Perampanel, an AMPA receptor antagonist: From clinical research to practice in clinical settings.

Epileptic seizures are refractory to treatment in approximately one-third of patients despite the recent introduction of many newer antiepileptic drugs (AEDs). Development of novel AEDs therefore remains a high priority. Perampanel is a first-in-class non-competitive selective AMPA receptor antagonist with a unique mechanism of action. Clinical efficacy and safety of perampanel as adjunctive treatment for focal seizures with/without secondary generalization (±SG) and primary generalized tonic-clonic (PGTC) seizures have been established in five phase 3 randomized controlled trials (RCTs), and a long-term extension study, and perampanel is approved as monotherapy for focal seizures ±SG in the USA. In patients with focal seizures ±SG, add-on perampanel resulted in median percent reduction in seizure frequency 23.3%-34.5% and ≥50% responder rate 28.5%-37.6%; in PGTC seizures, these results were 76.5% and 64.2%, respectively. Efficacy among adolescents (reduction in seizure frequency 34.8%-35.6%; ≥50% responder rate 40.9%-45.0%) and elderly people (reduction in seizure frequency 12.5%-16.9%; ≥50% responder rate 22.2%-42.9%) is similar to those in adults, and results remain comparable between Asian (reduction in seizure frequency 17.3%-38.0%) and global populations. Perampanel has been extensively studied in real-world clinical practice, with similar efficacy and safety results to the RCTs (≥50% responder rate 12.8%-75.0%; adverse events of somnolence/sedation, dizziness, ataxia, and behavioral changes). Real-world observational studies suggest that perampanel tolerability can be improved by slow titration (2 mg every 2-4 weeks), and bedtime administration can mitigate somnolence and dizziness. Counseling about the potential for behavioral changes and close monitoring are recommended.

[Re-evaluate the value of orbital decompression for thyroid associated ophthalmopathy].

Thyroid-associated ophthalmopathy (TAO) is a common autoimmune syndrome affecting the thyroid and orbit. It can result in the fibrosis of extraoular muscles and hyperplasia of adipose tissue. The mechanism of TAO is not clear and there was few effective treatment. Recently, orbital decompression was performed on more and more patients. The surgery can improve the appearance of the patient and relieve the symptoms caused by the high orbital pressure. Therefore, it is necessary to re-evaluate the clinical value of the orbital decompression and surgical indications. The principles and techniques of orbital decompression with relative factors were discussed in this review. (Chin J Ophthalmol, 2017, 53: 401-403).

[The role of the high-level public health school in the development of the Center for Disease Control and Prevention].

The Ministry of Education and other four departments jointly issued the Notice on the Construction of high-level schools of public Health, proposing that "it will take ten years to build a number of high-level schools of public health, and form a high-quality education development system to adapt to the construction of modern public health system". At present, the construction of high-level public health schools in various universities in China is in full swing. The high-level School of Public Health and the CDC have played an important role in constructing the national public health system and the human health community. The high-level public health schools are of strategic significance and important value to the development of the CDC. The review presents reflections and insights on the role of high-level public health schools in the development of the CDC and the challenges they might face.

[Summary of tools for assessment of public health emergency response capability].

With the progress of globalization, the public health emergencies represented by major infectious diseases have become a major challenge for the public health management in China. The article briefly describes the emergency response capability assessment tools in China, and introduces two emergency response assessment tools with complete content structure and wide application in the world. Then the advantages and disadvantages of the tools are compared and discussed in order to provide reference for improvement of the assessment tools for public health emergency response capability in China.

Heart transplantation outcomes in cardiac sarcoidosis.

