Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line treatment in cisplatin-ineligible patients with advanced urothelial carcinoma: A randomised phase II trial (VINGEM).

BACKGROUND: The present study (VINGEM) is the first randomised trial comparing vinflunine/gemcitabine (VG) to standard carboplatin/gemcitabine (CG) in patients with advanced urothelial carcinoma (aUC) ineligible for treatment with cisplatin. PATIENTS AND METHODS: Patients with aUC, creatinine clearance 30-60 ml/min, performance status ≤1 and no prior chemotherapy for metastatic disease were randomised to the experimental arm (vinflunine 280 or 250 mg/m2 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days) or the control arm (carboplatin AUC 4.5 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days). Primary end-point was progression-free survival (PFS). RESULTS: Sixty-two patients were randomised; a total of 59 patients were treated (29 VG, 30 CG). There was no significant difference in PFS between the treatment arms: median 6.2 months for VG versus 6.3 months for CG (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.44-1.28; P = 0.293). Median overall survival was 12.5 months for VG versus 10.6 months for CG. The overall response rate (ORR) was higher in the VG arm than in the CG arm (63% versus 40%) but was not statistically significant in the intention-to-treat analysis. Furthermore, VG showed a high complete response (CR) rate, 22% versus 3% in CG. In the per-protocol group, both ORR and CR were significantly higher for VG than for CG. The most common adverse events (AEs) were fatigue, haematological toxicities, gastrointestinal disorders and nausea/vomiting. Common grade III/IV AEs were neutropenia (VG 62%, CG 43%), thrombocytopenia (VG 7%, CG 37%) and febrile neutropenia (VG 31%, CG 7%). CONCLUSIONS: The combination of VG did not improve PFS compared with standard treatment with CG in patients unfit for cisplatin due to renal impairment. The response rate of VG indicates, however, an active regimen and warrants further studies. CLINICALTRIALS. GOV NUMBER: NCT02665039.

Age-related differences in postural adjustments in connection with different tasks involving weight transfer while standing.

Weight transfer designed to change the area of the supportive base during the performance of three different motor tasks (one-leg stance, tandem stance and gait initiation) was examined both in healthy, physically active elderly people and younger adults. The former two tasks are balance tests used clinically. Our hypothesis was that the elderly subjects would demonstrate age-related changes in their postural adjustments that could be detected by analysis of the ground reaction forces. While 24 healthy elderly adults (65-77 years of age) and 26 younger adults (24-40 years of age) performed these three tasks, the ground reaction forces were recorded from two force plates. Prior to the onset of all three tasks, the elderly placed significantly more weight on the leg that was to provide support (the stance leg), than did the younger individuals. The analyses revealed two distinct phases of weight transfer, i.e., an initial thrust and a subsequent unloading phase. The elderly individuals exhibited a significantly longer unloading phase, as well as a higher frequency of peaks of vertical and lateral forces during this phase. Moreover, the maximal force rate during this phase was achieved at an earlier time point by the elderly. However, both groups generated forces of similar magnitudes and force rates. In conclusion, our findings indicate the presence of age-related differences in the temporal phasing of the ground reaction forces in all three of these tasks involving weight transfer, whereas the magnitude and rates of change of these forces are independent of age.

Postural steadiness and weight distribution during tandem stance in healthy young and elderly adults.

BACKGROUND: Tandem stance is a clinical measure of standing balance considered to assess postural steadiness in a heel-to-toe position by a temporal measurement. To our knowledge, no studies have evaluated the change of postural steadiness, expressed as force variability, over time. The objective of this paper is to investigate postural steadiness during 30 s of tandem stance in healthy elderly and young adults, and to explore the weight distribution between legs during tandem stance. METHODS: A cross-sectional analysis comparing ground reaction forces and muscle activity in 26 healthy elderly adults (mean age 70.6 years) and 27 healthy young adults (mean age 30.0 years). Ground reaction forces beneath both feet and muscle activity of ankle muscles were recorded while the subjects performed 30 s of tandem stance during two conditions. FINDINGS: Two phases were identified in both groups: First a dynamic phase, a decrease in force variability during the first 3-4 s after foot placement, and thereafter a static phase, maintaining a certain level of force variability. Age-related changes were seen in the decrease in force variability (P<0.001) and ankle muscle activity (P<0.001). However, both groups placed more weight on the rear leg (P<0.001). INTERPRETATION: The first few seconds of tandem stance pose the greatest challenge to postural steadiness and influence the static phase. We suggest that the dynamic phase is the most crucial period of time for assessing balance requirements. Independent of age, tandem stance is not a task for equal weight bearing.

One-leg stance in healthy young and elderly adults: a measure of postural steadiness?

OBJECTIVE: To investigate postural steadiness during 30 s of one-leg stance in healthy young and elderly adults, by analysing the pattern of the ground reaction force variability. DESIGN: A laboratory set-up was used to analyse the variability of the ground reaction forces in relation to time as a measure of postural steadiness. BACKGROUND: The one-leg stance test is a measure considered to assess postural steadiness in a static position by a temporal measurement. The common notion is that a better postural steadiness, i.e. less force variability, allows for longer time standing on one leg. However, there is lack of evidence how postural steadiness during one-leg stance changes over time. METHODS: Twenty-eight healthy elderly and 28 healthy young adults were tested by means of force plates assessing ground reaction forces while performing one-leg stance. RESULTS: During one-leg stance, two phases could be identified in both groups: First a dynamic phase, a rapid decrease of force variability, and thereafter a static phase, maintaining a certain level of force variability. During the first 5 s of one-leg stance the force variability decreased significantly more in the young group resulting in a lower force variability level during the static phase than in the elderly. CONCLUSIONS: The difficulties in maintaining the static position in elderly seems dependent on the reduced initial decrease in force variability and/or musculoskeletal components. We suggest that the first 5 s are crucial when assessing balance during one-leg stance.

Does the functional reach test reflect stability limits in elderly people?

OBJECTIVE: To explore how the Functional Reach test correlates with the displacement of the centre of pressure and whether the test is a measure of the stability limits in healthy elderly people. Also to explore the performance parameters during the Functional Reach test. DESIGN: Method comparison study. SUBJECTS: Twenty-seven healthy elderly subjects. METHODS: Whole body kinematics (ELITE systems), ground reaction forces (AMTI) and muscle activity (EMG) parallel with clinical yardstick measure while performing the Functional Reach test. RESULTS: This study showed a low correlation (r = 0.38) between reach distance and displacement of centre of pressure and a moderate correlation (r = 0.68) between forward rotation of the trunk and reach distance. The movement during the Functional Reach test was characterized by a large forward rotation of the trunk and a small extension in the ankle. The latter constraining centre of pressure forward displacement. CONCLUSIONS: The results suggest that the Functional Reach test is a weak measure of the stability limits. Movement of the trunk seems to influence the test more than the displacement of the centre of pressure. When using the Functional Reach test for assessing balance, compensatory mechanisms should be taken into account.