A systematic review of the evidence supporting post-operative antithrombotic use following cardiopulmonary bypass in children with CHD

Objectives: To determine the optimal antithrombotic agent choice, timing of initiation, dosing and duration of therapy for paediatric patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: We used PubMed and EMBASE to systematically review the existing literature of clinical trials involving antithrombotics following cardiac surgery from 2000 to 2020 in children 0–18 years. Studies were assessed by two reviewers to ensure they met eligibility criteria. Results: We identified 10 studies in 1929 children across three medications classes: vitamin K antagonists, cyclooxygenase inhibitors and indirect thrombin inhibitors. Four studies were retrospective, five were prospective observational cohorts (one of which used historical controls) and one was a prospective, randomised, placebo-controlled, double-blind trial. All included were single-centre studies. Eight studies used surrogate biomarkers and two used clinical endpoints as the primary endpoint. There was substantive variability in response to antithrombotics in the immediate post-operative period. Studies of warfarin and aspirin showed that laboratory monitoring levels were frequently out of therapeutic range (variably defined), and findings were mixed on the association of these derangements with bleeding or thrombotic events. Heparin was found to be safe at low doses, but breakthrough thromboembolic events were common. Conclusion: There are few paediatric prospective randomised clinical trials evaluating antithrombotic therapeutics post-cardiac surgery; most studies have been observational and seldom employed clinical endpoints. Standardised, validated endpoints and pragmatic trial designs may allow investigators to determine the optimal drug, timing of initiation, dosing and duration to improve outcomes by limiting post-operative morbidity and mortality related to bleeding or thrombotic events.

DELAYED ORAL FEEDING IN PATIENTS OF SALVAGE LARYNGECTOMY AND ITS EFFECT ON DEVELOPMENT OF PHARYNGOCUTANEOUS FISTULA

Objective: Pharyngocutaneous fistula (PCF) is a complication of post radiotherapy total laryngectomy. Early post operative feeding is a risk factor for development of PCF. Delayed oral feeding (DOF) and inserting a nasogastric tube has been considered a safe practice among head and neck surgeons, and there is no general agreement on the timing of initiation of the oral intake. This study compared the effect of EOF and DOF on PCF formation. Study Design: Prospective case-controlled trial. Place and Duration of Study: Combined Military Hospital Rawalpindi, from Apr 2019 to Jul 2020. Methodology: Non-probability convenience sampling was done for both groups. The patients were not matched and were assigned to either EOF or DOF alternately. EOF was defined as feeding at seventh post operative day and DOF criterion was feeding on fourteenth post operative day. The primary outcome was development of PCF within the 30th post operative day. A total of 20 patients with prior radiotherapy for laryngeal cancer who presented with recurrence of carcinoma were included in the study. Same technique closure of neopharynx was done in all cases of laryngectomy. Results: Overall PCF frequency was 20% (4/20). In EOF group, 30% (3/10) of patients developed PCF whereas 10% (1/10) of patients in DOF developed PCF. However, the difference in outcome of two groups was not statistically significant. Conclusion: DOF in cases of Salvage total laryngectomy is a safe practice and it might help to reduce the frequency of pharyngocutaneous fistula.

When did the North Anatolian fault reach southern Marmara, Turkey?

We dated syntectonic calcites on fault planes from the southern branch of the western North Anatolian fault (NAF) in northern Turkey using U-Th geochronology. We selected strike-slip faults that are kinematically related to the current regional strain field. The isotopic ages cluster around different periods during the past ~700 k.y. The most prominent cluster peak of 510.5 ± 9.5 ka (1σ) is consistent with the maximum cumulative strike-slip offset data and tectonic plate motions measured by GPS data, highlighting the fact that the present configuration of the NAF in the southern Marmara region started at ca. 500 ka or earlier. These new isotopic ages, combined with previous considerations of regional tectonics, reveal that faulting along the western NAF initiated primarily in the southern Marmara region at least a few hundred thousand years earlier than the timing suggested for the northern branch of the western NAF. This study presents an innovative approach to constrain the timing of initiation of currently active fault segments along the NAF in southern Marmara. U-Th geochronology of fault-hosted calcite thus has a wide application in determining absolute ages of fault episodes in wider shear zones along plate boundaries.

“Fear of stopping” vs “wanting to get off the medication”: exploring women’s experiences of using domperidone as a galactagogue - a qualitative study

Background Domperidone is the most frequently prescribed medicine used to increase breast milk supply. There is considerable controversy surrounding the use of domperidone in lactation, due to limited evidence about efficacy and concerns about rare but life-threatening side-effects. Despite this, in many high-income settings such as Australia, use of domperidone among breastfeeding mothers appears to be increasing. The aim of this paper was to explore women’s experiences of using domperidone during breastfeeding. Methods Semi-structured interviews were conducted in 2019 with 15 women in Australia who reported using domperidone as a galactagogue during breastfeeding. Interviews were recorded, transcribed and analysed thematically. Results Women reported a wide variety of practices concerning the timing of initiation of domperidone use, including prophylactic use, as well as the dose and duration of use. Prolonged periods of use and unsupervised dosing were commonly reported, these practices were sometimes associated with a fear of the consequences of stopping, insufficient provision of information about the drug or feeling dismissed by health professionals. Some women indicated that when doctors refused to prescribe domperidone they responded by doctor shopping and seeking anecdotal information about benefits and risks online, leading to unsupervised practices. Women often reported high expectations surrounding the effectiveness of domperidone, and most used the medication in conjunction with food/herbal galactagogues and non-galactagogue support. Positive outcomes following domperidone use included having greater confidence in breastfeeding and pride at achieving breastfeeding goals. Conclusions This study identified a variety of practices concerning domperidone use, including potentially unsafe practices, linked in some cases to inconsistent advice from health professionals and a reliance on online, anecdotal information sources. These findings emphasise the urgent need for development of clinical practice guidelines and a greater focus on translating existing evidence concerning domperidone into clinical practice, including clinical support that is tailored to women’s needs.

