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Crowdsourcing Difficult-to-Collect Epidemiological Data in Pandemics: Lessons from Ebola to the current COVID-19 Pandemic

 

Curator: Stephen J. Williams, Ph.D.

 

At the onset of the COVID-19 pandemic, epidemiological data from the origin of the Sars-Cov2 outbreak, notably from the Wuhan region in China, was sparse.  In fact, official individual patient data rarely become available early on in an outbreak, when that data is needed most. Epidemiological data was just emerging from China as countries like Italy, Spain, and the United States started to experience a rapid emergence of the outbreak in their respective countries.  China, made of 31 geographical provinces, is a vast and complex country, with both large urban and rural areas.

 

 

 

As a result of this geographical diversity and differences in healthcare coverage across the country, epidemiological data can be challenging.  For instance, cancer incidence data for regions and whole country is difficult to calculate as there are not many regional cancer data collection efforts, contrasted with the cancer statistics collected in the United States, which is meticulously collected by cancer registries in each region, state and municipality.  Therefore, countries like China must depend on hospital record data and autopsy reports in order to back-extrapolate cancer incidence data.  This is the case in some developed countries like Italy where cancer registry is administered by a local government and may not be as extensive (for example in the Napoli region of Italy).

 

 

 

 

 

 

Population density China by province. Source https://www.unicef.cn/en/figure-13-population-density-province-2017

 

 

 

Epidemiologists, in areas in which data collection may be challenging, are relying on alternate means of data collection such as using devices connected to the internet-of-things such as mobile devices, or in some cases, social media is becoming useful to obtain health related data.  Such as effort to acquire pharmacovigilance data, patient engagement, and oral chemotherapeutic adherence using the social media site Twitter has been discussed in earlier posts: (see below)

Twitter is Becoming a Powerful Tool in Science and Medicine at https://pharmaceuticalintelligence.com/2014/11/06/twitter-is-becoming-a-powerful-tool-in-science-and-medicine/

 

 

 

 

 

Now epidemiologists are finding crowd-sourced data from social media and social networks becoming useful in collecting COVID-19 related data in those countries where health data collection efforts may be sub-optimal.  In a recent paper in The Lancet Digital Health [1], authors Kaiyuan Sun, Jenny Chen, and Cecile Viboud present data from the COVID-19 outbreak in China using information collected over social network sites as well as public news outlets and find strong correlations with later-released government statistics, showing the usefulness in such social and crowd-sourcing strategies to collect pertinent time-sensitive data.  In particular, the authors aim was to investigate this strategy of data collection to reduce the time delays between infection and detection, isolation and reporting of cases.

The paper is summarized below:

Kaiyuan Sun, PhD Jenny Chen, BScn Cécile Viboud, PhD . (2020).  Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study.  The Lancet: Digital Health; Volume 2, Issue 4, E201-E208.

Summary

Background

As the outbreak of coronavirus disease 2019 (COVID-19) progresses, epidemiological data are needed to guide situational awareness and intervention strategies. Here we describe efforts to compile and disseminate epidemiological information on COVID-19 from news media and social networks.

Methods

In this population-level observational study, we searched DXY.cn, a health-care-oriented social network that is currently streaming news reports on COVID-19 from local and national Chinese health agencies. We compiled a list of individual patients with COVID-19 and daily province-level case counts between Jan 13 and Jan 31, 2020, in China. We also compiled a list of internationally exported cases of COVID-19 from global news media sources (Kyodo News, The Straits Times, and CNN), national governments, and health authorities. We assessed trends in the epidemiology of COVID-19 and studied the outbreak progression across China, assessing delays between symptom onset, seeking care at a hospital or clinic, and reporting, before and after Jan 18, 2020, as awareness of the outbreak increased. All data were made publicly available in real time.

Findings

We collected data for 507 patients with COVID-19 reported between Jan 13 and Jan 31, 2020, including 364 from mainland China and 143 from outside of China. 281 (55%) patients were male and the median age was 46 years (IQR 35–60). Few patients (13 [3%]) were younger than 15 years and the age profile of Chinese patients adjusted for baseline demographics confirmed a deficit of infections among children. Across the analysed period, delays between symptom onset and seeking care at a hospital or clinic were longer in Hubei province than in other provinces in mainland China and internationally. In mainland China, these delays decreased from 5 days before Jan 18, 2020, to 2 days thereafter until Jan 31, 2020 (p=0·0009). Although our sample captures only 507 (5·2%) of 9826 patients with COVID-19 reported by official sources during the analysed period, our data align with an official report published by Chinese authorities on Jan 28, 2020.

