Second-dose intravenous thrombolysis with tenecteplase in alteplase-resistant medium-vessel-occlusion strokes: A retrospective and comparative study.

INTRODUCTION: In intracranial medium-vessel occlusions (MeVOs), intravenous thrombolysis (IVT) shows inconsistent effectiveness and endovascular interventions remains unproven. We evaluated a new therapeutic strategy based on a second IVT using tenecteplase for MeVOs without early recanalization post-alteplase. PATIENTS AND METHODS: This retrospective, comparative study included consecutively low bleeding risk MeVO patients treated with alteplase 0.9 mg/kg at two stroke centers. One center used a conventional single-IVT approach; the other applied a dual-IVT strategy, incorporating a 1-h post-alteplase MRI and additional tenecteplase, 0.25 mg/kg, if occlusion persisted. Primary outcomes were 24-h successful recanalization for efficacy and symptomatic intracranial hemorrhage (sICH) for safety. Secondary outcomes included 3-month excellent outcomes (modified Rankin Scale score of 0-1). Comparisons were conducted in the overall cohort and a propensity score-matched subgroup. RESULTS: Among 146 patients in the dual-IVT group, 103 failed to achieve recanalization at 1 h and of these 96 met all eligible criteria and received additional tenecteplase. Successful recanalization at 24 h was higher in the 146 dual-IVT cohort patients than in the 148 single-IVT cohort patients (84% vs 61%, p < 0.0001), with similar sICH rate (3 vs 2, p = 0.68). Dual-IVT strategy was an independent predictor of 24-h successful recanalization (OR, 2.7 [95% CI, 1.52-4.88]; p < 0.001). Dual-IVT cohort patients achieved higher rates of excellent outcome (69% vs 44%, p < 0.0001). Propensity score matching analyses supported all these associations. CONCLUSION: In this retrospective study, a dual-IVT strategy in selected MeVO patients was associated with higher odds of 24-h recanalization, with no safety concerns. However, potential center-level confounding and biases seriously limit these findings' interpretation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05809921.

An Analgesic Technique for Orogastric Tube Insertion in Newborns: DOLATSONG, a Randomized Multicentric Controlled Trial.

BACKGROUND: Gastric tube insertion is necessary to support early enteral feeding of newborns during their neonatal intensive care stay. This frequent and invasive procedure is known to be painful. Very few analgesic techniques (sweet solutions, sucking, swaddling, and skin-to-skin contact) are available to reduce the pain caused by orogastric tube insertion procedure. OBJECTIVE: To determine whether a new orogastric tube insertion technique modifies the pain response in newborns, we hypothesize that inserting an orogastric tube through the nipple of a bottle reduces pain caused by this procedure. DESIGN: Prospective, controlled, randomized, multicentered and open label study. SETTINGS: Three neonatal intensive care units in France (2 level 3 units and 1 level 2B). PARTICIPANTS: Full-term or premature newborns at 32 weeks of gestation or more, postnatal age between 48 hours and 21 days, not ventilated and requiring enteral feeding, were randomized into 2 groups: usual technique (n = 36) and experimental technique (n = 35). METHODS: Our experimental technique was to insert the orogastric tube through a modified nipple of a bottle. This method was compared with the usual technique of inserting the tube directly into the newborn's mouth without a support to guide it accompanied by a nipple encouraging sucking with a nonnutritive solution. An association of nonnutritive sucking and orally administered 30% glucose was given to all children for analgesic purposes. Pain during the orogastric tube insertion was assessed on video recordings by 2 independent experts, using a heteroassessment behavioral scale for pain (DAN-Douleur Aiguë du Nouveau-né; APN-Acute Pain in Newborns). The primary outcome was an Acute Pain in Newborns score of less than 3 at the time of the procedure. Comparisons were made using Fisher exact test or Mann-Whitney U test. Factors associated with an Acute Pain in Newborns score of 3 and greater were explored using univariable and multivariable regression models. RESULTS: All but 1 video recording in each group were analyzed. Among the 34 neonates in the experimental group, 71.4% (95% CI: [53.7-85.4]) had an Acute Pain in Newborns score of less than 3 during orogastric tube insertion versus 41% (95% CI: [27.9-61.9]) in the control group (P = .031). Gagging was frequent and nonsignificantly different between the 2 groups (69% in the control group, 51% in the experimental group, P = .13). In multivariable analysis, the experimental technique was an independent factor of pain prevention compared with the usual technique (odds ratio = 0.21 [0.06-0.71], P = .015). CONCLUSIONS: This study suggests that a simple, inexpensive, and feasible technique of orogastric tube insertion through the nipple of a bottle limits pain associated with this procedure in newborns.

Implementation of lung ultrasonography by general practitioners for lower respiratory tract infections: a feasibility study.

OBJECTIVE: To evaluate the feasibility of lung ultrasonography (LUS) performed by novice users' general practitioners (GPs) in diagnosing lower respiratory tract infections (LRTIs) in primary health care settings. DESIGN: A prospective interventional multicenter study (December 2019-March 2020). SETTINGS AND SUBJECTS: Patients aged >3 months, suspected of having LRTI consulting in three different general practices (GPs) (rural, semirural and urban) in France. MAIN OUTCOME MEASURES: Feasibility of LUS by GPs was assessed by (1) the proportion of patients where LUS was not performed, (2) technical breakdowns, (3) interpretability of images by GPs, (4) examination duration and (5) patient perception and acceptability. RESULTS: A total of 151 patients were recruited, and GPs performed LUS for 111 (73.5%) patients (LUS group). In 99.1% (n = 110) of cases, GPs indicated that they were able to interpret images. The median [IQR] exam duration was 4 [3-5] minutes. LRTI was diagnosed in 70.3% and 60% of patients in the LUS and no-LUS groups, respectively (p = .43). After LUS, GPs changed their diagnosis from 'other' to 'LRTI' in six cases (+5.4%, p < .001), prescribed antibiotics for five patients (+4.5%, p = .164) and complementary chest imaging for 10 patients (+9%, p < .001). Patient stress was reported in 1.8% of cases, 81.7% of patients declared that they better understood the diagnosis, and 82% of patients thought that the GP diagnosis was more reliable after LUS. CONCLUSIONS: LUS by GPs using handheld devices is a feasible diagnostic tool in primary health care for LRTI symptoms, demonstrating both effectiveness and positive patient reception. TRIAL REGISTRATION NUMBER: Clinicaltrial.gov: NCT04602234, 20/10/2020.

Treatment times, functional outcome, and hemorrhage rates after switching to tenecteplase for stroke thrombolysis: Insights from the TETRIS registry.

Introduction: The encouraging efficacy and safety data on intravenous thrombolysis with tenecteplase in ischemic stroke and its practical advantages motivated our centers to switch from alteplase to tenecteplase. We report its impact on treatment times and clinical outcomes. Methods: We retrospectively analyzed clinical and procedural data of patients treated with alteplase or tenecteplase in a comprehensive (CSC) and a primary stroke center (PSC), which transitioned respectively in 2019 and 2018. Tenecteplase enabled in-imaging thrombolysis in the CSC. The main outcomes were the imaging-to-thrombolysis and thrombolysis-to-puncture times. We assessed the association of tenecteplase with 3-month functional independence and parenchymal hemorrhage (PH) with multivariable logistic models. Results: We included 795 patients, 387 (48.7%) received alteplase and 408 (51.3%) tenecteplase. Both groups (tenecteplase vs alteplase) were similar in terms of age (75 vs 76 years), baseline NIHSS score (7 vs 7.5) and proportion of patients treated with mechanical thrombectomy (24.1% vs 27.5%). Tenecteplase patients had shorter imaging-to-thrombolysis times (27 vs 36 min, p < 0.0001) mainly driven by patients treated in the CSC (22 vs 38 min, p < 0.001). In the PSC, tenecteplase patients had shorter thrombolysis-to-puncture times (84 vs 95 min, p = 0.02), reflecting faster interhospital transfer for MT. 3-month functional independence rate was higher in the tenecteplase group (62.8% vs 53.4%, p < 0.01). In the multivariable analysis, tenecteplase was significantly associated with functional independence (ORa 1.68, 95% CI 1.15-2.48, p < 0.01), but not with PH (ORa 0.68, 95% CI 0.41-1.12, p = 0.13). Conclusion: Switch from alteplase to tenecteplase reduced process times and may improve functional outcome, with similar safety profile.

Evaluation of Iodine Supplementation in Pregnant Women with Gestational Diabetes: IODIAB Study.

BACKGROUND: Iodine supplementation is indicated by the French National Authority for Health (HAS) and the World Health Organization (WHO) during pregnancy. This study investigates whether this supplementation is consistently prescribed in line with WHO recommendations in pregnant women diagnosed with gestational diabetes mellitus. METHOD: A total of 99 women with a diagnosis of gestational diabetes were included in the study and were all closely monitored. RESULTS: Only 17 (17.2%) patients received the recommended iodine supplementation. The follow-up, whether conducted by a gynecologist or midwife, did not influence the prescription of iodine supplements. By contrast, 72 (72.7%) of patients received folic acid supplementation. CONCLUSIONS: The prescription of iodine supplementation for the pregnant women included in our study is insufficient. Few practitioners seem aware of the recommendations, even when the pregnancy is complicated by gestational diabetes.

Post-healing follow-up study of patients in remission for diabetic foot ulcers Pied-REM study.

The rate of recurrence for diabetic foot ulcer (DFU) is 50% at 2 years Armstrong DG, 2017. International recommendations call for regular monitoring to prevent DFU recurrence. We aim to investigate the relation between post-healing follow-up and recurrence rates. The study will begin in November 2021 and end in April 2022; final study results are scheduled for December 2022. The purpose of the study is to evaluate the benefit of the multidisciplinary follow-up of healed DFU patients at the rate of two annual consultations and its impact on foot wound recurrence.

Impact of the Rapid Normalization of Chronic Hyperglycemia on the Receptor Activator of Nuclear Factor-Kappa B Ligand and the Osteoprotegerin System in Patients Living with Type 2 Diabetes: RANKL-GLYC Study.

The RANKL-GLYC study aims to explore the impact of the rapid correction of chronic hyperglycemia on the receptor activator of nuclear factor-kappa B ligand (RANKL) and its antagonist osteoprotegerin (OPG). RANKL and OPG are considered the main factors in the pathophysiology of Charcot neuroarthropathy, a devastating complication of the joints that remains poorly understood. The study began recruiting patients in September 2021 and ends in June 2022; the final study results are scheduled for January 2023.

Comparison of Biological Agent Monotherapy and Associations Including Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis: Literature Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: Update the available evidence comparing biologic disease-modifying antirheumatic drugs (bDMARDs) in combination with conventional synthetic disease-modifying antirheumatic drugs (CsDMARDs) to bDMARDs in monotherapy in patients with rheumatoid arthritis. METHODS: Research was limited to randomized controlled trials. Major outcome: ACR 20 response criteria at 24 weeks. SECONDARY OUTCOMES: clinical and radiographic criteria at week 24, 52 and 104. RESULTS: 23 trials (6358 patients), including seven bDMARDs and one other molecule: Anbainuo (anti-TNF-R). No study satisfied our search criteria for anakinra, certolizumab and infliximab. Compared to bDMARD monotherapy, combination therapy gives a better ACR 20 at 24 weeks (RR: 0.88 (0.84-0.94)) in fixed and random effect models, and this result is sustained at 52 and 104 weeks. The results were mostly similar for all other outcomes without increasing the risk of adverse effects. CONCLUSION: This meta-analysis confirms the superiority of combination therapy over monotherapy in rheumatoid arthritis, in accordance to the usual guidelines.

Functional Outcome, Recanalization, and Hemorrhage Rates After Large Vessel Occlusion Stroke Treated With Tenecteplase Before Thrombectomy.

