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BackgroundVB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM).MethodsPatients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS).ResultsVB-111 was well tolerated. The most common adverse event was transient mild-moderate fever. Median OS time was significantly longer in the primed combination group compared with both LE (414 vs 223 days; hazard ratio [HR], 0.48; P = 0.043) and unprimed combination (414 vs 141.5 days; HR, 0.24; P = 0.0056). Patients in the combination phase of the primed combination group had a median PFS time of 90 days compared with 60 in the LE group (HR, 0.36; P = 0.032), and 63 in the unprimed combination group (P = 0.72). Radiographic responders to VB-111 exhibited characteristic, expansive areas of necrosis in the areas of initial enhancing disease.ConclusionsPatients with rGBM who were primed with VB-111 monotherapy that continued after progression with the addition of bevacizumab showed significant survival and PFS advantage, as well as specific imaging characteristics related to VB-111 mechanism of action. These results warrant further assessment in a randomized controlled study.

BackgroundVB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM).MethodsPatients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS).ResultsVB-111 was well tolerated. The most common adverse event was transient mild-moderate fever. Median OS time was significantly longer in the primed combination group compared with both LE (414 vs 223 days; hazard ratio [HR], 0.48; P = 0.043) and unprimed combination (414 vs 141.5 days; HR, 0.24; P = 0.0056). Patients in the combination phase of the primed combination group had a median PFS time of 90 days compared with 60 in the LE group (HR, 0.36; P = 0.032), and 63 in the unprimed combination group (P = 0.72). Radiographic responders to VB-111 exhibited characteristic, expansive areas of necrosis in the areas of initial enhancing disease.ConclusionsPatients with rGBM who were primed with VB-111 monotherapy that continued after progression with the addition of bevacizumab showed significant survival and PFS advantage, as well as specific imaging characteristics related to VB-111 mechanism of action. These results warrant further assessment in a randomized controlled study.

Summary Obstructive sleep apnea and sleep‐related hypoxia have been associated with higher rates of hospitalization and mortality among patients with Coronavirus disease 2019 (COVID‐19). We further explored the association between obstructive sleep apnea, COVID‐19 severity and related mortality. In addition, we examined the effects of clinical and demographic parameters on COVID‐19. In this retrospective study, we included adult patients who were diagnosed with COVID‐19 prior to the Omicron variant identification. We compared the severity of COVID‐19 and mortality with the diagnosis of obstructive sleep apnea. The study population included 44,275 patients who tested positive for COVID‐19. Of these, 97% had mild or asymptomatic disease, 1.2% had moderate disease, and 1.8% had severe disease. Obstructive sleep apnea was diagnosed in 980 (2.2%) patients. In a multivariate analysis, obstructive sleep apnea diagnosis increased the risk of severe COVID‐19 by 1.6 (95% confidence interval: 1.1–2.4) compared with mild disease. However, no increase in mortality was associated with obstructive sleep apnea. Interestingly, patients with moderate and high socioeconomic status had a 1.6 times higher risk for severe COVID‐19 than patients from the low socioeconomic status group (95% confidence interval: 1.2–2.1 and 95% confidence interval: 1.1–2.3, respectively). The risk of dying due to COVID‐19 was 1.6 (95% confidence interval: 1.1–2.5) and 3.1 (95% confidence interval: 1.8–5.3) times higher in patients with medium and high socioeconomic status, respectively, compared with patients with low socioeconomic status. Diagnosis of obstructive sleep apnea was found to be an independent risk factor for severe COVID‐19. The higher the socioeconomic status, the higher the risk of severe COVID‐19 morbidity and mortality. [ABSTRACT FROM AUTHOR]

BackgroundWhile certain inherited syndromes (e.g. Neurofibromatosis or Li-Fraumeni) are associated with an increased risk of glioma, most familial gliomas are non-syndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained from 14 centres in the United States (US), Europe and Israel as part of the Gliogene Consortium.MethodsFamilies with 2 or more verified gliomas were recruited between January 2007 and February 2011. Distributions of demographic characteristics and clinical variables of gliomas in the families were described based on information derived from personal questionnaires.FindingsThe study population comprised 841 glioma patients identified in 376 families (9797 individuals). There were more cases of glioma among males, with a male to female ratio of 1.25. In most families (83%), 2 gliomas were reported, with 3 and 4 gliomas in 13% and 3% of the families, respectively. For families with 2 gliomas, 57% were among 1st-degree relatives, and 31.5% among 2nd-degree relatives. Overall, the mean (±standard deviation [SD]) diagnosis age was 49.4 (±18.7) years. In 48% of families with 2 gliomas, at least one was diagnosed at