Interpretation

News reports and social media can help reconstruct the progression of an outbreak and provide detailed patient-level data in the context of a health emergency. The availability of a central physician-oriented social network facilitated the compilation of publicly available COVID-19 data in China. As the outbreak progresses, social media and news reports will probably capture a diminishing fraction of COVID-19 cases globally due to reporting fatigue and overwhelmed health-care systems. In the early stages of an outbreak, availability of public datasets is important to encourage analytical efforts by independent teams and provide robust evidence to guide interventions.

A Few notes on Methodology:

  • The authors used crowd-sourced reports from DXY.cn, a social network for Chinese physicians, health-care professionals, pharmacies and health-care facilities. This online platform provides real time coverage of the COVID-19 outbreak in China
  • More data was curated from news media, television and includes time-stamped information on COVID-19 cases
  • These reports are publicly available, de-identified patient data
  • No patient consent was needed and no ethics approval was required
  • Data was collected between January 20, 2020 and January 31,2020
  • Sex, age, province of identification, travel history, dates of symptom development was collected
  • Additional data was collected for other international sites of the pandemic including Cambodia, Canada, France, Germany, Hong Kong, India, Italy, Japan, Malaysia, Nepal, Russia, Singapore, UK, and USA
  • All patients in database had laboratory confirmation of infection

 

Results

  • 507 patient data was collected with 153 visited and 152 resident of Wuhan
  • Reported cases were skewed toward males however the overall population curve is skewed toward males in China
  • Most cases (26%) were from Beijing (urban area) while an equal amount were from rural areas combined (Shaanzi and Yunnan)
  • Age distribution of COVID cases were skewed toward older age groups with median age of 45 HOWEVER there were surprisingly a statistically high amount of cases less than 5 years of age
  • Outbreak progression based on the crowd-sourced patient line was consistent with the data published by the China Center for Disease Control
  • Median reporting delay in the authors crowd-sourcing data was 5 days
  • Crowd-sourced data was able to detect apparent rapid growth of newly reported cases during the collection period in several provinces outside of Hubei province, which is consistent with local government data

The following graphs show age distribution for China in 2017 and predicted for 2050.

projected age distribution China 2050. Source https://chinapower.csis.org/aging-problem/

 

 

 

 

 

 

 

 

 

 

 

 

The authors have previously used this curation of news methodology to analyze the Ebola outbreak[2].

A further use of the crowd-sourced database was availability of travel histories for patients returning from Wuhan and onset of symptoms, allowing for estimation of incubation periods.

The following published literature has also used these datasets:

Backer JA, Klinkenberg D, Wallinga J: Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20-28 January 2020. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 2020, 25(5).

Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, Azman AS, Reich NG, Lessler J: The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Annals of internal medicine 2020, 172(9):577-582.

Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, Ren R, Leung KSM, Lau EHY, Wong JY et al: Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. The New England journal of medicine 2020, 382(13):1199-1207.

Dataset is available on the Laboratory for the Modeling of Biological and Socio-technical systems website of Northeastern University at https://www.mobs-lab.org/.

References

  1. Sun K, Chen J, Viboud C: Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study. The Lancet Digital health 2020, 2(4):e201-e208.
  2. Cleaton JM, Viboud C, Simonsen L, Hurtado AM, Chowell G: Characterizing Ebola Transmission Patterns Based on Internet News Reports. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2016, 62(1):24-31.

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Opinion Articles from the Lancet: COVID-19 and Cancer Care in China and Africa

Reporter: Stephen J. Williams, PhD

Cancer Patients in SARS-CoV-2 infection: a nationwide analysis in China

Wenhua Liang, Weijie Guan, Ruchong Chen, Wei Wang, Jianfu Li, Ke Xu, Caichen Li, Qing Ai, Weixiang Lu, Hengrui Liang, Shiyue Li, Jianxing He

Lancet Oncol. 2020 Mar; 21(3): 335–337. Published online 2020 Feb 14. doi: 10.1016/S1470-2045(20)30096-6

PMCID: PMC7159000

 

The National Clinical Research Center for Respiratory Disease and the National Health Commission of the People’s Republic of China collaborated to establish a prospective cohort to monitor COVID-19 cases in China.  As on Jan31, 20202007 cases have been collected and analyzed with confirmed COVID-19 infection in these cohorts.

