Communication of survival data in US Food and Drug Administration-approved labeling of cancer drugs

This cross-sectional study examines how information on overall survival benefits of novel cancer drug indications is communicated in labeling

Wireless transfer of power by a 35-GHz metamaterial split-ring resonator rectenna

Wireless transfer of power via high frequency microwave radiation using a miniature split ring resonator rectenna is reported. RF power is converted into DC power by integrating a rectification circuit with the split ring resonator. The near-field behavior of the rectenna is investigated with microwave radiation in the frequency range between 20-40 GHz with a maximum power level of 17 dBm. The observed resonance peaks match those predicted by simulation. Polarization studies show the expected maximum in signal when the electric field is polarized along the edge of the split ring resonator with the gap and minimum for perpendicular orientation. The efficiency of the rectenna is on the order of 1% for a frequency of 37.2 GHz. By using a cascading array of 9 split ring resonators the output power was increased by a factor of 20

The Notch pathway is a critical regulator of angiogenesis in a skin model of ischemia

WOS: 000355334000001PubMed ID: 25834117The Notch pathway is definitely required for normal vascular development. Although the contribution of Notch in postnatal angiogenesis is the focus of intense investigation, the implication of Notch in reparative neovascularization in the skin remains unexplored. In this study, we investigated Notch changes using a skin model of ischemia. Thirty Sprague-Dawley rats were divided into two groups. In the surgery group (n = 24), a caudally based dorsal skin flap was raised and sutured back into its initial position. In the control group, no surgical procedure was performed. Tissue biopsies were obtained at different time intervals. Tissue specimens were assessed for Delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF) gene expression by real-time polymerase chain reaction (PCR). Immunohistochemical staining was used for detection of DLL4 in tissue materials. Quantitative assessment of skin flap microvasculature was made. Compared with normoperfused tissue, VEGF and DLL4 expressions increased significantly (p < 0.01). Immunohistochemical analysis revealed weak and patchy expression of DLL4 in microvascular endothelial cells of normoperfused tissues. Conversely, DLL4 expression was upregulated in capillary endothelial cells after ischemia. In conclusion, in this study we have shown that the Notch ligand DLL4 is upregulated in skin tissue after ischemia. A deeper understanding of these fundamental principles will aid in the development of new avenues for the treatment of blood vessel-related skin pathologies.Baskent University Research FundBaskent UniversityThis study was approved by Baskent University Ethical Committee for Experimental Research on Animals and supported by Baskent University Research Fund

Serum Adipokine and Ghrelin Levels in Nonalcoholic Steatohepatitis

Adipokines and ghrelin play role in insulin resistance, the key pathophysiological abnormality in patients with nonalcoholic fatty liver diseases. In the present study, relationship between nonalcoholic steatohepatitis (NASH) and serum adipokine and ghrelin levels was investigated. Thirty seven patients with biopsy-proven NASH and 25 age- and sex-matched controls were enrolled. Ten of NASH patients (27%) had diabetes mellitus (n = 5) or impaired glucose tolerance (n = 5). Body mass index (BMI) was less than 30 kg/m(2) in 67.6% of patients, while in the remaining 32.4% it was more than 30 kg/m(2). Serum adiponectin, leptin, TNF-α, and ghrelin were determined. Serum leptin (15.49 ± 4.84 vs 10.31 ± 2.53) and TNF-α (12.1 ± 2.7 vs 10.31 ± 2.56) levels were significantly higher in the NASH group compared to in the control group (P < .001 for each). Nevertheless, adiponectin (11.1±2.1 vs 17.3±2.8) and ghrelin (6.46±1.1 vs 7.8±1.1) levels were lower in the NASH group than in the control group (P < .001 for each). Serum levels of the adipokines and ghrelin, however, were comparable in the subgroups of patients regardless of whether BMI was < 30 or > 30 or glucose tolerance was impaired or not (P > .05). Additionally, neither adipokines nor ghrelin was correlated with histopathological grade and stage (P > .05). In conclusion; there is a significant relationship between NASH and adipokines and ghrelin independent from BMI and status of the glucose metabolism. These cytokines that appear to have role in the pathogenesis of NASH, however, do not have any effect upon the severity of the histopathology

