Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS): Protocol for a randomized controlled trial

Rationale Atrial fibrillation causes one-fifth of ischemic strokes, with a high risk of early recurrence. Although long-term anticoagulation is highly effective for stroke prevention in atrial fibrillation, initiation after stroke is usually delayed by concerns over intracranial hemorrhage risk. Direct oral anticoagulants offer a significantly lower risk of intracranial hemorrhage than other anticoagulants, potentially allowing earlier anticoagulation and prevention of recurrence, but the safety and efficacy of this approach has not been established. Aim Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS) will investigate whether early treatment with a direct oral anticoagulant, within four days of stroke onset, is as effective or better than delayed initiation, 7 to 14 days from onset, in atrial fibrillation patients with acute ischemic stroke. Methods and design OPTIMAS is a multicenter randomized controlled trial with blinded outcome adjudication. Participants with acute ischemic stroke and atrial fibrillation eligible for anticoagulation with a direct oral anticoagulant are randomized 1:1 to early or delayed initiation. As of December 2021, 88 centers in the United Kingdom have opened. Study outcomes The primary outcome is a composite of recurrent stroke (ischemic stroke or symptomatic intracranial hemorrhage) and systemic arterial embolism within 90 days. Secondary outcomes include major bleeding, functional status, anticoagulant adherence, quality of life, health and social care resource use, and length of hospital stay. Sample size target A total of 3478 participants assuming event rates of 11.5% in the control arm and 8% in the intervention arm, 90% power and 5% alpha. We will follow a non-inferiority gatekeeper analysis approach with a non-inferiority margin of 2 percentage points. Discussion OPTIMAS aims to provide high-quality evidence on the safety and efficacy of early direct oral anticoagulant initiation after atrial fibrillation-associated ischemic stroke. Trial registrations: ISRCTN: 17896007; ClinicalTrials.gov: NCT03759938

Influencing Factors Associated with Delayed Initiation of Insulin Among Patients with Type 2 Diabetes Mellitus at The Diabetes Clinic of a Tertiary Hospital in Ethiopia

Background Guidelines recommend the initiation of insulin in patients with type 2 diabetes mellitus who failed on maximum dose of oral medications. However, time to initiation is inconsistent due to different barriers resulting in delay and thus leads to failure to achieve glycemic control which in turn may lead to different complications. The aim of this study was to explore factors influencing the delayed initiation of insulin among patients with type 2 diabetes being managed at the Diabetes Clinic of Tikur Anbessa Specialized Hospital. Methods A qualitative descriptive study design was employed. Data was collected using in-depth interviews with 27 participants, including patients and healthcare providers. Audio-recorded data was transcribed and then thematically analyzed. Results Different factors influencing the delayed initiation of insulin in patients with type 2 diabetes mellitus were revealed. Patient factors included beliefs about the necessity of insulin and concerns related to starting insulin. Physician factors included perceived patient’s situation and lack of clinical competency. Health institution factors included inadequate laboratory set up and absence of contextual guidelines for diabetes management including insulin initiation. Conclusions The study findings indicated different influencing factors some of which were similar to those reported from other settings while there were others which somehow were unique to study setting. These are indicative of the need to implement interventions such as strengthening the patients’ diabetes health education program that is considerate of the religious, cultural, and social aspects of the society.

Delays in Infant Hearing Detection and Intervention During the COVID-19 Pandemic: Commentary

Early detection and intervention for congenital hearing loss are critical for speech and language development. Newborns should receive hearing screening, diagnosis, and intervention by 1, 3, and 6 months, respectively. The COVID-19 pandemic has caused delays in each step of this process. Increased out-of-hospital births and shortages of essential health care services likely reduced the proportion of newborns completing screening. Additional factors have contributed to delayed diagnosis. We estimate that up to 50% of infants born with hearing loss in Maryland in 2021 may be delayed in diagnosis. Hearing loss interventions have been affected due to delayed initiation, reduced availability, and lack of in-person services. Delayed diagnosis and treatment of congenital hearing loss are likely to have significant effects on individual patients and public health, the full magnitude of which will not be known for years. Opportunities exist for providers to mitigate the negative effects of COVID-19 on pediatric hearing health care.

Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock

Gpr19 encodes an evolutionarily conserved orphan G-protein-coupled receptor (GPCR) with currently no established physiological role in vivo. We characterized Gpr19 expression in the suprachiasmatic nucleus (SCN), the locus of the master circadian clock in the brain, and determined its role in the context of the circadian rhythm regulation. We found that Gpr19 is mainly expressed in the dorsal part of the SCN, with its expression fluctuating in a circadian fashion. A conserved cAMP-responsive element in the Gpr19 promoter was able to produce circadian transcription in the SCN. Gpr19−/− mice exhibited a prolonged circadian period and a delayed initiation of daily locomotor activity. Gpr19 deficiency caused the downregulation of several genes that normally peak during the night, including Bmal1 and Gpr176. In response to light exposure at night, Gpr19−/− mice had a reduced capacity for light-induced phase-delays, but not for phase-advances. This defect was accompanied by reduced response of c-Fos expression in the dorsal region of the SCN, while apparently normal in the ventral area of the SCN, in Gpr19−/− mice. Thus, our data demonstrate that Gpr19 is an SCN-enriched orphan GPCR with a distinct role in circadian regulation and may provide a potential target option for modulating the circadian clock.

