1.Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial
Mayank GOYAL ; Bijoy K. MENON ; Johanna OSPEL ; Mohammed ALMEKHLAFI ; Charlotte ZERNA ; Raul NOGUEIRA ; Ryan MCTAGGART ; Andrew M. DEMCHUK ; Alexandre Y. POPPE ; Brian BUCK ; Kathy HEARD ; Manish JOSHI ; Diogo HAUSSEN ; Shawna CUTTING ; Shelagh B. COUTTS ; Daniel ROY ; Jeremy L. REMPEL ; Thalia S. FIELD ; Dar DOWLATSHAHI ; Brian van ADEL ; Richard SWARTZ ; Ruchir SHAH ; Eric SAUVAGEAU ; Volker PUETZ ; Frank L. SILVER ; Bruce CAMPBELL ; René CHAPOT ; Michael TYMIANSKI ; Michael D. HILL ;
Journal of Stroke 2025;27(1):95-101
Background:
and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups.
Methods:
ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model.
Results:
Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome.
Conclusion
Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.
2.Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial
Mayank GOYAL ; Bijoy K. MENON ; Johanna OSPEL ; Mohammed ALMEKHLAFI ; Charlotte ZERNA ; Raul NOGUEIRA ; Ryan MCTAGGART ; Andrew M. DEMCHUK ; Alexandre Y. POPPE ; Brian BUCK ; Kathy HEARD ; Manish JOSHI ; Diogo HAUSSEN ; Shawna CUTTING ; Shelagh B. COUTTS ; Daniel ROY ; Jeremy L. REMPEL ; Thalia S. FIELD ; Dar DOWLATSHAHI ; Brian van ADEL ; Richard SWARTZ ; Ruchir SHAH ; Eric SAUVAGEAU ; Volker PUETZ ; Frank L. SILVER ; Bruce CAMPBELL ; René CHAPOT ; Michael TYMIANSKI ; Michael D. HILL ;
Journal of Stroke 2025;27(1):95-101
Background:
and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups.
Methods:
ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model.
Results:
Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome.
Conclusion
Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.
3.Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial
Mayank GOYAL ; Bijoy K. MENON ; Johanna OSPEL ; Mohammed ALMEKHLAFI ; Charlotte ZERNA ; Raul NOGUEIRA ; Ryan MCTAGGART ; Andrew M. DEMCHUK ; Alexandre Y. POPPE ; Brian BUCK ; Kathy HEARD ; Manish JOSHI ; Diogo HAUSSEN ; Shawna CUTTING ; Shelagh B. COUTTS ; Daniel ROY ; Jeremy L. REMPEL ; Thalia S. FIELD ; Dar DOWLATSHAHI ; Brian van ADEL ; Richard SWARTZ ; Ruchir SHAH ; Eric SAUVAGEAU ; Volker PUETZ ; Frank L. SILVER ; Bruce CAMPBELL ; René CHAPOT ; Michael TYMIANSKI ; Michael D. HILL ;
Journal of Stroke 2025;27(1):95-101
Background:
and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups.
Methods:
ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model.
Results:
Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome.
Conclusion
Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.
4.Clinical efficacy of 0.75% ropivacaine vs. 2% lignocaine hydrochloride with adrenaline (1:80,000) in patients undergoing removal of bilateral maxillary third molars:a randomized controlled trial
Aniket Narayan KAKADE ; Sanjay S. JOSHI ; Charudatta Shridhar NAIK ; Bhupendra Vilas MHATRE ; Arsalan ANSARI
Journal of Dental Anesthesia and Pain Medicine 2021;21(5):451-459
Background:
Lignocaine with adrenaline is routinely used as a local anesthetic for dental procedures. Adrenaline was added to increase the duration of anesthesia. However, epinephrine containing a local anesthetic solution is not recommended in conditions such as advanced cardiovascular diseases and hyperthyroidism. Recently, ropivacaine has gained popularity as a long-acting anesthetic with superior outcomes. The goal of this study was to assess and compare the effectiveness of 0.75% ropivacaine alone and 2% lignocaine with adrenaline (1:80,000) in the removal of bilateral maxillary wisdom teeth using the posterior superior alveolar nerve block technique.
Methods:
This was a single-blind, randomized, split-mouth, prospective study assessing 15 systemically sound outpatients who needed bilateral removal of maxillary third molars. We randomly allocated the sides and sequences of ropivacaine and lignocaine with adrenaline administration. We evaluated the efficacy of both anesthetics with regard to the onset of anesthesia, intensity of pain, variation in heart rate, and blood pressure.
