Expenditure and financial burden for the diagnosis and treatment of colorectal cancer in China:a hospital.based,multicenter,cross-sectional survey

Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment. We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods: We conducted a multicenter, cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014. Each enrolled patient was interviewed using a structured questionnaire. All expenditure data were inflated to the 2014 Chinese Yuan(CNY; 1 CNY = 0.163 USD). We quantified the overall expenditure and financial burden and by subgroup(hospital type, age at diagnosis, sex, education, occupation, insurance type, household income, clinical stage, pathologic type, and therapeutic regimen). We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results: A total of 2356 patients with a mean age of 57.4 years were included, 57.1 % of whom were men; 13.9% of patients had stage I cancer; and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY, and the expenditures for stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ disease were 56,099 CNY, 59,952 CNY, 67,292 CNY, and 82,729 CNY, respectively. Non-medical expenditure accounted for 8.3%of the overall expenditure. The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY, which accounted for 59.9% of their previous-year household income and caused 75.0% of families to suffer an unmanageable financial burden. Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups(P < 0.05), except for sex. Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less(all P < 0.05).Conclusions: For patients in China, direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable. The financial burden varied among subgroups, especially among patients with different clinical stages of disease, which suggests that, in China, CRC screening might be cost-effective.

Progressing our knowledge of enterovirus:Epidemiology,diagnosis,prevention,control,and beyond

We are thrilled to present this dedicated issue spotlighting enterovirus infections and health in Biosafety and Health.The articles presented in this issue span the broad spectrum of current research in this vital field,providing insights into the epidemiology,diagnostic procedures,and pathogenesis of enterovirus infections.Enteroviruses,a genus of RNA viruses encompassing polioviruses,coxsackieviruses,and echoviruses,play a crucial role in public health.

Characterizing a large outbreak of dengue fever in Guangdong Province, China

Background:Dengue cases have been reported each year for the past 25 years in Guangdong Province,China with a recorded historical peak in 2014.This study aims to describe the epidemiological characteristics of this large outbreak in order to better understand its epidemic factors and to inform control strategies.Methods:Data for clinically diagnosed and laboratory-confirmed dengue fever cases in 2014 were extracted from the China Notifiable Infectious Disease Reporting System.We analyzed the incidence and characteristics of imported and indigenous cases in terms of population,temporal and spatial distributions.Results:A total of 45224 dengue fever cases and 6 deaths were notified in Guangdong Province in 2014,with an incidence of 47.3 per 100000 people.The elderly(65+years)represented 11.7%of total indigenous cases with the highest incidence(72.3 per 100000).Household workers and the unemployed accounted for 23.1%of indigenous cases.The majority of indigenous cases occurred in the 37th to 44th week of 2014(September and October)and almost all(20 of 21)prefecture-level cities in Guangdong were affected.Compared to the non-Pearl River Delta Region,the Pearl River Delta Region accounted for the majority of dengue cases and reported cases earlier in 2014.Dengue virus serotypes 1(DENV-1),2(DENV-2)and 3(DENV-3)were detected and DENV-1 was predominant(88.4%).Conclusions:Dengue fever is a serious public health problem and is emerging as a continuous threat in Guangdong Province.There is an urgent need to enhance dengue surveillance and control,especially for the high-risk populations in high-risk areas.

Transmission Dynamics of an Outbreak of the COVID-19 Delta Variant B.1.617.2——Guangdong Province,China,May-June 2021

On May 21,2021,a local case of coronavirus disease 2019(COVID-19)was confirmed in a 75-year-old woman(experienced onset of symptoms on May 18)in Liwan District,Guangzhou City,Guangdong Province,China.The number of infections has increased in the following 10 days and led to 5 generations of transmission.

Medical expenditure for esophageal cancer in China:a 10-year multicenter retrospective survey(2002-2011)

Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan(CNY; 1 CNY = 0.155 USD) based on the2011 value and inflated using the year-specific health care consumer price index for China.Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27% was observed from 2002(25,111 CNY) to 2011(46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ,39,302 CNY for stage Ⅱ,40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases(P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy(P < 0.05).Drugs contributed to 45.02% of the overall expenditure.Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

Long-Term Trend Analysis of Major Human Helminth Infections — Guangdong Province, China, 1988–2021

