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

Study of the Agreement of the Apnea&ndash;Hypopnea Index Measured Simultaneously by Pressure Transducer via Respiratory Polygraphy and by Thermistor via Polysomnography in Real Time with the Same Individuals

Background: Obstructive sleep apnea (OSA) is a common disorder and can lead to many severe complications; however, the majority of patients remain undiagnosed. Although polysomnography (PSG) remains the gold standard of diagnosis, it is usually uncomfortable and costly for patients. Purpose: The study aims to assess the agreement of the AHI measured by polygraphy (PG) (Philips Alice NightOne) with that of polysomnography (Philips Alice PDx) simultaneously recorded in-lab. Methods: A total of 11 voluntary participants over 18 years old underwent one night of simultaneous PSG and PG recording in sleep laboratories. Studied parameters (AHI, OAI, CAI, MAI, and minSpO2) were analyzed and reported by the Philips Sleepware G3 software. PSG and PG results were scored by qualified staff. Results: In terms of AHI, the mean AHI derived from PG was different from that of PSG&mdash;7.78 and 2.37 events/h, respectively. A Bland&ndash;Altman analysis of the AHI on PSG versus PG showed a mean difference of 5.41; limits of agreement (equal to &plusmn;2 standard deviations) were from &minus;6.74 to 17.56. The Bland&ndash;Altman analysis showed a slight difference between the two methods, with a mean difference of &minus;0.12 events/h in CAI, 1.35 events/h in OAI, and 0.42 events/h in MAI. Conclusions: In the population with a low suspicion of OSA, the PG showed a low agreement with the simultaneous PSG in the sleep lab. Therefore, PG should only be used as a screening method. Further studies with sufficient sensors in the expanded populations of OSA are needed

Study of the Agreement of the Apnea–Hypopnea Index Measured Simultaneously by Pressure Transducer via Respiratory Polygraphy and by Thermistor via Polysomnography in Real Time with the Same Individuals

Background: Obstructive sleep apnea (OSA) is a common disorder and can lead to many severe complications; however, the majority of patients remain undiagnosed. Although polysomnography (PSG) remains the gold standard of diagnosis, it is usually uncomfortable and costly for patients. Purpose: The study aims to assess the agreement of the AHI measured by polygraphy (PG) (Philips Alice NightOne) with that of polysomnography (Philips Alice PDx) simultaneously recorded in-lab. Methods: A total of 11 voluntary participants over 18 years old underwent one night of simultaneous PSG and PG recording in sleep laboratories. Studied parameters (AHI, OAI, CAI, MAI, and minSpO2) were analyzed and reported by the Philips Sleepware G3 software. PSG and PG results were scored by qualified staff. Results: In terms of AHI, the mean AHI derived from PG was different from that of PSG—7.78 and 2.37 events/h, respectively. A Bland–Altman analysis of the AHI on PSG versus PG showed a mean difference of 5.41; limits of agreement (equal to ±2 standard deviations) were from −6.74 to 17.56. The Bland–Altman analysis showed a slight difference between the two methods, with a mean difference of −0.12 events/h in CAI, 1.35 events/h in OAI, and 0.42 events/h in MAI. Conclusions: In the population with a low suspicion of OSA, the PG showed a low agreement with the simultaneous PSG in the sleep lab. Therefore, PG should only be used as a screening method. Further studies with sufficient sensors in the expanded populations of OSA are needed

Study of Nasal Fractional Exhaled Nitric Oxide (FENO) in Children with Allergic Rhinitis

(1) Background: Exhaled nitric oxide (NO) has been considered as a biomarker of airway inflammation. The measurement of fractional exhaled NO (FENO) is a valuable test for assessing local inflammation in subjects with allergic rhinitis (AR). (2) Objective: To evaluate (a) the correlation between nasal FENO with anthropometric characteristics, symptoms of AR and nasal peak flows in children without and with AR; and (b) the cut-off of nasal FENO for diagnosis of AR in symptomatic children. (3) Methods: The study was a descriptive and cross-sectional study in subjects with and without AR &lt; 18 years old. All clinical and functional characteristics of the study subjects were recorded for analysis. They were divided into healthy subjects for the control group and subjects with AR who met all inclusion criteria. (4) Results: 100 subjects (14 ± 3 years) were included, including 32 control subjects and 68 patients with AR. Nasal FENO in AR patients was significantly higher than in control subjects: 985 ± 232 ppb vs. 229 ± 65 ppb (p &lt; 0.001). In control subjects, nasal FENO was not correlated with anthropometric characteristics and nasal inspiratory or expiratory peak flows (IPF or EPF) (p &gt; 0.05). There was a correlation between nasal FENO and AR symptoms in AR patients and nasal IPF and EPF (p = 0.001 and 0.0001, respectively). The cut-off of nasal FENO for positive AR diagnosis with the highest specificity and sensitivity was ≥794 ppb (96.7% and 92.6%, respectively). (5) Conclusion: The use of nasal FENO as a biomarker of AR provides a useful tool and additional armamentarium in the management of allergic rhinitis

