Effect of ginseng on fatigue related to neuromyelitis optica spectrum disorder: A double-blinded randomized controlled clinical trial.

Background: The effects of ginseng on fatigue have been proven in patients with multiple sclerosis (MS), which have several similar manifestations to neuromyelitis optica spectrum disorder (NMOSD) patients. This study was designed to evaluate the effects of ginseng on fatigue in NMOSD patients. Methods: In this double-blinded randomized controlled clinical trial, 64 patients were recruited and were allocated into two study groups (ginseng or placebo) via block randomization. The participants received either 250-mg ginseng or placebo twice daily for a 3-month period. Also, the measurement of outcome was performed using the valid and reliable Persian version of fatigue severity scale (FSS) questionnaire, which was filled by patients once after enrollment in the study and once at the end of the study post-intervention. Results: In total, 58 patients finished the study with no major side effects. There were no significant differences in demographic, clinical, as well as FSS between two study groups (p>0.05). Ginseng supplementation significantly reduced fatigue (40.21±13.51 vs. 28.97±14.18; p˂0.01), while patients in the placebo group showed significantly higher fatigue score after 3 months post-intervention (35.03±13.51 vs. 38.79±12.27; P: 0.02). The extent of changes in the fatigue score in the ginseng group was significantly greater than in the placebo group (p ˂0.01). Conclusion: This study revealed positive effects of ginseng on reducing fatigue in NMOSD patients with no major side effects. In this regard, further studies are warranted to evaluate and clarify the effects of ginseng on fatigue in NMOSD.

Effect of Rituximab on the cognitive impairment in patients with secondary progressive multiple sclerosis.

Background: The present study aimed to address the effect of Rituximab on the cognitive impairment in patients with secondary progressive MS (SPMS). Methods: The present interventional study used a convenience sampling method to select the study participants from SPMS patients. All these patients had progressive disability over the last two years before being admitted in the study. Prior to the administration of Rituximab, the minimal assessment of cognitive function in the multiple sclerosis (MACFIMS) test was performed for each patient who was a candidate to be included in this study. This test was repeated by passing 6 and 12 months from the initial treatment with Rituximab. Since the data needed for this study were obtained at different time intervals, so a linear mixed model was used for their analysis. Analysis of variance (ANOVA) was also used to investigate whether time and sex generally affect the cognitive impairments in SPMS patients. A p-value <0.05 was considered as statistically significant in this study. Results: Of the total 35 patients, 34% and 66% were men and women with a mean age of 41.33 and 41.39 years old, respectively. Rituximab showed a significant positive effect on a number of subgroups of MACFIMS test, including Controlled Oral Word Association Test (COWAT) (P-value: 0.038) and Brief Visuospatial Memory Test (BVMT-total) (P: 0.019). Conclusion: The present study revealed that Rituximab has a positive effect on the cognitive impairment resulted from MS in secondary progressive patients.

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial.

BACKGROUND: Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. METHODS: This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. RESULTS: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). CONCLUSION: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

Nasogastric tube insertion in intubated patients with the guide of wire rope: A prospective randomised controlled study.

INTRODUCTION: Nasogastric tube (NGT) insertion is sometimes required in intubated patients. NGTs are prone to kink and coil during blind insertion. We hypothesised that wire rope guide-assisted NGT insertion with chin lift can significantly improve the first-attempt success rate over the conventional technique during its insertion in intubated patients. OBJECTIVE: Mean time to successful insertion of NGT, the failure rate of NGT insertion in the first attempt, the failure rate of NGT insertion in the second attempt and overall failure rate were assessed along with the incidence of any complications. METHOD: This prospective clinical trial conducted 100 adult patients presenting for abdominal surgery under general anaesthesia. These patients were randomised to an experimental technique of Wire rope guide with chin lift (wire group) or a control technique of head flexion (control group) for insertion of the NGT. RESULTS: The first-attempt success rate was 98% in wire group compared with 74% in the control group (P = .001). Thus, the first-attempt failure rate was 2% in wire group compared with 26% in the control group (P = .001). The median time required to insert the NGT was significantly shorter in wire group (35.3 ± 4.8 vs 61.5 ± 6.2 seconds, P = .001). The incidences of kinking/coiling, bleeding, and moderate injuries were significantly lower in wire group. CONCLUSION: The use of rope wire guide for correct positioning of the NGT in intubated patients is less time-consuming with the high first-attempt success rate and lower incidence of procedure-related injuries compared to the conventional method.

Sleep disorders as a possible predisposing attack factor in neuromyelitis optica spectrum disorder (NMOSD): A case-control study.

BACKGROUND: Sleep disturbances are common in neuromyelitis optica spectrum disorder (NMOSD) and have a great impact on patients' quality of life. According to a report, there is a 64% prevalence of poor sleep quality in NMOSD patients. Therefore, this study was done to evaluate the effect of sleep disturbances on NMOSD acute exacerbations. MATERIALS AND METHODS: This case-control study was conducted at Sina Hospital in 2019. A total of 60 patients with NMOSD diagnosis were enrolled in the study (30 patients were in the remission phase while 30 patients were hospitalized due to acute attacks). Sleep disorders were evaluated in both groups. Sleep quality was assessed during the last month using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Data were analyzed by SPSS software version 21. RESULTS: Among 60 patients who were evaluated in both the control and attack groups, 86.7% were female. The duration of the disease was 68.23 ±â€¯42.89 months in the control group and 69.83 ±â€¯6.90 in the attack group. The mean age of patients was 34.15 years old. Sleep quality was unfavorable in 30% and 56% of patients in control and attack groups, respectively. There were significant differences between the two groups in sleep latency, habitual sleep efficiency, sleep duration, and sleep disturbance. CONCLUSION: The present study revealed that there was a significant difference in sleep quality between controls and attack patients and could show a direct relationship between sleep disorders and NMOSD attacks.

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial.

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.

Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies.

BACKGROUND: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown. METHODS: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count <20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes >3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts. CONCLUSIONS: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19.