonavir-boosted darunavir once daily, with similar tolerability. We present secondary efficacy and safety results analysed at 96 weeks. METHODS: FLAMINGO was a multicentre, open-label, phase 3b, non-inferiority study of HIV-1-infected treatment-naive adults. Patients were randomly assigned (1:1) to dolutegravir 50 mg or darunavir 800 mg plus ritonavir 100 mg, with investigator-selected combination tenofovir and emtricitabine or combination abacavir and lamivudine background treatment. The main endpoints were plasma HIV-1 RNA less than 50 copies per mL and safety. The non-inferiority margin was -12%. If the lower end of the 95% CI was greater than 0%, then we concluded that dolutegravir was superior to ritonavir-boosted darunavir. This trial is registered with ClinicalTrials.gov, number NCT01449929. FINDINGS: Of 595 patients screened, 488 were randomly assigned and 484 included in the analysis (242 assigned to receive dolutegravir and 242 assigned to receive ritonavir-boosted darunavir). At 96 weeks, 194 (80%) of 242 patients in the dolutegravir group and 164 (68%) of 242 in the ritonavir-boosted darunavir group had HIV-1 RNA less than 50 copies per mL (adjusted difference 12·4, 95% CI 4·7-20·2; p=0·002), with the greatest difference in patients with high viral load at baseline (50/61 [82%] vs 32/61 [52%], homogeneity test p=0·014). Six participants (three since 48 weeks) in the dolutegravir group and 13 (four) in the darunavir plus ritonavir group discontinued because of adverse events. The most common drug-related adverse events were diarrhoea (23/242 [10%] in the dolutegravir group vs 57/242 [24%] in the darunavir plus ritonavir group), nausea (31/242 [13%] vs 34/242 [14%]), and headache (17/242 [7%] vs 12/242 [5%]). INTERPRETATION: Once-daily dolutegravir is associated with a higher virological response rate than is once-daily ritonavir-boosted darunavir. Dolutegravir compares favourably in efficacy and safety to a boosted darunavir regimen with nucleoside reverse transcriptase inhibitor background treatment for HIV-1-infected treatment-naive patients. FUNDING: ViiV Healthcare and Shionogi & Co.

A qualitative study of adolescents with medically unexplained symptoms and their parents. Part 1: Experiences and impact on daily life.

Medically unexplained symptoms (MUS) are common among adolescents and are frequently encountered in primary care. Our aim was to explore how these adolescents and their parents experience the condition and its impact on their daily lives and to provide recommendations for health professionals. Using a qualitative approach, six focus groups and two individual interviews were conducted. These involved a total of ten adolescents with different types of MUS and sixteen parents. The respondents were recruited in a university hospital in Switzerland. A thematic analysis was conducted according to the Grounded Theory. The analysis of the data highlighted four core themes: disbelief, being different, concealing symptoms, and priority to adolescent's health. Transcending these themes was a core issue regarding the discrepancy between the strategies that adolescents and their parents use to cope with the symptoms. Health professionals should be made aware of the emotional needs of these patients and their families.