Objectives: We investigated the outcomes of Ivermectin-Doxycycline vs. Hydroxychloroquine-Azithromycin combination therapy in mild to moderate COVID19 patients. Methods: Patients were divided randomly into two groups: Ivermectin 200µgm/kg single dose + Doxycycline 100mg BID for ten days in group A, and Hydroxychloroquine 400mg for the first day, then 200mg BID for nine days + Azithromycin 500mg daily for five days in group B (Control group). RT-PCR for SARS-CoV-2 infection was repeated in all symptomatic patients on the second day onward without symptoms. Repeat PCR was done every two days onward if the result found positive. Time to the negative PCR and symptomatic recovery was measured for each group. Results: All subjects in Group A reached a negative PCR, at a mean of 8.93 days, and reached symptomatic recovery, at a mean of 5.93 days, with 55.10% symptom-free by the fifth day. In group B, 96.36% reached a negative PCR at a mean of 9.33 days and were symptoms-free at 6.99 days. In group A 31.67% of patients expressed symptoms caused by medication, this was 46.43% in group B. Conclusion: The combination therapy of Ivermectin-Doxycycline showed a trend towards superiority to the combination of Hydroxychloroquine-Azithromycin for mild to moderate COVID19 disease. Keywords: Azithromycin, Bangladesh, COVID-19, Doxycycline, Hydroxychloroquine, Ivermectin, randomized controlled trial (RCT)
Importance Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown. Objective To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19. Design, Setting, and Participants The HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US. Interventions Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status. Main Outcomes and Measures The primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data. Results Of 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P
Cisplatin is a well-known cancer chemotherapeutic agent but how extensively long non-coding RNA (lncRNA) expression is modulated by cisplatin is unknown. It is imperative to employ a comprehensive approach to obtain a better account of cisplatin-mediated changes in the expression of lncRNAs. In this study, we used a transcriptomics approach to profile lncRNAs in cisplatin-treated HeLa cells, which resulted in identification of 10,214 differentially expressed lncRNAs, of which 2,500 were antisense lncRNAs. For functional analyses, we knocked down one of the cisplatin inducible lncRNAs, death receptor 5 antisense (DR5-AS) lncRNA, which resulted in a morphological change in HeLa cell shape without inducing any cell death. A second round of transcriptomics-based profiling revealed differential expression of genes associated with immune system, motility and cell cycle in DR5-AS knockdown HeLa cells. Cellular analyses showed that DR5-AS reduced cell proliferation and caused a cell cycle arrest at S and G2/M phases. Moreover, DR5-AS knockdown reduced the invasive capacity of HeLa cells in zebrafish xenograft model. These results suggest that cisplatin-mediated pleiotropic effects, such as reduction in cell proliferation, metastasis and cell cycle arrest, may be mediated by lncRNAs.
Context: Chronic pain (CP) is a common and serious medical condition, with an estimated 100 million people affected in the United States. In the 1990s, opioids were increasingly prescribed to manage chronic pain, and this practice contributed to the opioid epidemic of the 21st century. To combat this epidemic, multidisciplinary approaches to chronic pain management are being researched and implemented. Objective: To evaluate the clinical effectiveness of an 8-week mindfulness-based stress reduction (MBSR) course implemented in a semi-rural population with chronic pain. Methods: Participants were recruited from a community-based teaching hospital in Corvallis, Oregon, for a pre-post study. Participants aged 34 to 77 years who reported having chronic pain lasting for at least 1 year before enrollment were included. Participants took an 8-week group MBSR course in 2.5-hour weekly sessions taught by an experienced MBSR instructor. Techniques were self-practiced between sessions with a goal of 30 minutes per day, 6 days per week. Pre- and postsurvey measurements of pain, depression, and functional capacity were taken via online surveys using the patient health questionnaire (PHQ-9), the Pain Catastrophizing Scale (PCS), and a shortened version of the Modified Oswestry Disability Index (MO). Participants were asked about their satisfaction with the program content, instructor, timing, and location. Results: Twenty-eight participants were included in the study. Paired t tests found significant improvements in PHQ-9, PCS, and MO percent scores from before to after the course. PHQ-9 scores decreased by a mean of 3.7 points (95% CI, -5.5, -1.8), PCS scores decreased by a mean of 4.6 points (95% CI: -7.2, -2.0), and MO percent score decreased by a mean of 9.4% (95% CI: -14.2%, -4.6%). Results showed an overall downward shift in the distribution of depression, disability, and pain scores after the course. Conclusions: MBSR classes were found to benefit participants with chronic pain and depression in this setting, fostering significant improvement in participant perceptions of pain, mood, and functional capacity.
Photobiomodulation therapy (PBMT) efects an important role in neural regeneration and function enhancement, such as expression of nerve growth factor and nerve regeneration, in neuronal tissues, and inhibition of cell death by amyloid beta in neurons is inhibited by PBMT. However, there no studies evaluated the efects of PBMT on oxidative stress in the hippocampus. The aim of this study is to evaluate the efects of PBMT on oxidative stress in the hippocampus. This study assessed the antioxidative efect, the expression of BDNF and antioxidant enzymes, as well as the activation of cAMP response element binding (CREB) and extracellular signal-regulated kinase (ERK) signal transduction pathways assess using a hippocampal cell line (HT-22) and mouse organotypic hippocampal tissues by PBMT (LED, 660nm, 20mW/cm2). PBMT inhibited HT-22 cell death by oxidative stress and increased BDNF expression via ERK and CREB signaling pathway activation. In addition, PBMT increased BDNF expression in hippocampal organotypic slices and the levels of phosphorylated ERK and CREB, which were reduced by oxidative stress, as well as the expression of the antioxidant enzyme superoxide dismutase. These data demonstrate that PBMT inhibits hippocampal damage induced by oxidative stress and increases the expression of BDNF, which can be used as an alternative to treat a variety of related disorders that lead to nerve damage. Activation and redox homeostasis in neuronal cells may be a notable mechanism of the 660-nm PBMT-mediated photobioreactivity
OBJECTIVE: To assess benefits of mindfulness meditation and cognitive behavioral therapy (CBT)-based intervention for opioid-treated chronic low back pain (CLBP). DESIGN: 26-week parallel-arm pilot randomized controlled trial (Intervention and Usual Care versus Usual Care alone). SETTING: Outpatient. SUBJECTS: Adults with CLBP, prescribed ≥30 mg/day of morphine-equivalent dose (MED) for at least 3 months. METHODS: The intervention comprised eight weekly group sessions (meditation and CLBP-specific CBT components) and 30 minutes/day, 6 days/week of at-home practice. Outcome measures were collected at baseline, 8, and 26 weeks: primary-pain severity (Brief Pain Inventory) and function/disability (Oswestry Disability Index); secondary-pain acceptance, opioid dose, pain sensitivity to thermal stimuli, and serum pain-sensitive biomarkers (Interferon-γ; Tumor Necrosis Factor-α; Interleukins 1ß and 6; C-reactive Protein). RESULTS: Thirty-five (21 experimental, 14 control) participants were enrolled and completed the study. They were 51.8 ± 9.7 years old, 80% female, with severe CLBP-related disability (66.7 ± 11.4), moderate pain severity (5.8 ± 1.4), and taking 148.3 ± 129.2 mg/day of MED. Results of the intention-to-treat analysis showed that, compared with controls, the meditation-CBT group reduced pain severity ratings during the study (P = 0.045), with between-group difference in score change reaching 1 point at 26 weeks (95% Confidence Interval: 0.2,1.9; Cohen's d = 0.86), and decreased pain sensitivity to thermal stimuli (P