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Germline TSC1 or TSC2 mutations cause Tuberous Sclerosis Complex (TSC), a hamartoma syndrome with lung involvement. To explore the potential interaction between TSC1 and KRAS activation in lung cancer, mice were generated in which Tsc1 loss and KrasG12D expression occur in a small fraction of lung epithelial cells. Mice with combined Tsc1-KrasG12D mutation had dramatically reduced tumor latency (median survival 11.6 – 15.6 weeks) in comparison to KrasG12D alone mutant mice (median survival 27.5 weeks). Tsc1-Kras G12D tumors showed consistent activation of mTORC1, and responded to treatment with rapamycin leading to significantly improved survival, while rapamycin had minor effects on cancers in KrasG12D alone mice. Loss of heterozygosity for TSC1 or TSC2 was found in 22% of 86 human lung cancer specimens. However, none of 80 lung cancer lines studied showed evidence of lack of expression of either TSC1 or TSC2 or a signaling pattern corresponding to complete loss. These data indicate Tsc1 loss synergizes with Kras mutation to enhance lung tumorigenesis in the mouse, but that this is a rare event in human lung cancer. Rapamycin may have unique benefit for lung cancer patients in which TSC1/TSC2 function is limited.

BackgroundAs the world’s largest developing country, China has entered into the epidemiological phase characterized by high life expectancy and high morbidity and mortality from chronic diseases. Cardiovascular diseases, chronic obstructive pulmonary diseases, and malignant tumors have become the leading causes of death since the 1990s. Constant payments for maintaining the health status of a family member who has chronic diseases could exhaust household resources, undermining fiscal support for other necessities and eventually resulting in poverty. The purpose of this study is to probe to what degree health expenditure for chronic diseases can impoverish rural families and whether the New Cooperative Medical Scheme can effectively protect families with chronic patients against catastrophic health expenditures.MethodsWe used data from the 4th National Health Services Survey conducted in July 2008 in China. The rural sample we included in the analysis comprised 39,054 households. We used both households suffering from medical impoverishment and households with catastrophic health expenditures to compare the financial protection for families having a chronic patient with different insurance coverage statuses. We used a logistic regression model to estimate the impact of different benefit packages on health financial protection for families having a chronic patient.ResultsAn additional 10.53% of the families with a chronic patient were impoverished because of healthcare expenditure, which is more than twice the proportion in families without a chronic patient. There is a higher catastrophic health expenditure incidence in the families with a chronic patient. The results of logistic regression show that simply adding extra benefits did not reduce the financial risks.ConclusionsThere is a lack of effective financial protection for healthcare expenditures for families with a chronic patient in rural China, even though there is a high coverage rate with the New Cooperative Medical Schemes. Given the coming universal coverage by the New Cooperative Medical Scheme and the increasing central government funds in the risk pool, effective financial protection for families should be possible through systematic reform of both financing mechanisms and payment methods.

BackgroundSubsidizing healthcare costs through insurance schemes is crucial to overcome financial barriers to health care and to avoid high medical expenditures for patients in China. The health insurance could decrease financial risk by less out-of-pocket (OOP) payment, but not promise the protection equity. With the growth of New Cooperative Medical Scheme (NCMS) financing and coverage since 2008, the protection effectiveness and equity of the modified NCMS policies on financial burden should be further evaluated.MethodsA cross-sectional household survey was conducted in Zhejiang, Hubei, and Chongqing provinces by multi-stage stratified random sampling in 2011. A total of 1,525 households covered by the NCMS were analyzed. The protection effectiveness and protection equity of NCMS was analyzed by comparing the changes in health care utilization and medical expenditures, and the changes in the prevalence of catastrophic health expenditure (CHE) and its concentration indices (CIs) between pre- and post-NCMS reimbursement, respectively.ResultsThe medical financial burden was still remarkably high for the low income rural residents in China due to high OOP payment, even after NCMS reimbursement. In Hubei province, the OOP payment of the poorest quintile was almost same as their households’ annual expenditures. Even it was higher than their annual expenditures in Chongqing municipality. Effective reimbursement ratio of both outpatient and inpatient services were far lower than nominal reimbursement ratio originally designed by NCMS plans. After NCMS reimbursement, the prevalence of CHE was considerably high in all three provinces, and the absolute values of CIs were even higher than those before reimbursement, indicating the inequity exaggerated.ConclusionPolicymakers should further modify NCMS policy in rural China. The high OOP payment could be decreased by expanding the drug list and check directory for benefit package of NCMS to minimize the gap between nominal reimbursement ratio and effective reimbursement ratio. And the increase in medical expenditures should be controlled by monitoring excess demand from both medical service providers and patients, and changing fee-for-service payment for providers to a prospective payment system. Service accessibility and affordability for vulnerable rural residents should be protected by modifying regressive financing in NCMS, and by providing extra financial aid and reimbursement from government.

