scholarly journals A Feasibility Trial to Evaluate the Composite Efficacy of Inhaled Nitric Oxide in the Treatment of Covid 19 Pneumonia : Impact on Viral Load and Clinical Outcomes

Author(s):  
Merlin Moni ◽  
Thushara Madathil ◽  
Dipu Sathyapalan ◽  
Veena Menon ◽  
Georg Gutjahr ◽  
...  

Background: Hypoxic patients with Covid 19 pneumonia are at high risk of adverse outcomes. Inhaled Nitric Oxide (iNO) inhibits viral entry and replication of SARS-CoV2 and in vivo proof of its antiviral actions is unavailable to date. This feasibility study was conducted to test the antiviral effects of iNO and to describe clinical outcomes. Methods: The phase II open label, randomised controlled feasibility trial(ISRCTN 16806663) conducted at a South Indian tertiary care referral centre, recruited COVID-19 pneumonia patients with hypoxic respiratory failure and allocated them into iNO cases and control groups(1:1). iNO was administered as pulses for 30 minutes for three consecutive days at 12-hour intervals in cases, in addition to standard of care received by the control group. The primary outcome was decline in viral load, as defined by a surrogate change in the RT-PCR cycle threshold. The co-primary clinical outcome was time to improvement of >2 points on the WHO Ordinal Scale(WOS). Results: Among the 29 patients enrolled, 14 iNO cases and 11 controls completed the study protocol. Longitudinal analysis revealed a significant difference in the decline (p <0.002, N= 23) in viral load among the iNO cases compared to controls. The proportion of patients achieving 2-point improvement in the WOS within 14 days of randomisation was significantly higher in the iNO cases (n=11, 79%), as compared to the controls (n=4, 36%) (p=0.05). Conclusions: Our study demonstrated significant improvement in virological and clinical outcomes among patients with adjunct iNO therapy and no adverse effects were reported.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Keivan Ranjbar ◽  
Mohsen Moghadami ◽  
Alireza Mirahmadizadeh ◽  
Mohammad Javad Fallahi ◽  
Vahid Khaloo ◽  
...  

Abstract Background Although almost a year has passed since the Coronavirus disease 2019 (COVID-19) outbreak and promising reports of vaccines have been presented, we still have a long way until these measures are available for all. Furthermore, the most appropriate corticosteroid and dose in the treatment of COVID-19 have remained uncertain. We conducted a study to assess the effectiveness of methylprednisolone treatment versus dexamethasone for hospitalized COVID-19 patients. Methods In this prospective triple-blinded randomized controlled trial, we enrolled 86 hospitalized COVID-19 patients from August to November 2020, in Shiraz, Iran. The patients were randomly allocated into two groups to receive either methylprednisolone (2 mg/kg/day; intervention group) or dexamethasone (6 mg/kg/day; control group). Data were assessed based on a 9-point WHO ordinal scale extending from uninfected (point 0) to death (point 8). Results There were no significant differences between the groups on admission. However, the intervention group demonstrated significantly better clinical status compared to the control group at day 5 (4.02 vs. 5.21, p = 0.002) and day 10 (2.90 vs. 4.71, p = 0.001) of admission. There was also a significant difference in the overall mean score between the intervention group and the control group, (3.909 vs. 4.873 respectively, p = 0.004). The mean length of hospital stay was 7.43 ± 3.64 and 10.52 ± 5.47 days in the intervention and control groups, respectively (p = 0.015). The need for a ventilator was significantly lower in the intervention group than in the control group (18.2% vs 38.1% p = 0.040). Conclusion In hospitalized hypoxic COVID-19 patients, methylprednisolone demonstrated better results compared to dexamethasone. Trial registration The trial was registered with IRCT.IR (08/04/2020-No. IRCT20200204046369N1).


Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 919
Author(s):  
Pitchaporn Waiyamitra ◽  
Mehmet Arif Zoral ◽  
Aksorn Saengtienchai ◽  
Amorn Luengnaruemitchai ◽  
Olivier Decamp ◽  
...  

