Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Novel cryptomelane nanosheets for the superior catalytic combustion of oxygenated volatile organic compounds.

International audienceThis work offers a novel pathway to prepare cryptomelane manganese oxides nanosheets as an superior catalyst for the catalytic combustion of oxygenated volatile organic compounds. The tunnel cryptomelane manganese oxides nanosheets were prepared from layered birnessite via simultaneously tuning pH and molar ratio (ROK) of the redox-precipitation between oxalic acid and KMnO4. Thus, few-layered cryptomelane nanosheets possessing the most predominantly exposed (211) facet are generated at low pH (5.2–5.6), which intensifies the surface area of thin crystal cryptomelane nanosheets up to 177 m2 g-1 and weakens Mn-O bonds. Moreover, high ROK results in low manganese average oxidation state (AOS), greater oxygen vacancies and better low-temperature reduction and oxygen mobility. Such features significantly maneuver the catalytic activity of the cryptomelane nanosheets catalysts for the complete oxidation of oxygenated volatile organic compound (e.g., 2-propanol, acetone) at low temperature (170–230 °C). Moreover, the catalysts show high stability for 48 h. The presented catalyst discloses an avenue to address current obstacles in the catalytic oxidation of volatile organic compounds

Hilar asymmetry in endobronchial tuberculosis patients: An often-overlooked clue

Background: Endobronchial tuberculosis (EBTB) is a challenging diagnosis because of its varied clinical and radiological manifestations. Hilar asymmetry on chest radiograph (CXR) may be found in patient with EBTB but is often overlooked, which may lead to delayed diagnosis. Case report: We present five cases with EBTB. Clinicians failed to identify unilateral hilar abnormalities on CXR, and these patients were treated initially for pharyngitis, bronchitis, or pneumonia with no improvement. Subsequently, they visited the pulmonary clinic and bronchoscopy revealed endobronchial lesions and microbial/histopathological evidence of tuberculous infection consistent with EBTB. Anti-tuberculosis therapy resulted in complete clinical resolution in four of the five patients; one patient had persistent bronchial stenosis. Conclusion: Hilar asymmetry on CXR may occur with EBTB and may suggest this diagnosis in the appropriate clinical setting. Bronchoscopy has an important role in establishing the final diagnosis. Keywords: Bronchoscopy, Chest radiograph, Endobronchial tuberculosis, Hilar asymmetr

Hg2+-Promoted Spirolactam Hydrolysis Reaction: A Design Strategy for the Highly Selective Sensing of Hg2+ over other Metal Ions in Aqueous Media

A mercury sensor (N-(rhodamine-6G)lactam-ethylenediamine-4-dimethylamino-cinnamaldehyde&mdash;RLED) based on the Hg2+-promoted hydrolysis reaction has been designed and developed with a combination of theoretical calculations and experimental investigations. The interaction between RLED and Hg2+ goes through a fast-initial stage with formation of a 1:1 complex, followed by a slow hydrolysis process. The formation of durable intermediate complexes is due to quite a long hydrolysis reaction time. As a result, RLED can selectively detect Hg2+ in the presence of other metal ions, with a detection limit of 0.08 &mu;M for the colorimetric method, and of 0.008 &mu;M with the fluorescent method. In addition, the RLED sensor can work in a solution with a small amount of organic solvent, with a wide pH range from 5 to 10. The time-dependent density functional theory has been used for investigations of the excitation and de-excitation processes in RLED, intermediate complexes, and reaction products, thereby clarifying the changes in the fluorescence intensity before and after the RLED interacts with Hg2+ ions

Medical-Waste Chain: A Medical Waste Collection, Classification and Treatment Management by Blockchain Technology

To prevent the spread of the COVID-19 pandemic, 2019 has seen unprecedented demand for medical equipment and supplies. However, the problem of waste treatment has not yet been given due attention, i.e., the traditional waste treatment process is done independently, and it is not easy to share the necessary information. Especially during the COVID-19 pandemic, the interaction between parties is minimized to limit infections. To evaluate the current system at medical centers, we also refer to the traditional waste treatment processes of four hospitals in Can Tho and Ho Chi Minh cities (Vietnam). Almost all hospitals are handled independently, lacking any interaction between the stakeholders. In this article, we propose a decentralized blockchain-based system for automating waste treatment processes for medical equipment and supplies after usage among the relevant parties, named Medical-Waste Chain. It consists of four components: medical equipment and supplies, waste centers, recycling plants, and sorting factories. Medical-Waste Chain integrates blockchain-based Hyperledger Fabric technology with decentralized storage of medical equipment and supply information, and securely shares related data with stakeholders. We present the system design, along with the interactions among the stakeholders, to ensure the minimization of medical waste generation. We evaluate the performance of the proposed solution using system-wide timing and latency analysis based on the Hyperledger Caliper engine. Our system is developed based on the hybrid-blockchain system, so it is fully scalable for both on-chain and off-chain-based extensions. Moreover, the participants do not need to pay any fees to use and upgrade the system. To encourage future use of Medical-Waste Chain, we also share a proof-of-concept on our Github repository

Medical-Waste Chain: A Medical Waste Collection, Classification and Treatment Management by Blockchain Technology

To prevent the spread of the COVID-19 pandemic, 2019 has seen unprecedented demand for medical equipment and supplies. However, the problem of waste treatment has not yet been given due attention, i.e., the traditional waste treatment process is done independently, and it is not easy to share the necessary information. Especially during the COVID-19 pandemic, the interaction between parties is minimized to limit infections. To evaluate the current system at medical centers, we also refer to the traditional waste treatment processes of four hospitals in Can Tho and Ho Chi Minh cities (Vietnam). Almost all hospitals are handled independently, lacking any interaction between the stakeholders. In this article, we propose a decentralized blockchain-based system for automating waste treatment processes for medical equipment and supplies after usage among the relevant parties, named Medical-Waste Chain. It consists of four components: medical equipment and supplies, waste centers, recycling plants, and sorting factories. Medical-Waste Chain integrates blockchain-based Hyperledger Fabric technology with decentralized storage of medical equipment and supply information, and securely shares related data with stakeholders. We present the system design, along with the interactions among the stakeholders, to ensure the minimization of medical waste generation. We evaluate the performance of the proposed solution using system-wide timing and latency analysis based on the Hyperledger Caliper engine. Our system is developed based on the hybrid-blockchain system, so it is fully scalable for both on-chain and off-chain-based extensions. Moreover, the participants do not need to pay any fees to use and upgrade the system. To encourage future use of Medical-Waste Chain, we also share a proof-of-concept on our Github repository

Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration

Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. REGISTRATION: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921