Incidence and predictors of preterm neonatal mortality at Mbarara Regional Referral Hospital in South Western Uganda

Introduction Preterm neonatal mortality contributes substantially to the high neonatal mortality globally. In Uganda, preterm neonatal mortality accounts for 31% of all neonatal deaths. Previous studies have shown variability in mortality rates by healthcare setting. Also, different predictors influence the risk of neonatal mortality in different populations. Understanding the predictors of preterm neonatal mortality in the low-resource setting where we conducted our study could guide the development of interventions to improve outcomes for preterm neonates. We thus aimed to determine the incidence and predictors of mortality among preterm neonates born at Mbarara Regional Referral Hospital (MRRH) in South Western Uganda. Methods We prospectively enrolled 538 live preterm neonates born at MRRH from October 2019 to September 2020. The neonates were followed up until death or 28 days, whichever occurred first. We used Kaplan Meier survival analysis to describe preterm neonatal mortality and Cox proportional hazards regression to assess predictors of preterm neonatal mortality over a maximum of 28 days of follow up. Results The cumulative incidence of preterm neonatal mortality was 19.8% (95% C.I: 16.7–23.5) at 28 days from birth. Birth asphyxia (adjusted hazard ratio [aHR], 14.80; 95% CI: 5.21 to 42.02), not receiving kangaroo mother care (aHR, 9.50; 95% CI: 5.37 to 16.78), delayed initiation of breastfeeding (aHR, 9.49; 95% CI: 2.84 to 31.68), late antenatal care (ANC) booking (aHR, 1.81 to 2.52; 95% CI: 1.11 to 7.11) and no ANC attendance (aHR, 3.56; 95% CI: 1.51 to 8.43), vaginal breech delivery (aHR, 3.04; 95% CI: 1.37 to 5.18), very preterm births (aHR, 3.17; 95% CI: 1.24 to 8.13), respiratory distress syndrome (RDS) (aHR, 2.50; 95% CI: 1.11 to 5.64) and hypothermia at the time of admission to the neonatal unit (aHR, 1.98; 95% CI: 1.18 to 3.33) increased the risk of preterm neonatal mortality. Attending more than 4 ANC visits (aHR, 0.35; 95% CI: 0.12 to 0.96) reduced the risk of preterm neonatal mortality. Conclusions We observed a high cumulative incidence of mortality among preterm neonates born at a low-resource regional referral hospital in Uganda. The predictors of mortality among preterm neonates were largely modifiable factors occurring in the prenatal, natal and postnatal period (lack of ANC attendance, late ANC booking, vaginal breech delivery, birth asphyxia, respiratory distress syndrome, and hypothermia at the time of admission to the neonatal unit, not receiving kangaroo mother care and delayed initiation of breastfeeding). These findings suggest that investment in and enhancement of ANC attendance, intrapartum care, and the feasible essential newborn care interventions by providing the warm chain through kangaroo mother care, encouraging early initiation of breastfeeding, timely resuscitation for neonates when indicated and therapies reducing the incidence and severity of RDS could improve outcomes among preterm neonates in this setting.

Association of methicillin resistance with mortality of hospital-acquired Staphylococcus aureus bacteremia

Objective Methicillin-resistant (MR) Staphylococcus aureus bacteremia (SAB) is associated with higher mortality rates than methicillin-susceptible (MS) SAB. This study assessed potential predictors of mortality and evaluated the association of methicillin resistance with mortality in patients with SAB. Methods We conducted a retrospective cohort study in patients with hospital-acquired SAB, from 2009 to 2018. Clinical features of patients with MR-SAB were compared with those of patients with MS-SAB and predictors of 30-day mortality were determined using Cox regression analysis. Results Among 162 patients, 56.8% had MR-SAB. Overall 30-day mortality was 19.1%; MR-SAB had higher mortality (25.0%) than MS-SAB (11.4%). Univariate analysis highlighted long-term hospitalization, prior antibiotics use, and delayed initiation of appropriate antibiotics as risk factors. Cox regression analysis showed that respiratory tract source, Pitt bacteremia score, Charlson comorbidity index, and appropriate antibiotic therapy within 24 hours were independently and significantly associated with 30-day mortality outcome. Conclusions Methicillin resistance was not an independent risk factor for mortality in patients with SAB. Early, appropriate antibiotic treatment is an important prognostic factor.

