Feasibility and Diagnostic Value of Recording Smartwatch Electrocardiograms in Neonates and Children.

OBJECTIVE: The objective of this study was to evaluate the agreement of smartwatch-derived single-lead electrocardiogram (ECG) recordings with 12-lead ECGs for diagnosing electrocardiographic abnormalities. STUDY DESIGN: A 12-lead ECG and an ECG using Apple Watch were obtained in 110 children (aged 1 week to 16 years) with normal (n = 75) or abnormal (n = 35) 12-lead ECGs (atrioventricular block [7], supraventricular tachycardia [SVT] {5}, bundle branch block [12], ventricular preexcitation [6], long QT [5]). In children aged <6 years, the ECG recording was performed with the active participation of an adult who applied the neonate or child's finger to the crown of the watch. In older children, tracings were obtained after brief teaching without adult guidance. All 12-lead ECGs were independently evaluated by 2 blinded cardiologists. Apple Watch ECGs were independently evaluated by another blinded cardiologist. RESULTS: In 109 children (99.1%), the smartwatch tracing was of sufficient quality for evaluation. Smartwatch tracings were 84% sensitive and 100% specific for the detection of an abnormal ECG. All 75 normal tracings were correctly identified. Of the 35 children with abnormalities on 12-lead ECGs, 5 (14%) were missed, most often because of baseline wander and artifacts. Rhythm disorders (atrioventricular block or SVT) and bundle branch blocks were correctly detected in most cases (11 of 12 and 11 of 12, respectively); preexcitation and long QT was detected in 4 of 6 and 4 of 5, respectively. CONCLUSION: Smartwatch ECGs recorded with parental assistance in children aged up to 6 years and independently in older children have the potential to detect clinically relevant conditions.

Implantation of a leadless pacemaker in young adults.

AIMS: Leadless pacing has emerged as an alternative to conventional transvenous pacemakers to mitigate the risks of pocket- and lead-related complications but its use remains controversial in young adults mostly because experience in this patient population is limited. We sought to examine the feasibility and safety of implanting leadless single chamber pacemakers in young adults. METHODS: This multicenter, retrospective, observational study sought to evaluate the safety, efficacy, and electrical performance of the Micra VR Transcatheter Pacemaker System (Medtronic) in patients between 18 and 40 years who underwent implantation of a leadless pacemaker for any indication at the university medical centers of Bordeaux, Clermont-Ferrand, Toulouse, and Tours (France), between 2015 and 2021. The primary safety endpoint was freedom from system-related or procedure-related major complications at 6 months. The primary efficacy endpoint was the combination of a low (≤2 V) and stable (increase within 1.5 V) pacing capture threshold at 6 months. RESULTS: Leadless pacemaker implantation was successful in all 35 patients. At 6 months, safety endpoint was met for 35 (100%) and efficacy endpoint for 34 (97%) patients. During a follow-up of 26 ± 15 months (range: 6-60 months), Safety endpoint remained 100% and efficacy endpoint was 94%. Leadless pacemaker retrieval was not required in any patient. Approximately one-third of patients (n = 13, 37%) had >40% ventricular pacing burdens at 1 year, including all 10 patients with a complete AV block but also 3 patients with normal AV conduction during implantation. One patient reported symptoms of pacemaker syndrome which was confirmed using Holter recording and successfully treated using reprogramming. CONCLUSION: In this observational study, leadless pacemakers demonstrated favorable short- and intermediate-term safety and effectiveness in young adults.

Clinical and echocardiographic evolution of patients with arrhythmogenic cardiomyopathy before heart transplantation.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterized by fibrofatty myocardial replacement, and accurate diagnosis can be challenging. The clinical course of patients expressing a severe phenotype of the disease needing heart transplantation (HTx) is not well described in the literature. Therefore, this study aims to describe the clinical and echocardiographic evolution of patients with ACM necessitating HTx. METHODS: We retrospectively studied all patients who underwent HTx in our institution between 1998 and 2019 with a definite diagnosis of ACM according to the explanted heart examination. RESULTS: Ten patients with confirmed ACM underwent HTx. Only four of them had a diagnosis of ACM before HTx. These patients were 28 ± 15 years old at the time of their first symptoms. Patients received a diagnosis of heart failure (HF) after 5.9 ± 8.7 years of symptom evolution. The mean age at transplantation was 40 ± 17 years old. All the patients experienced ventricular tachycardia (VT) at least once before their HTx and 50% were resuscitated after sudden death. The mean left ventricular ejection at diagnosis and before transplantation was similar (32% ± 21% vs. 35.0% ± 19.3%, p = NS). Right ventricular dysfunction was present in all patients at the time of transplantation. CONCLUSION: Patients with ACM necessitating HTx show a high burden of ventricular arrhythmias and frequently present a biventricular involvement phenotype, making early diagnosis challenging. HF symptoms are the most frequent reason leading to the decision to transplant.

