Friday, January 30, 2009
Dengue and Chikungunya in Singapore - endemicity and ecdemicity
The other thing that caught my eye when I was browsing through the Ministry Of Health Weekly Infectious Disease Bulletins, was the incidence of the two similar viral infectious diseases, Dengue and Chikungunya. They kinda jogged my memory with respect to a recent report that Malaysia was grappling with the worst dengue outbreak ever with about 14 deaths and 5062 cases in the first month of 2009. Malaysia had 49,335 cases with 112 deaths in 2008 and 48,846 cases with 98 deaths the previous year.
Singapore, according to the MOH IDB, seems to have the dengue infections under control over this rainy season. Other than a brief spike over the first week of 2009, the number of reported cases have generally hovered pretty much a levels lower than the mid 2007 cluster.
Interestingly the Chikungunya infections have gone up, and is now hovering at an incidence of about 40-60/week. These two viruses produce a similar kind of illness although chikungunya infections tends to be less likely to cause death. They also probably share the same mosquito vectors, principally Aedes aegypti and Aedes albopictus as well as the same ecological niches. The rise in chikungunya infections relative to dengue is probably related to the fact that chikungunya is a relative newcomer compared to dengue.
Dengue is an infection that is regarded as endemic to Singapore, whereas chikugunya is generally regarded as being ecdemic. The supposed ecdemicity of chikungunya implies that the presence of the disease within the community cannot be sustained without being introduced from external sources. The Ministry of Health data does however, suggest that the chikungunya is fast establishing itself as an endemic problem. Most of the cases are now transmitted locally and are not dependent on imported cases.
Given the similarity in vectors and transmissability between dengue and chikungunya, I don't think there is any doubt chikungunya will establish itself firmly within the community, as it has in many other parts of Asia, and it will only be a matter of time before it will be declared to be endemic in Singapore.
Does it bother me? Not really, because it is a relatively mild disease compared dengue. If we can control the mosquito population in Singapore, we should be able to control both fairly well.
Salmonella
The salmonella does not normally live in the human intestines (at least people don't think they do...). It is however a gut commensal in other animal species, particularly birds.. When we ingest these bugs, the salmonella can cause a bad diarheal disease, sometimes leading to severe dehydration or to a blood borne infection of other organs and even death. This infection is called samonellosis. One specific form of salmonellosis is what is normally recognized by the public as typhoid. See also review from US CDC on Salmonellosis.
Approximately 2 million to 4 million people get sick from salmonella in the United States each year, leading to close to 1,000 deaths. (see report). Our Ministry of Health reported that over the first 3 weeks of January, we had 9 cases of typhoid, 50 cases of salmonellosis and 1 case of paratyphoid. The equivalent figures for 2008 were 5, 76 and 1. For the whole of 2008, the figures were 84, 722 and 29.
The salmonella is frequently is contaminant of diary products, meat and eggs. But the recent contamination of peanut butter is a bit surprising. Normally contamination is disease causing only if the food is uncooked, but here, the contamination of peanut butter (how is not very clear...) led to an epidemic of salmonellosis in the US, with at least 500 people across 43 states affected and eight dying. The puzzle is that the salmonella should have been destroyed by the peanuts roasting and food processing. But this apparently is not a new problem because it happened once before in 2007 (also in Georgia). See Criminal Probe.
Our AVA, after their inspections, have declared us to be safe and free from this strange salmonellosis probelm affecting peanut butter.
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Consumer Advisory- Update on Salmonella Contamination of US Produced Peanut Butter and Products Containing Peanut Butter
25 Jan 09: Further to the Agri-Food and Veterinary Authority of Singapore's (AVA) alert notification on 18 Jan 09 regarding the outbreak of illnesses in the USA caused by Salmonella Typhimurium in peanut butter and peanut paste produced by the Peanut Corporation of America (PCA) at Blakely, Georgia processing plant, AVA has been actively monitoring the developments of the Salmonella contamination incident in the USA. AVA has also intensified its checks on products that contain peanut butter as an ingredient from the USA and other countries.
AVA’s checks confirmed that there is no import of peanut butter products from the affected PCA manufacturing facility into Singapore. Major brands of peanut butter produced in the US are not affected by the recall.