BACKGROUND AND OBJECTIVES: To investigate in routine care the efficacy and safety of IV thrombolysis (IVT) with tenecteplase prior to mechanical thrombectomy (MT) in patients with large vessel occlusion acute ischemic strokes (LVO-AIS), either secondarily transferred after IVT or directly admitted to a comprehensive stroke center (CSC). METHODS: We retrospectively analyzed clinical and procedural data of patients treated with 0.25 mg/kg tenecteplase within 270 minutes of LVO-AIS who underwent brain angiography. The main outcome was 3-month functional independence (modified Rankin Scale score ≤2). Recanalization (revised Treatment in Cerebral Ischemia score 2b-3) was evaluated before (pre-MT) and after MT (final). RESULTS: We included 588 patients (median age 75 years [interquartile range (IQR) 61-84]; 315 women [54%]; median NIH Stroke Scale score 16 [IQR 10-20]), of whom 520 (88%) were secondarily transferred after IVT. Functional independence occurred in 47% (n = 269/570; 95% confidence interval [CI] 43.0-51.4) of patients. Pre-MT recanalization occurred in 120 patients (20.4%; 95% CI 17.2-23.9), at a similar rate across treatment paradigms (direct admission, n = 14/68 [20.6%]; secondary transfer, n = 106/520 [20.4%]; p > 0.99) despite a shorter median IVT to puncture time in directly admitted patients (38 [IQR 23-55] vs 86 [IQR 70-110] minutes; p < 0.001). Final recanalization was achieved in 492 patients (83.7%; 95%CI 80.4-86.6). Symptomatic intracerebral hemorrhage occurred in 2.5% of patients (n = 14/567; 95% CI 1.4-4.1). DISCUSSIONS: Tenecteplase before MT is safe, effective, and achieves a fast recanalization in everyday practice in patients secondarily transferred or directly admitted to a CSC, in line with published results. These findings should encourage its wider use in bridging therapy. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that tenecteplase within 270 minutes of LVO-AIS increases the probability of functional independence.

Rapid glycemic regulation in poorly controlled patients living with diabetes, a new associated factor in the pathophysiology of Charcot's acute neuroarthropathy.

OBJECTIVE: Aggressive antidiabetic therapy and rapid glycemic control are associated with diabetic neuropathy. Here we investigated if this is also the case for Charcot neuroarthropathy. RESEARCH DESIGN AND METHODS: HbA1c levels and other relevant data were extracted from medical databases of 44 cases of acute Charcot neuroarthropathy. RESULTS: HbA1c levels significantly declined from 8.25% (67mmol/mol) [7.1%-9.4%](54-79mmol/mol), at -6 months (M-6), to 7.40%(54mmol/mol) [6.70%-8.03%] (50-64 mmol/mol) during the six months preceding the diagnosis of Charcot neuroarthropathy (P <0.001). CONCLUSIONS: HbA1c levels significantly declined during the six months preceding the onset of Charcot neuroarthropathy. This decline seems to be a associated factor with the appearance of an active phase of Charcot neuroarthropathy in poorly controlled patients with diabetic sensitive neuropathy.

Multifocal (tarsus and knee) activation of neuroarthropathy following rapid glycaemic correction.

OBJECTIVE: To report a case of neuroarthropathy in the tarsus and knee following rapid glycaemic normalisation in a female patient with type I diabetes. METHODS: A retrospective review of case notes. RESULTS: We describe the case of a female patient with type I diabetes who had developed a multifocal neuroarthropathy in only six months, probably due to a rapid glycaemic normalisation. The onset of this neuroarthropathy was not only fast but mostly multifocal affecting two levels of joints. CONCLUSION: The link between the onset of multifocal neuroarthropathy and the rapid correction of chronic hyperglycaemia is probably proven in our case. Patients with chronic hyperglycaemia with sensitive neuropathy should benefit from a gradual correction of their glycaemic imbalance in order to avoid the apparition of neuroarthropathy.

Decision to deploy coronary reperfusion is not affected by the volume of ST-segment elevation myocardial infarction patients managed by prehospital emergency medical teams.

OBJECTIVE: Mortality in patients with ST-segment elevation myocardial infarction (STEMI) has been associated with the volume of activity of percutaneous coronary intervention (PCI) facilities. This observational study investigated whether the coronary reperfusion-decision rate is associated with the volume of activity in a prehospital emergency setting. METHODS: Prospectively collected data for the period 2003-2013 were extracted from a regional registry of all STEMI patients handled by eight dispatch centers (SAMUs) in and around Paris [41 mobile ICU (MICUs)]. A possible association between volume of activity (number of STEMIs) and coronary reperfusion-decision rate, and subsidiarily between volume of activity and choice of technique (fibrinolysis vs. primary PCI), were investigated. Explanatory factors (patient age, sex, delay between pain onset and first medical contact, and access to a PCI facility) were analyzed in a multivariate analysis. RESULTS: Overall, 18 162 patients; male/female 3.5/1; median age 62 (52-72) years were included in the analysis. The median number of STEMIs per MICU was 339 (IQ 220-508) and that of reperfusion-decisions was 94% (91-95). There was no association between the decision rate and the number of STEMIs (P = 0.1). However, the decision rate was associated with age, sex, delay, and access to a PCI facility (P < 0.0001) in a highly significant way. Fibrinolysis was a more frequent option for low-volume (remoter PCI facilities) than high-volume MICUs (30 vs. 16%). CONCLUSION: The decision of coronary reperfusion in a prehospital emergency setting depended on patient characteristics, delay between pain onset and first medical contact, and access to a PCI facility, but not on volume of activity. Promoting fibrinolysis use in underserved areas might help increase the reperfusion-decision rate.