Acute pacing threshold elevation during simultaneous Micra leadless pacemaker implantation and AV node ablation: Clinical cases, computer model and practical recommendations.

BACKGROUND: In patients with refractory atrial fibrillation (AF), atrioventricular nodal (AVN) ablation and permanent pacemaker implantation is recommended. The Micra Transcatheter Pacing System (Micra) is a single chamber leadless pacemaker (LPM) and thus offers the possibility of AV node (AVN) ablation in the same procedure. Pacing threshold (PT) elevation after radiofrequency (RF) ablation is a potential complication. METHODS: We conducted a single center retrospective cohort study. Patients implanted with a Micra (n = 84) and concomitant or delayed AVN ablation (n = 12) from 2014 to 2022 were included. Two cases of acute Micra PT elevation immediately following RF AVN ablation required device retrieval and implantation of a new Micra. Procedural characteristics and electrophysiological parameters were analyzed, and a computer model was performed to determine factors responsible for acute PT elevations. RESULTS: A total of 84 patients were included. Mean age was 74 ± 10 and 48% were women. Twelve patients (14%) underwent AVN ablation. Two patients had acute PT elevation requiring device retrieval despite no direct contact of the ablation catheter with the Micra. Computer modeling shows that significant dissipated power due to electrical field coupling can occur at the tip or ring electrode if the catheter is not kept at a safe distance (≥35 mm) from the Micra when a maximum power of 100 W is delivered. CONCLUSION: Concurrent AVN ablation and Micra implantation is safe in most patients. To prevent acute PT elevation, keeping a safe distance of ≥35 mm from the tip and ring electrodes of the Micra and using lower power output may prevent this complication.

Accuracy of stroke volume measurement with phase-contrast cardiovascular magnetic resonance in patients with aortic stenosis.

BACKGROUND: Phase contrast (PC) cardiovascular magnetic resonance (CMR) in the ascending aorta (AAo) is widely used to calculate left ventricular (LV) stroke volume (SV). The accuracy of PC CMR may be altered by turbulent flow. Measurement of SV at another site is suggested in the presence of aortic stenosis, but very few data validates the accuracy or inaccuracy of PC in that setting. Our objective is to compare flow measurements obtained in the AAo and LV outflow tract (LVOT) in patients with aortic stenosis. METHODS: Retrospective analysis of patients with aortic stenosis who had CMR and echocardiography. Patients with mitral regurgitation were excluded. PC in the AAo and LVOT were acquired to derive SV. LV SV from end-systolic and end-diastolic tracings was used as the reference measure. A difference ≥ 10% between the volumetric method and PC derived SVs was considered discordant. Metrics of turbulence and jet eccentricity were assessed to explore the predictors of discordant measurements. RESULTS: We included 88 patients, 41% with bicuspid aortic valve. LVOT SV was concordant with the volumetric method in 79 (90%) patients vs 52 (59%) patients for AAo SV (p = 0.015). In multivariate analysis, aortic stenosis flow jet angle was a strong predictor of discordant measurement in the AAo (p = 0.003). Mathematical correction for the jet angle improved the concordance from 59 to 91%. Concordance was comparable in patients with bicuspid and trileaflet valves (57% and 62% concordance respectively; p = 0.11). Accuracy of SV measured in the LVOT was not influenced by jet eccentricity. For aortic regurgitation quantification, PC in the AAo had better correlation to volumetric assessments than LVOT PC. CONCLUSION: LVOT PC SV in patients with aortic stenosis and eccentric jet might be more accurate compared to the AAo SV. Mathematical correction for the jet angle in the AAo might be another alternative to improve accuracy.