Introduction:Although helminth infections threaten millions of people worldwide,the spatiotemporal characteristics remain unclear across China.This study systematically describes the spatiotemporal changes of major human helminth infections and their epidemiological characteristics from 1988 to 2021 in Guangdong Province,China.Methods:The survey data in Guangdong Province were primarily obtained from 3 national surveys implemented during 1988–1992,2001–2004,and 2014–2016,respectively,and from the China Information System for Disease Control and Prevention during 2019–2021.A modified Kato-Katz technique was used to detect parasite eggs in collected fecal samples.Results:The overall standardized infection rates(SIRs)of any soil-transmitted helminths(STH)and Clonorchis sinensis decreased from 65.27%during 1988–1992 to 4.23%during 2019–2021.In particular,the SIRs of STH had even more of a decrease,from 64.41%during 1988–1992 to 0.31%during 2019–2021.The SIRs of Clonorchis sinensis in the 4 surveys were 2.40%,12.17%,5.20%,and 3.93%,respectively.This study observed different permutations of gender,age,occupation,and education level on the SIRs of helminths.Conclusions:The infection rate of STH has substantially decreased.However,the infection rate of Clonorchis sinensis has had fewer changes,and it has become the dominant helminth.

Seroprevalence of human enterovirus A71 in Guangzhou,China,2019-2021

Enterovirus A71 (EV-A71) is a significant hand-foot-mouth disease (HFMD) etiology. The inactivated EV-A71 vaccines were approved in China in 2016. However, the seroprevalence of EV-A71 after the vaccine application and its potential association with the EV-A71 epidemic in the population are rarely studied. In this study, we analyzed the incidence of EV-A71 infection and seroepidemiology in Guangzhou City, China. From 2019 to 2021, 167,920 clinically confirmed HFMD cases were reported in Guangzhou. In 6,868 enterovirus-positive samples, Coxsackievirus A6 and Coxsackievirus A16 were dominant genotypes, and only 3 EV-A71-positive samples were detected, highlighting the deficient epidemic activity of EV-A71. Microneutralization assay was performed on 1,000 representative serum samples. Notably, the seroprevalence and geometric mean titer (GMT) decreased significantly in 2020, and that in the < 3-year age group were increased and even higher than that in 3–5-year age group in 2019 and 2021, which was contrary to our previous surveillance result and other studies in Guangzhou. Furthermore, a moderate decline of GMT level was observed following the vaccination, but the seropositive serums were still detected for 49 months after second immunization, suggesting the long-term persistence of the immunity. Our seroepidemiology study revealed relatively higher neutralizing antibody activity in the susceptible population after the EV-A71 vaccine was adopted in 2016 in Guangzhou. It may be one of the reasons for the lower epidemic activity of EV-A71 in Guangzhou from 2019 to 2021.

STING and TLR9 agonists synergistically enhance the immunogenicity of SARS-CoV-2 subunit vaccine

Vaccines that are reliable and efficacious are essential in the fight against the COVID-19 pandemic.In this study,we designed a dual-adjuvant system with two pathogen-associated molecular patterns(PAMPs),MnOx and CpG.This system can improve the retention of antigens at the injection site,facilitate pro-inflammatory cytokines secretion,further recruit and activate dendritic cells(DCs).As a result,antigens can be delivered to lymph nodes specifically,and adaptive immunity was strengthened.The immunized group showed an enhanced and broadened humoral and cellular immune response in systemic immunity and lung protection when combined with a tandem repeat-linked dimeric antigen version of the SARS-CoV-2 receptor binding domain(RBDdimer).Remarkably,even with a significant reduction in antigen dosage(three times lower)and a decrease in injection frequencies,our nanovaccine was able to produce the highest neutralizing antibody titers against various mutants.These titers were four-fold higher for the wild-type strain and two-fold higher for both the Beta and Omicron variants in comparison with those elicited by the Alum adjuvant group.In conclusion,our dual-adjuvant formulation presents a promising protein subunit-based candidate vaccine against SARS-CoV-2.

Durable and enhanced immunity against SARS-CoV-2 elicited by manganese nanoadjuvant formulated subunit vaccine

Dear editor,Vaccines are the most efficient and effective means to prevent infectious diseases,but improving the long-term protective efficacy is still a major challenge in contemporary vaccine development.1 The waning immunity varies depending on the diversification of the pathogen and the number of booster doses.1 Strategies to overcome this warrant is using adjuvants that amplify the immune response,and drive the production of memory B and T cells or long-lived plasma cells that recognize the pathogen for durable protection.2–4 Although existing adjuvants have achieved promising results,research on generating durable protective immunity is lacking in promoting vaccine development and staying ahead of global pandemics such as coronavirus disease 2019(COVID-19).The precisely designed nanoadjuvants can enhance lymph node targeting and increase antigenpresenting cell(APCs)uptake,achieving the co-delivery of adjuvants and antigens and activating innate and adaptive immune responses.5 Previously,we reported a manganese nanoadjuvant(MnARK)and receptor-binding domain(RBD)monomer antigen formulated nanovaccine.6 MnARK transported antigens to lymph nodes,activated the STING pathway,elicited strong neutralizing abilities and increased immune memory T cell percentage against the infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).6 Regarding the long-term protection potential of MnARK for subunit vaccine development,we further explored the durable immune regulation abilities of MnARK to a SARS-CoV-2 RBD dimer antigen,which has been used in an approved COVID-19 subunit vaccine ZF2001 with aluminum adjuvant(alum).7,8 TEM result revealed that RBD dimer could interact with BSA on MnARK surface and epitope can be well preserved(Supplementary Fig.1a).The size and zeta potential of MnARK-RBD dimer nanovaccine was~58 nm and-14 mV,respectively(Supplementary Fig.1b,c).