Rebaudioside A inhibits pentylenetetrazol-induced convulsions in rats

AbstractThe safety of patients with epilepsy consuming sweetening agents, which is becoming increasingly prevalent for various reasons, is a topic that should be emphasized as sensitively as it is for other diseases. Patients with epilepsy consume sweetening agents for different reasons such being diabetic or overweight. They can occasionally be exposed to sweetening agents unrestrainedly through consuming convenience food, primarily beverages. This study aimed to investigate the effects of rebaudioside A (Reb-A), which is a steviol glycoside produced from the herb Stevia rebaudiana (Bertoni), on epileptic seizures and convulsions induced by pentylenetetrazole (PTZ). Forty-eight male rats were used. Twenty-four rats were administered 35 mg/kg PTZ to trigger epileptiform activity; the remaining 24 rats were administered 70 mg/kg PTZ to trigger the convulsion model. The epileptiform activity was evaluated by spike percentage, whereas convulsion was evaluated by Racine's Convulsion Scale and the onset time of the first myoclonic jerk. Statistical analysis revealed a statistically significant decrease in the Racine's Convulsion Scale score and increase in the latency of first myoclonic jerk in a dose-dependent manner for the rat groups in which PTZ epilepsy had been induced and Reb-A had been administered. For the groups that were administered Reb-A, the spike decrease was apparent in a dose-dependent manner, based on the spike percentage calculation. These results indicated that Reb-A has positive effects on PTZ-induced convulsions

Overall survival benefits of cancer drugs approved in China from 2005 to 2020

Importance: Of approximately 9 million patients with cancer in China in 2020, more than half were diagnosed with late-stage cancers. Recent regulatory reforms in China have focused on improving the availability of new cancer drugs. However, evidence on the clinical benefits of new cancer therapies authorized in China is not available. Objective: To characterize the clinical benefits of cancer drugs approved in China, as defined by the availability and magnitude of statistically significant overall survival (OS) results. Design, Setting, and Participants: This mixed-methods study comprising a systematic review and cross-sectional analysis identified antineoplastic agents approved in China between January 1, 2005, and December 31, 2020, using publicly available data and regulatory review documents issued by the National Medical Products Administration. The literature published up to June 30, 2021, was reviewed to collect results on end points used in pivotal trials supporting cancer drug approvals. Main Outcomes and Measures: The primary outcome measure was a documented statistically significant positive OS difference between a new cancer therapy and a comparator treatment. Secondary outcome measures were the magnitude of OS benefit and other primary efficacy measures in pivotal trials. Results: Between 2005 and 2020, 78 cancer drugs corresponding to 141 indications were authorized in China, including 20 drugs (25.6%) (for 30 indications) approved in China only. Of all indications, 26 (18.4%) were evaluated in single-arm or dose-optimization trials, most of which were authorized after 2017. By June 30, 2021, 34 drug indications (24.1%) had a documented lack of OS gain. For 68 indications (48.2%) that had documented evidence of OS benefit, the median magnitude of OS improvement was 4.1 (range, 1.0-35.0) months. After a median follow-up of 1.9 (range, 1.0-11.1) years from approval, OS data for 13 indications (9.2%) were either not reported or were still not mature. Fewer than one-third of cancer drug indications approved in China only had documented evidence of OS benefits (9 of 30 [30.0%]), whereas more than one-half of the cancer drug indications also available in the US or Europe had OS benefits (59 of 111 [53.1%]). Conclusions and Relevance: In this study, almost half of cancer drug indications approved in China had demonstrated OS gain. With the increase of cancer drug approvals based on single-arm trials or immature survival data in recent years, these findings highlight the need to routinely monitor the clinical benefits of new cancer therapies in Chin

Analysis of Episodes of Care in Medicare Beneficiaries Newly Diagnosed with Alzheimer’s Disease