Tilapia lake virus (TiLV) causes an emerging viral disease associated with high mortality and economic damage in tilapia farming around the world. The use of probiotics in aquaculture has been suggested as an alternative to antibiotics and drugs to reduce the negative impact of bacterial and viral infections. In this study, we investigate the effect of probiotic Bacillus spp. supplementation on mortality, viral load, and expression of immune-related genes in red hybrid tilapia (Oreochromis spp.) upon TiLV infection. Fish were divided into three groups, and fed with: control diet, 0.5% probiotics-supplemented diet, and 1% probiotics-supplemented diet. After 21 days of experimental feeding, the three groups were infected with TiLV and monitored for mortality and growth performances, while organs were sampled at different time points to measure viral load and the transcription modulation of immune response markers. No significant difference was found among the groups in terms of weight gain (WG), average daily gain (ADG), feed efficiency (FE), or feed conversion ratio (FCR). A lower cumulative mortality was retrieved from fish fed 0.5% and 1% probiotics (25% and 24%, respectively), compared to the control group (32%). Moreover, fish fed with 1% probiotic diet had a significantly lower viral load, than those fed with 0.5% probiotic and control diet at 5, 6, 9, and 12 days post infection-challenge (dpc). The expression patterns of immune-related genes, including il-8 (also known as CXCL8), ifn-γ, irf-3, mx, rsad-2 (also known as VIPERIN) showed significant upregulation upon probiotic treatment during the peak of TiLV pathogenesis (between 9 and 12 dpc) and during most of the study period in fish fed with 1% probiotics-supplemented diet. Taken together, these findings indicate that dietary supplementation using Bacillus spp. probiotics may have beneficial effects to strengthen tilapia immunity and resistance against TiLV infections. Therefore, probiotic treatments may be preventively administered to reduce losses caused by this emerging viral infection in tilapia aquaculture.


2020 ◽  
Vol 8 (5_suppl5) ◽  
pp. 2325967120S0005
Author(s):  
Cheng Jin ◽  
Jia-yi Zhao ◽  
Jong-Keun Seon ◽  
Asep Santoso

This study, we aim to determine whether intraoperative over-release of MCL that is treated with primary repair can achieve satisfactory clinical results when compared to those who did not have over-release of MCL. At the same time, we seek to look into the difference between two methods of primary repair (anchor suture and staple) in terms of clinical outcomes. Purposes: We determined whether, after TKA, patients with CIA versus patients with CACB demonstrated (1) decreased pain scores (2) greater ambulatory ability postoperatively (3) decreased daily opioid consumption and hospital length of stay Methods: 3897 TKAs were performed from year 2003-2014. Sixty-five patients with MCL injury due to over-release during TKA who were repaired with suture anchor or staple (suture anchor: 36 vs. staple: 29) were studied whereas matched group of 65 patients without MCL injury were selected and served as the control group. Subjective feeling of instability and functional score were assessed using Knee Society Score (KSS) and Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC). Objective stability was evaluated through measurement of opening angles in extension and 30° of knee flexion on valgus stress radiographs. The clinical and stability results of repair between the suture anchor and staple were compared. Results: The KSS and WOMAC scores in patients with primary repair of MCL during TKA from 50.6±14.8 to 87.3±8.3 and 65.9±16.3 to 17.7±8.3, respectively. However, there were neither statistical nor clinical significant difference when comparing between the group with primary repair and the control group. Radiographic stability also showed no differences between repair and control groups in extension and 30° of flexion (p= .63 and p= .37). Regarding the subgroups, There were no significant differences between the suture anchor and staple in terms of the stability and clinical outcomes Conclusion: Primary repair either with suture anchor or with staple for injury of the MCL in varus gonarthrosis during TKA provides a good stability and clinical outcomes as those of result with no MCL injury.


2016 ◽  
Vol 2 (1) ◽  
pp. 00060-2015 ◽  
Author(s):  
Thông Hua-Huy ◽  
Sy Duong-Quy ◽  
Hoa Pham ◽  
Julien Pansiot ◽  
Jean-Christophe Mercier ◽  
...  

