1.Protocol and Rationale: A 24-week Double-blind, Randomized, Placebo Controlled Trial of the Efficacy of Adjunctive Garcinia mangostana Linn. (Mangosteen) Pericarp for Schizophrenia
Alyna TURNER ; John J MCGRATH ; Olivia M DEAN ; Seetal DODD ; Andrea BAKER ; Susan M COTTON ; James G SCOTT ; Bianca E KAVANAGH ; Melanie M ASHTON ; Adam J WALKER ; Ellie BROWN ; Michael BERK
Clinical Psychopharmacology and Neuroscience 2019;17(2):297-307
OBJECTIVE: Garcinia mangostana Linn., commonly known as mangosteen, is a tropical fruit with a thick pericarp rind containing bioactive compounds that may be beneficial as an adjunctive treatment for schizophrenia. The biological underpinnings of schizophrenia are believed to involve altered neurotransmission, inflammation, redox systems, mitochondrial dysfunction, and neurogenesis. Mangosteen pericarp contains xanthones which may target these biological pathways and improve symptoms; this is supported by preclinical evidence. Here we outline the protocol for a double-blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp (1,000 mg/day), compared to placebo, in the treatment of schizophrenia. METHODS: We aim to recruit 150 participants across two sites (Geelong and Brisbane). Participants diagnosed with schizophrenia or schizoaffective disorder will be randomized to receive 24 weeks of either adjunctive 1,000 mg/day of mangosteen pericarp or matched placebo, in addition to their usual treatment. The primary outcome measure is mean change in the Positive and Negative Symptom Scale (total score) over the 24 weeks. Secondary outcomes include positive and negative symptoms, general psychopathology, clinical global severity and improvement, depressive symptoms, life satisfaction, functioning, participants reported overall improvement, substance use, cognition, safety and biological data. A 4-week post treatment interview at week 28 will explore post-discontinuations effects. RESULTS: Ethical and governance approvals were gained and the trial commenced. CONCLUSION: A positive finding in this study has the potential to provide a new adjunctive treatment option for people with schizophrenia and schizoaffective disorder. It may also lead to a greater understanding of the pathophysiology of the disorder.
Cognition
;
Depression
;
Fruit
;
Garcinia mangostana
;
Garcinia
;
Inflammation
;
Neurogenesis
;
Outcome Assessment (Health Care)
;
Oxidation-Reduction
;
Oxidative Stress
;
Psychopathology
;
Psychotic Disorders
;
Schizophrenia
;
Synaptic Transmission
;
Xanthones
2.Mechanical Thrombectomy Versus Intravenous Thrombolysis in Distal Medium Vessel Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Matched Study
Hamza Adel SALIM ; Vivek YEDAVALLI ; Basel MUSMAR ; Nimer ADEEB ; Muhammed Amir ESSIBAYI ; Kareem El NAAMANI ; Nils HENNINGER ; Sri Hari SUNDARARAJAN ; Anna Luisa KÜHN ; Jane KHALIFE ; Sherief GHOZY ; Luca SCARCIA ; Benjamin Y.Q. TAN ; Benjamin PULLI ; Jeremy J. HEIT ; Robert W. REGENHARDT ; Nicole M. CANCELLIERE ; Joshua D. BERNSTOCK ; Aymeric ROUCHAUD ; Jens FIEHLER ; Sunil SHETH ; Ajit S. PURI ; Christian DYZMANN ; Marco COLASURDO ; Xavier BARREAU ; Leonardo RENIERI ; João Pedro FILIPE ; Pablo HARKER ; Razvan Alexandru RADU ; Thomas R. MAROTTA ; Julian SPEARS ; Takahiro OTA ; Ashkan MOWLA ; Pascal JABBOUR ; Arundhati BISWAS ; Frédéric CLARENÇON ; James E. SIEGLER ; Thanh N. NGUYEN ; Ricardo VARELA ; Amanda BAKER ; David ALTSCHUL ; Nestor R. GONZALEZ ; Markus A. MÖHLENBRUCH ; Vincent COSTALAT ; Benjamin GORY ; Christian Paul STRACKE ; Mohammad Ali AZIZ-SULTAN ; Constantin HECKER ; Hamza SHAIKH ; David S. LIEBESKIND ; Alessandro PEDICELLI ; Andrea M. ALEXANDRE ; Illario TANCREDI ; Tobias D. FAIZY ; Erwah KALSOUM ; Boris LUBICZ ; Aman B. PATEL ; Vitor Mendes PEREIRA ; Adrien GUENEGO ; Adam A. DMYTRIW ;
Journal of Stroke 2024;26(3):434-445
Background:
and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone.
Methods:
This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage.
Results:
The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001).
Conclusion
The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.