Results:
The onset of anesthesia was faster with lignocaine (138 s) than with ropivacaine (168 s), with insignificant differences (p = 0.001). There was no need for additional local anesthetics in the ropivacaine group, while in the lignocaine with adrenaline group, 2 (13.3%) patients required additional anesthesia. Adequate intraoperative anesthesia was provided by ropivacaine and lignocaine solutions. No significant difference was observed in the perioperative variation in blood pressure and heart rate.
Conclusion
Ropivacaine (0.75%) is a safe and an adrenaline-free local anesthetic option for posterior superior alveolar nerve block, which provides adequate intraoperative anesthesia and a stable hemodynamic profile for the removal of the maxillary third molar.
5.Functional Outcome of Open Latarjet Procedure in NonAthletic Middle-Aged Patie
Joshi S ; Rao VKV ; Shetty UC ; Rai S ; Arora S ; Kumar SR
Malaysian Orthopaedic Journal 2021;15(No.2):151-158
Introduction: The movement and steadiness of the shoulder
joint is due to both the dynamic and static stabilisers.
Recurrent anterior shoulder instability is common due to the
Bankart lesion or the Hill Sachs lesion. The bone loss and
soft tissue failure due to these lesions causing instability is
well compensated by Latarjet procedure which acts by triple
blocking effect of the bone graft, the sling effect of the
conjoint tendon of subscapularis and the ligament of the
coracoacromial ligament stump.
Materials and methods: Middle-aged patients with
recurrent anterior shoulder dislocation and a mid-range
instability on clinical assessment with an isolated glenoid
bone loss of 20% or Bankart lesion with engaging Hill Sachs
lesion were selected for the study. The surgical procedure
included a subscapularis split to expose the glenoid. The
coracoid graft harvested was prefixed with Kirschner wires
and placed flush over the glenoid ensuring no medial or
lateral overhang and fixed with 4.0mm cancellous screws
with the washer. The functional outcome was measured with
the ROWE score and ASES score and the movements were
evaluated.
Results: A total of 24 patients fulfilled the inclusion criteria.
Post-operatively at final follow-up, the mean ROWE score
was 97.08 ±8.45 and the mean ASES score was 94.4±9.10.
One patient had screw breakage as a complication and
another had restriction of movement which was managed
with physiotherapy.
Conclusion: Open Latarjet is an effective procedure for
recurrent anterior shoulder instability in non-athletic middleaged patients as a excellent functional outcome was achieved
with this technique. We therefore recommend open Latarjet
as an alternative to arthroscopic treatment in developing
countries where patient affordability and the availability of
the resources are the issues.
6.Clinical efficacy of 0.75% ropivacaine vs. 2% lignocaine hydrochloride with adrenaline (1:80,000) in patients undergoing removal of bilateral maxillary third molars:a randomized controlled trial
Aniket Narayan KAKADE ; Sanjay S. JOSHI ; Charudatta Shridhar NAIK ; Bhupendra Vilas MHATRE ; Arsalan ANSARI
Journal of Dental Anesthesia and Pain Medicine 2021;21(5):451-459
Background:
Lignocaine with adrenaline is routinely used as a local anesthetic for dental procedures. Adrenaline was added to increase the duration of anesthesia. However, epinephrine containing a local anesthetic solution is not recommended in conditions such as advanced cardiovascular diseases and hyperthyroidism. Recently, ropivacaine has gained popularity as a long-acting anesthetic with superior outcomes. The goal of this study was to assess and compare the effectiveness of 0.75% ropivacaine alone and 2% lignocaine with adrenaline (1:80,000) in the removal of bilateral maxillary wisdom teeth using the posterior superior alveolar nerve block technique.
Methods:
This was a single-blind, randomized, split-mouth, prospective study assessing 15 systemically sound outpatients who needed bilateral removal of maxillary third molars. We randomly allocated the sides and sequences of ropivacaine and lignocaine with adrenaline administration. We evaluated the efficacy of both anesthetics with regard to the onset of anesthesia, intensity of pain, variation in heart rate, and blood pressure.
Results:
The onset of anesthesia was faster with lignocaine (138 s) than with ropivacaine (168 s), with insignificant differences (p = 0.001). There was no need for additional local anesthetics in the ropivacaine group, while in the lignocaine with adrenaline group, 2 (13.3%) patients required additional anesthesia. Adequate intraoperative anesthesia was provided by ropivacaine and lignocaine solutions. No significant difference was observed in the perioperative variation in blood pressure and heart rate.