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Background:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has progressed to a pandemic associated with substantial morbidity and mortality. The WHO and the United States Center for Disease Control and Prevention (CDC) have issued interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19), but there is limited data on the virologic and clinical characteristics for prognosis of severe COVID-19. Methods:A total of 50 patients with severe COVID-19 were divided into good and poor recovery groups. The dynamic viral shedding and serological characteristics of SARS-CoV-2 were explored. The risk factors associated with poor recovery and lung lesion resolutions were identified. In addition, the potential relationships among the viral shedding, the pro-inflammatory response, and lung lesion evolutions were characterized. Results:A total of 58% of the patients had poor recovery and were more likely to have a prolonged interval of viral shedding. The longest viral shedding was 57 days after symptom onset. Older age, hyperlipemia, hypoproteinemia, corticosteroid therapy, consolidation on chest computed-tomography (CT), and prolonged SARS-CoV-2 IgM positive were all associated with poor recovery. Additionally, the odds of impaired lung lesion resolutions were higher in patients with hypoproteinemia, hyperlipemia, and elevated levels of IL-4 and ferritin. Finally, viral shedding and proinflammatory responses were closely correlated with lung lesion evolutions on chest CT. : medRxiv preprint ConclusionsPatients with severe COVID-19 have prolonged SARS-CoV-2 infection and delayed intermittent viral shedding. Older age, hyperlipemia, hypoproteinemia, corticosteroid usage, and prolonged SARS-CoV-2 IgM positive might be utilized as predicative factors for the patients with poor recovery.

BackgroundWith the rise in popularity of Web 2.0 technologies, the sharing of patient experiences about physicians on online forums and medical websites has become a common practice. However, negative comments posted by patients are considered to be more influential by other patients and physicians than those that are satisfactory.ObjectiveThe aim of this study was to analyze negative comments posted online about physicians and to identify possible solutions to improve patient satisfaction, as well as their relationship with physicians.MethodsA Java-based program was developed to collect patient comments on the Good Doctor website, one of the most popular online health communities in China. A total of 3012 negative comments concerning 1029 physicians (mean 2.93 [SD 4.14]) from 5 highly ranked hospitals in Beijing were extracted for content analysis. An initial coding framework was constructed with 2 research assistants involved in the codification.ResultsAnalysis, based on the collected 3012 negative comments, revealed that unhappy patients are not alike and that their complaints cover a wide range of issues experienced throughout the whole process of medical consultation. Among them, physicians in Obstetrics and Gynecology (606/3012, 20.12%; P=.001) and Internal Medicine (487/3012, 16.17%; P=.80) received the most negative comments. For negative comments per physician, Dermatology and Sexually Transmitted Diseases (mean 5.72, P<.001) and Andrology (mean 5, P=.02) ranked the highest. Complaints relating to insufficient medical consultation duration (577/3012, 19.16%), physician impatience (527/3012, 17.50%), and perceived poor therapeutic effect (370/3012, 12.28%) received the highest number of negative comments. Specific groups of people, such as those accompanying older patients or children, traveling patients, or very important person registrants, were shown to demonstrate little tolerance for poor medical service.ConclusionsAnalysis of online patient complaints provides an innovative approach to understand factors associated with patient dissatisfaction. The outcomes of this study could be of benefit to hospitals or physicians seeking to improve their delivery of patient-centered services. Patients are expected to be more understanding of overloaded physicians’ workloads, which are impacted by China’s stretched medical resources, as efforts are made to build more harmonious physician-patient relationships.

BackgroundIt has reached a consensus that patients with amyotrophic lateral sclerosis (ALS) could display cognitive impairment characterized by executive dysfunction or even dementia, but cognitive spectrum of Chinese patients with ALS still waits to be documented.MethodsA total of 106 incident patients with sporadic ALS were enrolled and comprehensive neuropsychological tests covering memory, executive function, attention, language, and visuospatial function were administered to them. Neuropsychological performances of 76 age- and education- matched healthy controls were used for the purpose of classification and comparison.Results106 patients were categorized into 4 subtypes:84 (79.2%) ALS with normal cognition (ALS-NC), 12 (11.3%) ALS with executive cognitive impairment (ALS-ECI), 5 (4.7%) ALS with non-executive cognitive impairment (ALS-NECI), and 5 (4.7%) ALS with frontotemporal lobe degeneration (ALS-FTLD). Under the same criteria, 2 (2.6%) and 1 (1.3%) healthy controls were diagnosed as ECI and NECI, respectively. The proportion of ECI was significantly higher in non-demented ALS than that in healthy controls, but it was not for NECI. Patients with ALS-FTLD had significantly severer bulbar function and older age than those with ALS-NC.ConclusionComorbid FTLD occurred in around 5% of Chinese sporadic ALS cases. Different genetic background and unique age distribution of Chinese ALS patients might be the reasons for the relatively low rate of comorbid FTLD. Cognitive dysfunction, predominant but not exclusive in executive area, was present in around 16% of non-demented ALS patients.