The half-degree matters for heat-related health impacts under the 1.5℃ and 2℃ warming scenarios: Evidence from ambulance data in Shenzhen, China

The Paris Agreement has prompted much interest in the societal and health impacts of limiting global warming to 1.5 ℃ and 2 ℃. Previous assessments of differential impacts of two targets indicate that 1.5 ℃ warming target would substantially reduce the impact on human health compared to 2 ℃, but they mainly focused on the magnitude of temperature changes under future climate change scenarios without any consideration of greater frequency of cumulative heat exposures within a day. Here we quantified the health risks of compound daytime and nighttime hot extremes using morbidity data in a megacity of China, and also identified the time-period of heat exposure with higher risks. Then we projected future morbidity burden attributable to compound hot extremes due to the half-degree warming. We estimated that the 2 ℃ warming scenario by 2100 as opposed to 1.5 ℃ would increase annual heat-related ambulance dispatches by 31% in Shenzhen city. Substantial additional impacts were associated with occurrence of consecutive hot days and nights, with ambulance dispatches increased by 82%. Our results suggested that compound hot extremes should be considered in assessment of heat-related health impacts, particularly in the context of climate change. Minimizing the warming of climate in a more ambitious target can significantly reduce the health damage.

Environmental siblings of black agents of human chromoblastomycosis

Agents of human chromoblastomycosis,a skin disease almost exclusively caused by members of the order Chaetothyriales,are assumed to be traumatically inoculated into the skin with sharp environmental materials such as plant thorns or wooden splinters carrying the respective opportunist.In the supposition that such fungi should have their main habitat in the environment,we investigated the occurrence of black fungi in living areas of patients with chromoblastomycosis.In South America Fonsecaea agents are prevalent as agents of the disease,while also related Cladophialophora species,known from other types of skin infections,are known from the continent.Ninety environmental isolates were preliminarily selected as possible agents of chromoblastomycosis,based on morphology.Judging from ITS sequence data isolates were attributed to the genera Cladophialophora,Cyphellophora,Exophiala,Fonsecaea,Phialophora,and Veronaea.A total of 45 fungi morphologically identified as Fonsecaea or Cladophialophora isolated from debris and thorns of living prickly plants in Brazil were processed for taxonomic studies.Phylogenetic analysis revealed that the isolates indeed belonged to the Chaetothyriales,but only rarely an agent of chromoblastomycosis was concerned;only two strains of F.pedrosoi and one F.monophora were isolated from debris plants.The remaining isolates belonged to hitherto unknown molecular siblings of Fonsecaea.Two novel taxa are introduced.

Experiences and Lessons of Combating COVID-19 that Chinese Experts Shared with the World

At the end of 2019,a novel viral pneumonia was detected in Wuhan City(1)and has spread rapidly throughout 215 countries,areas,and territories with more than 3.8 million cases and over 260,000 deaths as of May 8,2020.This pneumonia,later named coronavirus disease 2019(COVID-19),has become a global public security challenge.

Temporal trend of mortality from major cancers in Xuanwei, China

Although a number of studies have examined the etiology of lung cancer in Xuanwei County, China, other types of cancer in this county have not been reported systematically. This study aimed to investigate the temporal trend of eight major cancers in Xuanwei County using data from three mortality surveys （1973-1975, 1990-1992, and 2004-2005）. The Chinese population in 1990 was used as a standard population to calculate age- standardized mortality rates. Cancers of lung, liver, breast, brain, esophagus, leukemia, rectum, and stomach were identified as the leading cancers in this county in terms of mortality rate. During the three time periods, lung cancer remained as the most common type of cancer. The mortality rates for all other types of cancer were lower than those of the national average, but an increasing trend was observed for all the cancers, particularly from 1990-1992 to 2004-2005. The temporal trend could be party explained by changes in risk factors, but it also may be due to the improvement in cancer diagnosis and screening. Further epidemiological studies are warranted to systematically examine the underlying reasons for the temporal trend of the major cancers in Xuanwei County.