Results: 18 or 1% of COVID-19 cases had a history of cancer (the overall average cancer incidence in the overall China population is 0.29%) {2015 statistics}.  It appeared that cancer patients had an observable higher risk of COVID related complications upon hospitalization. However, this was a higher risk compared with the general population.  There was no comparison between cancer patients not diagnosed with COVID-19 and an assessment of their risk of infection.  Interestingly those who were also cancer survivors showed an increased incidence of COVID related severe complications compared to the no cancer group.

Although this study could have compared the risk within a cancer group, the authors still felt the results warranted precautions when dealing with cancer patients and issued recommendations including:

  1. Postponing of adjuvant chemotherapy or elective surgery for stable cancer should be considered
  2. Stronger personal protection for cancer patients
  3. More intensive surveillance or treatment should be considered when patients with cancer are infected, especially in older patients

Further studies will need to address the risk added by specific types of chemotherapy: cytolytic versus immunotherapy e.g.

 

Preparedness for COVID-19 in the oncology community in Africa

Lancet Oncology, Verna Vanderpuye, Moawia Mohammed,Ali Elhassan

Hannah Simonds: Published:April 03, 2020DOI:https://doi.org/10.1016/S1470-2045(20)30220-5

Africa has a heterogeneity of cultures, economies and disease patterns however fortunately it is one of the last countries to be hit by the COVID-19 pandemic, which allows some time for preparation by the African nations.  The authors note that with Africa’s previous experiences with epidemics, namely ebola and cholera, Africa should be prepared for this pandemic.

However, as a result of poor economic discipline, weak health systems, and poor health-seeking behaviors across the continent, outcomes could be dismal. Poverty, low health literacy rates, and cultural practices that negatively affect cancer outcomes will result in poor assimilation of COVID-19 containment strategies in Africa.”

In general African oncologists are following COVID-19 guidelines from other high-income countries, but as this writer acknowledges in previous posts, there was a significant lag from first cases in the United States to the concrete formulation of guidelines for both oncologists and patients with regard to this pandemic.  African oncologist are delaying the start of adjuvant therapies and switching more to oral therapies and rethink palliative care.

However the authors still have many more questions than answers, however even among countries that have dealt with this pandemic before Africa (like Italy and US), oncologists across the globe still have not been able to answer questions like: what if my patient develops a fever, what do I do during a period of neutropenia, to their satisfaction or the satisfaction of the patient.  These are questions even oncologists who are dealing in COVID hotspots are still trying to answer including what constitutes a necessary surgical procedure? As I have highlighted in recent posts, oncologists in New York have all but shut down all surgical procedures and relying on liquid biopsies taken in the at-home setting. But does Africa have this capability of access to at home liquid biopsy procedures?

In addition, as I had just highlighted in a recent posting, there exists extreme cancer health disparities across the African continent, as well as the COVID responses. In West Africa, COVID-19 protocols are defined at individual institutions.  This is more like the American system where even NCI designated centers were left to fashion some of their own guidelines initially, although individual oncologists had banded together to do impromptu meetings to discuss best practices. However this is fine for big institutions, but as in the US, there is a large rural population on the African continent with geographical barriers to these big centers. Elective procedures have been cancelled and small number of patients are seen by day.  This remote strategy actually may be well suited for African versus more developed nations, as highlighted in a post I did about mobile health app use in oncology, as this telemedicine strategy is rather new among US oncologists (reference my posts with the Town Hall meetings).

The situation is more complicated in South Africa where they are dealing with an HIV epidemic, where about 8 million are infected with HIV. Oncology services here are still expecting to run at full capacity as the local hospitals deal with the first signs of the COVID outbreak. In Sudan, despite low COVID numbers, cancer centers have developed contingency plans. and are deferring new referrals except for emergency cases.  Training sessions for staff have been developed.