Pattern of improvement in upper limb pointing task kinematics after a 3-month training program with robotic assistance in stroke.

BACKGROUND: When exploring changes in upper limb kinematics and motor impairment associated with motor recovery in subacute post stroke during intensive therapies involving robot-assisted training, it is not known whether trained joints improve before non-trained joints and whether target reaching capacity improves before movement accuracy. METHODS: Twenty-two subacute stroke patients (mean delay post-stroke at program onset 63 ± 29 days, M2) underwent 50 ± 17 (mean ± SD) 45-min sessions of robot-assisted (InMotion™) shoulder/elbow training over 3 months, in addition to conventional occupational therapy. Monthly evaluations (M2 to M5) included Fugl-Meyer Assessment (FM), with subscores per joint, and four robot-based kinematic measures: mean target distance covered, mean velocity, direction accuracy (inverse of root mean square error from straight line) and movement smoothness (inverse of mean number of zero-crossings in the velocity profile). We assessed delays to reach statistically significant improvement for each outcome measure. RESULTS: At M5, all clinical and kinematic parameters had markedly improved: Fugl-Meyer, +65% (median); distance covered, +87%; mean velocity, +101%; accuracy, +134%; and smoothness, +96%. Delays to reach statistical significance were M3 for the shoulder/elbow Fugl-Meyer subscore (+43%), M4 for the hand (+80%) and M5 for the wrist (+133%) subscores. For kinematic parameters, delays to significant improvements were M3 for distance (+68%), velocity (+65%) and smoothness (+50%), and M5 for accuracy (+134%). CONCLUSIONS: An intensive rehabilitation program combining robot-assisted shoulder/elbow training and conventional occupational therapy was associated with improvement in shoulder and elbow movements first, which suggests focal behavior-related brain plasticity. Findings also suggested that recovery of movement quantity related parameters (range of motion, velocity and smoothness) might precede that of movement quality (accuracy). TRIAL REGISTRATION: EudraCT 2016-005121-36 . Date of Registration: 2016-12-20. Date of enrolment of the first participant to the trial: 2009-11-24 (retrospective data).

Preparing Drugs for Infusion Via Syringe Pump: A Key Step to Ensure Homogeneous Concentration.

OBJECTIVE: Preparation of drug solutions used with electronic syringe infusion pumps plays a crucial role in the delivery of an accurate drug concentration. Is there a correlation between drug concentrations during syringe pump infusion and preparation protocols? METHOD: Norepinephrine, insulin, and sufentanil were prepared in 3 different ways: (1) the drug was taken from the vial, then the solvent was added followed by an air bubble, and mixing was performed by turning the syringe top-to-bottom in a 180° shaking movement 5 consecutive times; (2) the drug was taken from the vial, then the solvent was added and not mixed; and (3) the solvent was taken from a stock solution, then the drug was added and not mixed. Concentrations of drugs were determined at different times during administration by reverse-phase high-performance liquid chromatography with ultraviolet detection. All analyses were performed in triplicate and were based on measurement of peak areas. RESULTS: With no shaking of the syringe, the concentration of the injected drugs varies widely. In any case, mixing of the syringe contents by turning the syringe in a top-to-bottom 180° shaking movement 5 times with an air bubble would ensure administration of the drug at a constant concentration. CONCLUSIONS: Without mixing, the concentrations of all drug solutions varied widely when administered via an electronic syringe infusion pump. Mixing syringe contents should be made part of the compulsory curriculum for administering medications at all levels of medical education. (Critical Care Nurse. 2016;36[4]:36-45).