Effect of Combination Therapy of Hydroxychloroquine and Azithromycin on Mortality in Patients With COVID-19.

Conflicting evidence regarding the use of hydroxychloroquine (HCQ) and azithromycin for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection do exist. We performed a retrospective single-center cohort study including 377 consecutive patients admitted for pneumonia related to coronavirus disease 2019 (COVID-19). Of these, 297 were in combination treatment, 17 were on HCQ alone, and 63 did not receive either of these 2 drugs because of contraindications. The primary end point was in-hospital death. Mean age was 71.8 ± 13.4 years and 34.2% were women. We recorded 146 deaths: 35 in no treatment, 7 in HCQ treatment group, and 102 in HCQ + azithromycin treatment group (log rank test for Kaplan-Meier curve P < 0.001). At multivariable Cox proportional hazard regression analysis, age (hazard ratio (HR) 1.057, 95% confidence interval (CI) 1.035-1.079, P < 0.001), mechanical ventilation/continuous positive airway pressure (HR 2.726, 95% CI 1.823-4.074, P < 0.001), and C reactive protein above the median (HR 2.191, 95% CI 1.479-3.246, P < 0.001) were directly associated with death, whereas use of HCQ + azithromycin (vs. no treatment; HR 0.265, 95% CI 0.171-0.412, P < 0.001) was inversely associated. In this study, we found a reduced in-hospital mortality in patients treated with a combination of HCQ and azithromycin after adjustment for comorbidities. A large randomized trial is necessary to confirm these findings.

Effects of tDCS on spontaneous spike activity in a healthy ambulatory rat model.

BACKGROUND: The neurophysiological effects of transcranial direct current stimulation (tDCS) are typically described with respect to changes in cortical excitability, defined by using transcranial magnetic stimulation pulses to determine changes in motor evoked potentials. However, how individual cortical neurons change firing patterns under the influence of tDCS is largely unknown. While the relatively weak currents produced in the brain by tDCS may not be adequate to directly depolarize neuronal membranes, ongoing neuronal activity, combined with subthreshold changes in membrane polarization might be sufficient to alter the threshold for neural firing. OBJECTIVES: The purpose of this study was to determine the effects of tDCS on neurophysiological activity in motor cortex of freely moving, healthy rats. METHODS: In nine healthy, ambulatory rats, each studied under six different stimulation conditions varying in current intensity (maximum current density = 39.8 A/m2 at 0.4 mA) and polarity (anodal or cathodal), neural activity was analyzed in response to 20 min of tDCS applied through bone screws insulated from the overlying scalp. RESULTS: After analysis of 480 multi-unit channels that satisfied a rigid set of neurophysiological criteria, we found no systematic effect of tDCS stimulation condition on firing rate or firing pattern. Restricting the analysis to the most responsive units, subtle, but statistically significant changes occurred only in the highest intensity anodal condition. CONCLUSIONS: These results confirm that at current densities typically used in human or animal tDCS studies, observed effects of tDCS are likely to occur via mechanisms other than direct neuronal depolarization.

Literature Review on the Effects of tDCS Coupled with Robotic Therapy in Post Stroke Upper Limb Rehabilitation.

Today neurological diseases such as stroke represent one of the leading cause of long-term disability. Many research efforts have been focused on designing new and effective rehabilitation strategies. In particular, robotic treatment for upper limb stroke rehabilitation has received significant attention due to its ability to provide high-intensity and repetitive movement therapy with less effort than traditional methods. In addition, the development of non-invasive brain stimulation techniques such as transcranial Direct Current Stimulation (tDCS) has also demonstrated the capability of modulating brain excitability thus increasing motor performance. The combination of these two methods is expected to enhance functional and motor recovery after stroke; to this purpose, the current trends in this research field are presented and discussed through an in-depth analysis of the state-of-the-art. The heterogeneity and the restricted number of collected studies make difficult to perform a systematic review. However, the literature analysis of the published data seems to demonstrate that the association of tDCS with robotic training has the same clinical gain derived from robotic therapy alone. Future studies should investigate combined approach tailored to the individual patient's characteristics, critically evaluating the brain areas to be targeted and the induced functional changes.