For more articles in this online open access journal on Cancer and COVID-19 please see our

Coronovirus Portal
Responses to the #COVID-19 outbreak from Oncologists, Cancer Societies and the NCI: Important information for cancer patients

 

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The Implications of a Newly Discovered  CYP2J2 Gene Polymorphism  Associated with Coronary Vascular Disease in the Uygur Chinese Population

Author, Curator: Larry H Bernstein, MD, FCAP

This is an interesting genomic study of the relationship of genetic polymorphism in the Chinese Uygur population that highlights the difficulty in CVD genomics, and casts a promising light on difficulties over
1.  possibly no more than 8 genetic signatures to account for all of human CVD conditions
2.  genetic signatures may no be equally distributed over studied populations
3.  genetic signatures may be more pronounced in different populations
4.  there is little predictable validity in such studies over large assimilated populations (such as African-Americans
5.  the best genomic evidence for meaningful associations does appear to tie in with endothelial metabolism
6.  the greatest difficulty in all studies is the small dose of information provided by an such linkage
7.  there has been too little information provided in studies of the effect of dietary factors on the affected population, which would entail nutrigenomics.
8.  there is an association between certain distinct CVD’s and later development of coronary heart disease (CHD).
This study concepts, methods and difficulties were recently reviewed in the following articles:
Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging
Aviva Lev-Ari, PhD, RN
Genomics & Genetics of Cardiovascular Disease Diagnoses: A Literature Survey of AHA’s Circulation Cardiovascular Genetics, 3/2010 – 3/2013
Aviva Lev-Ari, PhD, RN and Larry H Bernstein, MD, FCAP
Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems
Aviva Lev-Ari, PhD, RN and Larry H Bernstein, MD, FCAP
Hypertension and Vascular Compliance: 2013 Thought Frontier – An Arterial Elasticity Focus
Justin D. Pearlman, MD, PhD, and Aviva Lev-Ari, PhD, RN
Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination?
Aviva Lev-Ari, PhD, RN
Vascular Medicine and Biology: CLASSIFICATION OF FAST ACTING THERAPY FOR PATIENTS AT HIGH RISK FOR MACROVASCULAR EVENTS Macrovascular Disease – Therapeutic Potential of cEPCs
Aviva Lev-Ari, PhD, RN
Endothelial Function and Cardiovascular Disease
Larry H Bernstein, MD, FCAP
Reversal of Cardiac Mitochondrial Dysfunction
Larry H Bernstein, MD, FCAP
A Second Look at the Transthyretin Nutrition Inflammatory Conundrum
Larry H Bernstein, MD, FCAP

A Novel Polymorphism of the CYP2J2 Gene is Associated with Coronary Artery Disease in Uygur Population in China

Qing Zhu, Zhenyan Fu, Yitong Ma, Hong Yang, Ding Huang, Xiang Xie, Fen Liu, Yingying Zheng, Erdenbat Cha
PII: S0009-9120(13)00174-4    Available online 15 May 2013
Reference: CLB 8375
To appear in: Clinical Biochemistry
Received date: 17 February 2013
Revised date: 13 April 2013
Accepted date: 3 May 2013
Background: Cytochrome P450 (CYP) 2J2 is expressed in the vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs).
  • The EETs are potent endogenous vasodilators and
  • inhibitors of vascular inflammation.
The aim of the present study was to assess the association between the human CYP2J2 gene polymorphism and coronary artery disease (CAD) in a Han and Uygur population of China.
We use two independent case-control studies:
  1. a Han population (206 CAD patients and 262 control subjects) and
  2. a Uygur population (336 CAD patients and 448 control subjects).
All CAD patients  and controls were genotyped for the same three single nucleotide polymorphisms (SNPs)
  1. rs890293
  2. rs11572223
  3. rs2280275
of CYP2J2 gene by a Real-time PCR instrument.
Results: In the Uygur population, for total, the distribution of SNP3 (rs2280275) genotypes showed a significant difference between CAD and control participants (P=0.048).
For total and men, the distribution of SNP3 (rs2280275) alleles and the dominant model (CC vs CT + TT)
  • showed a significant difference between CAD and control participants (for allele: P=0.014 and P=0.035, respectively; for dominant model: P=0.014 and P=0.034, respectively).
The significant difference in dominant model was retained after adjustment for covariates (OR: 0.279, 95% confidence interval [CI]: 0.176-0.440, P=0.001; OR: 0.240, 95% CI: 0.128-0.457, P=0.001, respectively).
Conclusions: The CC genotype of rs2280275 in CYP2J2 gene could be a protective genetic marker of CAD and T allele may be a risk genetic marker of CAD in men of Uygur population in China.
Highlights:
1. We used two independent case-control studies: one was in a Han population and the other was in a Uygur population.
2. The CC genotype of rs2280275 in CYP2J2 gene could be a protective genetic marker of CAD and T allele may be a risk genetic marker of CAD in men of Uygur population in China.
3. Polymorphism of the CYP2J2 gene can affect the synthesis of epoxyeicosatrienoic acids (EETs).
Reviewer Observations:
This article describes the association between CYP2J2 polymorphism(SNP1, SNP2 and SNP3) and coronary artery disease (CAD) in two populations of China (Han and Uygur).
Results show that
  1. the frequency of T allele of rs2280275 (SNP3 of the CYP2J2) is higher in CAD patients than in control subjects and
  2. that CC genotype of rs 2280275 is significantly lower in CAD patients than in control subjects.
  3. “T allele of rs2280275 was significantly higher in CAD patients than in control participants. CC genotype of rs2280275 was significantly lower in CAD patients than in control participants.”;
  4. It appears that CC is the homozygous and dominant state of this SNP3 sequence in a pairing-combination.
  5. The effect of decreased CHD is seen only in the CC double combination, in men and not women. The difference between men and women with CAD is in LDL.
For Uygur population,
(1) after adjusting major confounding factors such as Glu、LDL、EH、DM and smoking, the effect of decreased CAD is seen only in the CC double combination, in men and not women.
(2) for men, the LDL level is higher in CAD than in control, for women, there isn’t a difference of LDL level between CAD and control.
(3) for men, the distribution of T and C allele is different between CAD and control (p=0.035), and not in women (p=0.118).
The T allele of SNP3 is increased in CAD. So the C allele is important, and a CT pair is neutral. Neither SNP1 or SNP2, or presumably both have lower incidence.