Conclusion
Ropivacaine (0.75%) is a safe and an adrenaline-free local anesthetic option for posterior superior alveolar nerve block, which provides adequate intraoperative anesthesia and a stable hemodynamic profile for the removal of the maxillary third molar.
7.Analysis of the Bioactive Metabolites of the Endangered Mexican LostFungi Campanophyllum – A Report from India
Madhusmita BORTHAKUR ; Arun Bahadur GURUNG ; Atanu BHATTACHARJEE ; S. R. JOSHI
Mycobiology 2020;48(1):58-69
Meghalaya, (in India), in the region of the mega-biodiversity hotspots, is home to a plethoraof wild mushrooms. The present study concerns the exploration of the order Agaricales,which includes rare gilled mushrooms considered endangered under IUCN A4c criteria, dueto the declining habitat. Electron microscopy of the gill sections revealed an abundance ofclamp connections, hyphal cell walls, cystidia, and basidia. This rare species which belongsto the family Cyphellaceae, exhibits morphological and molecular differences from theCyphella spp. Phylogenetic analysis revealed that it formed a clade under the genusCampanophyllum of the order Agaricales, confirmed by both Neighbor Joining (NJ) andBayesian phylogenetic analysis. Being nutritionally potent along with its efficient antioxidantvalue, the fungal extract shows significant rise of two-fold in the antimicrobial activity alongwith the commercial antibiotics. The compound, Phenol, 2, 4-bis (1, 1-Dimethylethyl) (2, 4-DTBP) showed in ample range in the fungal extract along with aliphatic hydrocarbons,terpene, alcohol and volatile organic compounds on further characterization in GCMS. Thepresent study indicates the endangered Campanophyllum proboscideum could be a richsource of natural antioxidants and an effective pharmaceutical agent.
8.Analysis of the Bioactive Metabolites of the Endangered Mexican LostFungi Campanophyllum – A Report from India
Madhusmita BORTHAKUR ; Arun Bahadur GURUNG ; Atanu BHATTACHARJEE ; S. R. JOSHI
Mycobiology 2020;48(1):58-69
Meghalaya, (in India), in the region of the mega-biodiversity hotspots, is home to a plethoraof wild mushrooms. The present study concerns the exploration of the order Agaricales,which includes rare gilled mushrooms considered endangered under IUCN A4c criteria, dueto the declining habitat. Electron microscopy of the gill sections revealed an abundance ofclamp connections, hyphal cell walls, cystidia, and basidia. This rare species which belongsto the family Cyphellaceae, exhibits morphological and molecular differences from theCyphella spp. Phylogenetic analysis revealed that it formed a clade under the genusCampanophyllum of the order Agaricales, confirmed by both Neighbor Joining (NJ) andBayesian phylogenetic analysis. Being nutritionally potent along with its efficient antioxidantvalue, the fungal extract shows significant rise of two-fold in the antimicrobial activity alongwith the commercial antibiotics. The compound, Phenol, 2, 4-bis (1, 1-Dimethylethyl) (2, 4-DTBP) showed in ample range in the fungal extract along with aliphatic hydrocarbons,terpene, alcohol and volatile organic compounds on further characterization in GCMS. Thepresent study indicates the endangered Campanophyllum proboscideum could be a richsource of natural antioxidants and an effective pharmaceutical agent.
9.Minimally Invasive Augmented Fixation for Anatomical Reduction of Grade 2 and Grade 3 Listhesis in Patients with Osteoporosis
Parichay J PERIKAL ; Umesh SRIKANTHA ; Krishna C JOSHI ; Aniruddha T JAGANNATH ; Kiran KHANAPURE ; Ravi Gopal VARMA ; Sathyaranjandas Alanga HEGDE
Asian Spine Journal 2018;12(5):887-892
STUDY DESIGN: A retrospective study. PURPOSE: To study the efficacy of augmented fixation for anatomical reduction of grade 2 and grade 3 listhesis in patients with osteoporosis. OVERVIEW OF LITERATURE: Spondylolisthesis in osteoporotic patients requiring spinal fixation are associated with complications such as loss of surgical construct stability, screw pulling out, and screw loosening. Augmented fixation is a novel strategy to achieve necessary construct integrity. METHODS: Thirteen consecutive patients with grade 2 or grade 3 listhesis, with proven osteoporosis on dual energy X-ray absorptiometry (DEXA) scan, and who underwent augmented fixation for reduction of listhesis were retrospectively analyzed. In all patients, surgical access was achieved with a fixed 22 mm tubular retractor. A modified technique of bilateral, sequential, transforaminal decompression and discectomy, followed by reduction of listhesis using unilaterally placed augmented screws was employed in all the cases. Patients were followed up with plain X-rays at regular intervals to assess for implant stability and fusion status. All patients were started on medical treatment for osteoporosis. RESULTS: The mean age of the patients was 52.46 years, with 12 females and one male. The median T-score on DEXA scan was −3.0. Of the 13 patients, listhesis was at L4–L5 in five and at L5–S1 in eight. Nine patients had grade 2 listhesis, while four patients had grade 3 listhesis. Complete reduction was achieved in 10 patients. The median duration of follow-up was 18 months. Postoperative outcomes were satisfactory in all cases. CONCLUSIONS: Augmented fixation is a useful technique for achieving anatomical reduction of listhesis in patients with osteoporosis.
Absorptiometry, Photon
;
Decompression
;
Diskectomy
;
Female
;
Follow-Up Studies
;
Humans
;
Male
;
Minimally Invasive Surgical Procedures
;
Osteoporosis
;
Retrospective Studies
;
Spinal Fusion
;
Spondylolisthesis
10.Respiratory symptoms and illnesses related to the concentration of airborne particulate matter among brick kiln workers in Kathmandu valley, Nepal.
Seshananda SANJEL ; Sanjay N KHANAL ; Steven M THYGERSON ; William S CARTER ; James D JOHNSTON ; Sunil K JOSHI
Annals of Occupational and Environmental Medicine 2017;29(1):9-
BACKGROUND: Bricks have been manufactured in Nepal for hundreds of years and are seen as a component of Nepalese sculpture and architecture. Large quantities of hazardous materials including high concentrations of particulate matter are emitted on a daily basis from brick kilns. Exposure to these hazardous materials can lead to adverse consequences on the environment and human health. This study was conducted to estimate the prevalence of respiratory symptoms/illnesses and the magnitude of respirable and total dust exposures among Nepalese brick kiln workers. METHODS: Respiratory symptoms/illnesses were evaluated by questionnaire among brickfield workers (n = 400) and a referent group of grocery workers (n = 400) in Kathmandu valley. Work zones (WZs): green brick molding (GBM), green brick stacking/carrying (GBS/C), red brick loading/carrying (RBL/C), coal preparation (CP) and firemen (FM) were the similar exposure groups (SEGs) from where personal air samples and interviews were taken. Among brickfield workers, personal monitoring was conducted across SEGs for total (n = 89) and respirable (n = 72) dust during February–March 2015 and March–April 2016. Applying multi-stage probability proportionate to size sampling technique, 16 kilns and 400 brick workers for interview were selected. Proportions, means, medians and ranges were calculated for the demographics, samples and respiratory symptoms/illnesses. One-way ANOVA was applied to compare the significance differences of the level of particulate matter among SEGs. Bivariate and multivariate logistic regression analysis were performed to evaluate association between respiratory symptoms/illnesses and participants groups, and SEGs among brick kiln workers at 0.05 level. Statistical analyses were performed using IBM SPSS Statistics 21. RESULTS: Chronic cough (14.3%), phlegm (16.6%) and bronchitis (19.0%) were higher (P < 0.05) among brickfield compared with grocery workers (6.8, 5.8 and 10.8%). Mean respirable (5.888 mg/m3) and total (20.657 mg/m3) dust exposures were highest for red brick loading tasks. The prevalence of chronic cough, chronic phlegm, chronic bronchitis, wheezing and asthma were significantly higher for other WZs workers (p < 0.05) compared with CP; for GBM: 22.9, 34.6, 15.0 and 7.5%; for GBS/C: 13.5, 15.8, 10.0, 8.8 and 7.5%; for RBL/C: 11.1, 17.1, 27.4, 19.0 and 11.9%; for FM: 18.4, 12.5, 28.4, 4.9 and 0.0%; and for CP: 4.9, 6.3, 13.3, 9.3 and 4.0% respectively. CONCLUSION: High dust exposures identified in this study may explain the increased prevalence of respiratory symptoms/illnesses among Nepalese brickfield workers, warranting action to reduce exposures.
Asthma
;
Bronchitis
;
Bronchitis, Chronic
;
Coal
;
Cough
;
Demography
;
Dust
;
Fungi
;
Hazardous Substances
;
Humans
;
Logistic Models
;
Nepal*
;
Particulate Matter*
;
Prevalence
;
Respiratory Sounds
;
Sculpture


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