The efficacy and safety of a combination of glucosamine hydrochloride, chondroitin sulfate and bio-curcumin with exercise in the treatment of knee osteoarthritis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Knee osteoarthritis (OA) conservative treatment aims to delay cartilage degeneration; chondroprotective agents are a valid approach in this sense. A commercially available dietary supplement, CartiJoint Forte, containing glucosamine hydrochloride (GH), chondroitin sulfate (CS) and Bio-Curcumin BCM-95®, was used in this trial. AIM: The aim of this study was to assess efficacy and safety of CartiJoint Forte combined with physical therapy in treating subjects with knee OA. DESIGN: A multicenter, prospective, randomized, double blind, placebo-controlled clinical trial. SETTING: Outpatients referred to the Rehabilitation Departments of two University Hospitals. POPULATION: Fifty-three patients were randomly assigned to an experimental group (N=26) or a control group (N.=27). Experimental subjects received two tablets of CartiJoint Forte each day for 8 weeks, while those in the control group were provided with a placebo. Three subjects dropped out during the course of the study. METHODS: The two groups both received 20 sessions of physical therapy during the course of the trial. Primary outcome was pain intensity, measured both at motion and at rest, using the Visual Analogue Scale (VAS). A secondary outcome was an assessment of knee function by Western Ontario and McMaster Universities Arthritis Index and Lequesne Index, knee ROM, and two inflammation markers (C-reactive protein and erythrocyte sedimentation rate). Each assessment was carried out at baseline (T0), at 8 weeks (T1) and at 12 weeks (T2). RESULTS: VAS at rest was found to be reduced between T0 and T1, as well as between T0 and T2 (F=13.712; P=0.0001), with no differences between groups (F=1.724; P=0.191). VAS at motion revealed a significant "group × time-check" interaction (F=2.491; P=0.032), with increasing effect of time on VAS reduction (F=17.748; P=0.0001). This was most pronounced in the experimental group at 8 weeks (F=3.437; P=0.045). The Lequesne Index showed reductions at T1 and T2 compared to T0 (F=9.535; P=0.0001), along with group effect, since the experimental group presented a lower score at T2 (F=7.091; P=0.009). No significant changes were found in the knee ROM and inflammation markers. CONCLUSION: CartiJoint Forte, added to physical therapy, may ameliorate pain and help to improve algofunctional score in knee OA patients. CLINICAL REHABILITATION IMPACT: Treatment of knee OA with curcuminoids plus glycosaminoglycans, added to physical therapy, improves VAS at motion and Lequesne Index scores.

Combining Robotic Training and Non-Invasive Brain Stimulation in Severe Upper Limb-Impaired Chronic Stroke Patients.

Previous studies suggested that both robot-assisted rehabilitation and non-invasive brain stimulation can produce a slight improvement in severe chronic stroke patients. It is still unknown whether their combination can produce synergistic and more consistent improvements. Safety and efficacy of this combination has been assessed within a proof-of-principle, double-blinded, semi-randomized, sham-controlled trial. Inhibitory continuous Theta Burst Stimulation (cTBS) was delivered on the affected hemisphere, in order to improve the response to the following robot-assisted therapy via a homeostatic increase of learning capacity. Twenty severe upper limb-impaired chronic stroke patients were randomized to robot-assisted therapy associated with real or sham cTBS, delivered for 10 working days. Eight real and nine sham patients completed the study. Change in Fugl-Meyer was chosen as primary outcome, while changes in several quantitative indicators of motor performance extracted by the robot as secondary outcomes. The treatment was well-tolerated by the patients and there were no adverse events. All patients achieved a small, but significant, Fugl-Meyer improvement (about 5%). The difference between the real and the sham cTBS groups was not significant. Among several secondary end points, only the Success Rate (percentage of targets reached by the patient) improved more in the real than in the sham cTBS group. This study shows that a short intensive robot-assisted rehabilitation produces a slight improvement in severe upper-limb impaired, even years after the stroke. The association with homeostatic metaplasticity-promoting non-invasive brain stimulation does not augment the clinical gain in patients with severe stroke.