I might conjecture that having(heterozygous rs2280275), a C & a T, and eating a lot of fish and/or flax seed would show a difference

  • because of the intimal enzymatic conversion of arachidonic acid to EETs.

Arachidonic acid is a derivative of linoleic acid,an n-6 PUFA, while linolenic acid is an omega-3 PUFA. Substantial documentation of the effect of EETs is given. The anti-inflammatory advantage of an n-3 PUFA is also known.
It appears that the intimal conversion results in an omega-3 product.  In addition, the EET activates eNOS, so that there is endothelial NO produced.

The studies of both Spiecker and Ping Yin Liu showed the polymorphism of CYP2J2 (rs890293, SNP1) has relation with CAD. However, in this study, the authors found there was no association between the polymorphism of CYP2J2 (rs890293, SNP1) and CAD in Han population and Uygur population. We found (rs 2280275, SNP3) has association with CAD.
  • “The CC genotype of rs2280275 in CYP2J2 gene could be a protective genetic marker of CAD and T allele may be a risk genetic marker of CAD in men of Uygur population in China”
All participants had a differential diagnosis for chest pain encountered in the Cardiac Catheterization Laboratory of First Affiliated Hospital of Xinjiang Medical University. We recruited randomly CAD group and control group, subjects with valvular disease were excluded, control subjects were not healthy individuals, some of them have hypertension, some of them have DM, some of them have hyperlipidemia, which means control group expose to the same risk factors of CAD while the results of coronary angiogram is normal. All control subjects underwent a coronary angiogram and have no coronary artery stenosis.
The analysis was a logistic regression analysis, we used the major variables of CAD to analysis and found the CC genotype was the dependent useful factor after adjusting for major confounding factors such as Glu、LDL、EH、DM and smoking.
Schematic of EET interactions with cardiovascularion channels.
A: In the cardiac myocyte, EETs activate sarcolemmal or mitochondrial KATP channels.
B: In the vasculature, EETs activate endothelial small-(SKCa) or intermediate (IKCa)–conductance calcium-activated channels to cause hyperpolarization, which can be transmitted to the vascular smooth muscle via myoendothelial gap junctions. EETs also activate TRPV4 channels to activate Ca2+influx. In the vascular smooth muscle, EETs activate large conductance, calcium-activated (BK-Ca) channels through a G protein-Coupled event.
C: In platelets, EETs activate BK-Ca channels.calcium-activated (BK-Ca) channels through a G-protein-coupled event. C, In platelets, EETs activate BK-Ca channels.