Timing of Initiation of Calcineurin Inhibitors in Pediatric Haploidentical Transplantation with Post-Transplantation Cyclophosphamide: Effects on Survival, Relapse, and Cytokine Release Syndrome

Background: The use of unmanipulated haploidentical stem cell transplantations (haplo-HSCT) with post-transplant cyclophosphamide (PTCY) in children has emerged as an acceptable alternative to the patients without a matched donor. However, the timing of calcineurin inhibitors (CNI) used in combination with PTCY is increasingly becoming a topic of controversy. Method: We evaluated 49 children with acute leukemia who underwent unmanipulated haplo-HSCT with PTCY according to the initiation day of CNIs (pre- or post-CY). Results: There were no significant differences in the overall survival analysis between the two groups. The cumulative incidence of relapse at 2 years was 21.2% in the pre-CY group and 38.9% in the post-CY group (p=0.33). Cytokine release syndrome (CRS) was observed more frequently in the post-CY group (p=0.04). The OS and EFS at 2 years in patients with and without CRS in the pre-Cy group were 42.9% vs 87.5% (p=0.04) and 38.1% vs 87.5% (p=0.04), respectively. Conclusion: Our study shows that the argument for starting CNI administration after CY is tenuous, and the rationale for not starting CNI before CY needs to be reconsidered.

Anticoagulation after Spontaneous Intraparenchymal Hemorrhage in Patients with Mechanical Heart Valves and Concomitant Atrial Fibrillation

Aim Patients with mechanical heart valves and coexisting atrial fibrillation (AFib-MHV) who suffer an intraparenchymal hemorrhage (IPH, defined as bleeding solely within the brain parenchyma and/or ventricle) are at a high risk of thromboembolism without anticoagulation. Data are lacking regarding the safety of early re-initiation of anticoagulation in these patients. Patients and Methods We performed a descriptive, single-institution retrospective analysis of patients with AFib-MHV who suffered a non-traumatic, supratentorial IPH between July 2013 and June 2017. We analyzed the patients and IPH characteristics, anticoagulation and antiplatelet use, the occurrence of thrombotic and hemorrhage complications, and discharge disposition. We described the timing of initiation of anticoagulation and outcomes after IPH while in-patient. Results Six patients with AFib-MHV suffered a spontaneous IPH. Four were initiated on anticoagulation prior to discharge, of whom two were initiated within 3 days post-hemorrhage. These patients suffered no bleeding complications and were discharged home with a modified Rankin Scale of 1. Conclusion Patients with AFib-MHV who suffer a spontaneous IPH are a rare population to study. Further studies to guide the management of restarting anticoagulation in this select population are warranted.

Efficacy versus abundancy: which vaccination schemes can better prohibit deaths and active infections?

In this paper, we introduce a general novel compartmental model accounting for the effects of vaccine efficacy, deployment rates and timing of initiation of deployment. It consists of compartments corresponding to susceptible, vaccinated susceptible, infectious, vaccinated infectious, active, and dead populations with various vaccine efficacies and vaccination deployment rates.We simulate different scenarios and initial conditions, and we find that the abundance and higher rate of deployment of low efficacy vaccines would lower the cumulative number of deaths in comparison to slower deployment of high efficacy vaccines. However, the latter can lower the number of active cases and achieve faster and higher herd immunity. We also forecast that, at the same daily deployment rate, the earlier introduction of vaccination schemes with lower efficacy would also lower the number of deaths with respect to a delayed introduction of high efficacy vaccines, which can however, still achieve lower numbers of infections and better herd immunity.

Evaluation and Comparison of the Maxillary Palatal Volume of the Unilateral Cleft Lip and Palate Cases Treated with and without Presurgical Naso-Alveolar Molding as Compared to the Non-Cleft Children – A 3D DVT Study

BACKGROUND Cleft individuals have a significant altered growth of the craniofacial structures since birth. The treatments available for infants are mostly associated with controversies regarding timing of initiation, types & timing in surgery, grafting etc. Maxilla is affected in all three dimensions; due to surgery alone or in conjugation with the infant orthopaedics, intrinsic growth retardation or combination of all. Considering the current conflict over the use of pre-surgical nasoalveolar molding (PNAM) and to evaluate the efficacy of PNAM technique, this postdoctoral research was done to compare the maxillary palatal volume in unilateral cleft lip and palate (UCLP) cases treated with and without PNAM as compared to non-cleft individuals. METHODS This is an observational cross-sectional study. The palate alveolar volume was assessed and analysed using 3D-DVT angiography machine. RESULTS There was significant difference between cleft group and non-cleft individuals. The cases treated with PNAM had lesser palatal volume. CONCLUSIONS Restrictive effect on maxilla was evident in PNAM cases, but this altered growth could also be an amalgamation of numerous factors like surgery, infant orthopaedics, and intrinsic growth. Therefore, judicious use, current concepts, and biomechanics of PNAM is the need of an hour. KEY WORDS Maxillary Palatal Volume, Unilateral Cleft Cases, Presurgical Naso-Alveolar Molding, 3D-DVT