Sex Differences in Low-Density Lipoprotein Cholesterol Reduction With PCSK9 Inhibitors in Real-world Patients: The LIPID-REAL Registry.

BACKGROUND: Previous evidence supports that monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDLc) by 50%-65%, regardless of baseline treatments. We tested possible sex differences in a multicentre registry of real-world patients treated with PCSK9 inhibitors. METHODS: This is a multicentre and retrospective study of 652 patients initiating treatment with any PCSK9 inhibitor in 18 different hospitals. Before-treatment and on-treatment LDLc and medical treatments, clinical indication, and clinical features were recorded. RESULTS: Women represented 24.69% of the cohort. The use of statins was similar in both sexes, but women were receiving most frequently ezetimibe. Before-treatment median LDLc was 135 (interquartile range 115-166) mg, and it was higher in women. The median on-treatment LDLc was 57 (interquartile range 38-84) mg/dL, which represented a mean 54.5% reduction. On-treatment LDLc was higher in women, and the mean LDLc reduction was lower in women (47.4% vs. 56.9%; P = 0.0002) receiving evolocumab or alirocumab. The percentage of patients who achieved ≥50% LDLc reduction was higher in men (71.36% vs. 57.62%; P = 0.002). According to LDLc before-treatment quartiles, LDLc reduction was statistically lower in women in the 2 highest and a significant interaction of women and baseline LDLc >135 mg/dL was observed. Women were negatively associated with lower rates of LDLc treatment target achievement (odds ratio: 0.31). Differences were also observed in women with body mas index >25 kg/m2. Only 14 patients (2.14%) presented side effects. CONCLUSIONS: This multicentre and retrospective registry of real-world patients treated with PCSK9 inhibitors highlights significant gender differences in LDLc reduction.

Walking on a treadmill improves the stride length-cadence relationship in individuals with Parkinson's disease.

BACKGROUND: The gait pattern in Parkinson´s disease (PD) is characterized by a deficit in the internal regulation of stride length (SL), while the control of cadence (Cad) remains intact. The use of the treadmill as a gait rehabilitation tool has provided novel options for treatment of gait impairments in PD. However, it remains unclear whether walking on the treadmill changes the stride length-cadence relationship (SLCrel) in PD. The purpose of the present study was to analyze the SLCrel in PD subjects walking on a treadmill vs. overground, and to further compare the SLCrel to that of age-matched healthy subjects. METHODS: Fifteen PD subjects and fifteen age-matched controls walked overground and on a treadmill at five different self-selected speeds. Gait speed, SL and Cad were recorded at each self-selected speed. A linear regression analysis was conducted to explore the SLCrel and to determine the slope and intercept for each participant. RESULTS: PD subjects showed a lower intercept than control subjects when walking both overground and on a treadmill (F = 8.51, p = 0.007). In comparison with walking overground, walking on a treadmill resulted in a significant increase in the intercept in both PD and control groups (F = 12.17, p = 0.002). There were no significant differences in the slope of the SLCrel. CONCLUSION: PD subjects are able to improve the internal regulation of SL when walking on a treadmill. Our results confirm the potential therapeutic effects of treadmill training for gait rehabilitation in PD and suggest that the mechanisms underlying the positive effects of treadmill training on PD subjects are sustained.

Effect of surface stiffness on the neural control of stretch-shortening cycle movements.

AIM: It is accepted that leg stiffness (Kleg ) increases when surface stiffness decreases, and vice versa. However, little is known how the central nervous system fulfils this task. To understand the effect of surface stiffness on the neural control of stretch-shortening cycle movements, this study aimed to compare modulation of spinal and corticospinal excitability at distinct phases after ground contact during two-legged hopping when changing from solid to elastic ground. METHODS: Motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) and H-reflexes were elicited at the time of the short (SLR)-, medium (MLR)- and long (LLR)-latency responses of the soleus muscle (SOL) during two-legged hopping on different stiffness surfaces, elastic and stiff. RESULTS: Soleus H-reflexes during two-legged hopping on the elastic surface were lower at SLR and larger at LLR than on the stiff surface (P < 0.05 for both comparisons). SOL MEP size was higher at the time of SLR during hopping on the elastic surface than on the stiff surface (P < 0.05) although the background EMG was similar. CONCLUSION: It is argued that this phase-specific adaptation in spinal reflex excitability is functionally relevant to adjust leg stiffness to optimally exploit the properties of the elastic surface. Thus, the increased corticospinal excitability on the elastic surface may reflect a more supraspinal control of the ankle muscles to compensate the decrease in reflexive stiffness at the beginning of touchdown and/or counteract the higher postural challenges associated with the elastic surface.

The effects of treadmill or overground walking training program on gait in Parkinson's disease.

BACKGROUND: Gait impairment in Parkinson's disease (PD) patients is characterized by the inability to generate appropriate stride length. Treadmill training has been proposed as a therapeutic tool for PD patients. However, it remains unknown whether treadmill training effects are different from overground walking training. Thus, our goal was to explore the effects of two training programs, walking on a treadmill and walking overground, in PD patients. METHODS: 22 PD patients were randomly assigned to a treadmill or overground training group. The training program consisted of 5 weeks (3 sessions/week). Before and after the program we evaluated gait kinematics during walking at preferred and maximal speed; Timed Up and Go (TUG); static posturography and knee extensors strength. Gait parameters were reevaluated in the treadmill training group one month after the cessation of the training. RESULTS: Preferred speed walking improved in both groups after the training program. The treadmill training program, but not the overground, led to an improvement in the stride length at the preferred and maximal walking speed in the PD patients. In addition, the treadmill training group showed improvement of the TUG and static posturography tests. The improvement in gait parameters was maintained one month after the cessation of the treadmill training. CONCLUSIONS: This study provides evidence of a specific therapeutic effect of treadmill training on Parkinsonian gait and balance. Walking on a treadmill may be used as an easy, effective and accessible way to improve the stride length and balance in PD patients.

Isometric knee extensor fatigue following a Wingate test: peripheral and central mechanisms.

Central and peripheral fatigue have been explored during and after running or cycling exercises. However, the fatigue mechanisms associated with a short maximal cycling exercise (30 s Wingate test) have not been investigated. In this study, 10 volunteer subjects performed several isometric voluntary contractions using the leg muscle extensors before and after two bouts of cycling at 25% of maximal power output and two bouts of Wingate tests. Transcranial magnetic stimulation (TMS) and electrical motor nerve stimulation (NM) were applied at rest and during the voluntary contractions. Maximal voluntary contraction (MVC), voluntary activation (VA), twitch amplitude evoked by electrical nerve stimulation, M wave and motor potential evoked by TMS (MEP) were recorded. MVC, VA and twitch amplitude evoked at rest by NM decreased significantly after the first and second Wingate tests, indicating central and peripheral fatigue. MVC and VA, but not the twitch amplitude evoked by NM, recovered before the second Wingate test. These results suggest that the Wingate test results in a decrease in MVC associated with peripheral and central fatigue. While the peripheral fatigue is associated with an intramuscular impairment, the central fatigue seems to be the main reason for the Wingate test-induced impairment of MVC.

[Motor activity enablement by sensory stimuli in Parkinson's disease]. / Facilitación de la actividad motora por estímulos sensoriales en la enfermedad de Parkinson.

AIMS: In this paper we review the most significant studies that deal with the motor enablement experienced by patients with Parkinson's disease in the presence of external rhythmic auditory or visual signals; the different possible causes underlying this enablement are also discussed. DEVELOPMENT: The improvements to movement that can be achieved using external stimuli in patients suffering from Parkinson are well documented in the literature. This is why sensory stimulus has become one of the most important points of reference within the rehabilitative strategies that attempt to alleviate the motor difficulties these patients display. Yet, the neurophysiological mechanisms underlying this sensorial enablement have still to be determined. CONCLUSIONS: The data we currently have available allows us to consider this type of technique as a useful instrument for improving the motor autonomy of patients with Parkinson and which should be taken into account by health care professionals.

A simple procedure using auditory stimuli to improve movement in Parkinson's disease: a pilot study.

It has been suggested that sequential movements in Parkinsonian patients might be improved by the effects of external rhythmic cues, either visual or acoustic, acting as a sort of timekeeper. In line with that idea, we have developed a portable system which allows the patient suffering from bradykinesia and rigidity to initiate appropriate auditory stimulation when he/she is not able to move. Here we present data from six Parkinson's Disease (PD) patients studied with surface electromyography, while walking along an 8.5m walkway. All showed remarkable improvement in the EMG parameters studied while using the device. The results are consistent with prior reports on rhythmic auditory facilitation in Parkinson's disease gait,and suggest that this represents a novel and inexpensive tool to help people afflicted by PD in daily motor performance.