BACKGROUND: Cardiac sarcoidosis (CS) is a progressive inflammatory cardiomyopathy that can lead to heart failure, arrhythmia, and death. There is limited data on Orthotopic Heart Transplantation (OHT) outcomes in patients with CS. Here we examine outcomes in patients with CS who have undergone OHT at centers throughout the United States from 1987 to 2019. METHODS: This was an analysis of 63,947 adult patients undergoing OHT captured in the United Network for Organ Sharing (UNOS) registry. Patients were characterized as cardiac sarcoidosis (CS) or Non-CS. Baseline characteristics were compared using chi-square and Kruskal-Wallis Tests. Outcomes of interest included primary graft failure, patient survival, treated graft rejection, hospitalization for infection, and post-transplant malignancy. RESULTS: During the study period 227 patients with CS underwent OHT. Patients with CS were younger, had higher proportion of non-white patients, and received transplants at more urgent statuses. After multivariable modeling there was no difference in survival (HR 0.86, CI 0.59-1.3, p = 0.446) or graft failure (HR 0.849, CI 0.58-1.23, p = 0.394) between patients with CS and Non-CS. Patients with CS had lower odds of rejection (OR 0.558, CI 0.315- 0.985, p = 0.0444). Patients with CS had similar odds of hospitalization for infection and post-transplant malignancy, as Non-CS patients. CONCLUSIONS: Patients with CS and Non-CS had similar post OHT survival, odds of graft failure, hospitalizations for infection, and post-transplant malignancy. Results of this study confirm the role of heart transplantation as a viable option for patients with CS.

Occult hepatocellular carcinoma: a case report of a special icteric-type hepatoma and literature review.

Hepatocellular carcinoma (HCC) presenting with obstructive jaundice due to bile duct tumour thrombi is classified as icteric-type hepatoma. This report describes a case of unusual icteric-type HCC with common bile duct thrombus, which is herein named 'occult HCC', as no detectable primary lesion in liver was defined pre-operatively and intra-operatively. A thrombectomy followed by a T biliary drainage tube placement was carried out, and the final post-operative pathological evaluation demonstrated the tumour thrombus originated from a moderately differentiated HCC. The clinicopathological features and logical clinical interventions of this rare type of HCC were discussed with a review of the literature. The HCC patients with bile duct thrombi receiving palliative biliary drainage alone had a poor outcome. With respect to improving prognosis, a curative resection of primary HCC and tumour thrombi was suggested on the basis of performing an intensive post-operative monitoring for early detection of primary liver lesion.

[Advances in the prediction of the efficacy and sensitivity of neoadjuvant chemoradiotherapy in rectal cancer].

Rectal cancer has become one of the most common malignant tumors in our country. The treatment of total mesorectal excision after neoadjuvant chemoradiotherapy (NCRT) has become a standard treatment mode for locally advanced rectal cancer. However, the response of patients with rectal cancer to neoadjuvant chemotherapy varies, and treating all patients with NCRT may be suboptimal. Accurately predicting the efficacy and sensitivity of NCRT can help adjust treatment plan timely and avoid delay of condition in patients who are insensitive to NCRT. Existing research has confirmed that TNM staging, tumor regression grade and tumor markers and other clinical indicators can effectively predict the efficacy and sensitivity of NCRT, all kinds of clinical guidelines also recommend the three as a routine examination of patients with rectal cancer during NCRT. However, with the proposal of the concept of "Precise Medicine", the above clinical indexes cannot meet the clinical need of accurate treatment of rectal cancer. In recent years, with the accumulating studies on tumor immunotherapy, researchers have found that the sensitivity of NCRT is not only related to tumor biological characteristics, but also closely related to tumor microenvironment. Based on the current research, the indicators of tumor microenvironment, such as lymphocyte subsets count, neutrophil-lymphocyte ratio and programmed cell death ligand 1, have great potential clinical value in predicting the efficacy and sensitivity of rectal cancer. Further research based on relevant indicators of tumor microenvironment will enable accurate prediction of NCRT efficacy and sensitivity of NCRT and has important clinical significance for the realization of accurate and individualized treatment of rectal cancer.

Chinese medicinal herbs for acute bronchitis.

BACKGROUND: Acute bronchitis is one of the most common diagnoses made by primary-care physicians. It is traditionally treated with antibiotics (although the evidence for their effectiveness is weak and modest at best), and other even less effective treatments. Chinese medicinal herbs have also been used as a treatment. OBJECTIVES: This review aimed to summarise the existing evidence on the comparative effectiveness and safety of Chinese medicinal herbs for treating uncomplicated acute bronchitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007, Issue 1), which includes the Cochrane Acute Respiratory Infections Group's specialised register; MEDLINE (1966 to March Week 1, 2007); EMBASE (1988 to January 2007); The Chinese Cochrane Centre's Controlled Trials Register (up to January 2007); and the Chinese Biomedical Database (CBM) (1980 to January 2007). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing Chinese medicinal herbs with placebo, antibiotics or other Western medicines for the treatment of uncomplicated acute bronchitis. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data and assessed trial quality. MAIN RESULTS: No studies met the inclusion criteria for this review. One study with 300 participants but uncertain randomisation was analysed . The study showed that treatment with the Chinese medicinal herb Huoke granules leads to a shorter duration of cough, fever and sputum compared to using penicillin and Xiaoer Shangfeng Zhike tangjiang syrup. However, the study also lacked allocation concealment and blinding. There was a high possibility of conflict of interest as the Huoke granules were made by the trial author's hospital. AUTHORS' CONCLUSIONS: There is insufficient quality data to recommend the routine use of Chinese herbs for acute bronchitis. Study-design limitations of the individual studies meant that no conclusion about the benefits of Chinese herbs could be taken. In addition, the safety of Chinese herbs is unknown due to the lack of toxicological evidence on these Chinese herbs, though adverse events were reported in some case reports.

HPV DNA vaccines.

Human papillomaviruses (HPV), particularly HPV type 16, are the primary etiologic agent of cervical cancer. Thus, HPV-associated cervical malignancies might be prevented or treated by induction of the appropriate virus-specific immune responses in patients. HPV capsid proteins including L1 and L2 proteins have been shown to generate neutralizing antibodies against HPV particles in vaccinated individuals. Furthermore, HPV oncogenic proteins such as E6 and E7 proteins are important in the induction and maintenance of cellular transformation and are co-expressed in the majority of HPV-containing carcinomas. They represent ideal targets for the development of therapeutic vaccines against HPV infections and HPV-associated neoplasia. Vaccines targeting these proteins may provide an opportunity to control HPV-associated malignancies. Genetic immunization with naked DNA has emerged as an important strategy for vaccine development. Plasmid DNA encoding antigen of interest, such as capsid protein L1 and L2 (for preventive vaccines) and non-structural proteins E6 and E7 (for therapeutic vaccines) enters the host and stimulates an antigen-specific humoral and cellular immune response. Various strategies to enhance preventive and therapeutic effects of DNA vaccines are currently under active investigation. Should they fulfill their promise, these DNA vaccines may prevent HPV infection or control HPV-related cervical lesions.

Comprehensive quality management program for radiation oncology.

A quality management program for both external beam irradiation (electron and photon modes) and brachytherapy (high dose rate (HDR) and low dose rate (LDR) has been developed. The program follows current USA federal regulations for therapeutic administration of by-product materials. After implementation of the program, 54 HDR patients, 36 LDR brachytherapy patients and 311 external beam patients (including 30 stereotactic radiosurgery cases) were treated. The results of this program are presented.

Can regular multivitamin/mineral supplementation modify the relation between maternal smoking and select adverse birth outcomes?

PURPOSE: The purpose of this study was to examine whether or not regular multivitamin/mineral supplementation can modify the relation between maternal smoking and preterm birth (gestational age < 37 weeks), very-low-birthweight (VLBW) (< 1500 g), moderately-low-birthweight (MLBW) (< 2499 g), or small-for-gestational-age (SGA) (< 10th percentile of birth weight for gestational age). METHODS: Live birth data from the 1988 National Maternal and Infant Health Survey (NMIHS) were used for the analysis. Maternal smoking referred to self-reported average number of cigarettes smoked after recognition of pregnancy, while regular multivitamin/mineral supplementation referred to use of multivitamin/mineral supplements for at least three days per week during the three months before and/or after recognition of pregnancy. Sample sizes included 9402 singleton infants for the analysis of preterm birth, 9395 for very or moderately low birthweight, and 9363 for small-for-gestational-age. Odds ratios were derived from logistic regression analyses after adjusting for a number of demographic and reproductive variables. RESULTS: Major results include: 1) increased risks for the adverse outcomes studied were observed among smoking women; 2) no effect of regular multivitamin/mineral supplementation in the absence of maternal smoking was revealed; and 3) relative excess risks due to interaction at different smoking levels and overall interactions between smoking and supplementation were not observed. CONCLUSIONS: These results suggest that regular multivitamin/mineral supplementation does not minimize the adverse effects associated with maternal smoking.

Current trends and new approaches in the management of diabetes mellitus.

