Virus vs Bacterial Respiratory Infection

Share |Science Translational Medicine reports an RT-PCR that can distinguish a viral pneumonia from a bacterial pneumonia. Christopher Woods and Geoffrey Ginsburg at Duke claim that the assay monitors  human genes that react differently to viral disease than to a bacterial infection. 
Based on a trial of 102 patients with fever and respiratory symptoms, the test showed 94 percent sensitivity and 89 percent specificity.
PCR might be an expensive test at the clinical level. It would be nice to run such tests as a routine if the small clinical lab can have the technology without involving big pharma patents.
With the new terminology for basilar rales, namely "crackles," one might expect the new physician to be confused over the identification of the subtle left lower lobe sounds which sound nothing like crackles. The PCR might help and more so for upper respiratory infections. Professor Kemp once told me as a resident on pediatric rotation that I was treating an upper lobe pneumonia with a lower lobe antibiotic. It won't hurt to look at the gram stain either.
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Sci. Transl. Med. 5 203ra126 (2013)

Malaria Vaccine

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Science, Aug 8, 2013, DOI: 10.1126/science.124800, reports a new highly successful Malaria vaccine. Stephen Hoffman's intravenous (IV) vaccine consists of live attenuated plasmodium falciparum sporozoites -- labeled pfspz.

In a group of volunteers given four or five intravenous injections of the vaccine: 0/6 of the volunteers receiving five injections contracted malaria when later inoculated (p=0.018); 3/9 of the volunteers given only four injections (p=0.028); and 5/6 of the untreated volunteers contracted malaria. Despite the small population, the results were significant.

Prior experiments had shown that multiple mosquito bites by infected but radiated Mosquitos induced immunity. Hoffman took the process forward in employing numbers of radiated sporozoites. Sub-cutaneous injections did not work well, but the intravenous injections did.

Logistics in Africa may pose a problem in that the vaccine requires delivery in liquid Nitrogen containers. The IV dosing may not be so difficult because the volume is quite small, but getting patients back for four more injections likely will be. The authors suggest including the malaria vaccine along with other routinely delivered frozen veterinary products as a feasible avenue. Go.nature/mae5tu has a helpful summary on the background development of the vaccine.

Prior malaria vaccination attempts proved only slightly effective. Malaria remains, despite slow improvement, the number one killer worldwide with deaths estimated by WHO to be between 490,000 and 836,000 in 2010 and cases worldwide between 154 million and 289 million.

Global warming may once again result in Malaria's spread to northern regions, as p. vivax did in the first half of the twentieth century as far north as Archangel, Russia. (Lat: 64.5333)

The emergence of an effective vaccine comes at a good time. It remains to be seen if the vaccine works on other than the p. falciparum variety and on young children.

Under Diagnosis

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Even when we have the right diagnosis, the underlying cause is often ignored. This is a trend in part driven by economic expediency and the over simplification of practice guidelines. Better to just call it congestive heart failure, CHF, and forget the meriode of complex causes. The same can be said of valvular disease, arrhythmias, chronic kidney failure etc. How many times do we change the acronyms and theories of pathophysiology?  As we discredit each theory, we replace it with another one on equally shaky ground. Does obesity cause diabetes or does diabetes cause obesity? Does sleep apnea cause cardiovascular disease or does cardiovascular disease cause sleep apnea? When you cannot find anything wrong with the complaining patient, is it in her head, or is she suffering from environmental and genetic factors that are pulling her apart? Who is to say that the controlled study today is any better than the one done in the fifties?

Medicine is on the cusp of a breakthrough in knowledge. Genomics and proteinomics offer new understanding of etiology that will change much of what we think we know.  Even then, the theories will be a moving target. No wonder, faced with these vagaries, those who would presume to write standards of best evidence look for the four-digit diagnosis.

Disease is a mal adaptation to the environment. If you look at it that way you open a Pandora’s Box of considerations, but that is the art of medicine. If we continue to promote simplified guidelines for diagnosis and treatment, we reduce the physician to a technician. There are those who consider such standardization a good thing from the viewpoint of highly efficient industrial practices. One has to ask one’s self, can medicine be privatized and run like IBM with industrial standards of efficiency and performance, or does the patient suffer from an over simplification?

I want my doctor to open Pandora’s box looking for all the underlying causes.

Adult Onset Diabetes and Obesity

Share |Until legislators put the common good ahead of their fast food lobbyests and get sugars out of the packaged food supply, our only defence against the out of control epidemic of diabetes and obesity stems from early detection and agressive treatment. 

Unfortunately the current standard limits detection of diabetes to fasting blood sugar tests, and initial treatment to oral hypoglycemics. Juvenile diabetes is another matter, but protocals call for adult diabetes that does not respond to first line hypoglycemics to be treated by adding more powerful oral hypoglycemics. This polocy based on so called best evidence codifies the too little too late axium of treatment.

Early detection and early treatment will greatly reduce the mortality and morbidity of adult diabetes, but fasting blood sugars detect the disease long after the disease has damaged other organ systems. The damage results from the high osmotic pressure acompaning higher glusecose levels, like a storm front moving throughout the vascular system and extracellular fluid compartment damaging basement membranes and connective tissue.

In order to get a handle on the control of adult diabetes and obesity too, one needs the concept of pre-diabetes to catch the disease before it mets the current criteria for diagnosis. A hemaglobin A1c will help with an earlier detection. HbA1c measures the glucose on red blood cells. Red blood cells have an average life of 120 days in circulation; therefore, testing today measures the average high points of circulating glucose over that time span. The follow up diagnosis of pre diabetes might beter be with a 5 hour glucose tolerence test.

Interestingly, the first signs of diabetes seen in the clinic often include arcus senilis, A-V nicking, obesity or polyuria. Such is a testimony to our lack of rational preventive medicine guidelines.

The patient can often reverse pre-diabetes with diet and exercise. Failing that one might better turn to small doses of regular insulin before meals rather than oral hypoglycemics. Patients want a pill in order to perpetuate a denial of the disease or a denial of their obesity. The only way to overcome that resistance is by education. Here again the advertising by the drug companies for mor powerful and more toxic oral hyperglycemic medications works against us. If the physician believes in tight control and is passionent about it, that entheusiasm and passion can be transmited to the patient. 

Most endocrinologists and many internists urge treatment of adult onset diabetes with regular insulin or equivalent. Not the long acting kind but fast acting physiological insulin before meals.

I learned this technique and philosophy over fifty years ago in medical school. Why is knowledge forgotten? That may be another question. To the point, my clinic diagnosed pre diabetes and treated it aggressively with diet and exercise. HbA1c at frequent intervals identified early advances in the disease. We were very successful with the pediatric subcutaneous fine needle attached to thin tubing and a push button fountain pen like measured delivery device.

Patient compliance depends on patient education and an agreed upon strategy to protect vital organs and extend life expectancy. Life style changes come  easy when you have a needle in place as a reminder. It works.

With regard to the oral hypoglycemics, some have a use, but most are the promotion and advertising product of drug companies valorized by lobbying and tainted publications -- and yes the protocols of best evidence as well. Again early diagnosis is the key. Modern medicine lacks sufficient emphasis on diagnosis.

Diagnosis and the Physician’s Laboratory

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The curriculum renewal committee of the University Of Washington School Of Medicine[1] offers suggestions for curriculum changes that would enhance the numbers of graduates choosing a primary care specialty. Notably the report did not mention the issues of prestige nor the availability and training in the use of diagnostic tools for a primary care setting.

From a clinical viewpoint primary care is more of a science not less of one than the other more limited specialties. The training and clinical tools should match the challenge and they do not. Medical students need both the tools and the training to do serious diagnostic studies. Contrary to the image of a doctor making a snap diagnosis wherein the only problem is the treatment protocol, diagnosis is multifaceted and no simple matter. Multiple conditions, individual patient constitution, and multiple layers of symptoms compound the challenge. Many studies suggest a high percentage of missed and wrong diagnoses, 35.8% in this study.[2] We use to have the autopsy as a final arbitrator of diagnosis but no more. Autopsy has gone out of style; it is not profitable enough. Some medical schools have abandoned the microscope in favor of digital images in training. The microscope, however, remains one of the most essential diagnostic instruments. Today’s microscope should provide polarized light, dark field and fluoroscopy. This is realtime microbiology.

Historically, medical science advanced through the evolution of diagnostic tools and techniques. First, there was the autopsy, then the stethoscope, and the microscope, then statistics, the x-ray machine, ultrasound and more recently bio-molecular science. Today, hospitals excuse the autopsy with reliance on the CT scan. Largely the CT scan replaces the plain old x-ray. This is not progress. Today the stethoscope hangs around the neck unused. Offices send out most lab work, either to a reference lab or to the hospital. It should be obvious that the primary care doctor needs a small clinic version of all of the basic diagnostic tools and some that exist only in research labs. Basic equipment should include ultrasound, microscope, x-ray, and the skills to go with them. Looking to the future, the primary care physician needs to link current clinical research with his or her practice, especially in statistics and genomics. Polymerase Chain Reaction (PCR)[3] should find common use in the clinic; students should have enough undergraduate experience in proteinomics to manage it.

Many frustrations to the practice of good medicine come from outside the profession. These distortions, accepted as the way things are, limit both the role of the physician and his or her ability to diagnose conditions at hand. For instance, EPA limits a physician from conducting many laboratory tests in the doctor’s office, or requires burdensome licensing and exemptions.[4] While well intended to improve quality and control costs, it does the opposite. One fear suggests that physicians do laboratory studies because they produce more revenue. Perhaps some do, but the unintended consequence denies access to simple inexpensive tests. These tests done in realtime, while the patient is present, save time, save money and improve outcome. A trip to the hospital, results in delay and a much more expensive procedure. I cannot imagine a physician doing a gram stain, a peripheral blood smear, stool, a urine sediment, a sedimentation-rate or a culture and sensitivity for the money; although, payment for these services must cover the cost of time and equipment. Some of the tests are time and space sensitive with unstable chemicals and fragile structures. These further limitations also argue for on site availability in rural clinics.

The same argument can apply to office x-ray. The office machine requires the same inspections and calibrations as in the hospital. The machine may be identical. One does not have to use much imagination to see a political undercurrent persuading legislators that everything must be done in the hospital. Unfortunately, hospital profit motivates the lobbying.

In 1998 while on the Board of Directors of the South Peninsula Hospital, I attended a dinner seminar set up by the network of Alaska hospitals including legislators presumably for educational purposes. It had only begun when it became evident that this meeting had the primary agenda of promoting a bill prohibiting office x-ray machines. The program presented undocumented evidence that office x-ray machines were sub substandard and hazardous while hospital machines were new and operated by licensed technicians. Presenters built a case for eliminating office x-ray machines in favor of securing all x-ray business for hospital radiology units. I was sitting at a table next to Senator Murkowski. He turned with a questioning look. I simply compared the cost of flying a patient from a native village to an Anchorage hospital for an x-ray of the chest in order to assess a clinical pneumonia. The unfavorable cost and the poor medical treatment of a time sensitive illness delayed by a trip to the hospital were obvious. The bill did not pass. In today’s environment, a hospital x-ray becomes a CAT scan. The cost is a hundred fold greater and the information only marginally better. The accumulated CT radiation expositor falls into the danger zone.[5] Students should learn the physics of radiology, quantum physics and participate in research for the newer less toxic photonics.

In short, the primary care doctor should be educated as a scientist in the tradition of the great physicians, past and present. He or she needs the tools of science and of diagnosis and be expert in their use. One wonders, just what is the character we strive towards in a primary care physician? Do we want a doc who is indeed a scientist with the humanity of Hippocrates? Or, do we want a Feldsher with an unused stethoscope hanging indolently around the neck?

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[1] http://www.uwmedicine.org/Education/MD-Program/curriculum-renewal/Working-Groups/Documents/Report-Primary-Care-April-2013.pdf

[2] http://archinte.jamanetwork.com/article.aspx?articleid=1656540

[3] http://en.wikipedia.org/wiki/Polymerase_chain_reaction

^[4]  Clinical Laboratory Improvement Act (CLIA) 1988 http://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c16.pdf

^[5] http://radiology.rsna.org/content/251/1/175.abstract

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Anthracimycin

Share |found in deep ocean sediment from streptomyces. Bacteria, anthracimycin appears to be effective against MRSA and Anthrax. Watch for more.

Rural General Practice

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Conventional wisdom states that we have a shortage of physicians and more is better. A more careful look suggests that the problem is more of a mal distribution of physicians. We suffer a scarcity of primary care physicians. We need more of them in rural communities. Medical educators face both of these problems. The solutions are difficult without better insight into the challenges of both primary care and rural practice. The first problem is lumping pediatrics, internal medicine and family practice into the same category with family practice. Even OB/GYN wants to be considered primary care for women which adds to the confusion. General practice is still general practice. Calling it family practice as a specialty does not make it a specialty and therein lies a problem with identity, prestige and self image. Medical students soon sense this disparity. Thinking of it, however they may, students choose the specialties, and that perpetuates the problem with both distribution of health care and the competence level of those who do choose general practice or family practice. The intellectual filter works against both distribution and competence in rural areas.

Then what is the solution? Sadly, the one that prevails is the formation of a sub prime provider who acts as more of a technician following protocols and algorithms. He or she is glad for the opportunity, and works semi supervised in structured, mostly in public health or native corporation clinics in a team setting. On the surface this sounds good. The problem is in recognizing critical problems that do not fit the protocols and the distance to a center that handles the more difficult case. In reality practicing in any kind of isolation without multi specialty support requires more of a supper physician, rather than a lesser one.

The steps towards motivating the better talented physicians to undertake a rural practice from a clinical viewpoint are several. First, there must be prestige and assured remuneration sufficient to attract the best physicians and their families to live in a rural community. Forgiveness of medical school debt and tuition will not cut it. The only way I see to accomplish these two things is to extend the residency program to four or five years with extensive time spent in the various specialties to the extent of gaining a core competency in each and with extensive clinical experience in each. In addition these young doctors need the basic tools of genomic and proteomic research, biotechnology, computational biology, epidemiology, public health and bioinformatics leading to a PhD. In other words a supper physician. 

Having created a physician for all seasons, the rural practice clinic must match the capabilities of this now highly trained generalist. Here is where government in partnership with the university and the clinician can achieve what the one cannot. The university can focus its considerable computational, statistical, bioengineering, business and law capacities to create a state of the art network of rural clinics in not just a few but all of the underserved areas of the state. The university can additionally provide nursing, student, intern and resident support. The government presumably the state government must provide adequate funding for construction and implementation with the expectation of a payback from Medicaid and Workman's Compensation services more adequately and affordably provided. The physicians would be salaried giving their families an assurance of income and additionally receive a percentage of the fee for service clinic income. 

Such would be a partnership in which each participant contributes and gains more than any one of them acting alone. Underserved communities and all parties benefit.