The impact of delayed treatment of uncomplicated P. falciparum malaria on progression to severe malaria: A systematic review and a pooled multicentre individual-patient meta-analysis.

BACKGROUND: Delay in receiving treatment for uncomplicated malaria (UM) is often reported to increase the risk of developing severe malaria (SM), but access to treatment remains low in most high-burden areas. Understanding the contribution of treatment delay on progression to severe disease is critical to determine how quickly patients need to receive treatment and to quantify the impact of widely implemented treatment interventions, such as 'test-and-treat' policies administered by community health workers (CHWs). We conducted a pooled individual-participant meta-analysis to estimate the association between treatment delay and presenting with SM. METHODS AND FINDINGS: A search using Ovid MEDLINE and Embase was initially conducted to identify studies on severe Plasmodium falciparum malaria that included information on treatment delay, such as fever duration (inception to 22nd September 2017). Studies identified included 5 case-control and 8 other observational clinical studies of SM and UM cases. Risk of bias was assessed using the Newcastle-Ottawa scale, and all studies were ranked as 'Good', scoring ≥7/10. Individual-patient data (IPD) were pooled from 13 studies of 3,989 (94.1% aged <15 years) SM patients and 5,780 (79.6% aged <15 years) UM cases in Benin, Malaysia, Mozambique, Tanzania, The Gambia, Uganda, Yemen, and Zambia. Definitions of SM were standardised across studies to compare treatment delay in patients with UM and different SM phenotypes using age-adjusted mixed-effects regression. The odds of any SM phenotype were significantly higher in children with longer delays between initial symptoms and arrival at the health facility (odds ratio [OR] = 1.33, 95% CI: 1.07-1.64 for a delay of >24 hours versus ≤24 hours; p = 0.009). Reported illness duration was a strong predictor of presenting with severe malarial anaemia (SMA) in children, with an OR of 2.79 (95% CI:1.92-4.06; p < 0.001) for a delay of 2-3 days and 5.46 (95% CI: 3.49-8.53; p < 0.001) for a delay of >7 days, compared with receiving treatment within 24 hours from symptom onset. We estimate that 42.8% of childhood SMA cases and 48.5% of adult SMA cases in the study areas would have been averted if all individuals were able to access treatment within the first day of symptom onset, if the association is fully causal. In studies specifically recording onset of nonsevere symptoms, long treatment delay was moderately associated with other SM phenotypes (OR [95% CI] >3 to ≤4 days versus ≤24 hours: cerebral malaria [CM] = 2.42 [1.24-4.72], p = 0.01; respiratory distress syndrome [RDS] = 4.09 [1.70-9.82], p = 0.002). In addition to unmeasured confounding, which is commonly present in observational studies, a key limitation is that many severe cases and deaths occur outside healthcare facilities in endemic countries, where the effect of delayed or no treatment is difficult to quantify. CONCLUSIONS: Our results quantify the relationship between rapid access to treatment and reduced risk of severe disease, which was particularly strong for SMA. There was some evidence to suggest that progression to other severe phenotypes may also be prevented by prompt treatment, though the association was not as strong, which may be explained by potential selection bias, sample size issues, or a difference in underlying pathology. These findings may help assess the impact of interventions that improve access to treatment.

Use of rectal artesunate for severe malaria at the community level, Zambia.

OBJECTIVE: To determine whether the administration of rectal artesunate by trained community health volunteers before referral to a health-care facility reduces the case fatality rate of severe malaria in young children in hard-to-reach communities in Zambia. METHODS: We implemented a pilot project in Serenje District between July 2017 and July 2018. The project involved: (i) training community health volunteers to administer rectal artesunate to children with suspected severe malaria and refer them to a health facility; (ii) ensuring emergency transport with bicycle ambulances was available; (iii) ensuring adequate drug supplies; and (iv) ensuring health-care workers could treat severe malaria with injectable artesunate. Surveys of health facilities, volunteers and bicycle ambulance riders were performed near the beginning and end of the intervention period. In addition, data on severe malaria cases and associated deaths were obtained from health facilities and a community monitoring system. FINDINGS: In the year before the intervention, 18 deaths occurred in 224 cases of confirmed severe malaria among children younger than 5 years seen at intervention health facilities (case fatality rate: 8%); during the intervention, 3 of 619 comparable children with severe malaria died (case fatality rate: 0.5%). CONCLUSION: The administration of pre-referral rectal artesunate treatment to young children with severe malaria by community health volunteers was feasible, safe and effective in hard-to-reach communities in Zambia and was associated with a substantial decrease in the case fatality rate. The project's approach is highly adaptable and could be used in other countries with a high malaria burden.

Prescribing patterns and compliance with World Health Organization recommendations for the management of severe malaria: a modified cohort event monitoring study in public health facilities in Ghana and Uganda.

BACKGROUND: Injectable artesunate (AS) is the World Health Organization (WHO) recommended medication for the treatment of severe malaria followed with an oral artemisinin-based combination therapy (ACT). There are few studies indicating how physicians prescribe injectable AS, injectable quinine (Q) or injectable artemether (AR) and ACT for severe malaria. This study was undertaken to evaluate prescription compliance to the WHO recommendation in 8 public health facilities in Ghana and Uganda. This was a modified cohort event monitoring study involving patients who were administered with injectable anti-malarial for treatment of presumed or confirmed severe malaria. Patients prescribed at least one dose of injectable artesunate, artemether or quinine qualified to enrol in the study. Patients were recruited at inpatient facilities and followed up in the hospital, by phone or at home. Following WHO recommendations, patients are to be prescribed 3 doses of injectable AS, Q or AR for at least 24 h followed with oral ACT. Compliance rate was estimated as the number of patient prescriptions that met the WHO recommendation for treatment of severe malaria divided by the total number of patients who completed the study by end of follow up. Log-binomial regression model was used to identify predictors for compliance. Based on the literature and limitations of available data from the patients' record, the diagnosis results, age, gender, weight, and country were considered as potential predictors of prescriber adherence to the WHO recommendations. RESULTS: A total of 1191 patients completed the study, of which 93% were prescribed injectable AS, 3.1% (injectable AR or Q) with 32.5% prescribed follow-on oral ACT and 26% on concomitant antibiotics. 391 (32.8%) were in Ghana and 800 (67.2%) in Uganda. There were 582 (48.9%) women. The median age was 3.9 years (IQR = 2, 9) and median weight was 13 kg (IQR = 10, 20). Of the 1191 patients, 329 of the prescriptions complied with the WHO recommendation (compliance rate = 27.6%; 95% CI = [25.2, 30.2]). Diagnostic results (Adjusted prevalence ratio (aPR) = 4.56; 95% = [3.42, 6.08]; p < 0.0001) and weight (20 + kg vs < 10 kg: aPR = 0.65; 95% = [0.44, 0.96]; p = 0.015) were identified as factors independently associated with compliance. CONCLUSION: Injectable AS is the most commonly prescribed medicine in the management of severe malaria in Ghana and Uganda. However, adherence to the WHO recommendation of at least 3 doses of injectable anti-malarial in 24 h followed by a full course of ACT is low, at less than 30%.

An operational comparative study of quinine and artesunate for the treatment of severe malaria in hospitals and health centres in the Democratic Republic of Congo: the MATIAS study.

BACKGROUND: The Democratic Republic of the Congo (DRC) has the highest number of severe malaria cases in the world. In early 2012, the National Malaria Control Programme (NMCP) changed the policy for treating severe malaria in children and adults from injectable quinine to injectable artesunate. To inform the scaling up of injectable artesunate nationwide, operational research is needed to identify constraints and challenges in the DRC's specific setting. METHODS: The implementation of injectable quinine treatment in 350 patients aged 2 months or older in eight health facilities from October 2012 to January 2013 and injectable artesunate in 399 patients in the same facilities from April to June 2013 was compared. Since this was an implementation study, concurrent randomized controls were not possible. Four key components were evaluated during each phase: 1) clinical assessment, 2) time and motion, 3) feasibility and acceptability, and 4) financial cost. RESULTS: The time to discharge was lower in the artesunate (median=2, 90% central range 1-9) compared to the quinine group (3 (1-9) days; p<0.001). Similarly, the interval between admission and the start of intravenous (IV) treatment (2 (0-15) compared to 3 (0-20) hours; p<0.001) and parasite clearance time (23 (11-49) compared to 24 (10-82) hours; p<0.001) were lower in the artesunate group. The overall staff pre-administration time (13 (6-38) compared to 20 (7-50) minutes; p<0.001) and the personnel time spent on patient management (9 (1-24) compared to 12 (3-52) minutes; p<0.001) were lower in the artesunate group. In hospitals and health centres, the mean (standard deviation, SD) total cost per patient treated for severe malaria with injectable artesunate was USD 51.94 (16.20) and 19.51 (9.58); and USD 60.35 (17.73) and 20.36 (6.80) with injectable quinine. CONCLUSIONS: This study demonstrates that injectable artesunate in the DRC is easier to use and it costs less than injectable quinine. These findings provide the basis for practical recommendations for rapid national deployment of injectable artesunate in the DRC.

Plasmonic nanopipette biosensor.

Integrating a SERS immunoassay on a plasmonic "patch clamp" nanopipette enabled nanobiosensing for the detection of IgG. A SERS response was obtained using a sandwich assay benefiting from plasmon coupling between a capture Au nanoparticle (AuNP) on a nanotip and a second AuNP modified with a Raman active reporter and an antibody selective for IgG. The impact of nanoparticle shape and surface coverage was investigated alongside the choice of Raman active reporter, deposition pH, and plasmonic coupling, in an attempt to fully understand the plasmonic properties of nanopipettes and to optimize the nanobiosensor for the detection of IgG. These probes will find applications in various fields due to their nanoscale size leading to the possibility of spatially and temporally addressing their location near cells to monitor secretion of biomolecules.

Evaluation of Segmentation, Rotation, and Geographic Delivery Approaches for Deployment of Multiple First-Line Treatment (MFT) to Respond to Antimalarial Drug Resistance in Africa: A Qualitative Study in Seven Sub-Sahara Countries.

BACKGROUND: Several studies recently confirmed the emergence of resistance to antimalarial drugs in sub-Saharan Africa. Multiple first-line treatment (MFT) is one of the measures envisaged to respond to the emergence and spread of this resistance. The aim of this study was to identify the perceived advantages and disadvantages of several MFT deployment strategies and to better understand potential implementation drivers and barriers. METHODS: A qualitative survey was conducted in seven sub-Saharan countries amongst key opinion leaders, national decision makers, and end users. A total of 200 individual interviews were conducted and findings were analyzed following a thematic inductive approach. RESULTS: From a policy perspective, the new MFT intervention would require endorsement at the global, national, and regional levels to ensure its inclusion in guidelines. Funding of the MFT intervention could be a bottleneck due to costs associated with additional training of healthcare workers, adaptation of drug delivery mechanisms, and higher costs of drugs. Concerning the MFT deployment strategies, a slight preference for the segmentation strategy was expressed over the rotation and geographic approaches, due to the perception that a segmentation approach is already in place at country level. CONCLUSIONS: The findings highlighted the need for a collective approach to MFT deployment through the engagement of stakeholders at all levels of malaria management.

The use of smartwatch electrocardiogram beyond arrhythmia detection.

The adoption of wearables in medicine has expanded worldwide with a rapidly growing number of consumers and new features capable of real-time monitoring of health parameters such as the ability to record and transmit a single-lead electrocardiogram (ECG). Smartwatch ECGs are increasingly used but current smartwatches only screen for atrial fibrillation (AF). Most of the literature has focused on analyzing the smartwatch ECG accuracy for the detection of AF or other tachycardias. As with the conventional ECG, this tool may be used for many more purposes than only detection of AF. The objectives of this review are to describe the published literature regarding the accuracy and clinical value of recording a smartwatch ECG in other situations than diagnosis of tachycardia and discuss possible techniques to optimize the diagnostic yield.

Left Ventricular Abnormal Substrate in Brugada Syndrome.

