Hebron University

About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.

Prediction of outcome of nasal high flow use during COVID-19-related acute hypoxemic respiratory failure.

Abstract: Dear Editor, In the course of Coronavirus Disease 2019 (COVID19)-related acute hypoxemic respiratory failure (AHRF), nasal high flow (NHF) has been initially seldom used [1]. Reassessment of environmental contamination risk progressively led to broader NHF application [2, 3]. Our purpose was to evaluate the ROX index [4], defined as the ratio of SpO2/FiO2 to respiratory rate (RR), as an early marker of NHF response and a potential predictor of its failure in the ICU setting. In this single-center retrospective study, all 18-year-old or older patients admitted to the ICU during the peak of the COVID-19 outbreak were screened for eligibility. Participants presenting with AHRF related to SARS-CoV-2 infection (confirmed by molecular testing) and treated with NHF as first-line ventilatory support were included. Patients’ characteristics and NHF-related data were collected from admission until NHF weaning or intubation which defined NHF failure. The ROX index was recorded several times daily. Local Ethics Committee approved the study. Participants were informed of the research’s purpose and their right to decline participation. Statistical analysis included association between early response to NHF [i.e., the latest value of the ROX index within the first 4 h after NHF initiation (ROX-H0H4)] and risk for intubation (Cox’s model for patients still at risk at H4). Maximization of the Youden’s index led to an optimal cut-off of the ROX index to predict NHF outcome. Among all 116 consecutive patients admitted to ICU from March 8 to April 16, 2020, 32 were not COVID19-related, 20 were intubated prior to admission and 2 declined participation. Median age of the study population (N = 62) was 55 (IQR 48–63). Patients presented with profound hypoxemia at NHF initiation [median FiO2 and SpO2 were 0.8 (IQR 0.6–1) and 96% (IQR 94–98), respectively] with median RR of 25 breaths per minute (IQR 21–32). Initial NHF settings were: FiO2: 0.8 (0.6–1) and gas flow: 50 L/min (40–60). Twenty-one patients (34%) succeeded on NHF and were discharged from ICU, whereas 39 (63%) required MV and 2 (3%) died while under NHF because of do-not-intubate order (they were excluded from further analysis). Overall ICU mortality was 17%. Median time to intubation was 10 h (95% CI 7–57). Kaplan–Meier estimates of risk for intubation (N = 60) is illustrated in Fig. 1. Median ROX-H0H4 was 5.4 (IQR 3.9–7.1). In Cox’s model, ROX-H0H4 ≥ 5.37 was significantly associated with a lower risk for intubation after H4 (HR 0.59, 95% CI 0.41–0.84; P = 0.0037) for patients still at risk (N = 45). ROX-H0H4 demonstrated a good discrimination (area under the ROC curve 0.75, 95% CI 0.6–0.9; sensitivity 0.66, specificity 0.83). In conclusion, early application of NHF as first-line ventilatory support during COVID-19-related AHRF may have obviated the need for intubation in up to a third of cases. In this circumstance, the ROX index measured within the first 4 h after NHF initiation could be an easy-to-use marker of early ventilatory response. Its most accurate cut-off was slightly higher than previously validated in AHRF [4], probably because of specific *Correspondence: jean‐damien.ricard@aphp.fr 1 Assistance Publique‐Hôpitaux de Paris, DMU ESPRIT, Médecine Intensive Réanimation, Medico‐Surgical ICU, Louis Mourier Hospital, 92700 Colombes, France Full author information is available at the end of the article

Epilepsy in tuberous sclerosis complex: Findings from the TOSCA Study.

Abstract: Objective: To present the baseline data of the international TuberOus SClerosis registry to increase disease Awareness (TOSCA) with emphasis on the characteristics of epilepsies associated with tuberous sclerosis complex (TSC).Methods: Retrospective and prospective patients' data on all aspects of TSC were collected from multiple countries worldwide. Epilepsy variables included seizure type, age at onset, type of treatment, and treatment outcomes and association with genotype, seizures control, and intellectual disability. As for noninterventional registries, the study protocol did not specify any particular clinical instruments, laboratory investigations, or intervention. Evaluations included those required for diagnosis and management following local best practice.Results: Epilepsy was reported in 83.6% of patients (1852/2216) at baseline; 38.9% presented with infantile spasms and 67.5% with focal seizures. The mean age at diagnosis of infantile spasms was 0.4 year (median <1 year; range <1-30 years) and at diagnosis of focal seizures was 2.7 years (median 1 year; range <1-66 years). A total of 1469 patients (79.3%) were diagnosed with epilepsy <2 years. The rate of infantile spasms was higher in patients with a TSC2 mutation than in patients with a TSC1 mutation (47.3% vs 23%). ɣ-aminobutyric acid (GABA)ergic drugs were the most common treatment modality for both infantile spasms (78.7%) and focal seizures (65.5%). Infantile spasms and focal seizures were controlled in 76.3% and 58.2% of patients, respectively. Control of seizures was associated with lower rates of intellectual disability in both groups.Significance: This registry reports the largest international cohort of patients with TSC. Findings confirmed the typical onset pattern of infantile spasms and other focal seizures in the first 2 years of life, and the high rates of infantile spasms in patients with TSC2 mutation. Our results underscored the occurrence of focal seizures at all ages, including an onset that preceded emergence of infantile spasms. Seizure control was shown to be associated with lower rates of intellectual disability but did not preclude the presence of intellectual disability. (Less)

Barriers for Access to New Medicines: Searching for the Balance Between Rising Costs and Limited Budgets.

Abstract: Introduction: There is continued unmet medical need for new medicines across countries especially for cancer, immunological diseases and orphan diseases. However, there are growing challenges with funding new medicines at ever increasing prices along with funding increased medicine volumes with the growing prevalence of both infectious diseases and non-communicable diseases across countries. This has resulted in the development of new models to better manage the entry of new medicines, new financial models being postulated as well as strategies to improve prescribing efficiency. However, more needs to be done. Consequently, the primary aim of this paper is to consider potential ways to optimise the use of new medicines balancing rising costs with increasing budgetary pressures to stimulate debate especially from a payer perspective. Methods: A narrative review of pharmaceutical policies and implications, as well as possible developments, based on key publications and initiatives known to the co-authors principally from a health authority perspective. Results: A number of initiatives and approaches have been identified including new models to better manage the entry of new medicines based on three pillars (pre-, peri-, and post-launch activities). Within this, we see the growing role of horizon scanning activities starting up to 36 months before launch, managed entry agreements and post launch follow-up. It is also likely there will be greater scrutiny over the effectiveness and value of new cancer medicines given ever increasing prices. This could include establishing minimum effectiveness targets for premium pricing along with re-evaluating prices as more medicines for cancer lose their patent. There will also be a greater involvement of patients especially with orphan diseases. New initiatives could include a greater role of multicriteria decision analysis, as well as looking at the potential for de-linking research and development from commercial activities to enhance affordability. Conclusion: There are a number of ongoing activities across countries to try and fund new valued medicines whilst attaining or maintaining universal healthcare. Such activities will grow with increasing resource pressures and continued unmet need.

Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours

Abstract: The additional information of this manuscript originally stated that the authors declare no competing interests. This statement was incorrect, and should instead have stated the following: M.C.H. has the following competing interests to declare: Equity interest at Molecular MD; Consulting at Molecular MD, Blueprint Medicines, Deciphera Pharmaceuticals; Expert Testimony at Novartis; Licensed patent with royalty payments at Novartis. The remaining authors have no competing interests to declare. The authors apologise for any convenience this may have caused.