OBJECTIVES: To study transitions between healthcare settings and quantify the cost burdens associated with different combinations of transitions during a 6-month period before initial Alzheimer’s disease (AD) diagnosis so as to investigate how using an episode-of-care approach to payment for specific disease states might apply in AD. DESIGN: A retrospective observational cohort study. SETTING: United States. PARTICIPANTS: A random sample of 8,995 individuals aged 65 to 100 with a diagnosis of AD (International Classification of Diseases, Ninth Revision, Clinical Modification code 331.0) were identified from the Medicare database between January 1, 2011, and June 30, 2014. This analysis identified individuals with AD diagnosed in inpatient (18%), skilled nursing facility (SNF) (1%), hospice (4%), and home and outpatient (77%) settings and analyzed episodes that began in the index setting (defined as the care setting in which the individual was first diagnosed with AD). MEASUREMENTS: Study outcomes included number of transitions between settings, primary discharge diagnoses, and total all-cause healthcare costs during the 6 months after the AD diagnosis. RESULTS: The average numbers of transitions between care settings were 2.8 originating from an inpatient setting, 2.4 from a SNF, 0.3 from a hospice setting and 0.7 from a home or outpatient setting during 6 months post-AD diagnosis. The overall cost burden during the 6 months after AD diagnosis (including costs incurred at the index setting) was high for individuals diagnosed in a nonambulatory setting (mean $41,468). Individuals diagnosed in an ambulatory setting incurred only$12,597 in costs during the same period. CONCLUSION: Episodes of care can be defined and studied in individuals with AD. An episode-of-care approach to payment could encourage providers to use the continuum of care needed for quality medical management in AD more efficiently

Communication of anticancer drug benefits and related uncertainties to patients and clinicians: document analysis of regulated information on prescription drugs in Europe

Objective To evaluate the frequency with which relevant and accurate information about the benefits and related uncertainties of anticancer drugs are communicated to patients and clinicians in regulated information sources in Europe. Design Document content analysis. Setting European Medicines Agency. Participants Anticancer drugs granted a first marketing authorisation by the European Medicines Agency, 2017-19. Main outcome measures Whether written information on a product addressed patients’ commonly asked questions about: who and what the drug is used for; how the drug was studied; types of drug benefit expected; and the extent of weak, uncertain, or missing evidence for drug benefits. Information on drug benefits in written sources for clinicians (summaries of product characteristics), patients (patient information leaflets), and the public (public summaries) was compared with information reported in regulatory assessment documents (European public assessment reports). Results 29 anticancer drugs that received a first marketing authorisation for 32 separate cancer indications in 2017-19 were included. General information about the drug (including information on approved indications and how the drug works) was frequently reported across regulated information sources aimed at both clinicians and patients. Nearly all summaries of product characteristics communicated full information to clinicians about the number and design of the main studies, the control arm (if any), study sample size, and primary measures of drug benefit. None of the patient information leaflets communicated information to patients about how drugs were studied. 31 (97%) summaries of product characteristics and 25 (78%) public summaries contained information about drug benefits that was accurate and consistent with information in regulatory assessment documents. The presence or absence of evidence that a drug extended survival was reported in 23 (72%) summaries of product characteristics and four (13%) public summaries. None of the patient information leaflets communicated information about the drug benefits that patients might expect based on study findings. Scientific concerns about the reliability of evidence on drug benefits, which were raised by European regulatory assessors for almost all drugs in the study sample, were rarely communicated to clinicians, patients, or the public. Conclusions The findings of this study highlight the need to improve the communication of the benefits and related uncertainties of anticancer drugs in regulated information sources in Europe to support evidence informed decision making by patients and their clinicians

Electrospun polylactic acid/date palm polyphenol extract nanofibres for tissue engineering applications

In this study, a set of polylactic acid (PLA)/polyphenol extracted from date palm fruit (DP) blends were prepared by electrospinning process to be used as cell culture scaffolds for tissue engineering applications. For this purpose, PLA/DP blends with variable composition were dissolved in dichloromethane/dimethylformamide (70:30, v/v) mixture and then electrospun to obtain the fibres. Contact angle measurements, dynamic mechanical analysis, mechanical tensile and scanning electron microscopy (SEM) tools were used to study the physico-mechanical properties of the electrospun scaffolds. The results revealed that scaffolds became more hydrophilic with addition of DP. Increasing the polyphenol concentration caused the tensile strength and Young's modulus to decrease. The SEM graphs indicated a decrease in fibre diameter with increasing DP content. In addition, it was found that both cell proliferation and cell viability were enhanced with increased DP concentration within the scaffolds. The scratch test shows that there is an enhancement in cell migration through the scratch for PLA/DP scaffolds; again, higher DP content resulted better migration. Our results suggest that improved mechanical properties, decreased fibre diameter and enhanced hydrophilicity with addition of DP improved cell migration and cell adhesion for the scaffolds. Overall, these results demonstrate that DP is a potential natural cell-friendly product for tissue engineering applications such as tissue regeneration or wound healing assays