Association of the ADRA2A polymorphisms with the risk of type 2 diabetes: A meta-analysis

Xi Chen, Lei Liu, Wentao He, Yu Lu, Delin Ma, Tingting Du, Qian Liu, Cai Chen, Xuefeng Yu
Clinical Biochemistry 2013;  46 (9): 722–726   http://dx.doi.org/10.1016/j.clinbiochem.2013.02.004
Results from the published studies on the association of ADRA2A (adrenoceptor alpha 2A) variants with type 2 diabetes (T2D) are conflicting and call for further assessment. The aim of this meta-analysis was to quantitatively summarize the effects of the two recently reported ADRA2A single nucleotide polymorphisms (SNPs) rs553668 and rs10885122 on T2D risk.
Results
Twelve studies with 40,828 subjects from seven eligible papers were included in the meta-analysis. Overall, the present meta-analysis failed to support a positive association between ADRA2A SNPs (rs553668 and rs10885122) and susceptibility to T2D (OR = 1.05, p = 0.17, 95% CI: 0.98, 1.12; and OR = 1.06, p = 0.11, 95% CI: 0.99, 1.13; respectively).
However, in the subgroup analysis by ethnicity, the significant association between rs553668 and the risk of T2D was obtained in Europeans under the recessive genetic model (OR = 1.36, p = 0.02, 95% CI: 1.05, 1.76).
Conclusion
The results of the meta-analyses indicated that both SNPs were associated with CHD in Caucasians (P < 0.05) but not in Asians. The results from our case-control study and meta-analyses might be explained by genetic heterogeneity in the susceptibility of CHD and ethnic differences between Asians and Caucasians.

Association between PCSK9 and LDLR gene polymorphisms with coronary heart disease: Case-control study and meta-analysis

Lina Zhang, Fang Yuan, Panpan Liu, Lijuan Fei, Yi Huang, Limin Xu, et al.
Clinical Biochemistry 2013; 46 (9): 727–732
► Association of rs11206510 and rs1122608 with CHD in 813 Chinese participants.
► The first association test of rs1122608 with the risk of CHD in Han Chinese.
► Meta-analyses were performed for rs11206510 and rs1122608.
► The two SNPs were associated with CHD in Caucasians but not in Asians.
Objective
To explore the association of rs11206510 (PCSK9 gene) and rs1122608 (LDLR gene) polymorphisms with coronary heart disease (CHD) in Han Chinese.
Methods
A total of 813 participants (290 CHD cases, 193 non-CHD controls and 330 healthy controls) were recruited in the case-control study. DNA genotyping was performed on the SEQUENOM® Mass–ARRAY iPLEX® platform. χ2-test was used to compare the genotype distribution and allele frequencies. Two meta-analyses were performed to establish the association between the two polymorphisms with CHD.
Results
No significant associations between the two SNPs and the risk of CHD were observed in the present study. The meta-analysis of rs11206510 of PCSK9 gene comprises 11 case-control studies with a total of 69,054 participants. Significant heterogeneity was observed in Caucasian population in subgroup analysis of the association studies of rs11206510 with CHD (P = 0.003, I2 = 67.2%). The meta-analysis of LDLR gene rs1122608 polymorphism comprises 7 case-control studies with a total of 20,456 participants and the heterogeneity of seven studies was minimal (P = 0.148, I2 = 36.7%).
Conclusion
The results of the meta-analyses indicated that both SNPs were associated with CHD in Caucasians (P < 0.05) but not in Asians.

The effect of hyperhomocysteinemia on aortic distensibility in healthy individuals

I Eleftheriadou, P Grigoropoulou, I Moyssakis, A Kokkinos. et al.
Nutrition 18 Feb 2013; 29 (6): 876-880, PII: S0899-9007(13)00015-4
Elevated plasma homocysteine (HCY) levels have been associated with increased risk for cardiovascular disease. Aortic distensibility and aortic pulse wave velocity (PWV) are indices of aortic elasticity. The aim of the present study was to determine the effect of acute methionine-induced HHCY on aortic distensibility and PWV in healthy individuals and the effect of acute HHCY on myocardial performance of the left ventricle (Tei index).
Thirty healthy volunteers were included in this crossover study. Aortic distensibility and Tei index were determined non-invasively by ultrasonography at baseline and 3 h after methionine or water consumption, while PWV was measured by applanation tonometry at baseline and every 1 h for the same time interval.
Oral methionine induced an increase in total plasma HCY concentrations (P < 0.001), whereas HCY concentrations did not change after water consumption. Aortic distensibility decreased 3 h after methionine load (P < 0.001) and Tei index increased (P < 0.001), suggesting worsening compared with baseline values. Water consumption had no effect on aortic distensibility or Tei index values. PWV values did not change after either methionine or water consumption.
Acute methionine-induced HHCY reduces aortic distensibility and worsens myocardial performance in healthy individuals. Further research is warranted to examine in the long term the direct effects of HHCY on cardiovascular function and the indirect effects on structural remodeling.
Micrograph of an artery that supplies the hear...