3.Mechanical Thrombectomy Versus Intravenous Thrombolysis in Distal Medium Vessel Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Matched Study
Hamza Adel SALIM ; Vivek YEDAVALLI ; Basel MUSMAR ; Nimer ADEEB ; Muhammed Amir ESSIBAYI ; Kareem El NAAMANI ; Nils HENNINGER ; Sri Hari SUNDARARAJAN ; Anna Luisa KÜHN ; Jane KHALIFE ; Sherief GHOZY ; Luca SCARCIA ; Benjamin Y.Q. TAN ; Benjamin PULLI ; Jeremy J. HEIT ; Robert W. REGENHARDT ; Nicole M. CANCELLIERE ; Joshua D. BERNSTOCK ; Aymeric ROUCHAUD ; Jens FIEHLER ; Sunil SHETH ; Ajit S. PURI ; Christian DYZMANN ; Marco COLASURDO ; Xavier BARREAU ; Leonardo RENIERI ; João Pedro FILIPE ; Pablo HARKER ; Razvan Alexandru RADU ; Thomas R. MAROTTA ; Julian SPEARS ; Takahiro OTA ; Ashkan MOWLA ; Pascal JABBOUR ; Arundhati BISWAS ; Frédéric CLARENÇON ; James E. SIEGLER ; Thanh N. NGUYEN ; Ricardo VARELA ; Amanda BAKER ; David ALTSCHUL ; Nestor R. GONZALEZ ; Markus A. MÖHLENBRUCH ; Vincent COSTALAT ; Benjamin GORY ; Christian Paul STRACKE ; Mohammad Ali AZIZ-SULTAN ; Constantin HECKER ; Hamza SHAIKH ; David S. LIEBESKIND ; Alessandro PEDICELLI ; Andrea M. ALEXANDRE ; Illario TANCREDI ; Tobias D. FAIZY ; Erwah KALSOUM ; Boris LUBICZ ; Aman B. PATEL ; Vitor Mendes PEREIRA ; Adrien GUENEGO ; Adam A. DMYTRIW ;
Journal of Stroke 2024;26(3):434-445
Background:
and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone.
Methods:
This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage.
Results:
The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001).
Conclusion
The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.
4.Mechanical Thrombectomy Versus Intravenous Thrombolysis in Distal Medium Vessel Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Matched Study
Hamza Adel SALIM ; Vivek YEDAVALLI ; Basel MUSMAR ; Nimer ADEEB ; Muhammed Amir ESSIBAYI ; Kareem El NAAMANI ; Nils HENNINGER ; Sri Hari SUNDARARAJAN ; Anna Luisa KÜHN ; Jane KHALIFE ; Sherief GHOZY ; Luca SCARCIA ; Benjamin Y.Q. TAN ; Benjamin PULLI ; Jeremy J. HEIT ; Robert W. REGENHARDT ; Nicole M. CANCELLIERE ; Joshua D. BERNSTOCK ; Aymeric ROUCHAUD ; Jens FIEHLER ; Sunil SHETH ; Ajit S. PURI ; Christian DYZMANN ; Marco COLASURDO ; Xavier BARREAU ; Leonardo RENIERI ; João Pedro FILIPE ; Pablo HARKER ; Razvan Alexandru RADU ; Thomas R. MAROTTA ; Julian SPEARS ; Takahiro OTA ; Ashkan MOWLA ; Pascal JABBOUR ; Arundhati BISWAS ; Frédéric CLARENÇON ; James E. SIEGLER ; Thanh N. NGUYEN ; Ricardo VARELA ; Amanda BAKER ; David ALTSCHUL ; Nestor R. GONZALEZ ; Markus A. MÖHLENBRUCH ; Vincent COSTALAT ; Benjamin GORY ; Christian Paul STRACKE ; Mohammad Ali AZIZ-SULTAN ; Constantin HECKER ; Hamza SHAIKH ; David S. LIEBESKIND ; Alessandro PEDICELLI ; Andrea M. ALEXANDRE ; Illario TANCREDI ; Tobias D. FAIZY ; Erwah KALSOUM ; Boris LUBICZ ; Aman B. PATEL ; Vitor Mendes PEREIRA ; Adrien GUENEGO ; Adam A. DMYTRIW ;
Journal of Stroke 2024;26(3):434-445
Background:
and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone.
Methods:
This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage.
Results:
The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001).
Conclusion
The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.
5.Mechanical Thrombectomy Versus Intravenous Thrombolysis in Distal Medium Vessel Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Matched Study
Hamza Adel SALIM ; Vivek YEDAVALLI ; Basel MUSMAR ; Nimer ADEEB ; Muhammed Amir ESSIBAYI ; Kareem El NAAMANI ; Nils HENNINGER ; Sri Hari SUNDARARAJAN ; Anna Luisa KÜHN ; Jane KHALIFE ; Sherief GHOZY ; Luca SCARCIA ; Benjamin Y.Q. TAN ; Benjamin PULLI ; Jeremy J. HEIT ; Robert W. REGENHARDT ; Nicole M. CANCELLIERE ; Joshua D. BERNSTOCK ; Aymeric ROUCHAUD ; Jens FIEHLER ; Sunil SHETH ; Ajit S. PURI ; Christian DYZMANN ; Marco COLASURDO ; Xavier BARREAU ; Leonardo RENIERI ; João Pedro FILIPE ; Pablo HARKER ; Razvan Alexandru RADU ; Thomas R. MAROTTA ; Julian SPEARS ; Takahiro OTA ; Ashkan MOWLA ; Pascal JABBOUR ; Arundhati BISWAS ; Frédéric CLARENÇON ; James E. SIEGLER ; Thanh N. NGUYEN ; Ricardo VARELA ; Amanda BAKER ; David ALTSCHUL ; Nestor R. GONZALEZ ; Markus A. MÖHLENBRUCH ; Vincent COSTALAT ; Benjamin GORY ; Christian Paul STRACKE ; Mohammad Ali AZIZ-SULTAN ; Constantin HECKER ; Hamza SHAIKH ; David S. LIEBESKIND ; Alessandro PEDICELLI ; Andrea M. ALEXANDRE ; Illario TANCREDI ; Tobias D. FAIZY ; Erwah KALSOUM ; Boris LUBICZ ; Aman B. PATEL ; Vitor Mendes PEREIRA ; Adrien GUENEGO ; Adam A. DMYTRIW ;
Journal of Stroke 2024;26(3):434-445
Background:
and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone.
Methods:
This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage.
Results:
The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001).
Conclusion
The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.