Ambient Temperature and Years of Life Lost:A National Study in China

Although numerous studies have investigated premature deaths attributable to temperature,effects of temperature on years of life lost(YLL)remain unclear.We estimated the relationship between temperatures and YLL,and quantified the YLL per death caused by temperature in China.We collected daily meteorological and mortality data,and calculated the daily YLL values for 364 locations(2013–2017 in Yunnan,Guangdong,Hunan,Zhejiang,and Jilin provinces,and 2006–2011 in other locations)in China.A time-series design with a distributed lag nonlinear model was first employed to estimate the location-specific associations between temperature and YLL rates(YLL/100,000 population),and a multivariate meta-analysis model was used to pool location-specific associations.Then,YLL per death caused by temperatures was calculated.The temperature and YLL rates consistently showed U-shaped associations.A mean of 1.02(95%confidence interval:0.67,1.37)YLL per death was attributable to temperature.Cold temperature caused 0.98 YLL per death with most from moderate cold(0.84).The mean YLL per death was higher in those with cardiovascular diseases(1.14),males(1.15),younger age categories(1.31 in people aged 65–74 years),and in central China(1.34)than in those with respiratory diseases(0.47),females(0.87),older people(0.85 in people R75 years old),and northern China(0.64)or southern China(1.19).The mortality burden was modified by annual temperature and temperature variability,relative humidity,latitude,longitude,altitude,education attainment,and central heating use.Temperatures caused substantial YLL per death in China,which was modified by demographic and regional characteristics.

Roll-out of vaccination against COVID-19 pandemic

Background With the rebound of coronavirus disease 2019(COVID19)epidemic in some countries with high vaccination rate,many concerns on vaccine efcacy have emerged.For example,are the current vaccines inefective against severe acute respiratory syndrome coronavirus 2(SARSCOV-2)variants?What’s the status of breakthrough infection?To what extent are non-pharmacological interventions(NPIs)lifted after high vaccination rate?To clarify these questions,we summarized important fndings based on literature and Chinese experience.

Excess mortality, rather than case fatality rate, is a superior indicator to assess the impact of COVID-19 pandemic

Since the end of 2021,the world has been grappling with a series of coronavirus 2019(COVID-19)outbreaks caused by the highly transmissible Omicron variant.Though the Omicron variant has a fatality rate that is lower than other variants and high vaccine coverage,more countries have lifted their non-pharmaceutical interventions(NPIs)and tried to combine natural infection and vaccine immunity to achieve herd immunity so as to coexist with the virus.

When and How to Adjust Non-Pharmacological Interventions Concurrent with Booster Vaccinations Against COVID-19—Guangdong,China,2022

Introduction:With the large-scale roll-out of the coronavirus disease 2019(COVID-19)booster vaccination effort(a vaccine dose given 6 months after completing primary vaccination)in China,we explore when and how China could lift non-pharmacological interventions(NPIs)against COVID-19 in 2022.Methods:Using a modified susceptible-infectiousrecovered(SIR)mathematical model,we projected the COVID-19 epidemic situation and required medical resources in Guangdong Province,China.Results:If the number of people entering from overseas recovers to 20%of the number in 2019,the epidemic in 2022 could be controlled at a low level by a containment(215 local cases)or suppression strategy(1,397 local cases).A mitigation strategy would lead to 21,722 local cases.A coexistence strategy would lead to a large epidemic with 6,850,083 local cases that would overwhelm Guangdong’s medical system.With 50%or 100%recovery of the 2019 level of travelers from overseas,the epidemic could also be controlled with containment or suppression,but enormous resources,including more hotel rooms for border quarantine,will be required.However,coexistence would lead to an uncontrollable epidemic with 12,922,032 local cases.Discussion:With booster vaccinations,the number of travelers from overseas could increase slightly in 2022,but a suppression strategy would need to be maintained to ensure a controllable epidemic.

Association Between COVID-19 Vaccination Coverage and Case Fatality Ratio:a Comparative Study—Hong Kong SAR,China and Singapore,December 2021–March 2022

Summary What is already known about this topic?Hong Kong Special Administrative Region(SAR),China and Singapore are both facing considerable Omicron variant epidemic.However,the overwhelmed medical system and high case fatality ratio(CFR)just occurred in Hong Kong SAR,China but not in Singapore.What is added by this report?The low vaccination coverage in Hong Kong SAR,China,especially among the older adults,is shown to be a primary reason of its recent high CFR.What are the implications for public health practice?Facing the potential epidemic risk,non-vaccinated,non-fully-vaccinated,and non-booster-vaccinated people in China,especially the elderly,should get any type of accessible vaccine,which could save lives when the infection unfortunately befalls.