Personalized Medicine and Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a common disease that is often under-diagnosed and under-treated in all ages. This is due to differences in morphology, diversity in clinical phenotypes, and differences in diagnosis and treatment of OSA in children and adults, even among individuals of the same age. Therefore, a personalized medicine approach to diagnosis and treatment of OSA is necessary for physicians in clinical practice. In children and adults without serious underlying medical conditions, polysomnography at sleep labs may be an inappropriate and inconvenient testing modality compared to home sleep apnea testing. In addition, the apnea–hypopnea index should not be considered as a single parameter for making treatment decisions. Thus, the treatment of OSA should be personalized and based on individual tolerance to sleep-quality-related parameters measured by the microarousal index, harmful effects of OSA on the cardiovascular system related to severe hypoxia, and patients’ comorbidities. The current treatment options for OSA include lifestyle modification, continuous positive airway pressure (CPAP) therapy, oral appliance, surgery, and other alternative treatments. CPAP therapy has been recommended as a cornerstone treatment for moderate-to-severe OSA in adults. However, not all patients can afford or tolerate CPAP therapy. This narrative review seeks to describe the current concepts and relevant approaches towards personalized management of patients with OSA, according to pathophysiology, cluster analysis of clinical characteristics, adequate combined therapy, and the consideration of patients’ expectations

Guillain–Barré Syndrome due to COVID-19 Vero Cell Vaccination Associated with Concomitant COVID-19 Infection-induced ARDS and Treated Successfully by Therapeutic Plasma Exchange: A First Case Report from Vietnam

Abstract Post-vaccination adverse reactions have been reported with varying symptoms and severity owing to research and production time pressures during the coronavirus disease 2019 (COVID-19) pandemic. In this article, we report a rare case of Guillain–Barré syndrome (GBS) in a patient with COVID-19 with acute respiratory distress syndrome (ARDS) after receiving Sinopharm's Vero Cell vaccine (China). The patient who was initially negative for COVID-19 was diagnosed with GBS based on paralysis that developed from the lower extremities to the upper extremities, as confirmed by cytoalbuminologic dissociation in the cerebrospinal fluid. The patient's condition worsened with ARDS caused by COVID-19 infection during the hospital stay, and SpO2 decreased to 83% while receiving oxygen through a non-rebreather mask (15 l/min) on day 6. The patient was treated with standard therapy for severe COVID-19, invasive mechanical ventilation, and five cycles of therapeutic plasma exchange (TPE) with 5% albumin replacement on day 11 due to severe progression. The patient was weaned off the ventilator on day 28, discharged on day 42, and was completely healthy after 6 months without any neurological sequelae until now. Our report showed the potential of TPE for GBS treatment in critically ill patients with COVID-19 after COVID-19 vaccination

Predictive Factors of Mortality in Patients with Severe COVID-19 Treated in the Intensive Care Unit: A Single-Center Study in Vietnam

Abstract Introduction The fourth outbreak of COVID-19 with the delta variant in Vietnam was very fierce due to the limited availability of vaccines and the lack of healthcare resources. During that period, the high mortality of patients with severe and critical COVID-19 caused many concerns for the health system, especially the intensive care units. This study aimed to analyze the predictive factors of death and survival in patients with severe and critical COVID-19. Methods We conducted a cross-sectional and descriptive study on 151 patients with severe and critical COVID-19 hospitalized in the Intensive Care Unit of Binh Duong General Hospital. Results Common clinical symptoms of severe and critical COVID-19 included shortness of breath (97.4%), fatigue (89.4%), cough (76.8%), chest pain (47.7%), loss of smell (48.3%), loss of taste (39.1%), and headache (21.2%). The abnormal biochemical features were leukopenia (2.1%), anemia, thrombocytopenia (18%), hypoxia with low PaO2 (34.6%), hypocapnia with reduced PaCO2 (29.6%), and blood acidosis (18.4%). Common complications during hospitalization were septic shock (15.2%), cardiogenic shock (5.3%), and embolism (2.6%). The predictive factors of death were being female, age > 65 years, cardiovascular comorbidity, thrombocytopenia (< 137.109/l), and hypoxia at inclusion or after the first week or blood acidosis (pH < 7.28). The use of a high dose of corticosteroids reduced the mortality during the first 3 weeks of hospitalization but significantly increased risk of death after 3 and 4 weeks. Conclusions Common clinical symptoms, laboratory features, and death-related complications of critical and severe COVID-19 patients were found in Vietnamese patients during the fourth wave of the COVID-19 pandemic. The results of this study provide new insight into the predictive factors of mortality for patients with severe and critical COVID-19

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

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BackgroundEstimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period.Methods22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution.FindingsGlobal all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations.InterpretationGlobal adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic