Beta-Blocker Interruption or Continuation after Myocardial Infarction.

BACKGROUND: The appropriate duration of treatment with beta-blocker drugs after a myocardial infarction is unknown. Data are needed on the safety and efficacy of the interruption of long-term beta-blocker treatment to reduce side effects and improve quality of life in patients with a history of uncomplicated myocardial infarction. METHODS: In a multicenter, open label, randomized, noninferiority trial conducted at 49 sites in France, we randomly assigned patients with a history of myocardial infarction, in a 1:1 ratio, to interruption or continuation of beta-blocker treatment. All the patients had a left ventricular ejection fraction of at least 40% while receiving long-term beta-blocker treatment and had no history of a cardiovascular event in the previous 6 months. The primary end point was a composite of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons at the longest follow-up (minimum, 1 year), according to an analysis of noninferiority (defined as a between-group difference of <3 percentage points for the upper boundary of the two-sided 95% confidence interval). The main secondary end point was the change in quality of life as measured by the European Quality of Life-5 Dimensions questionnaire. RESULTS: A total of 3698 patients underwent randomization: 1846 to the interruption group and 1852 to the continuation group. The median time between the last myocardial infarction and randomization was 2.9 years (interquartile range, 1.2 to 6.4), and the median follow-up was 3.0 years (interquartile range, 2.0 to 4.0). A primary-outcome event occurred in 432 of 1812 patients (23.8%) in the interruption group and in 384 of 1821 patients (21.1%) in the continuation group (risk difference, 2.8 percentage points; 95% confidence interval [CI], <0.1 to 5.5), for a hazard ratio of 1.16 (95% CI, 1.01 to 1.33; P = 0.44 for noninferiority). Beta-blocker interruption did not seem to improve the patients' quality of life. CONCLUSIONS: In patients with a history of myocardial infarction, interruption of long-term beta-blocker treatment was not found to be noninferior to a strategy of beta-blocker continuation. (Funded by the French Ministry of Health and ACTION Study Group; ABYSS ClinicalTrials.gov number, NCT03498066; EudraCT number, 2017-003903-23.).

Flecainide to Prevent Atrial Arrhythmia after Patent Foramen Ovale Closure, the AFLOAT Study: A Randomized Clinical Trial.

BACKGROUND: The real incidence of atrial arrhythmia (AA) after patent foramen ovale (PFO) closure and whether this complication can be prevented remain unknown. This study assessed if flecainide is effective to prevent AA during the first 3 months after PFO closure, and if 6 months treatment by flecainide is more effective than 3 months to prevent AA after PFO closure. METHODS: AFLOAT is a prospective, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the endpoints (PROBE design). Patients were randomized in a 1:1:1 ratio after PFO closure to receive flecainide (150 mg once a day in a sustained-release (SR) dose) for 3 months, flecainide (150 mg od SR dose) for 6 months, or no additional treatment (standard-of-care) for 6 months. The primary endpoint was the percentage of patients with at least one episode AA (≥30s) recorded within 3 months after PFO closure on long-term monitoring with an insertable cardiac monitor (ICM). The secondary endpoint was the percentage of patients with at least one episode of AA (≥30s) recorded with ICM during the 3-6 months period after PFO closure. RESULTS: 186 patients were included (mean age 54 years, male 68.8%) and AA (≥30s) occurred in 53 (28.5%) patients during the 6-month follow-up; 86.8% of these AA events occurred in the first month after PFO closure. The primary outcome occurred in 33/123 (26.8%) and 16/63 (25.4%) patients receiving flecainide for at least 3 months or standard of care, respectively [Risk Difference (RD) 1.4%; 95% confidence interval (CI) -12.9% to 13.8%, NS]. The secondary endpoint occurred in 3/60 (5.0%), 4/63 (6.3%), and 5/63 (7.9%) patients receiving flecainide 6 months, 3 months or standard of care, respectively [RD -2.9%; 95% CI -12.7% to 6.9%, and RD -1.6%; 95% CI -11.8% to 8.6%, respectively]. CONCLUSIONS: In the first 6 months following successful PFO closure, AA (≥30s) occurred in 28.5% of cases, mostly in the first month after the procedure. Flecainide did not prevent AA after PFO closure.

Comparison Between Lung Ultrasonography Score in the Emergency Department and Clinical Outcomes of Patients With or With Suspected COVID-19: An Observational Multicentric Study.

OBJECTIVE: Chest CT is the reference test for assessing pulmonary injury in suspected or diagnosed COVID-19 with signs of clinical severity. This study aimed to evaluate the association of a lung ultrasonography score and unfavorable clinical evolution at 28 days. METHODS: The eChoVid is a multicentric study based on routinely collected data that was conducted in 8 emergency units in France; patients were included between March 19, 2020 and April 28, 2020 and underwent lung ultrasonography, a short clinical assessment by 2 emergency physicians blinded to each other's assessment, and chest CT. Lung ultrasonography consisted of scoring lesions from 0 to 3 in 8 chest zones, thus defining a global score (GS) of severity from 0 to 24. The primary outcome was the association of lung damage severity as assessed by the GS at day 0 and patient status at 28 days. Secondary outcomes were comparing the performance between GS and CT scan and the performance between a new trainee physician and an ultrasonography expert in scores. RESULTS: For the 328 patients analyzed, the GS showed good performance in predicting clinical worsening at 28 days (area under the receiver operating characteristic curve [AUC] 0.83, sensitivity 84.2%, specificity 76.4%). The GS showed good performance in predicting the CT severity assessment (AUC 0.84, sensitivity 77.2%, specificity 83.7%). CONCLUSION: A lung ultrasonography GS is a simple tool that can be used in the emergency department to predict unfavorable assessment at 28 days in patients with COVID-19.

Impact of preprocedural TIMI flow on clinical outcome in low-risk patients with ST-elevation myocardial infarction: Results from the ATLANTIC study.

OBJECTIVES: This study sought to analyze the impact of the preprocedural thrombolysis in myocardial infarction (TIMI) flow on clinical outcome in patients with ST-elevation myocardial infarction (STEMI). BACKGROUND: Previous studies have shown that the TIMI flow 0/1 prior to primary percutaneous coronary intervention (PCI) is associated with a poor clinical outcome. However, it is unclear whether the same is true in patients with ongoing STEMI of less than 6 hr duration, rapid reperfusion, and modern guideline-adherent therapy. METHODS: The ATLANTIC study compared prehospital versus inhospital treatment with ticagrelor in patients with acute STEMI. For this analysis, patients were divided into three groups according to the preprocedural TIMI flow grade of the infarct vessel: TIMI 0/1, TIMI 2, and TIMI 3. RESULTS: From a total of 1,680 patients, 1,113 had TIMI 0/1, 279 TIMI 2, and 288 TIMI 3 flow before primary PCI. At 30 days, the composite ischemic endpoint (5.5, 2.9, and 2.1%, p < .05) and all-cause death (3.0, 1.4, and 2.1%, p = .30) were highest in patients with TIMI flow 0/1. After adjustment, preprocedural TIMI flow <3 (versus 3) was not an independent predictor of major adverse ischemic events within 30 days (odds ratio 1.89, 95% confidence interval 0.74-4.85). However, definite stent thrombosis occurred only in patients with initial TIMI flow 0/1 (1.0%). Among these patients, those with prehospital administration of ticagrelor were less often affected (0.3% vs. 1.3%, p < .05). CONCLUSION: In this post-hoc analysis, preprocedural TIMI flow was not independently associated with a higher rate of adverse ischemic events.

Determinants of Transmission Risk During the Late Stage of the West African Ebola Epidemic.

Understanding risk factors for Ebola transmission is key for effective prediction and design of interventions. We used data on 860 cases in 129 chains of transmission from the latter half of the 2013-2016 Ebola epidemic in Guinea. Using negative binomial regression, we determined characteristics associated with the number of secondary cases resulting from each infected individual. We found that attending an Ebola treatment unit was associated with a 38% decrease in secondary cases (incidence rate ratio (IRR) = 0.62, 95% confidence interval (CI): 0.38, 0.99) among individuals that did not survive. Unsafe burial was associated with a higher number of secondary cases (IRR = 1.82, 95% CI: 1.10, 3.02). The average number of secondary cases was higher for the first generation of a transmission chain (mean = 1.77) compared with subsequent generations (mean = 0.70). Children were least likely to transmit (IRR = 0.35, 95% CI: 0.21, 0.57) compared with adults, whereas older adults were associated with higher numbers of secondary cases. Men were less likely to transmit than women (IRR = 0.71, 95% CI: 0.55, 0.93). This detailed surveillance data set provided an invaluable insight into transmission routes and risks. Our analysis highlights the key role that age, receiving treatment, and safe burial played in the spread of EVD.

Pre-hospital administration of ticagrelor in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: A sub-analysis of the ATLANTIC trial.

OBJECTIVE: We investigated, in the contemporary era of ST-elevation myocardial infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on cardiovascular outcomes, and whether pre-hospital administration of ticagrelor may affect these outcomes in a subgroup of STEMI patients with DM. BACKGROUND: DM patients have high platelet reactivity and a prothrombotic condition which highlight the importance of an effective antithrombotic regimen in this high-risk population. METHODS: In toal 1,630 STEMI patients enrolled in the ATLANTIC trial who underwent primary percutaneous coronary intervention (PCI) were included. Multivariate analysis was used to explore the association of DM with outcomes and potential treatment-by-diabetes interaction was tested. RESULTS: A total of 214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor myocardial reperfusion as reflected by less frequent ST-segment elevation resolution (≥70%) after PCI (OR 0.59, 95% CI 0.43-0.82, P < 0.01) and was an independent predictor of the composite 30-day outcomes of death/new myocardial infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80, 95% CI 1.62-4.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08-5.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54-28.22, P < 0.01). No significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor administration and DM was present for the clinical, electrocardiographic and angiographic outcomes as well as for thrombolysis in myocardial infarction major bleeding. CONCLUSIONS: DM remains independently associated with poor myocardial reperfusion and worse 30-day clinical outcomes. No significant interaction was found between pre-hospital vs in-hospital ticagrelor administration and DM status. Further approaches for the treatment of DM patients are needed. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.

Thrombus aspiration and prehospital ticagrelor administration in ST-elevation myocardial infarction: Findings from the ATLANTIC trial.

BACKGROUND: The potential interactions between prehospital (pre-H) ticagrelor administration and thrombus aspiration (TA) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) have never been studied. Therefore, we evaluated the potential benefit of TA and pre-H ticagrelor treatment in patients enrolled in the ATLANTIC trial (NCT01347580). METHODS: This analysis included 1,630 patients who underwent primary PCI. Multivariate analysis was used to explore the potential association of TA and pre-H treatment to clinical outcomes. Potential interactions between TA and pre-H ticagrelor were also explored. RESULTS: A total of 941 (57.7%) patients underwent TA. In adjusted multivariate logistic model, pre-H ticagrelor treatment was significantly associated with less frequent new MI or definite stent *thrombosis (ST) (odds ratio [OR] 0.43, 95% CI 0.20-0.92, P=.031), or definite ST (OR 0.26, 95% CI 0.07-0.91, P=.036) at 30 days. Patients treated with TA had higher frequency of Thrombolysis in Myocardial Infarction (TIMI) flow 0-1 compared with no-TA group (80.7% vs 51.9%, P<.0001). TA when also adjusted for TIMI flow 0-1 showed significant association only for higher bailout use of glycoprotein IIb/IIIa inhibitors (OR 1.72, 95% CI 1.18-2.50, P=.004) and more frequent 30-day TIMI major bleeding (OR 2.92, 95% CI 1.10-7.76, P=.032). No significant interactions between TA and pre-H ticagrelor were present for the explored end points. CONCLUSIONS: TA when left to physicians' discretion was used in high-risk patients, was associated with bailout use of glycoprotein IIb/IIIa inhibitors and TIMI major bleeding, and had no impact on 30-day clinical outcomes. Conversely, pre-H ticagrelor treatment predicted lower 30-day rates of ST or new MI without interaction with TA.

Duration of ischemia and treatment effects of pre- versus in-hospital ticagrelor in patients with ST-segment elevation myocardial infarction: Insights from the ATLANTIC study.

BACKGROUND: Among patients with STEMI in the ATLANTIC study, pre-hospital administration of ticagrelor improved post-PCI ST-segment resolution and 30-day stent thrombosis. We investigated whether this clinical benefit with pre-hospital ticagrelor differs by ischemic duration. METHODS: In a post hoc analysis we compared absence of ST-segment resolution post-PCI and stent thrombosis at 30 days between randomized treatment groups (pre- versus in-hospital ticagrelor) stratified by symptom onset to first medical contact (FMC) duration [≤1 hour (n = 773), >1 to ≤3 hours (n = 772), and >3 hours (n = 311)], examining the interaction between randomized treatment strategy and duration of symptom onset to FMC for each outcome. RESULTS: Patients presenting later after symptom onset were older, more likely to be female, and have higher baseline risk. Patients with symptom onset to FMC >3 hours had the greatest improvement in post-PCI ST-segment elevation resolution with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 2.9% vs. >1 to ≤3 hours, 3.6% vs. >3 hours, 12.2%; adjusted p for interaction = 0.13), while patients with shorter duration of ischemia had greater improvement in stent thrombosis at 30 days with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 1.3% vs. >1 hour to ≤3 hours, 0.7% vs. >3 hours, 0.4%; adjusted p for interaction = 0.55). Symptom onset to active ticagrelor administration was independently associated with stent thrombosis at 30 days (adjusted OR 1.89 per 100 minute delay, 95%CI 1.20-2.97, P < .01), but not post-PCI ST-segment resolution (P = .41). CONCLUSIONS: The effect of pre-hospital ticagrelor to reduce stent thrombosis was most evident when given early within 3 hours after symptom onset, with delay in ticagrelor administration after symptom onset associated with higher rate of stent thrombosis. These findings re-emphasize the need for early ticagrelor administration in primary PCI treated STEMI patients.

Stopping or continuing clopidogrel 12 months after drug-eluting stent placement: the OPTIDUAL randomized trial.

AIM: This open-label, randomized, and multicentre trial tested the hypothesis that, on a background of aspirin, continuing clopidogrel would be superior to stopping clopidogrel at 12 months following drug-eluting stent (DES) implantation. METHODS AND RESULTS: Patients (N = 1799) who had undergone placement of ≥1 DES for stable coronary artery disease or acute coronary syndrome were included in 58 French sites (January 2009-January 2013). Patients (N = 1385) free of major cardiovascular/cerebrovascular events or major bleeding and on aspirin and clopidogrel 12 months after stenting were eligible for randomization (1:1) between continuing clopidogrel 75 mg daily (extended-dual antiplatelet therapy, DAPT, group) or discontinuing clopidogrel (aspirin group). The primary outcome was net adverse clinical events defined as the composite of death, myocardial infarction, stroke, or major bleeding. Follow-up was planned from a minimum of 6 to a maximum of 36 months after randomization. Owing to slow recruitment, the study was stopped after enrolment of 1385 of a planned 1966 patients. Median follow-up after stenting was 33.4 months. The primary outcome occurred in 40 patients (5.8%) in the extended-DAPT group and 52 in the aspirin group (7.5%; hazard ratio 0.75, 95% confidence interval 0.50-1.28; P = 0.17). Rates of death were 2.3% in the extended-DAPT group and 3.5% in the aspirin group (HR 0.65, 95% CI 0.34-1.22; P = 0.18). Rates of major bleeding were identical (2.0%, P = 0.95). CONCLUSIONS: Extended DAPT did not achieve superiority in reducing net adverse clinical events compared to 12 months of DAPT after DES placement. The power of the OPTIDUAL trial was however low and reduced by premature termination of enrolment. CLINICALTRIALSGOV NUMBER: NCT00822536.

Artificial Intelligence for Detecting Acute Fractures in Patients Admitted to an Emergency Department: Real-Life Performance of Three Commercial Algorithms.

RATIONALE AND OBJECTIVES: Interpreting radiographs in emergency settings is stressful and a burden for radiologists. The main objective was to assess the performance of three commercially available artificial intelligence (AI) algorithms for detecting acute peripheral fractures on radiographs in daily emergency practice. MATERIALS AND METHODS: Radiographs were collected from consecutive patients admitted for skeletal trauma at our emergency department over a period of 2 months. Three AI algorithms-SmartUrgence, Rayvolve, and BoneView-were used to analyze 13 body regions. Four musculoskeletal radiologists determined the ground truth from radiographs. The diagnostic performance of the three AI algorithms was calculated at the level of the radiography set. Accuracies, sensitivities, and specificities for each algorithm and two-by-two comparisons between algorithms were obtained. Analyses were performed for the whole population and for subgroups of interest (sex, age, body region). RESULTS: A total of 1210 patients were included (mean age 41.3 ± 18.5 years; 742 [61.3%] men), corresponding to 1500 radiography sets. The fracture prevalence among the radiography sets was 23.7% (356/1500). Accuracy was 90.1%, 71.0%, and 88.8% for SmartUrgence, Rayvolve, and BoneView, respectively; sensitivity 90.2%, 92.6%, and 91.3%, with specificity 92.5%, 70.4%, and 90.5%. Accuracy and specificity were significantly higher for SmartUrgence and BoneView than Rayvolve for the whole population (P < .0001) and for subgroups. The three algorithms did not differ in sensitivity (P = .27). For SmartUrgence, subgroups did not significantly differ in accuracy, specificity, or sensitivity. For Rayvolve, accuracy and specificity were significantly higher with age 27-36 than ≥53 years (P = .0029 and P = .0019). Specificity was higher for the subgroup knee than foot (P = .0149). For BoneView, accuracy was significantly higher for the subgroups knee than foot (P = .0006) and knee than wrist/hand (P = .0228). Specificity was significantly higher for the subgroups knee than foot (P = .0003) and ankle than foot (P = .0195). CONCLUSION: The performance of AI detection of acute peripheral fractures in daily radiological practice in an emergency department was good to high and was related to the AI algorithm, patient age, and body region examined.

Obstetric referrals, complications and health outcomes in maternity wards of large hospitals during the COVID-19 pandemic: a mixed methods study of six hospitals in Guinea, Nigeria, Uganda and Tanzania.

OBJECTIVES: The COVID-19 pandemic affected provision and use of maternal health services. This study describes changes in obstetric complications, referrals, stillbirths and maternal deaths during the first year of the pandemic and elucidates pathways to these changes. DESIGN: Prospective observational mixed-methods study, combining monthly routine data (March 2019-February 2021) and qualitative data from prospective semi-structured interviews. Data were analysed separately, triangulated during synthesis and presented along three country-specific pandemic periods: first wave, slow period and second wave. SETTING: Six referral maternities in four sub-Saharan African countries: Guinea, Nigeria, Tanzania and Uganda. PARTICIPANTS: 22 skilled health personnel (SHP) working in the maternity wards of various cadres and seniority levels. RESULTS: Percentages of obstetric complications were constant in four of the six hospitals. The percentage of obstetric referrals received was stable in Guinea and increased at various times in other hospitals. SHP reported unpredictability in the number of referrals due to changing referral networks. All six hospitals registered a slight increase in stillbirths during the study period, the highest increase (by 30%-40%) was observed in Uganda. Four hospitals registered increases in facility maternal mortality ratio; the highest increase was in Guinea (by 158%), which had a relatively mild COVID-19 epidemic. These increases were not due to mortality among women with COVID-19. The main pathways leading to these trends were delayed care utilisation and disruptions in accessing care, including sub-optimal referral linkages and health service closures. CONCLUSIONS: Maternal and perinatal survival was negatively affected in referral hospitals in sub-Saharan Africa during COVID-19. Routine data systems in referral hospitals must be fully used as they hold potential in informing adaptations of maternal care services. If combined with information on women's and care providers' needs, this can contribute to ensuring continuation of essential care provision during emergency.

A mixed-methods study of maternal health care utilisation in six referral hospitals in four sub-Saharan African countries before and during the COVID-19 pandemic.

INTRODUCTION: In sub-Saharan Africa, referral hospitals are important sources of key maternal health services, especially during a crisis such as the COVID-19 pandemic. This study prospectively assessed the effect of the COVID-19 pandemic on maternal health service utilisation in six large referral hospitals in Guinea, Nigeria, Tanzania and Uganda during the first year of the pandemic. METHODS: Mixed-methods design combining three data sources: (1) quantitative data based on routine antenatal, childbirth and postnatal care data collected March 2019-February 2021, (2) qualitative data from recurring rounds of semi-structured interviews conducted July 2020-February 2021 with 22 maternity skilled heath personnel exploring their perceptions of service utilisation and (3) timeline data of COVID-19 epidemiology, global, national and hospital-level events. Qualitative and quantitative data were analysed separately, framed based on the timeline analysis and triangulated when reporting. RESULTS: Three periods including a first wave, slow period and second wave were identified. Maternal health service utilisation was lower during the pandemic compared with the prepandemic year in all but one selected referral hospital. During the pandemic, service utilisation was particularly lower during the waves and higher or stable during the slow period. Fear of being infected in hospitals, lack of transportation, and even when available, high cost of transportation and service closures were key reasons affecting utilisation during the waves. However, community perception that the pandemic was over or insinuation by Government of the same appeared to stabilise use of referral hospitals for childbirth. CONCLUSION: Utilisation of maternal health services across the continuum of care varied through the different periods and across countries. In crisis situations such as COVID-19, restrictions and service closures need to be implemented with consideration given to alternative options for women to access and use services. Information on measures put in place for safe hospital use should be communicated to women.

Early and short-term intensive management after discharge for patients hospitalized with acute heart failure: a randomized study (ECAD-HF).

AIMS: Hospitalization for acute heart failure (HF) is followed by a vulnerable time with increased risk of readmission or death, thus requiring particular attention after discharge. In this study, we examined the impact of intensive, early follow-up among patients at high readmission risk at discharge after treatment for acute HF. METHODS AND RESULTS: Hospitalized acute HF patients were included with at least one of the following: previous acute HF < 6 months, systolic blood pressure ≤ 110 mmHg, creatininaemia ≥ 180 µmol/L, or B-type natriuretic peptide ≥ 350 pg/mL or N-terminal pro B-type natriuretic peptide ≥ 2200 pg/mL. Patients were randomized to either optimized care and education with serial consultations with HF specialist and dietician during the first 2-3 weeks, or to standard post-discharge care according to guidelines. The primary endpoint was all-cause death or first unplanned hospitalization during 6-month follow-up. Among 482 randomized patients (median age 77 and median left ventricular ejection fraction 35%), 224 were hospitalized or died. In the intensive group, loop diuretics (46%), beta-blockers (49%), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (39%) and mineralocorticoid receptor antagonists (47%) were titrated. No difference was observed between groups for the primary endpoint (hazard ratio 0.97; 95% confidence interval 0.74-1.26), nor for mortality at 6 or 12 months or unplanned HF rehospitalization. Additionally, no difference between groups according to age, previous HF and left ventricular ejection fraction was found. CONCLUSIONS: In high-risk HF, intensive follow-up early post-discharge did not improve outcomes. This vulnerable post-discharge time requires further studies to clarify useful transitional care services.

'We are not going to shut down, because we cannot postpone pregnancy': a mixed-methods study of the provision of maternal healthcare in six referral maternity wards in four sub-Saharan African countries during the COVID-19 pandemic.

INTRODUCTION: Referral hospitals in sub-Saharan Africa are located in crowded urban areas, which were often epicentres of the COVID-19 pandemic. This paper prospectively assesses how maternal healthcare was provided in six referral hospitals in Guinea, Nigeria, Tanzania and Uganda during the first year of the COVID-19 pandemic. METHODS: Mixed-methods design using three data sources: (1) qualitative data from repeated rounds of semi-structured interviews conducted between July 2020 and February 2021 with 22 maternity skilled heath personnel (SHP) on perceptions of care provision; (2) quantitative monthly routine data on caesarean section and labour induction from March 2019 to February 2021; and (3) timeline data of COVID-19 epidemiology, national and hospital-level events. Qualitative and quantitative data were analysed separately, framed based on timeline analysis, and triangulated during reporting. RESULTS: We identified three periods: first wave, slow period and second wave. The first wave was challenging for SHP given little knowledge about COVID-19, lack of infection prevention and control training, and difficulties reaching workplace. Challenges that persisted beyond the first wave were shortage of personal protective equipment and no rapid testing for women suspected with COVID-19. We noted no change in the proportion of caesarean sections during the pandemic, and a small increase in the proportion of labour inductions. All hospitals arranged isolation areas for women suspected/confirmed with COVID-19 and three hospitals provided care to women with suspected/confirmed COVID-19. Breastfeeding was not discouraged and newborns were not separated from mothers confirmed with COVID-19. Care provision was maintained through dedication of SHP, support from hospital management and remote communication between SHP. CONCLUSION: Routine maternal care provision was maintained in referral hospitals, despite first wave challenges. Referral hospitals and SHP contributed to guideline development for pregnant women suspected/confirmed with COVID-19. Maternity SHP, women and pregnancy must always be included in priority setting when responding to health system shocks, including outbreaks.

Plasma procalcitonin may be an early predictor of liver injury in acetaminophen poisoning: A prospective cohort study.

BACKGROUND AND AIMS: Acetaminophen is a common cause of poisoning and liver injury worldwide; however, patient stratification is suboptimal. We aimed to assess the contribution of admission plasma procalcitonin concentration (PCT) to better identify acetaminophen-poisoned patients likely to develop liver injury. METHODS: We conducted a prospective observational cohort study including all acetaminophen-poisoned patients requiring N-acetylcysteine admitted in a toxicological intensive care unit between 2012 and 2017. Multivariate analysis was performed using a Cox regression model to investigate factors associated with liver injury, defined as an increase in alanine aminotransferase (ALT) >100 IU/L. RESULTS: One hundred seventeen patients (age, 32 years (21-53), median [25th-75th percentiles]) were included after self-ingesting 16 g (9-30) acetaminophen and received N-acetylcysteine infusion administered within a median 6 h-delay (4-12) from exposure. Co-ingestions were reported in 77% of patients. Rumack-Matthew nomogram was non-interpretable in 47% cases. Liver injury occurred in 38 patients (32%) with a median peak ALT of 2020 IU/L (577-4248). In liver injury patients, admission PCT was significantly increased in comparison to patients without liver injury (21.5 ng/ml (3.2-44.9) versus 0.1 ng/ml (0-0.4), respectively, p < 0.01). The increase in PCT preceded the increase in ALT by 33 h (10-74). In a multivariate analysis, PCT > 1 ng/ml was significantly associated with liver injury (hazard ratio, 7.2 [95% confidence interval, 2.3-22.6; p < 0.001]). PCT (area under the receiver-operating characteristics curve, 0.91 [95%CI: 0.84-0.97]) predicted liver injury with sensitivity, specificity, negative, and positive predictive values of 0.92, 0.84, 0.96, and 0.73, respectively. CONCLUSION: PCT on admission is associated with liver injury in acetaminophen poisoning. PCT might be used as a predictive tool of liver injury to improve clinical decision-making.

Bleeding in the Elderly: Risk Factors and Impact on Clinical Outcomes After an Acute Coronary Syndrome, a Sub-study of the Randomized ANTARCTIC Trial.

BACKGROUND: Elderly patients are at high-risk of bleeding, but are under-represented in clinical trials. OBJECTIVES: The aims were to determine the incidence and the predictive factors of bleeding and to assess the impact of bleeding on further ischemic outcomes in elderly patients after acute coronary syndrome (ACS) treated with percutaneous coronary intervention. METHODS: From the 877 patients aged ≥ 75 years included in the ANTARCTIC randomized trial, data on Bleeding Academic Research Consortium (BARC) bleeding complications and major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, and stroke, were collected over 1 year. RESULTS: Clinically relevant bleeding events (BARC types 2, 3, or 5) were observed in 20.6% of patients (n = 181) at 1 year, of which, one third occurred in the first month. Anemia (adjusted hazard ratio [adj.HR] 3.98, 95% confidence interval [CI] 1.41-11.22; p = 0.009), severe chronic renal failure (adj.HR 1.83, 95% CI 1.12-2.98; p = 0.015), and femoral access (adj.HR 2.54, 95% CI 1.71-3.77; p < 0.001) were independently associated with clinically relevant bleeding events, while age > 85 years (adj.HR 2.22, 95% CI 1.14-4.30; p = 0.018) was independently associated with major bleeding events (BARC types 3 or 5). Patients with a clinically relevant bleeding event had a higher rate of MACE at 1 year (adj.HR 2.04, 95% CI 1.24-3.38; p = 0.005), with a particularly strong effect on stroke (adj.HR 5.55, 95% CI 2.04-15.06; p < 0.001). CONCLUSIONS: Clinically relevant bleeding events were observed in one out of five elderly patients undergoing stenting for an ACS and were strongly associated with further stroke occurrence. Rather than the antiplatelet therapy, comorbidities and an age > 85 years predicted bleeding outcomes in this elderly population. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01538446. https://www.clinicaltrials.gov .

No evidence of tocilizumab treatment efficacy for severe to critical SARS-CoV2 infected patients: Results from a retrospective controlled multicenter study.

ABSTRACT: To assess tocilizumab (TCZ) efficacy associated to standard of care (SOC) compared to SOC alone in severe coronavirus associated disease 2019 (COVID-19) patients. In a matched case-control study from 3 French Hospital COVID-19 Departments, 27 patients with severe COVID-19 treated with TCZ and SOC were matched for baseline epidemiological and clinical features and compared to 27 severe COVID-19 patients treated with SOC alone. Baseline characteristics of the study population were comparable between groups. Eleven patients (20%) died. TCZ was not associated with clinical improvement as compared to SOC regarding oxygen-free status (44% vs 63%) and death (18.5% vs 22%), despite a higher decrease of the C-reactive protein at Day 7 (10.7 vs 52 mg/L; P < 10-3). Compared to the 43 patients alive at the end-of follow-up, patients who died were older (78 vs 64 years; P < 10-3), with 82% of them older than 72 years vs only 23% of live patients (P < 10-3). Age (OR = 1.15; 95%CI = 1.04-1.3; P = .008) and age over 72 years (OR) = 14.85; 95%CI = 2.7-80; P = .002) were independently associated with mortality. TCZ in addition to SOC for severe COVID-19 patients did not reduce mortality, subsequent need for invasive mechanical ventilation nor did it shorten the time of oxygen support, despite better control of the inflammatory response. More powerful and randomized controlled trials are warranted to determine if TCZ is effective in the management of COVID-19.

Predictors of Left Ventricular Dysfunction in Friedreich's Ataxia in a 16-Year Observational Study.

BACKGROUND: Friedreich's ataxia (FRDA) is a cerebellar ataxia due to GAA repeat expansions in the FXN gene, and in affected patients, lower left ventricular ejection fraction (LVEF) leads to poorer prognosis. We aimed to identify patients likely to develop worsening LVEF at an early stage. METHODS: We included 115 FRDA patients aged 30 ± 10 years with 620 ± 238 GAA repeats on the shorter allele and disease onset of 15 ± 7 years. RESULTS: At baseline, left ventricular (LV) hypertrophy was present in 53%, with LVEF 65 ± 7%, LV end diastolic diameter (LVEDD) 43 ± 5 mm, septal wall thickness (SWT) 11.8 ± 2.7 mm, and posterior wall thickness 11.1 ± 2.5 mm. After a mean follow-up of 13 ± 6 years, LVEF ≤ 50% was observed in 12 patients. The main determinants of LVEF ≤ 50% were GAA repeat number on the shorter allele (odds ratio [OR] 1.007, 95% confidence interval [CI] 1.003-1.012, p = 0.002), LVEDD (OR 1.217, 95% CI 1.058-1.399, p = 0.006), and SWT (OR 1.352, 95% CI 1.016-1.799, p = 0.04). High-risk patients were predicted 5 years before LVEF ≤ 50% occurred: area under the curve of 0.91, 95% CI 0.85-0.97. Patients with GAA repeats > 800 were categorized as high risk, patients with 500 < GAA < 800 were high risk if LVEDD was ≥ 52.6 mm and SWT was ≥ 13.3 mm, and patients with GAA < 500 were low risk if LVEDD was < 52.6 mm and SWT was < 13.3 mm. CONCLUSIONS: Echocardiographic follow-up combined with size assessment of GAA repeat expansions is a powerful tool to identify patients at high risk of developing LV systolic dysfunction up to 5 years before clinical symptoms. Further studies are mandatory to investigate if these patients would benefit from cardiac interventions.

Surgical Management of Urolithiasis of the Upper Tract - Current Trend of Endourology in Africa.

Urolithiasis is a global pathology with increasing prevalence rate. The lifetime recurrence of urolithiasis ranges from 10-75% creating a public health crisis in affected regions. The epidemiology of urolithiasis in most parts of Africa and Asia remains poorly documented as incidence and prevalence rates in these settings are extrapolated from hospital admissions. The surgical management of kidney and ureteral stones is based on the stone location, size, the patient's preference and the institutional capacity. To date, the available modalities in the management of urolithiasis includes external shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), ureterorenoscopy (URS) including flexible and semirigid ureteroscopy. However, regarding the lack of endourological equipment and expertise in most parts of Sub-Saharan Africa (SSA), most urological centers in these regions still consider open surgery for kidney and ureteral stones. This review explores the current trend and surgical management of upper tract urolithiasis in SSA with insight on the available clinical guidelines.

Review of Testicular Tumor: Diagnostic Approach and Management Outcome in Africa.

Testicular cancer is a common malignancy in young males with higher incidence in developed nations but with the lowest incidence in Africa (0.3-0.6/100 000). Ironically, the global testicular cancer mortality rate has shown a reverse trend to its incidence with higher rates in low- and middle-income countries (0.5 per 100 000) than in high-income countries. Data from GLOBOCAN 2008 have shown relatively high mortality rates in sub-Saharan countries like Mali, Ethiopia, Niger and Malawi. The prognosis of testicular tumor is good with remarkable chemosensitivity to cisplatin-based regimen. Early diagnosis, careful staging and a multidisciplinary management approach is crucial to achieve this optimal result. These results are achievable in the sub-Saharan region if the relevant resources are appropriated for cancer care and clinical guidelines are formulated in a regional context.