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

DESIGN A 2x2 COMPACT MODE SWITCHING USING MULTIMODE INTERFERENCE BASED ON SILICON MATERIAL

We propose a new design of a 2x2 optical chip for switching optical modes based on silicon material. Input lights at fundamental mode of transverse electric (TE) polarization can be selected at the output by appropriately controlling a 180-degree butterfly-shaped phase shifter. The proposed device consists of two multimode interference waveguides MMI and a phase shifter packed in a compact size of 4.2μm x 0.22μm x 110.4μm. We use 3D-BPM numerical simulation method to evaluate optical conversion efficiency of device. The result shows that insertion loss is always less than 1.5dB and crosstalk is always below -30dB in a wavelength range from 1.5  to 1.6 . Moreover, we continue to evaluate the proposed device on the system with signal’s bitrate of 35Gbps, the bit error rate is always less than 10-10 in the whole bandwidth of 100nm

All-Optical Half Adder Based on a 2x2 Multimode Interference Coupler

In this paper, an all-optical logic gate based on 2x2 (MMI) multimode interference coupler is theoretically designed and simulated using three-dimensional beam propagation method (3D-BPM) and effective index method (EIM) to analyze and evaluate the performance of the device. The proposed device is used to convert phase information of input optical signals to amplitude at the output ports of MMI. With this mechanism, the device can operates as a logical half adder. Simulation results show that the optical half adder archives with insertion loss and extinction ratio from ON to OFF logic–level below 0.7 dB and over 40 dB, respectively. Furthermore, wide bandwidth of 100nm is also an advantage of this devices. Therefore, it can be applied to all optical signal processing in next generation optical networks as well as in photonics integrated circuits

Design of Silicon TE0/TE1 Mode Router Using Mach-Zehnder and Multimode Interferometers

This paper proposes a new design of two-mode three-port optical mode router for mode division multiplexing systems. The device consists of a Mach-Zehnder interferometer (MZI) and a multimode interferometer (MMI), which utilizes silicon material for photonic integrated circuits (PIC). By setting appropriate values for the two butterfly-shaped phase shifters (PSs) at MZI and MMI, the input mode, either transverse electric (TE) modes TE0 or TE1, can be routed to the desired output among the three output ports. The device is designed and optimized via three-dimensional beam propagation method (3D BPM). The proposed device achieves very low insertion loss and small cross-talk, which are less than 0.4 dB and -24.5 dB, respectively, over the whole C band

HIV knowledge and risk behaviors among drug users in three Vietnamese mountainous provinces

Background: Globally, people who inject drugs are highly vulnerable to HIV transmission. Methadone maintenance treatment (MMT) programs are one of the most cost-effective mechanisms to substitute opioid use and improve the quality of life of patients. Since the coverage of MMT is still limited and even for those patients who are treated, improving their knowledge on HIV and maintaining healthy behaviors are key to maximizing the outcomes of HIV harm reduction programs. This study examined the knowledge on HIV, perceived risk and HIV testing among drug users accessing methadone maintenance services in three Vietnamese mountainous areas. Methods: A cross-sectional study of 300 people enrolling for MMT services in three provinces in Vietnam was conducted. The factors associated with the knowledge, attitudes, and practices of respondents about HIV/AIDS were exploited using multivariable logistic model. Results: Of the 300-people surveyed, 99% knew of HIV and 60.6% were identified as having good knowledge. While 75.2% identified that injecting drugs was a risk factor for HIV, 52.2% thought they were not at risk of HIV mainly as they did not share needles. 92.6% had undergone HIV testing with 17.4% being positive, a number which was significantly lower than Vietnam's national average for people who inject drugs. Age, ethnicity and education were associated with knowledge of HIV while ART treatment was linked to self-assessed HIV status. Conclusions: This study sheds new light on the knowledge attitudes and practices of people who inject drugs, particularly males in mountainous areas of Vietnam regarding HIV prevention. Overall, knowledge was good with most conducting safe practices towards transmission. Enhanced education and targeting of minority groups could help in increasing the numbers receiving MMT and HIV services.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Methadone maintenance treatment reduces the vulnerability of drug users on hiv/aids in vietnamese remote settings: Assessing the changes in hiv knowledge, perceived risk, and testing uptake after a 12-month follow-up

Methadone Maintenance Treatment (MMT) program has been considered a medium through which human immunodeficiency virus (HIV) risks assessment and prevention on drug use/HIV-infected population can be effectively conducted. Studies concerning the implementation of such idea on patients in remote, under-developed areas, however, have been limited. Having the clinics established in three mountainous provinces of Vietnam, this study aimed to evaluate the changes in knowledge of HIV, perceived risk, and HIV testing uptake of the patients. A longitudinal study was conducted at six MMT clinics in three provinces with a pre-and post-assessments among 300 patients. Outcomes of interest were compared between baseline and after 12 months. The magnitude of changes was extrapolated. The proportion of participants reporting that their HIV knowledge was not good fell by 4.4% (61.3% at the baseline vs. 56.8% at 12 months). The significant improvement seen was in the knowledge that needle sharing was a mode of transmission (82.7% vs. 89.6%). Nevertheless, the majority of participants reportedly considered mosquitoes/insect and eating with the HIV-infected patient were the route of transmission at both time points (84.7% vs. 89.1%, 92.2% vs. 93.3%, respectively). This study found a limited improvement in HIV knowledge and testing uptake among MMT patients following a 12-month period. It also highlighted some shortcomings in the knowledge, attitudes and practices (KAP) of these patients, in particular, incorrect identification of HIV transmission routes, among patients both at program initiation and follow-up. The findings lent support to the argument for enhancing education and counseling efforts at MMT clinics regarding HIV, as well as for improving access to preventive and health care services through the integration of MMT/HIV services.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

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