Posts Tagged ‘medicine’

An Overview of a Medical Clinic: Accra, Ghana

Monday, June 28th, 2010

This past semester I lived and studied at the University of Ghana. Located right outside the capital city of Accra I was within traveling distance of a great number of medical clinics and hospitals, two of which I visited frequently. No, I was not chronically sick or accident-prone, but was personally interested and invested in learning about the healthcare facilities of a third world country. There were lots of issues that I wanted to explore - what type of resources were these facilities provided? What demographics did they serve? What ailments presented most frequent? How did patients respond to advice? How did the doctor dispense advice? How was the chain of command established? … and more - of course.

I will first say that I had little autonomy of choosing which clinics I wanted to visit; the relationship was set up through a program facilitator and his previous connections. Actually, this ‘program facilitator’ was a retired doctor, Dr. Owusu, who remained on-call for any problems that our program’s students were having. One of the clinics he introduced to me was his own doing; he established the facility and served as the Medical Director for many decades until retirement. The other health facility - the one of which I will touch on in this article - is currently directed by a prior classmate and close friend. If given a choice, I would have preferred to also visit a more rural clinic; however, I was incredibly thankful for Dr. Owusu and his connections.

mapIn this article, I will give a general overview of my experience at one of these clinics. I will discuss the methods of the doctor, the facilities available, and peculiar trends established by the patients. The Phillips Clinic was, obviously, a ‘clinic’ by definition and provided ambulatory, out-patient care on a daily basis. It was only open from 8-2 (or as early as the doctor arrived, usually around 7) and was best equipped to handle general, non-severe ailments. There was a single doctor’s office and a single doctor (Dr. Jane). About two or three nurses and two nurses-in-training were always present, plus the ‘matron’ who could dispense medicine. Additionally, about three men staffed the laboratory. Besides the doctor’s office - which contained the doctor’s desk and one check-up bed - there was a dressing room, a holding room, a pharmacy, a laboratory, and a waiting room. Sounds extensive - right? Let me embellish.

The waiting room held about twenty seats where patients would line up - first come first serve. The dressing room housed any equipment and supplies needed to dress common ailments like ulcers and burns. The pharmacy and laboratory were about equal in size - not over 10′ x 10′ each. The pharmacy was, to some extent, with medications with one wall lined with three filled shelves. The pharmacy was additionally the social hub of the staff. Most of the time, you could find several staff members, sitting in fold-up seats, talking amongst each other.

The laboratory was stocked with one microscope whose resolution and quality were about the grade of a typical high school’s microscope. With this piece of equipment they could diagnose malaria - a vital procedure here in Ghana. I was even able to see a parasite myself! Additional blood tests could be done by applying certain chemicals to the blood sample and reading the color of the solution. Patient’s blood was kept in open tubes and often not labeled. This was much unlike the security and sanitation measures taken in the US to ensure no mix-ups or contamination. There was a point in time when I was sitting in the laboratory and the lab tech spilled a drop of blood on the counter and simply wiped it away with a paper towel. Such measures would be ruled unsanitary and dangerous in the USA.

The waiting room at the Phillips Clinic. This is what you see immediately after entering the building.

The waiting room at the Phillips Clinic. This is what you see immediately after entering the building.

Finally - the holding room was all of two hospital beds and maybe an IV. This room was never used in my time there but was present in case of a severely ill patient who would need to transported to a larger, 24-hour care facility after the clinic closed. Here’s my over-all summary of the facilities at the Phillips Clinic: Although the resources and facilities appeared minimal and rudimentary in comparison to standards set by the United States, it was my impression that the Phillips Clinic was a highly respected facility with loyal patrons.

I’ll speak more on Dr. Jane. Dr. Jane was the only doctor to practice at the Phillips Clinic. She received her secondary school education in what is arguably the best in Ghana - the Achimota School (originally the Prince of Wales School founded by British colonists). She moved to Germany for her medical degree and residency, and ever since has practiced family medicine in Ghana for 40-some-odd years. She is nearly 70 years old but always says she has plenty more years of practicing ahead of her. Dr. Jane always, always, emphasized the importance of a strong and cordial doctor-patient relationship. I observed this in her practice; she was kind to all individuals, greeting them with a smile, saying “happy new year” (despite it being March), and occasionally asking how their son/daughter/mother/father was if she had treated them before. From what Dr. Jane said, this mind-set - of showing kindness to patients- was not typical of doctors in Ghana. She asserted that many doctors were cold-shouldered and unsympathetic, they gave instructions of care without explanation of what ailed the patient. Patients don’t respond well to this attitude, she would tell me, when a patient feels demoralized and didn’t understand their condition, there was rarely motivation to change behaviors or faithfully administer the right medication. Dr. Jane was proud of the way patients trusted her and responded well to her advice. She even claimed that her most loyal patients have been with her for over 30 years and travel far beyond their means to meet with her. I was impressed by her approach to practicing medicine, especially because it follows the current trends in more developed countries, as far as encouraging bedside manner and a more egalitarian relationship than patriarchal one.

Dr. Jane seated at her desk with examination bed in the background. Patients would enter and sit at the chair next to her desk for consultations and moved to the examination bed only when necessary.

Dr. Jane seated at her desk with examination bed in the background. Patients would enter and sit at the chair next to her desk for consultations and moved to the examination bed only when necessary.

What surprised me the most was the ways in which my expectations were altered, with respect to the types of patients and the types of ailments they brought with them. When you think “Africa” or “third-world country,” what do you think? I thought about malaria and typhoid and yellow fever and malnutrition and HIV/AIDS and parasites, etc. What’s true about those expectations was that we saw a lot of malaria. To the point where, whenever a blood test was ordered, 95% of the time the doctor would check for parasites - just in case. Malaria symptoms are pretty general, fever, sweats, fatigue, and such symptoms don’t just apply to malaria. Additionally - a patient could come in complaining about a sore throat or respiratory infection but nonetheless, a malaria test would be conducted amongst other things especially because malaria weakens the immune system and is often the cause to secondary infections.

Another shot of the waiting room. The secretary's desk is in the foreground. The doctor's office is the door sighted on the left hand side. The dressing room, pharmacy, and lab are all located on the left-hand wall (not captured by this picture), across from the blue chairs.

Another shot of the waiting room. The secretary's desk is in the foreground. The doctor's office is the door sighted on the left hand side. The dressing room, pharmacy, and lab are all located on the left-hand wall (not captured by this picture), across from the blue chairs.

What I didn’t see of which I expected to were the other conditions - typhoid, yellow fever, HIV, parasites, or even Hep B (half of these diseases required expensive vaccines to be allowed into the country as a tourist!). What I did see of which I wasn’t expecting were a whole lot of diabetes and high blood pressure. Wait, what? Diabetes? High blood pressure? Aren’t these the chronic diseases that affect Americans because we’re unhealthy, fat, and lazy? I explained my complexion to the doctor. And, of course, Dr. Jane had an answer:

A huge problem in Ghana isn’t necessarily undernutrition but malnutrition. There’s a slight difference. Undernutrition signifies the lack of sufficient calories. Malnutrition signifies the lack of a balanced and vitamin-rich diet. It was this malnutrition that led to such chronic diseases such as diabetes and high blood pressure. First off - a lot of Ghanaians drank soda. Bottled soda was nearly half the price of bottled water, about 50 cents a bottle. If they didn’t drink soda - they drank beer or malted beverages - still, both drinks that incorporated an incredible amount of sugars. Ghanaians would look at me weirdly when I refused a drink of soda. To them - it’s a source of energy so it must be good for them (It was also marked as being filled with ‘minerals’ and ‘nutritious’). Long story short - this chronic pattern of soda consumption contributed to high and growing rates of diabetes. And of course, it’s not the only aspect, but Dr. Jane truly believed that it was a contributor.

Furthermore, the Ghanaian diet didn’t incorporate too many vegetables or fruit. Not to say that these items were unavailable - but in relative price - were a lot more pricier than, say, a bowl of jollof rice or bean stew. The ‘poor man’s diet’ here consisted of very heavy fermented dough (made from maize, cassava, or plantains) with a heavy, tomato based stew.  The main diet was overwhelmingly based off carbohydrates and lacked nutritious items. Additionally - there was little nutrition awareness or education in schools so people didn’t know what proper nutrition included. These issues induced conditions that I had always associated with richer, more affluent nations whose diets are filled with high-fructose corn syrup, processed foods, and trans fats.

The pharmacy at the Phillips Clinic. If the in-house pharmacy did not have the proper medication in supply, patients would have to travel elsewhere.

The pharmacy at the Phillips Clinic. If the in-house pharmacy did not have the proper medication in supply, patients would have to travel elsewhere.

Since there is a lack nutrition education within the primary schools, Dr. Jane’s advice to her patients seemed like common knowledge to me. Eat fruits and veggies five times a day, cut back on that palm oil (!), and watch your portions. She did her best to explain the causes of high blood pressure and diabetes in hopes to convince her patients that their health was in their hands. This tactic is, again, atypical of the “Ghanaian” mindset. Culturally, they accept a lot of events and conditions fatalistically; they saw themselves as not having control over unfortunate events and took it as it came. A common expression in any conversation was “it will come” signifies their belief in fate and a ‘if it’s meant to happen, it will happen’ type-of-attitude. I want to attribute this to the entire nation’s intense religiosity as they viewed themselves as vessels at the hands of their god; however, I only have anecdotal evidence for this so don’t take the previous statement as 100% fact. Anyway, this method of educating the patient is unorthodox since doctors in Ghana often just give direction and expect obedience. Dr. Jane recognized that a patient should be given information and should be informed of their role in maintaining their health. I observed that many of her patients were successful in stabilizing their blood sugar and lowering their blood pressure upon return. The patients who weren’t as successful often displayed their guilt when Dr. Jane gently chastised them for their elevated blood sugar or blood pressure. They acted in a way which indicated that they, logically, knew they were doing wrong but hadn’t made the personal choice to change their behaviors. I could imagine it’s often hard to do this, especially with a strong, culturally-enforced fatalistic attitude. In this case - Dr. Jane would, again, sit them down and describe more carefully how their health behaviors affect their body. It wasn’t a matter of prescribing the wrong dosage or the wrong medication, but informing the patient and connecting with them in a way that their behaviors changed.

Since the clinic was located in a middle class area of the city, we mostly saw local middle class citizens. Additionally, the pay-per-visit fee probably discriminated against lower class persons seeking help. There were certain companies and businesses whose insurance would pay for their clients’ personal visits; yet again, this signified that these patients were employed and had a relatively stable source of income (unlike a majority of the Ghanaian population). I walked into the clinic each week realizing that the patients diagnosed here, although representative of the Ghanaian population, was representative of a certain class of Ghanaians. I’m sure if I were located in the Northern Region, where health care is everything but available, that I would have seen a different incidence of disease.

Plenty more may be discussed about my experience in this clinic or even between the two clinics I visited. However, I will address these more specific topics in separate entries as to 1) keep the scope of this article limited to a ‘general overview’ and to 2) give myself more opportunities to embellish on my experience, without removing important aspects in sake of space. Hopefully, I have communicated the general sense of an ambulatory health clinic in middle-class, urban Ghana where the provision of care, although “different” from the health care we are used to in the United States, is impressive, organized, and patient-oriented.

A picture of the matron and me on duty.

A picture of the matron and me on duty.

Top Ten Global Health Stories of 2009

Saturday, January 2nd, 2010

Yes, the year has closed and so has the first decade of the 21st century. While many persons debate what to call this past decade - the one-ders, the double-Os, the M&M, the pre-teens, etc. - we reflect on more important things. Such as the top ten global health stories of the year (or, whichever stories we picked on a whim). A quick review:

Mosquito Sex Intervention Combats Malaria

Imperial College of London, published in PLoS Biology

After realizing that Anopheles gambiae only mate once in their lifetime, scientists decided to target the reproductive stage of these insects. When the male transfers sperm into the female, it is followed by a mass of protein and seminal fluid - known as a mating plug. This plug ensures that the sperm is stored correctly and is necessary for a successful fertilization. Scientists have ‘knocked-out’ a gene that controls for an enzyme involved in the synthesis of the mating plug. This discovery aims to control the population of malaria-spreading mosquitoes.

H1N1

No doubt that the spread of this influenza-like illness caught the attention of the world. Unlike other recent public-health threats like SARS or the bird-flu that only prevailed in the national conscious, the H1N1 virus appeared to penetrate itno communities and local populations. States called the virus a state-wide emergency and Obama follows with a declaration of a national emergency. Computer Generated Image of H1N1 virus. Citation: CDC at http://www.cdc.gov/h1n1flu/images/3D_Influenza_transparent_key_pieslice_med.gif  After 120 million doses of the vaccine were promised in the United States, very few trickle in on time due to delays in production and quality-testing. Internationally, over 12,000 die and a CDC mid-level estimate of 47 million infected.
Nano Filter Created for Water Purification

A water-filter using nano-technology was released in India under the name Tata Swatch. Each filter is able to provide enough clean drinking water for a family of five for one year.

Tata Group chairman Ratan Tata holds a glass of water as he stands next to The Tata Swach water purifier during its launch in Mumbai, India, Monday, Dec. 7, 2009. At about two feet tall, it may turn out to be the world's most compact revolution: The Tata Swach, launched Monday, is a water purifier priced for the masses, which India's Tata Group hopes will help save the lives of millions of people who die each year of waterborne diseases. (AP Photo/Rafiq Maqbool)

Tata Group chairman Ratan Tata holds a glass of water as he stands next to The Tata Swach water purifier during its launch in Mumbai, India, Monday, Dec. 7, 2009. At about two feet tall, it may turn out to be the world's most compact revolution: The Tata Swach, launched Monday, is a water purifier priced for the masses, which India's Tata Group hopes will help save the lives of millions of people who die each year of waterborne diseases. (AP Photo/Rafiq Maqbool)

No electricity, boiling water, or running water is necessary - just rice husk ash. This by-product of the rice industry acts as the framework on which silver particles mount and are able to kill bacteria. Tata Chemicals hopes to scale up production by 300% in the next 5 years and bring the technology to Africa.

AIDS Prevention Gel: FAIL

Not all news is good news. Once upon a time, there was hope that the microbicide, PR 20000, would be effective on HIV prevention. The largest study of its kind conducted by the British Medical Research Council followed 9,385 women from South Africa, Zambia, Uganda, and Tanzania for 4 years; results showed that 4.1% of the treatment group was infected as was 4.0% of the placebo group - no statistically significant difference. The microbicide, which acts by clumping around the virus before it reaches the vaginal wall, showed promising results in lab and animal-model trials.

The Spread of HIV/AIDS has Peaked

Joint United Nations Programme on HIV/AIDS (UNAIDS), World Health Organization

In other news… the spread of HIV/AIDS has begun to slow down. Since 1996, the rate of new HIV infections has dropped. By 2009, annual infection rates were down by 30% from 1996 figures. Additionally, AIDS related deaths have dropped nearly 10% since 2004. The director of UNAIDS points out that the majority of this decrease is due to HIV prevention programs (as opposed to treatment programs).

As Cancer Becomes More Treatable, Racial and Minority Disparities in Treatment Increase

Columbia University’s Mailman School of Public Health and Herbert Irving Comprehensive Cancer Center (HICCC) at Columbia University Medical Center/NewYork-Presbyterian Hospital in Cancer Epidemiology, Biomarkers, and Prevention

Cancers like prostate and breast cancer have become much easier to detect and treat thanks to generous advancements in medical knowledge. Yet, these advancements are not equally felt between racial and ethnic divides. The authors of this study suggest that disparities increase as interventions improve survival because individuals of higher SES are more able to exploit medical advancements. Pancreatic and lung cancer - which are harder to detect and treat- often have little to none disparities between racial and economic class.

Motility Mechanism of Malaria Pathogens Discovered

Citation: http://www.sciencedaily.com/releases/2009/12/091223094736.htm

Citation: http://www.sciencedaily.com/releases/2009/12/091223094736.htm

The molecular basis of malaria pathogen mobility has been unlocked. The pathway of these one-celled parasites from the salvitory gland of the mosquito to a human’s red blood cells has been a mystery until now. The parasite alternates between to modes of modulation; rapid gliding and adhesion to cell-surface complexes. The combination of both allows the parasite to move quickly and effectively over a long period of time. They adhere to the surface via the TRAP protein and use short actin filaments to drive themselves forward, called the ’slip-stick’ method. The consequences of this discovery are yet to be known.

Nigerian Campaign Against Guinea Worm Tentatively Declared a Success

Once the worst-afflicted country of Guinea worm in the world, Nigeria appears to have defeated the assault of this worm. At it’s peak, Nigeria had nearly 653,000 infections that cause prolonged suffering when the worm emerges through painful blisters and sometimes crippling after-effects.  It has been over 12 months since a

A Woman Cleans in Muddled Waters - Once a Danger Zone for Guinea Worm. Citation: http://www.sustainlane.com/listingPhotos.do?listing=4Y23OZSJZMCB3NZTLW38H9CZMVYD&image=38064

A Woman Cleans in Muddled Waters - Once a Danger Zone for Guinea Worm. Citation: http://www.sustainlane.com/listingPhotos.do?listing=4Y23OZSJZMCB3NZTLW38H9CZMVYDℑ=38064

single case has been reported; the hesitation to publically celebrate this success derives from the WHO needing two more years to officially declare the guinea worm eradicated.  The Carter Administration initiated eradication efforts nearly 20 years ago and is now looked upon as one of the penultimate public health successes. Only 4 countries now have the worms; Ethiopia, Ghana, Mali and Sudan.

Ebola Virus Vaccine Promising in Animal Models

The ebola virus is one of the most virulent viral disease known to man. 3 of the 5 distinct species of ebola virus have a mortality rate between 25-90% of all cases. Epidemics still occur today, usually in sporadic outbreaks and spread within a health-care setting. Soon, this virus may be a disease of the past. Researchers have developed a derivative of the ebola virus, which contains an essential gene knock-out. In the lab, mice inoculated with this derivative and then exposed to the virulent form of the ebola virus were protected. Scientists predict that this vaccine would most effectively protect health care personnel, laboratory works, and those at risk during outbreaks.

Uganda Announces Anti-Gay Legislation

While Uganda’s anti-gay legislation is more directly related to gay rights than to global health, there are significant consequences within the realm of HIV/AIDS. A Huffington Post blogger quotes that legislation would “undermine efforts to combat its HIV epidemic. It would be a tragedy in any country, but perhaps more so in a place with a record of leadership and success on HIV prevention.” Part of its previous success relies on the social marketing scheme promoting the use of a STI self-treatment kit, “Clear Seven,” which targeted the drivers of the spread of HIV - including homosexual men. The legislation would prevent public health officials from addressing some of pathways of HIV infection since any homosexual male or supporter of homosexuality would be prosecuted. Without knowledge of the drivers of HIV, implemented programs would not be effective because they would only part-way address the root of the problem. This story highlights how global health is not just scientifically or medically based but intersects with human rights issues as well.

Counterfeit Malaria Drugs as a Global Health Issue

Thursday, December 10th, 2009

This summer in Ghana an antimalarial drug came under suspicion; presumably, this medication was counterfeit. After chemical analyses, the drug sold under the name “Coartem” confirmed these doubts, lacking any active ingredient. This incident exposes a threat that is not common in the United States, but wide-spread and under-addressed in the developing world. Counterfeit drugs pose a threat to public health on an individual level as well as an international scale and often bias the poor socio-economic classes. Although there are regulatory frameworks in place, further pursuit of imitation and ineffective drugs are necessary to decrease the incidence of malaria.

Counterfeit artesunate anti-malarial tablet with fake 'X-52' stamp as seen under UV light. From www.worldvisionreport.org

Counterfeit artesunate anti-malarial tablet with fake 'X-52' stamp as seen under UV light. From www.worldvisionreport.org

Counterfeit drugs pose a major barrier in combating malaria throughout much of the underdeveloped world. The most direct reason why fakes are dangerous is those persons relying on a drug for protection against malaria presume they are safe, often ignoring other pathways for protection. To make an analogy within another spectrum of public health- it’s like protecting yourself against pregnancy without using birth control pills because you’re already using a condom… with holes in it.

Counterfeit drug makers have also learned how to thwart the system by adding minimal levels of active ingredients so that quality-screening tests reveal a false-positive.  Not only are these types of counterfeits ineffective at killing the parasite infection but they also increase the likelihood of mutation and resistance. Several studies have already indicated that the prevalence of counterfeit drugs has is induced some strains of malaria to become resistant (How? Some counterfeits do have small traces of the active ingredient, but not a heavy enough dose to kill the parasite completely. The strains that survive this ineffective dose may replicate and pass on their drug-resistant genome to all following progeny. Whatever doesn’t kill them makes them stronger…).

The prevalence of counterfeit drugs has increased over the past decade. At the end of the 20th century in southeast Asia, 38% of over-the-counter counterfeit artesunate tablets containing no active ingredient; in 2004 this percentage rose to 53%.  In certain countries, mainly in Africa, over a half of the available medications are fake (compare this to developed nations, like the USA, where only 1% of all medications are counterfeit) . The WHO estimates that counterfeits contribute to nearly 200,000 preventable deaths each year from malaria.

A recent study conducted a quality assessment test of available antimalarials in six urban or rural setting of southeast Nigeria. Their findings? Thirty seven percent of the tested drugs did not meet USP standards. Furthermore, this study implied that drug quality in rural settings was significantly worse than in urban settings, where 66% of quinine medications were substandard as compared to 43%, respectively.  The private and low-level providers observed in this study were predominantly used by low socio-economic status (SES) individuals. This suggests that the poor SES groups often receive the lowest quality of treatment, perpetuating a cycle of poverty in endemic areas.

To understand why this large discrepancy exists in a developing country and not developed countries, we must look at how these citizens go about obtaining their drugs and how this is different than the process in the USA.

A drug dealing holding a counterfeit medication. From NYTimes.com

A drug dealing holding a counterfeit medication. From NYTimes.com

A majority of malaria cases in Nigeria are usually treated by private providers, purchasing drugs through shops and/or peddlers - we’ll call this the “informal private sector.” These providers do not have to hold standards or requirements (the USA has the FDA to do this); this is where counterfeits or poor drugs are often obtained. But these vendors may not have any choice but to sell faulty products. It is the drug makers who ultimately receive the most economic incentive to fudge-up their product. Medicine has relatively high production costs and when legislation (or a lack thereof) provides minimal penalties, counterfeiters are given an economic incentive to produce fakes. The providers, whether it be vendors or pharmacists, often lack awareness of the existence and/or consequence of counterfeits. The peddlers are victim to competition; they have to buy the cheapest drug marketed to them to stay in business. Public providers, such as pharmacies or retail outlets, may also have pitfalls in dispensing the correct medication. Their gaps in quality assurance result from the lack of quality control during manufacture and faulty storage environments.

There is some framework to catch these counterfeits - the U.S. Pharmacopeial (USP) Convention is a nonprofit scientific organization who develops international standards for medicine quality. They have been supported by USAID to create a Drug Quality and Information (DQI) program for developing countries to ‘verify, assure, and improve the quality of medicines intended to treat life-threatening neglected diseases.’ The recent seizure of the Ghanaian counterfeits strengthens the USP’s DQI reputation as a way to regulate fake drugs, yet the statistics prove there is a lot of ground to make up .

Other movements throughout the world are also effective in combating the market of counterfeit drugs. In China, collaboration between public health advocates, scientists, and law regulators has developed a technique called forensic palynology to track down the location of manufacture. They study the chemical makeup of the pollen contaminants in the medicine; in their studies, some of the pollen had traces of the mineral calcite which is commonly mined in southern China. This lead brought officials to a suspect in the Yunnan Province of China, eventually seizing over 24,000 doses of fake medications in 2008.

Where can we move from here? A report published in the PLoS Medicine Journal suggests ways to decrease the prevalence of counterfeit drugs. It sets out some goals; 1) the provision of effective, available, and inexpensive drugs, 2) effective drug regulatory networks, 3) openness of governments on the severity of counterfeit drug prevalence (many governments have often denied the problem), 4) cooperation between countries where counterfeit drugs are crossing borders, and 5) improved education of patients, drug sellers, and health workers. It is quite obvious from these suggestions that we cannot rely on developing nations to individually attack or pursue fraudulent manufacturers. Instead, the drug regulation and standardization process must be the responsibility of non-governmental industry manufacturers, governments, and the international community. Ultimately, if counterfeits induce drug resistance, the mutant malaria strain does not discriminate and will cross country borders whenever given the chance. By that time, the infection will be more than a local or national issue, but a looming threat to the international community.  


References:

http://www.eurekalert.org/pub_releases/2009-07/up-cad072209.php

http://www.sciencedaily.com/releases/2006/06/060619005440.htm

http://www.ashp.org/import/news/HealthSystemPharmacyNews/newsarticle.aspx?id=3115

http://www.malariajournal.com/content/8/1/22

http://www.sciencedaily.com/releases/2008/02/080212085828.htm

http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020100#s1