Current trends in the management of type 2 diabetes mellitus, based on the 20-year United Kingdom Prospective Diabetic Study, include intensive treatment to control the blood glucose level and blood pressure in order to prevent or delay microvascular and cardiovascular complications. In the new millennium, type 2 diabetes will become epidemic in developing countries. If diabetes were to develop in 10% of the 1.2 billion population of China, the expense of intensive treatment would be immense. Laboratory tests are useful for detecting risk factors before the onset of the disease and convincing the general public to take preventive measures. Glucose tolerance testing is one of these tests. When glucose tolerance is impaired, 25% of beta-cell function is lost. Determining the plasma proinsulin level is another useful evaluation; impaired glucose tolerance accompanied by increased plasma proinsulin level is indicative of an enhanced risk that type 2 diabetes will develop within 5 years. Educating the public about eating a healthy diet and exercising may prevent the development of diabetes and thereby reduce the global prevalence of type 2 diabetes.

[Chronic rheumatic cardiopathy in a patient with of hemophilia successfully treated with surgery]. / Cardiopatia reumática crônica em portador de hemofilia submetido com sucesso a tratamento cirúrgico.

A 52 year-old man, with rheumatic cardiopathy and hemophilia was admitted to the hospital for aortic valve replacement and mitral valve commisurotomy. He had a history of allergic reaction to cryoprecipitate, and to undergo to the cardiac surgery, the ideal level of factor VIII was estimated to be 100%. To reach this level he first received 2,500UI of the factor VIII:C increasing the factor VIII:C level from 20 to 58%. During the surgery he received an additional dose of 1,500UI of factor VIII plus 3,500,000UI of aprotinin (Trasylol), which was started at the beginning of the anaesthesia and maintained during the surgical procedure, increasing the factor VIII level to 220%. The patient was discharged 11 days after the surgery without any hemorrhagic complication.

Therapeutic human papillomavirus DNA vaccination strategies to control cervical cancer.

A persistent human papillomavirus (HPV) infection is considered causal and necessary for the continued growth of cervical cancer. Thus, vaccination against HPV represents a plausible approach to prevent and treat cervical cancer. A report in the current issue of the European Journal of Immunology describes a therapeutic HPV DNA vaccination strategy using the HPV-16 E7 antigen fused to the invariant chain to enhance the E7-specific CD8+ and CD4+ T cell immune responses, resulting in a potent anti-tumor effect against E7-expressing tumors. Continued exploration of HPV therapeutic DNA vaccines may lead to eventual clinical application.

Medical services in urban China: does the 'free' care policy induce greater demand?

In this paper we discuss the nature of the medical services and the free medical care programs in urban China, then using the data collected in a large city, we also explored the differences between those covered by a free program and those not in perceived illness, doctor visit, hospital admission, and emergency use. Our findings may show that Chinese experience in medical service use is consistent with the common idea that a free medical care policy could induce greater demand while it also has its own nature.

Skeletal effects of constant and terminated use of sodium risedronate in ovariectomized rats.

AIM: To study the skeletal effects of constant and terminated use of sodium risedronate (Ris) treatment in the ovariectomized (Ova) rats. METHODS: Ris 5 micrograms.kg-1, s.c., twice a wk. The proximal tibial metaphysis (PTM) were processed undecalcified for quantitive bone histomorphometry. RESULTS: (1) Placebo-treated (normal saline) Ova rats were characterized by decreased trabecular area (TA) on d 60, d 81, and d 150 compared with aging controls, and bone resorption was over formation with high bone turnover. (2) Ova rats were treated with Ris for 60, 81, and 150 d (Ris-on) increased. (TA 217%, 108%, and 101%) respectively, vs Ova rats and depressed bone turnover indices to aging control level, but bone mass did not maintain at high level in 150-d group as in the early stage. (3) Ova rats were pretreated with Ris for 60 d and then terminated (Ris-on/off), followed by sequential sacrifice of rats on 21 and 90 d. Withdrawal on 21 d showed the same results as the match-age Ris-on group. Withdrawal on 90 d still maintained cancellous bone mass at a high level vs 150 d Ris-on groups (+26%) and aging control group (+27%). CONCLUSION: Regimen of Ris 60 d on then 90 d off prevented the development of osteoporosis in Ova rats.