Micrograph of an artery that supplies the heart with significant atherosclerosis and marked luminal narrowing. Tissue has been stained using Masson’s trichrome. (Photo credit: Wikipedia)

Estimated propability of death or non-fatal my...

Estimated propability of death or non-fatal myocardial-infarction over one year corresponding ti selectet values of the individual scores. Ordinate: individual score, abscissa: Propability of death or non-fatal myocardial infarction in 1 year (in %) (Photo credit: Wikipedia)

 

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Reporter: Aviva Lev-Ari, PhD, RN

Gordon H. Sun, M.D., Jeffrey D. Steinberg, Ph.D., and Reshma Jagsi, M.D., D.Phil.

N Engl J Med 2012; 367:687-690   August 23, 2012

Since the founding of the National Institutes of Health (NIH) and the National Science Foundation (NSF) more than six decades ago, the United States has maintained a preeminent position as a government sponsor of medical research. That primacy is being tested, however, by potent economic challenges. The NIH’s proposed budget for fiscal year 2013 would freeze baseline funding at 2012 levels, continuing a decade-long failure to keep pace with the rising costs of conducting medical research. Across-the-board cuts mandated by the Budget Control Act (BCA) of 2011 will also affect medical research, with the NIH, NSF, and other federal research sponsors sustaining budgetary reductions of about 8% next year.

Cuts to government-funded research will have adverse long-term effects on the health care system and the economy and may irreversibly compromise the work of laboratories long accustomed to receiving stable federal support. Moreover, many medical researchers could transfer their knowledge and resources abroad. In fact, five emerging Asian economic or technological powers — China, India, South Korea, Taiwan, and Singapore — already have medical research policies in place that are filling the void being created by ever more restrictive U.S. funding.

Several U.S.-based economists have justified increasing research budgets on the premise that medical discoveries have intrinsically high economic value. For example, Murphy and Topel have suggested that eliminating deaths related to heart disease had an estimated worth of $48 trillion, and a 1% reduction in cancer-related mortality could save $500 billion.1 Beyond these ambitious goals, however, are more practical arguments favoring support for medical research.

Local and regional economic benefits are one example. A June 2008 analysis by Families USA showed that during the NIH’s fiscal year 2007, nearly $23 billion in grants and contracts supported more than 350,000 jobs, with each dollar generating more than twice as much in direct state economic output in the form of goods and services. The NIH reported that almost 1 million Americans worked in for-profit medical businesses in 2008, earning $84 billion and generating $90 billion in goods and services, reinforcing the importance of preserving the U.S. position as a “knowledge hub” for medical research.2 Nevertheless, BCA cuts next year could result in at least 2500 fewer NIH grants, 33,000 fewer jobs, and a $4.5 billion loss in economic activity.3 Since the NIH’s budget represents less than 1% of overall federal spending, policymakers must reconsider whether shaving 8% from NIH outlays will have a noticeable positive effect on the national deficit or economy.

Fallout from funding cuts could include shifts in the U.S. medical research workforce. In 2000, the National Research Council noted both an overall shortage of medical researchers and inadequate funding for scientists working in the United States, which coincided with a decline in the number of funded NIH grant applications from 31% in fiscal year 2002 to 19% in 2010. This change is particularly critical for postdoctoral researchers, who represent the majority of the U.S. biomedical science workforce. According to the NSF, nearly half the 14,601 new postdoctoral-level researchers who were trained in the United States in 2009 were not U.S. citizens or permanent residents. If U.S. institutions are willing to devote money, training, and infrastructure to support talented, committed researchers, it would be an illogical waste of resources and poor long-term strategy to reduce federal grant mechanisms and wipe out potential job opportunities. Indeed, declining financial support may well encourage medical researchers to seek employment elsewhere.