Castration-resistant prostate cancer (CRPC) is a devastating and incurable disease. Combined therapy using conventional anticancer drugs and a proprietary medical nutriment, fermented wheat germ extract (FWGE), also known as Avemar, has been suggested as a treatment for progressing prostate cancer (PCa) patients, who have become resistant to first line hormonal therapy (gonadotropin releasing hormone, GnRH). The primary aim of this study was to test if this combined therapy would slow down disease progression in CRPC patients. We tested the nontoxic, readily available, inexpensive FWGE, together with the conventional treatment, GnRH analogue, in 36 CRPC patients. Although this is a pilot study, with the drawback of a statistically small sample size, some anticancer clinical activity of FWGE could be seen in the CRPC patients, as measured by prostate specific antigen doubling time (PSADT). We found that the intake of GnRH with FWGE for at least 4 months, improved the overall health as well as the quality of life (QOL) in 4 patients (11%) and was instrumental in extending the PSADT in about 17 (out of 26) patients (65.4%), six of whom were significant. Since no mentionable adverse events were noticed, this treatment may permit the postponement of chemotherapy for these patients. [ABSTRACT FROM AUTHOR]

Background: Administrative data has been used to quantify the amount of medication use in order to identify at-risk asthma patients. In our previous study we used short-acting beta-agonists (SABA) inhalers as a marker for asthma control. Methods: We further analyzed patient data from the SABA inhalers study in which asthma control was classified by GINA guidelines, physician assessment and the patients overall estimation. We identified all short-acting bronchodilator purchases (SABA and anticholinergic inhalers and solutions) in the year prior to administering the questionnaire relating to asthma control, and compared inhaled and systemic steroid use. Results: Of 241 asthma patients, 83 completed questionnaires. Using the GINA guidelines criteria, 26 were symptom controlled, 46 were partially controlled and 11 were uncontrolled. Using patients' overall impression of their asthma control, mean annual short-acting bronchodilator purchases were significantly higher in the partially controlled and uncontrolled patients (10 and 8.9 respectively) than in the controlled patients (2, p = 0.005). Most asthma patients purchase less than half of the controller medications prescribed to them. Conclusion: When using administrative data, 3 or more -of all types of short-acting bronchodilator purchases in one year should alert the physician to evaluate asthma control and purchase alerts should notify both physicians and patients when controller consumption is low. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess associations of physician's work overload, successive work shifts, and work experience with physicians' risk to err.Materials and Methods: This large-scale study included physicians who prescribed at least 100 systemic medications at Sheba Medical Center during 2012-2017 in all acute care departments, excluding intensive care units. Presumed medication errors were flagged by a high-accuracy computerized decision support system that uses machine-learning algorithms to detect potential medication prescription errors. Physicians' successive work shifts (first or only shift, second, and third shifts), workload (assessed by the number of prescriptions during a shift) and work-experience, as well as a novel measurement of physicians' prescribing experience with a specific drug, were assessed per prescription. The risk to err was determined for various work conditions.Results: 1 652 896 medical orders were prescribed by 1066 physicians; The system flagged 3738 (0.23%) prescriptions as erroneous. Physicians were 8.2 times more likely to err during high than normal-low workload shifts (5.19% vs 0.63%, P < .0001). Physicians on their third or second successive shift (compared to a first or single shift) were more likely to err (2.1%, 1.8%, and 0.88%, respectively, P < .001). Lack of experience in prescribing a specific medication was associated with higher error rate (0.37% for the first 5 prescriptions vs 0.13% after over 40, P < .001).Discussion: Longer hours and less experience in prescribing a specific medication increase risk of erroneous prescribing.Conclusion: Restricting successive shifts, reducing workload, increasing training and supervision, and implementing smart clinical decision support systems may help reduce prescription errors. [ABSTRACT FROM AUTHOR]

Background: Symptom control is a primary goal in asthma. We hypothesized that administrative data regarding rescue inhaler purchases may correlate with asthma symptom control. Methods: We identified all patients who purchased short-acting beta-agonist (SABA) inhalers during the course of one year in the database of a Health Maintenance Organization (HMO). Primary physicians identified asthma patients and classified their asthma symptom control into three groups according to the Global Initiative for Asthma (GINA) guidelines. Asthma patients were asked to answer symptom questionnaires and grade their asthma control. SABA inhaler purchases were compared between asthma control groups as classified by the guidelines, the physicians and the patients. We also compared the agreement on asthma control between the three methods of classification. Results: Of 241 asthma patients, 83 completed the questionnaires. Using the GINA guidelines criteria, 26 were symptom controlled, 46 were partially controlled and 11 were uncontrolled. SABA inhaler purchases were not significantly lower in the controlled group. Using patients' overall impression of their asthma control, the mean numbers of SABA inhalers purchased were 1.5, 4.4 and 6.4 per year in the controlled, partially controlled and uncontrolled groups, respectively (p = 0.03). Patients' classification of asthma control had better agreement (kappa = 0.34) with GINA guidelines than physician's' agreement (kappa = 0.05). Conclusion: When using administrative data for asthma patients, 2 or more SABA inhaler purchases in one year should alert the physician for the need for asthma control evaluation. Purchase of at least 4 SABA inhalers a year may be regarded as a marker for asthma that is not controlled. [ABSTRACT FROM AUTHOR]