Inhaled nitric oxide (iNO) is commonly used in the treatment of very ill pre-term newborns. Previous studies showed that exogenous NO could affect endothelial NO synthase (eNOS) activity and expression in vascular endothelial cell cultures or adult rat models, but this has never been fully described in newborn rat lungs. We therefore aimed to assess the effects of iNO on eNOS expression and activity in newborn rats.Rat pups, post-natal day (P) 0 to P7, and their dams were placed in a chamber containing NO at 5 ppm (iNO-5 ppm group) or 20 ppm (iNO-20 ppm group), or in room air (control group). Rat pups were sacrificed at P7 and P14 for evaluation of lung eNOS expression and activity.At P7, eNOS protein expression in total lung lysates, in bronchial and arterial sections, was significantly decreased in the iNO-20 ppm versus control group. At P14, eNOS expression was comparable among all three groups. The amounts of eNOS mRNA significantly differed at P7 between the iNO-20 ppm and control groups. NOS activity decreased in the iNO-20 ppm group at P7 and returned to normal levels at P14. There was an imbalance between superoxide dismutase and NOS activities in the iNO-20 ppm group at P7.Inhalation of NO at 20 ppm early after birth decreases eNOS gene transcription, protein expression and enzyme activity. This decrease might account for the rebound phenomenon observed in patients treated with iNO.


Author(s):  
Shubhneek Kaur Dhillon Utaal ◽  
Rupali Chopra ◽  
Nitin Batra

Background: To study the association of ocular biometric parameters {Spherical equivalent (SE), Axial length (AL), Anterior chamber depth (ACD) and Corneal curvature (CC)} with diabetic retinopathy (DR) in subjects with Type 2 diabetes mellitus (DM).Methods: This prospective observational study was conducted in the Outpatient Department of Ophthalmology of a tertiary care teaching hospital in North India. The study included 100 subjects having various grades of DR as cases and 100 diabetics without DR as controls. The SE was assessed using objective autorefraction, while AL, CC and ACD were measured using the NIDEK AL SCAN.  International Clinical Diabetic Retinopathy Disease Severity Scale was used for grading of DR.Results: A total of 181 eyes in the study group and 200 eyes in the control group were analysed.  Progressive decrease in the mean AL was observed with the increasing severity of DR (p=0.017). Deeper ACD had a negative correlation with severity of DR (p=0.037). No statistically significant difference was observed for AL and ACD with the incidence of DR (p=0.147 and p=0.091 respectively). Likewise, there was no significant relation of DR with SE or CC.Conclusions: Longer AL and deep ACD were protective against progression to the severe forms of DR. However, there was no correlation of AL and ACD with the incidence of DR. The SE and CC were not found to be significant determinants for either development or severity of DR.


2021 ◽  
Author(s):  
Fang Ke ◽  
Zijin Shen ◽  
Cheng Wu ◽  
Lin Zhang ◽  
Rong Dong

Abstract Background Deep neuromuscular blockade may be beneficial on surgical space conditions during laparoscopic surgery. The effects of moderate neuromuscular blockade combined with transverse abdominal plane block (TAPB) on the surgical space conditions during laparoscopic surgery has not been described. We investigated if moderate neuromuscular blockade combined with TAPB would be associated with similar surgical space conditions compared with deep neuromuscular blockade. Methods Eighty patients undergoing elective laparoscopic surgery for colorectal cancer were randomly divided into two groups. The intervention group was treated with moderate neuromuscular blockade (train-of-four (TOF) count between 1 and 3) combined with TAPB (M group), while the control group was treated with deep neuromuscular blockade (D group), with a TOF count of 0 and a post-tetanic count (PTC) ≥ 1. Both groups received the same anesthesia management. The distance between the sacral promontory and the umbilical skin during the operation was compared between the two groups. The surgeon scored the surgical space conditions according to a five-point ordinal scale. Patients’ pain scores were evaluated eight hours after the operation. Results The 95% confidence intervals of the difference in the distance from the sacral promontory to the umbilical skin between the groups were − 1.45–0.77cm. According to the preset non-inferior standard of 1.5cm, (-1.45, ∞) completely fell within (-1.50, ∞), and the non-inferior effect test was qualified. There was no significant difference in the surgical rating score between the two groups. The dosage of rocuronium in group D was significantly higher than that in group M (P < 0.01). The M group had significantly lower pain scores than the D group eight hours after the operation (P < 0.05). Conclusions In laparoscopic colorectal cancer surgery, moderate neuromuscular blockade combined with TAPB can provide surgical space conditions similar to those of deep neuromuscular blockade, and at the same time, reduces the use of muscle relaxants, relieves postoperative pain within 4 hours after operation, shorten the time to extubation and stay in PACU. Trial registration: chictr.org.cn (ChiCTR2000034621), registered on 12, July, 2020


2020 ◽  
Vol 7 (3) ◽  
pp. 520
Author(s):  
Tushar R. Jadhav ◽  
Shailaja S. Jaywant

Background: Premature infants with Peri-natal asphyxia leading to a hypoxic-ischemic encephalopathy (HIE) are at greater risk for cerebral palsy. HIE grade II infants have long term neurological complications due to maladaptive brain wiring during NICU stay. Ladder approach, with graded stimulation program is administered by Occupational therapist, plays a vital role to minimize the maladaptive responses to environment. Objective of this study was to effect of Ladder Approach on preterm low birth weight Infants with HIE-2 as compared to conventional treatment. Design of this study was to Prospective Block Randomized Convenient Sampling Control Trial, Experimental design study. The study was carried out in the NICU and PU ward of Tertiary care hospital in metropolitan city from April 2015 to October 2016. The study subjects included a convenient sample of 30 preterm Low birth weight HIE-2 infants randomly selected into study or control groups. Neonatal behavioural Assessment scale (NBAS), Infant Neurological International Battery (INFANIB).Methods: The preterm infants from study group who received Ladder Approach and control group who received routine conventional care only. Outcome measures NBAS was at baseline and first follow up. INFANIB was administered at second follow up to assess neurodevelopment.Results: Showed that the premature infants of the study had significant difference in neuro behavioral status with mean for all subcomponents from to post intervention mean 39.6 in experimental group and from baseline mean of 24.3 to post intervention mean score of 33.2 in control group on neurobehavioral scale. Further neurodevelopmental status showed similar results on INFANIB in experimental group.Conclusions: The premature Infants with HIE grade 2, receiving ladder approach have shown more mature responses resulting into well-organized Neurobehavioral status, and resulted in improved brain wiring as evident in INFANIB.


Author(s):  
AG Radhika ◽  
Chetna Dengri ◽  
Abhishek Kumar ◽  
Shalini Singh

Introduction: India contributes to about 18% of global maternal deaths and 22.6% of still births. Efforts to improve the quality of care are challenged by the lack of reliable documentation of data. Hence, a concise, structured maternity case sheet (PrasavRecord) was designed with the aim to bring about an improvement in documentation of treatment and events related to woman in labour from the time of admission till her discharge from the hospital. Aim: To study the improvement in quality of documentation from the time of admission till discharge of a woman in labour with the help of structured format i.e., PrasavRecord. Materials and Methods: The study was conducted in February 2017. A quasi experimental study design was used, and the completeness of data recorded by the resident doctors in the existing hospital case sheet (control group) with those recorded in PrasavRecord (intervention group) were assessed in a total of 65 deliveries in each arm. Details of the patient from admission to the labour room followed by the entire sequence of events during labour as well as hospital stay in postpartum period were recorded over 130 parameters under different sections in PrasavRecord. Statistical analysis was done by using SPSS version 21.0. Results: Completeness of the documentation in terms of history, investigations and findings at examination including those at labour, nearly, 92% of the doctors rated PrasavRecord as “good and very good” for appearance, recommended its routine use, and 75% agreed that the format will be useful for conversion to electronic medical record. There was highly significant difference between the average percentage of completeness in PrasavRecord 75.8 {95% CI (74.2-77.4)} and hospital case sheets 42.2 {95% CI (40.9-43.6)} i.e., z=5.38 p-value <0.001. Conclusion: PrasavRecord is a simple, acceptable and user-friendly data entry format which improves the quality of documentation of the processes and practices during childbirth. Larger trials are required to finetune it to facilitate its widespread use thereby, ensuring a uniform documentation process of labour and postpartum.


Author(s):  
Klinger Soares Faíco-Filho ◽  
Danielle Dias Conte ◽  
Luciano Kleber de Souza Luna ◽  
Joseane Mayara Almeida Carvalho ◽  
Ana Helena Sitta Perosa ◽  
...  

ABSTRACTBackgroundSome studies have shown that hydroxychloroquine (HCQ) is an effective drug in reducing the in vitro replication of SARS-CoV-2. However, the in vivo effect of HCQ still unclear. This study aims to evaluate viral load clearance in patients with COVID-19 who underwent HCQ treatment in comparison with a control group that did not receive the drug.MethodsThis prospective study comprised consecutive viral load measurements in patients with COVID-19 hospitalized with a moderate illness. Patients received 400 mg of HCQ every 12 hours for 10 days according to the medical decision. Nasal swab samples were collected at the 1st, 7th, and 14th days of the admission.Results155 samples were collected from 66 patients with COVID-19 (60% female), with a median age of 58 years. The viral load between studied groups, assumed as a semiquantitative measure of cycle threshold (Ct) values, presented no significant difference within the three consecutive measures (ΔCt) (p>0.05). We also analyzed the ΔCt viral load at different intervals of sample collection (Δt <7; 7-12 and >12 days) without significant differences at any ΔCt (p>0.05).ConclusionIn this study, we did not observe any change in viral load in vivo with the use of HCQ.SummaryWe evaluate viral load clearance in patients with COVID-19 who took hydroxychloroquine (HCQ) for treatment and those who not. Prospective viral load measurements have shown any change in viral load in vivo with the use of HCQ.


2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Shahan Waheed ◽  
Ayaz Ghouse Kalsekar ◽  
Ayeesha Kamran Kamal ◽  
Nathan S. Bryan ◽  
Asad I. Mian

Introduction. Acute stroke incites an inflammatory reaction in the brain’s microvasculature, activating formation of nitric oxide oxidative metabolites, nitrate and nitrite (NOx, collectively), measurable in plasma. Our objectives were to investigate plasma NOx in patients with acute stroke presenting to the Emergency Department (ED) and to determine if it could (i) differentiate between ischemic and hemorrhagic stroke; (ii) predict clinical outcomes. Methods. A cross-sectional study was conducted in the ED of Aga Khan University Hospital, from January 1 to December 31, 2016. Participants were enrolled if they had clinical acute stroke with confirmatory brain imaging to differentiate between ischemia and hemorrhage. Clinical demographic information, ancillary blood, and diagnostic specimens were collected as per standard of care since the center follows stroke algorithmic guidelines. Plasma NOx analysis was performed using high performance liquid chromatography. Clinical outcomes were assessed using Barthel Index and Modified Rankin Score. Data was analyzed using SPSS 19 and expressed in medians with interquartile ranges. Nonparametric tests were applied for comparing among groups. Pearson’s correlation was used to determine associations with aforementioned stroke severity and disability scales. Results. Seventy-five patients were enrolled, with median age of 57 years (IQR 47-66 years), 53 (71%) were males, and 46 (61%) had ischemic stroke. Overall, median NOx was 20.8 μM (IQR 13.4-35.3); there was no statistically significant difference between NOx in ischemic versus hemorrhagic stroke (21.2 μM vs. 17.9 μM; p=0.2). However, there was a significant positive correlation between NOx levels and aforementioned acute stroke scales [r(73)=0.417, p=0.0001], for both. Conclusion. Although plasma NOx could not differentiate between ischemia and hemorrhage, higher levels of the biomarker did show associations with poststroke disability scales. Further study with more patients in a multicenter trial is warranted to establish the real biomarker potential of plasma NOx in acute stroke.


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