Abstract 1122‐000147: Factors associated with the Delayed Door to Puncture Time for the Basilar Artery Occlusion patient

Introduction : Performing mechanical thrombectomy (MT) in patients with basilar artery occlusion (BAO) is currently not evidence‐based. In the real‐world practice, it is also often encountered that the delayed initiation of the MT happens for this particular patient groups due to lack of cortical signs and other medical confounding factors. Methods : We retrospectively analyzed the angiographical and clinical outcomes of consecutive BAO patient who underwent MT in single institution. Onset to treatment (OTT), Door to Puncture (DTP) time were compared with those in anterior circulation large vessel occlusion (ACLVO) group who underwent MT in the same time period. For those showed significantly longer DTP time, the factors associated with the delayed initiation of the MT were analyzed. Results : A total of 271 patients underwent mechanical thrombectomy at UCI Medical Center between Jan 2016 and June 2021. Of these, 32 patients diagnosed as BAO by CTA and underwent MT were included in the study. Successful recanalization was achieved in 28 cases (87.5%), and symptomatic ICH occurred in 3 cases (9.4%). Nine patients (28.1%) showed good clinical outcomes (mRS 0–3) at 3 months. The median Onset to Puncture Time (OTT) was 340 min. The median DTP time (145 min) was significantly longer as compared to the ACLVO patients (99 min) (p value = 0.04). Of the 6 patients who showed significant delay in the initiation of intervention (DTP>300 min), 5 patients (83.3%) did not have the initial “stroke‐code activation” at the time of ED arrival. The cause of the delay was due to lack of cortical sign (3), bilateral spontaneous sustained clonus, which misinterpreted as seizure (1), AMS with non‐focal neurological signs interpreted as encephalopathy (2). Conclusions : DTP of the patients who underwent MT for BAO was significantly longer than that in ACLAO. Lack of cortical sings which are markers of ACLVO were associated with delayed activation of stroke code. Establishment of BAO screening in the ED assessment and prompt activation of Stroke code may contribute to the improvement of MT treatment for the BAO patients.

Cardiac and non-cardiac characteristics of Jervell-Lange-Nielsen syndrome

We aimed to analyze the management of children with Jervell-Lange-Nielsen syndrome based on their clinical and genetic characteristics and to assess the effectiveness of their therapy.Methods. We analyzed medical data from 12 Jervell and Lange-Nielsen syndrome patients. Mean follow-up was 8.3±5.1 years. Comprehensive cardiological examination include the standard 12-lead electrocardiography (ECG), echocardiography, stress-test, 24-hour Holter recordings, blood tests, thyroid ultrasound, and assessment of thyroid hormone levels, and if necessary, consultation with a neurologist.Results. At the first visit, the mean age was 3.0±2 years old, girls prevailed (67%). All patients are alive now. The mean QTc was 578.9±57.3 ms. Cardiac events had 10 patients (83%), mean age at the first event was 1.9±1.6 years. In 67% of children, syncope was initially regarded as epileptic. All patients received beta-blockers, which were prescribed at mean age 3.0±2.3 years (from 1 month to 7 years). In 8 patients cardiac events recurred despite regular and adequate beta-blocker therapy, all of them were implanted with implanted cardioverter-defibrillator. It was found that patients with the first syncope under the age of 1.5 and delayed initiation of therapy (at the mean age 4.3±1.7 years) had multiple recurrences of syncope despite therapy. Non-cardiac symptoms include sensorineural hearing loss in 100% of cases and hypochromic anemia in 75% of cases.Conclusion. In Jervell-Lange-Nielsen patients who are characterized by resistant ventricular tachyarrhythmia aggressive antiarrhythmic therapy at a very early age is essential for increasing the risk of life-threatening cardiac events. Consequently, diagnosis of the disease in the first days of life is extremely relevant. ECG screening is crucial in solving the problem of early diagnosis of the disease. Extracardiac pathology in patients with Jervell-Lange-Nielsen syndrome necessitates the interaction of doctors of different specialties together when managing a patient.

Renal replacement therapy in heart transplant recipients

Kidney injury in cardiac transplant recipients is one of the most severe complications affecting both short- and long-term transplant outcomes. The need for renal replacement therapy (RRT) is determined not only and not so much by the degree of renal dysfunction, as by the need for correction of fluid balance and metabolic disorders. These circumstances are associated with the specificity of extracorporeal renal replacement therapy in donor heart recipients. In this review, we discuss the problems of early versus delayed initiation of RRT, anticoagulation and vascular access, advantages and disadvantages of continuous and intermittent techniques. Special attention is paid to chronic kidney injury and peculiarities of kidney transplantation in heart recipients.