BACKGROUND: Slow-conductive structural abnormalities located in the epicardium of the right ventricle (RV) underlie Brugada syndrome (BrS). The extent of such substrate in the left ventricle (LV) has not been investigated. OBJECTIVES: This study sought to characterize the extent of epicardial substrate abnormalities in BrS. METHODS: We evaluated 22 consecutive patients (mean age 46 ± 11 years, 21 male) referred for recurrent ventricular arrhythmias (mean 10 ± 13 episodes) in the setting of BrS. The patients underwent clinical investigations and wide genetic screening to identify SCN5A mutations and common risk variants. High-density biventricular epicardial mapping was performed to detect prolonged (>70 ms) fragmented electrograms, indicating abnormal substrate area. RESULTS: All patients presented with abnormal substrate in the epicardial anterior RV (27 ± 11 cm2). Abnormal substrate was also identified on the LV epicardium in 10 patients (45%), 9 at baseline and 1 after ajmaline infusion, covering 15 ± 11 cm2. Of these, 4 had severe LV fascicular blocks. Patients with LV substrate had a longer history of arrhythmia (11.4 ± 6.7 years vs 4.3 ± 4.3 years; P = 0.003), longer PR (217 ± 24 ms vs 171 ± 14 ms; P < 0.001) and HV (60 ± 12 ms vs 46 ± 5 ms; P = 0.005) intervals, and abnormal substrate also extending into the inferior RV (100% vs 33%; P = 0.001). SCN5A mutation was present in 70% of patients with LV substrate (vs 25%; P = 0.035). SCN5A BrS patients with recurrent ventricular arrhythmias present a higher polygenic risk score compared with a nonselected BrS population (median of differences: -0.86; 95% CI: -1.48 to -0.27; P = 0.02). CONCLUSIONS: A subset of patients with BrS present an abnormal substrate extending onto the LV epicardium and inferior RV that is associated with SCN5A mutations and multigenic variants.

Angle-dependent resonance of localized and propagating surface plasmons in microhole arrays for enhanced biosensing.

The presence of microhole arrays in thin Au films is suited for the excitation of localized and propagating surface plasmon (SP) modes. Conditions can be established to excite a resonance between the localized and propagating SP modes, which further enhanced the local electromagnetic (EM) field. The co-excitation of localized and propagating SP modes depends on the angle of incidence (θ(exc)) and refractive index of the solution interrogated. As a consequence of the enhanced EM field, enhanced sensitivity and an improved response for binding events by about a factor of 3 to 5 was observed with SPR sensors in the Kretschmann configuration for a set of experimental conditions (λ(SPR), θ(exc), and η). Thus, microhole arrays can improve sensing applications of SPR based on classical prism-based instrumentation and are suited for SP-coupled spectroscopic techniques.

Smartwatch Electrocardiograms for Automated and Manual Diagnosis of Atrial Fibrillation: A Comparative Analysis of Three Models.

AIMS: The diagnostic accuracy of proprietary smartwatch algorithms and the interpretability of smartwatch ECG tracings may differ between available models. We compared the diagnostic potential for detecting atrial fibrillation (AF) of three commercially available smartwatches. METHODS: We performed a prospective, non-randomized, and adjudicator-blinded clinical study of 100 patients in AF and 100 patients in sinus rhythm, patients with atrial flutter were excluded. All patients underwent 4 ECG recordings: a conventional 12-lead ECG, Apple Watch Series 5®, Samsung Galaxy Watch Active 3®, and Withings Move ECG® in random order. All smartwatch ECGs were analyzed using their respective automated proprietary software and by clinical experts who also graded the quality of the tracings. RESULTS: The accuracy of automated AF diagnoses by Apple and Samsung outperformed that of Withings, which was attributable to a higher proportion of inconclusive ECGs with the latter (sensitivity/specificity: 87%/86% and 88%/81% vs. 78%/80%, respectively, p < 0.05). Expert interpretation was more accurate for Withings and Apple than for Samsung (sensitivity/specificity: 96%/86% and 94%/84% vs. 86%/76%, p < 0.05), driven by the high proportion of uninterpretable tracings with the latter (2 and 4% vs. 15%, p < 0.05). CONCLUSION: Diagnosing AF is possible using various smartwatch models. However, the diagnostic accuracy of their automated interpretations varies between models as does the quality of ECG tracings recorded for manual interpretation.

Cyanotoxin release from the benthic, mat-forming cyanobacterium Microseira (Lyngbya) wollei in the St. Lawrence River, Canada.

Benthic cyanobacterial mats occurring in the St. Lawrence River fluvial lakes Saint-Louis and Saint-Pierre are dominated by Microseira (Lyngbya) wollei which produce several cyanotoxins including LWTX-1 that is characteristic of Microseira wollei. This cyanotoxin is not only present in the filaments forming benthic mats, but was also measured in the water overlying the mats. LWTX-1 was found in all cyanobacterial filament samples (75.29-103.26 ng mg-1) and all overlying water samples (3.01-11.03 ng L-1). Toxin concentrations measured in overlying water and dry biomass were strongly correlated (r = 0.94). Furthermore, LWTX-1 concentration in water was positively correlated with the dissolved organic carbon in water (r = 0.74) and % nitrogen content in cyanobacterial filaments (r = 0.52). A preliminary study was conducted to determine the release and degradation rates of LWTX-1 from a M. wollei mat kept under laboratory conditions over a 3-month period. Toxin measurements revealed an early, massive toxin release followed by a typical decaying function, with a half-life in the order of 17 days. Our results raise concerns about the occurrence and downstream advection of dissolved cyanotoxins from Microseira mats in the aquatic environment. Graphical abstract.

Safety Experience During Real-World Use of Injectable Artesunate in Public Health Facilities in Ghana and Uganda: Outcomes of a Modified Cohort Event Monitoring Study (CEMISA).

INTRODUCTION: Injectable artesunate (Inj AS) is the World Health Organization (WHO)-recommended product for treating severe malaria. However, despite widespread usage, there are few published safety studies involving large populations in real-world settings. In this study, we sought to assess the incidence of common adverse events (AEs) following the intake of Inj AS in real-life settings. METHODS: This is a modified cohort event monitoring study involving patients who were administered with Inj AS at eight sites (four each in Ghana and Uganda) between May and December 2016. Patients were eligible for inclusion if they had severe/complicated malaria and were able and willing to participate in the study. Eligible patients were followed up by telephone or hospital or home visit on Days 7, 14, 21 and 28 after drug administration to document AEs and serious AEs (SAEs). Patients were also encouraged to report all AEs at any time during the study period. The Kaplan-Meier method was used to estimate the proportion of patients with any AEs by end of Day 28. Causality assessment was made on all AEs/SAEs using the WHO/UMC (Uppsala Monitoring Centre) causality method. RESULTS: A total of 1103 eligible patients were administered Inj AS, of which 360 patients were in Ghana and 743 in Uganda. The incidence of any AE by the end of follow-up among patients treated with AS was estimated to be 17.9% (197/1103) (95% confidence interval [CI] 15.8-20.3). The median time-to-onset of any AEs was 9 days (interquartile range (IQR) = 4, 14). The top five AEs recorded among patients treated with AS were pyrexia (3.5%), abdominal pain (2.5%), diarrhoea (1.7%), cough (1.5%) and asthenia (1.5%). Most of these top five AEs occurred in the first 14 days following treatment. Regarding the relatedness of these AEs to Inj AS, 78.9% of pyrexia (30/38), 63.0% of pain (17/27), 68.4% of diarrhoea (13/19), 85.5% of cough (14/16) and 75.0% of asthenia (12/16) were assessed as 'possibly' related. There were 17 SAEs including 13 deaths. Two of the deaths are 'possibly' related to Inj AS, as were three non-fatal SAEs: severe abdominal pain, failure of therapy and severe anaemia. CONCLUSION: The incidence of common AEs among patients treated with Inj AS in real-world settings was found to be relatively low. Future studies should consider larger cohorts to document rare AEs as well. CLINICALTRIALS. GOV IDENTIFIER: NCT02817919.

Delayed anemia after treatment with injectable artesunate in the Democratic Republic of the Congo: a manageable issue.

Cases of delayed hemolytic anemia have been described after treatment with injectable artesunate, the current World Health Organization (WHO)-recommended first-line drug for the treatment of severe malaria. A total of 350 patients (215 [61.4%] < 5 years of age and 135 [38.6%] ≥ 5 years of age) were followed-up after treatment with injectable artesunate for severe malaria in hospitals and health centers of the Democratic Republic of the Congo. Complete series of hemoglobin (Hb) measurements were available for 201 patients. A decrease in Hb levels between 2 and 5 g/dL was detected in 23 (11.4%) patients during the follow-up period. For five patients, Hb levels decreased below 5 g/dL during at least one follow-up visit. All cases of delayed anemia were clinically manageable and resolved within one month.