AVA’s tests for Salmonella in food products that contain peanut butter as an ingredient imported/sold in Singapore, found that all the products are not contaminated with Salmonella. Products tested included biscuits, candy, cereal/snack bars, chocolate, and ice cream.
In the USA, many other manufacturers have initiated the recall of their products on a voluntary basis as they may have used peanut butter from PCA as an ingredient for their products, although none of these products have been linked to the Salmonella outbreak. To date, more than 360 products have been recalled by these manufacturers, and more manufacturers are expected to recall their products on a voluntary basis.
Consumers need not be alarmed by these voluntary recalls initiated by the manufacturers in the USA. AVA has been monitoring the list of products that are recalled in the USA to ensure that they are also not sold in Singapore.
Consumers may search or download the updated list of products that have been recalled in the USA at the following website of the US Food and Drug Administration.
http://www.accessdata.fda.gov/scripts/peanutbutterrecall/index.cfm
AVA advises consumers to discard the products containing peanut butter that have been recalled by the US manufacturers if they had purchased the products.
Government in cyberspace
To me it is really not a tremendous deal, although I must admit it is something of a milestone. Cyberspace has been in existence for a very long time, and as has been pointed out by other netizens, it by now not really a new technology platform where information is moved around and discussed. The big issue was really about the way government policy makers and bureaucracy/officialdom interacts with (and shapes?) such information dynamics in cyberspace.
Despite the hype about online discussion forums etc, I have been fairly disappointed generally in the level and sophistication of the discussions. Most are dominated by a relatively vocal minority who tend to get quite repetitious (sianz ahh....). Most netizens prefer to just lurk silently. Who knows what they think, and what opinions they hold? Take for instance, the ST online forum where this issue is being debated...at this moment the published stats show that 484 have visited the site, but only 18 comments have been sent in by 15 accounts (~3% of total visits?). I think the stats are fairly representative of the cyberspace culture. Most are happy to read, but online opinions are far from being representative of cyberspace, let alone the community at large.
Does this mean that cyberspace discussions and opinions are not to be taken seriously? Clearly not so. Opinions expressed through blogs, discussion boards and chat rooms do get noticed. And they do get repreated and propagated, sometimes in its original state, but often morphed into something else. Good responsible ideas do persist, and i am guessing that these do get noticed by agencies who should take notice.
I am told by reliable sources that big government has already been scanning and eavesdropping cyberspace. It may be that their primary focus may be on politically sensitive issues, but I think as their ability to do so improves and matures, their eavesdropping of cyberspace chatter will also allow them to pick out good ideas that ministries and other agencies can act upon.
There is no doubt the government is already in cyberspace. They'd be pretty incompetent if they do not already have a good ear to the cyberspace ground. How they respond is another thing altogether. That they have responded to an online letter says something of a shift in their mindset, in that they are publicly ackowledging their presence in cyberspace.
For me it is relatively unimportant if the government responds to an online letter, or becomes an active discussant on discussion boards. Commonsense will tell you that it is not easy for them to actually do that. Far more important for me is to know that they are listening to the cyberspace ground. And if and when they do respond to the ebb and flow of ideas and opinions in cyberspace, it is not important for me where and in what form this response comes in. I personally think that many netizens do approach the issue with more than a little bit of ego, i.e. it is important that their letter is answered, the discussions must take place in the forum of their choosing etc etc ... They want to feel that if they press a button someone in 'gahment' must respond etc etc... But I think this is not necessarily a good or even workable model.
I have a different take on this. I am happy to know that the gahment does eavesdrop in cyberspace. I am grateful for a certain space to express opinions and ideas without the intimidation of having to submit nric numbers and addresses etc... and am pleased to know that these ideas, feedback and even whistleblowings will not only get picked up, but will eventually find expression in some form of governmental response.
We do have a responsible and fairly responsive government at the moment.They are still somewhat bureaucratic (as you might expect from governments), and can be quite monolithic in their ideas (as can be expected by the single party dominance of our political scene) but overall still doing a half decent job. That they are listening and beginning to respond to cyberspace is a good sign.
Jia you!
Thursday, January 29, 2009
Compassion (and ethics) in clinical studies?
Clinical scientific research tries to close the gap between the lab and the patient. The gap has always been there. This takes time to close. However commercial pressures have been driving very hard towards expediting the process. Ostensibly this is to benefit patients earlier, but we all know the pressures are mostly revenue related. Every day of delay in getting a new drug into the market costs the company developing it, millions of dollars.
Ms Sim is correct in pointing out that instead of taking "'discoveries from the laboratory to the patient'. It seems it is expanding the walls of the laboratory and taking the patient into the laboratory". The patient is very quickly becoming the guinea pig that serves the commercial interests of big pharma.
But surely new drugs benefit patients? Yeah...well, we can't deny that. But in reality, newer drugs benefit fewer and fewer patients, and become more and more costly to develop. Even where good drugs are developed, the incremental benefits are small. For example, it is not as if we do not have good anti-cancer drugs, we just want better ones. There are very good anti-diabetic drugs...though, apparently not good enough. In practice, most newer drugs often only produce marginal benefits.... and then often get hastily withdrawn from the market because of previously unrecognized toxicity.
The people pushing biomedical research in Singapore are usually those in support of trade and industry. Ministry of Health seems often to be dragged reluctantly into this as such activities tend to drive up health care costs with only marginal health benefits for the patients.
I have always been chary abut the ethics of many clinical studies. Most appear to benefit the investigators (fame, glory, and lots of money) much more than producing any real benefits for the patients (present or future).
'But aren't all these regulated by ethics committees?' You might ask.
Yes, they are. But without casting any aspersions of my colleagues who serve on ethics committees, it has always seemed to me odd that while the ethics committees are supposedly independent, they are all appointed by institutions who benefit from the research activities. Often, they end up been advocates of the research rather than being advocates of the people being experimented on. To be fair, they do look after interests of the 'experimented upon' but often when there is a conflict between who comes first, the balance can sometimes fall on the side of the 'experimenters' rather than the 'experimented upon'.
We certainly need more scrutiny of this process. But sadly I doubt we will get it.
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The article is strong and logical on the need for immunity studies to shift from mouse-based research to human beings. However, it seems to be of scientific interest rather than medical or therapeutic interest.
The medical and scientific research industry has been given a lot of room and trust in internal regulation. It is not obvious to most people what the difference is between therapeutic research and scientific research, and sometimes the line is unclear, as in the case of writer Paola Castagnoli's proposition of human research in immunity studies.
A convincing hypothesis is still a hypothesis. While there are regulatory authorities and ethics review boards in place, their interest is in ensuring that the protocol and methodology comply with state laws and do not infringe on human rights.
I believe there is no one to question the necessity of the study in the first place, except the investigators themselves. Is it not possible that a patient who meets the inclusion criteria of a study, who may not need to go on a study because of the side effects it can have on the quality of his life, is recruited by the investigator anyway?
I am not too convinced when Ms Castagnoli said such research 'takes discoveries from the laboratory to the patient'. It seems it is expanding the walls of the laboratory and taking the patient into the laboratory.
It may take small sacrifices in order to find solutions for the greater good, but then, it is entirely a researcher's morals and value system that decide whether a study really comes from therapeutic interest or from scientific interest.
If people know exactly what is involved in them getting an answer to their rather innocent question, 'Is my immunity good or bad?', they may think twice about whether they want it answered. I hope that soon, scientists and researchers will be instrumental in instilling a culture of compassion and moral empathy in scientific studies.
Seng Ann Sim (Ms)
Saturday, January 24, 2009
Year of the Ox - ruminations
The first part of their stomach is called the rumen (hence ruminant) where the plant-based swallowed food undergoes some early digestion. The more solid part of the partially digested food, is recalled periodically into the mouth for more chewing when the ox is not grazing. The re-chewed food passes then into a larger compartment (the biggest) called the reticulum. The is the definitive fermentation chamber where gut bacteria help digest the otherwise indigestible plant products such as cellulose so that valuable nutrients may be extracted. The presence of this enormous fermentation chamber is really why ruminants have such a large barrel-sized belly. You may think the ox or cow isn't doing very much standing in the middle of the field, but actually he is happily fermenting away stuff, and producing lots of gas to be burped out or farted out.
By contrast, herbivores such as the rabbit do not have such an efficient process for extracting nutrients from the food they eat. They are not true ruminants. However, they do have also a fermentation chamber for doing pretty much the same thing. Their caecum (the part of the large intestine where the appendix is attached to) is where this occurs. But because this is so far down the alimentary tract, the valuable nutrients cannot be easily absorbed from the fermented food. Rabbits therefore have to re-eat their s*** (called scientifically coprophagy). The rabbit produce a softer form of s*** called caecotrope, which they regularly re-eat. This is an essential part of their diet, and rabbits denied this s*** eating, suffer from severe malnutrition.
Why do I belabour this point?
Well.... times are going to get really tough this year. Resources are pretty limited. That's why the gahment (Singlish for 'government') is digging into our reserves. At our level, we need to be more efficient in our personal lives and work practices, and maximize the utility of whatever resources we can muster. The Year of the Ox, does remind us of the need to 'ruminate'.
The question is whether we will be like the ox, that is able to redigest our food by regurgitation (true rumination), or whether we will be like the rabbit engaging in s*** eating.
Food for thought.
Have happy Lunar New Year in this Year of the Ox!!
Tuesday, January 20, 2009
Barack Obama - A President for the world
This man is a strange and unique personality. I don't know of anybody else who has that charismatic appeal who can command such a strong global following. It has been reported that some 2 million people will be present at the ceremony. But beyond that the whole world watches. And it doesn't matter one bit what nationality you are, what race, colour or creed, the global community celebrates tonight.
A girl could easily fall for this tall, virile young man. Smart, sensitive and principled, he stands head and shoulders above his peers. A distinct lack of stuffiness that characterises most politicians, he is both serious and hip at the same time.
But what a burden he carries upon his shoulders. Easily the hope of the whole world...that somehow under his leadership the world may be ushered into an era of peace and tolerance, where the colour of one's skin does not matter. President Obama, you have our prayers, and I am sure the prayers of the world as well. Be strong for us. There are not many opportunities to make the wrongs right again. If there is anyone can humanly do this you can.
President Obama, jia you!
Monday, January 19, 2009
Hard to swallow - Human Organ Transplantation Amendment Bill
It will also allow paired living donor organ transplant and the extension of the cadaveric donation age to beyond 60. It also aims to increase the penalties on organ trading.
- CNA/vm
Pacific Swallow
Had to stop at a traffic light beside the canal and was delighted to be able to sight a couple of Pacific Swallows (Hirundo rustica) perched on the rails overlooking the water. Utterly regretted not having had my camera with me. I thought initially they might have been swifts but managed to Google them out, and confirmed they were indeed Pacific Swallows. I had never seen one so close before and was pleasantly surprised at how handsome they were. Usually they are just ethereal shadows against the sky.
Thank God for the traffic light!!
Thursday, January 15, 2009
Seasons of the heart - sudden death
I have posted a bit about this before. In an adult, usually the more senior ones, the commonest cause of such sudden deaths are usually related to an fatal arrhythmia (cardiac seizure) due to coronary insufficiency. Although these patients are getting younger and younger, coronary insufficiency is unable to account for the cases who are very young, who die suddenly. Most certainly, this young boy would not have died of coronary insufficiency. Coincidentally, there is a current report in CNN about the same kind of problem but in patients treated with antipsychotic drugs.
Just Googling the problem turns up various reviews about this problem. A fairly representative review can be found here. It always amazes me that the heart can maintain such intricate rhythms without failing. Something of a miracle no matter how you look at it. Yet I believe sometimes it does seize up....but very very rarely. Sometimes it occurs in the context of coronary insufficiency, when the heart does not get enough oxygen. But in the very young it may inexplicably just seize up for no other reason than the delicate mechanisms driving the heart rhythms just screw up. Sometimes this may be the consequence of a rare (very rare) genetic abnormality of the various mechanisms (ion channels etc) regulating the flow of ions and electrical currents of the heart. This may often require some sort of environmental trigger, such as exercise or some medicine/chemical. There is a particular genetic abnormality of calcium handling that confers a high risk of a heart seizing up particularly during exercise. I don't think we will ever know what really happened to this boy. Such deaths leave no footprints, and I can imagine it will be very difficult for the forensic team to figure this out (CSI or no).
Understanding this, of course presents little comfort to the family of Tan Yan Chyuan. My heart goes out to them. It is a very tragic and painful loss. I can't imagine the pain of ever losing any of my own bao beis (precious ones).
Wednesday, January 14, 2009
Regulatory oversight - the Health Sciences Authority & the FDA
I was afraid that my comments about AVA might give the impression that I am somehow picking on them, that I had some bone of contention. Not so. Just so happened they had contemporary issues when I am blogging. From a medical perspective, actually the Health Sciences Authority (HSA) is the agency I should perhaps be picking on.
Actually they have their share of problems. Many of the problems arise from the same weaknesses in the system, not just locally but at a global level as well. I did a quick Google of FDA (US Food and Drug Administration) related news, and wasn't really surprised by what I found. A number of recent reports are worth looking at. Both point to the major conflict of interest problems affecting the FDA.
http://www.msnbc.msn.com/id/28619597/
http://www.ft.com/cms/s/0/454ad290-e016-11dd-9ee9-000077b07658.html
The Financial Times says it's time for a fresh start to the FDA. It says, "The first action of the new administration should be the swift appointment of a strong, respected, knowledgeable and independent new commissioner. For more than four years, the FDA suffered under bosses not formally confirmed, or who failed to defend it robustly. Its next leader needs to take full responsibility for the agency with maximum political support.That person must investigate allegations of conflicts of interest. Just as important, he or she must ensure clearer future rules. Products that fail to meet regulatory hurdles should be rejected, but the FDA must be clearer with companies in how it makes decisions, and stick to them."
Too often the FDA has been regulating with one eye on the big business interests of big pharma industries. This is something that struck me...the FDA is an enormous animal with major government backing. It is the biggest drug regulator in the world. Yet it is not free of the conflicts of interest problems that you expect might be infecting smaller regulatory agencies. I couldn't help wondering how our HSA deals with this problem. Like other regulatory agencies in Singapore, it has a strong promotional mission. It must support the establishment of the Singapore Medical Hub. It must support the Ministry of Trade and Industry's efforts to bring big Pharma into Singapore. It must support Biomedical Research and Clinical Trials. How I wonder, does it find time to support its mission to protect consumer interests?
The HSA is supposed to regulate clinical trials (read protect trial subjects), yet it is supposed to promote and support the clinical trials initiatives. It is supposed to protect consumers from dangerous drugs and chemicals, yet it is supposed to support and promote the market, not just big western pharma industry, but the traditional medicine herbal market, as well the nutritional supplement market. This is really megabucks stuff. Just imagine the number of phonecalls that get made, if they say no to a major pharma company.
At a governance level, the HSA apparently continues to be a Ministry of Health animal despite being a statutory board. Apparently this kind of relationship is quite common for our stat boards, so although it has a properly constituted Board with fiduciary responsibilities, it principally takes it's cues from the MOH. However, because a lot of its regulatory activities relate to Trade/Industry initiatives, it has to keep an eye on this front. At the very least, it cannot inhibit or stumble trade and economy related initiatives. We can only hope that the HSA can try harder to look beyond these pressures to its core role to protect the consumer public. But that may be expecting too much.
So the cynical person I am, I expect the s*** to hit the fan on a regular basis.
Human organ trade - fait accompli? Why am I not surprised....?
see MOH Press Release
Details in Annex
Apparently 86 % had favoured some sort of reimbursement (fair 'nuff) and a majority suggested appropriate sums of at least S$50,000. How this figure was arrived at, we do not know. The Press Release tells us that there were 55 respondents (wow!), 9 written submissions from various oprganizations (we are not told which organizations so we can't say if these were biased opinions..!) and 162 participants surveyed at the People's Association dialogue session.
Well, I seriously question the validity of such feedback...and doubt the representativeness of these opinions. It could well represent the first steps towards understanding the full range of public opinion, but currently these are very sparse numbers and likely to only represent interest groups.
Of particular concern for me has always been the issues pertaining to the 'reimbursements' for donors. I have nothing against this per se, and I think we should adequately compensate the donor. But reimbursements really open the way to unethical practices related to a] free market trading of human organs, and b] inducements/exploitation of the poor. The MOH has been deliberately vague about these issues preferring to defer the consideration until after the law has been amended. It says, "These are operational details which the Ministry will take into account after the law has been amended.". Ho hum. Isn't it clear that because these are sticking points in the deliberations, we do need to clarify these before we amend the law? Once the law has been amended we will all just be driven down the road by operational details which may not underpinned by ethical principles.
With regards to foreigners, the MOH says, "The law will have to apply equally to all donors and patients if the transplants take place in Singapore. Otherwise, there may be double standard. If the law is amended, MOH would issue guidelines to the Hospital Transplant Ethics Committees so that they can better judge between what is reasonable compensation and what is inducement."
What this means really is that if this is delegated downwards to the hospitals, the commercial interests of the hiospital will become paramount. Ethics Committees or no. The hospital ethics committees decide on how much to reimburse foreigners for organs...? Duhhh.... Imagine NUH and SGH bidding against each other for organs? This is somehow ethical?
Imagine every kidney failure in the world flocking to Singapore for their transplant (wooohoooo....big mega bucks business!), then imagine the major transplantation hospitals sending out recruitment teams to Indonesia, Bangladesh and Africa etc etc....sourcing for organs. ...
Can it ever be controlled?
I think MOH has to do a little bit more work to tell us specifically how they are going to manage this before I will go along with their scheme to turn us into the organ trading capital of the world. But the cynical me feels they die-die will push this through whether we like it or not, because it will bring in the patients for our MedicalHub.
Euthanasia here we come!
Friday, January 9, 2009
Regulatory oversight - any conflict of interest for AVA with respect to bisphenol-A?
What am I talking about? Well, Singapore is actually an important bisphenol manufacturer. The Japanese company Mitsui Chemicals has been an industrial partner since the 1960's and has to date invested about S$1 billion, contributing to the success of Jurong island etc.
http://www.mitsuichem.com/release/2008/080814e_05.htm
http://www.sedb.com/edb/sg/en_uk/index/news/articles/mitsui_chemicals_establishes.html
http://www.edb.gov.sg/edb/sg/en_uk/index/news/articles/mitsui_chemicals_receives.html
It is fortunate in this instance, that the problem with bisphenol-A is probably more hysteria than reality, but it represents a good example of how the present regulatory set up makes it difficult for regulators to keep their eye on the ball. Should bisphenol-A be eventually be shown to be toxic, how would the AVA act against Mitsui Chemicals? Can it bite the hand of an important industrial partner that has been feeding Singapore's economic growth for the last 40 years?
I think the public needs to know how regulatory agencies are 'china-walled' to minimize conflicts of interest such as these, and whether the wall is adequately sound.
Bisphenol-A: Hysteria developing?
Bisphenol-A is a funny small molecule that has two arms, and is used in the manufacture of hard plastic bottles. The concern is that there is some data in animal studies that bisphenol-A at low levels can act as 'endocrine disruptors'. Bisphenol-A has some estrogenic properties, and can leach out from those hard plastic bottles, so mothers and mothers-to-be are legitimately concerned about the effects this may have on their babies.
There are quite a lot of reviews written recently about this that summarize the state of ignorance quite well:
Wikipedia
NIEHS-NIH
AVA
Truth be told, I have had a look at the data and I am not so convinced. It's one thing to look at endocrine changes in lab animals, and another thing to exprapolate those effects to the real world. Much of the data is kinda iffy anyway. My feeling is that AVA doesn't really have much to act upon other than a lot of emotive rants from various interest groups.
Also if you look at bisphenol-A, the effects are largely due to its estrogenic properties....and there are a lot of estrogenic substances all over the place, in our diet etc. Bisphenol-A isn't the only chemical that does this. Our diet contains naturally occuring estrogens such as bioflavonoids (fruits, veges, soya beans)...inodole-carbinols (cruciferous veges) to name some. An article here from the Texas A&M Univeristy and funded by the NIEHS estimates that the contribution of industrial estrogens probably amount to only about "0.0000025% of the daily intake of estrogenic flavonoids in the diet". The presence of these dietary estrogenic flavonoids have in fact, often been touted as being the reason for the 'health giving' properties of many fruits and vegetables.
Hysteria in the making...yeah, probably.