As compared with the United States, China, India, South Korea, Taiwan, and Singapore have taken a sharply different view of medical research and have developed policies that foster medical research as an engine for economic growth and intellectual innovation (see tableMajor Government Agencies in Asia and Their Budgets for Medical Research.). Their national budgets are heavily based on scientific research and development, and funding is increasing, with budgetary targets ranging from 2 to 5% of their gross domestic products (GDPs). India’s funding goal for medical research alone is 2% of its GDP.

Increased funding for research infrastructure attracts scientists and organizations interested in high-quality research, including clinical trials. During the past two decades, increasing numbers of clinical trials have moved overseas, where benefits can include decreased costs of doing business, fewer administrative regulations, and greater enrichment of international relationships among researchers. The average annual rate of growth in clinical trials has been highest in China — 47% — while the number conducted in the United States has decreased by an average of 6.5% annually.4 In addition, the increased attention paid to Asia by private firms and other nongovernmental organizations has spurred rapid policy-level responses to concerns about the lack of informed consent, transparency, and other ethical issues, thus further strengthening the appeal of conducting research in the region.

Asian policies reflect a recognition of the extrinsic economic benefits of medical research. China and India have advocated for more government-funded medical research to improve health-related outcomes. China has espoused increased spending as part of achieving xiaokang, a Confucian term meaning a moderately prosperous society. In 2007, India inaugurated its Department of Health Research, which coordinates biomedical science and health-services research programs and translates their findings to address public health concerns. Since the signing of the Korean War Armistice Agreement in 1953, South Korea has leaned heavily on government-funded research to reduce poverty, allowing the country to gradually acquire advanced technologies and expertise. Medical research is part of at least two core technology areas in South Korea’s “577 Initiative”: medical technologies, such as neuroimaging, to address the needs of an aging population and research on issues pertaining to national safety and public health, such as infectious-disease preparedness and food safety.

National research and development programs have been a fundamental component of Taiwan’s economic policy for at least five decades. In 2005, the country began developing “intelligent medical care” — similar to earlier U.S. initiatives — which integrates medical information technology with quality-improvement measures. In Singapore, medical research and economic oversight are administratively linked. For example, the Biomedical Sciences Group of the Economic Development Board supports researchers financially and designs strategies that enhance Singapore’s status as a knowledge center, and the private firm Bio*One Capital invests directly in promising medical technologies.

The diverse strategies outlined above allow Asian countries to systematically recruit medical researchers from both home and abroad. China is particularly proactive in enticing Chinese-born, U.S.-educated researchers to return to their native country by offering generous financial and material incentives under its Knowledge Innovation Program. As the vice president of the Chinese Academy of Sciences stated more than a decade ago, modern “research and development is actually a war for more talented people.”5 In 2000, Singapore jump-started its Biomedical Sciences Initiative to attract medical researchers worldwide with a direct $2 billion investment, as well as with tax incentives for internal biotechnology start-ups and global pharmaceutical firms. In Singapore and India, English is the primary language for scientific communications, which alleviates concerns about language barriers.

For two decades, emerging Asian countries have been designing long-term strategies to reap the benefits of medical research. Meanwhile, the United States is relying on short-term solutions to support its medical research infrastructure, such as those offered by the Patient Protection and Affordable Care Act and the American Recovery and Reinvestment Act. Decreased investment in U.S. medical research could lead to long-term economic damage for the United States and the loss of its stature as a global leader in the field. Powerful incentives that can retain an elite biomedical-research workforce are necessary to strengthen the U.S. health care system and economy.

The views expressed in this article are those of the authors and do not necessarily reflect those of the Robert Wood Johnson Foundation, the Department of Veterans Affairs, or the Agency for Science, Technology, and Research.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

SOURCE INFORMATION

From the Robert Wood Johnson Foundation Clinical Scholars Program (G.H.S., R.J.), the Department of Otolaryngology (G.H.S.), and the Department of Radiation Oncology (R.J.), University of Michigan, and the Health Services Research and Development Service, VA Ann Arbor Healthcare System (G.H.S.) — both in Ann Arbor, MI; and the Singapore Bioimaging Consortium, Agency for Science, Technology, and Research, Singapore (J.D.S.).

http://www.nejm.org/doi/full/10.1056/NEJMp1206643?query=TOC

 

 

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