Primary care prevention project idea: PP4P

Novel Strategies for the prevention of type 2 diabetes: Pay the patient for performance (PP4P)


Eugene Scharf –MS3
3/9/11
Primary care rotation: Scarsdale medical group


Case:

Patient DM is a 36 year-old man with a past medical history of hypertension and obesity. He was last seen in the office two years ago for a check up. The interval history between now and his last visit is remarkable for an increase in bodyweight of 20lbs. He now presents to the clinic for an annual physical.

PMH:
Hypertension – diagnosed 2004, controlled with medication
Obesity –5’10” 223lbs BMI = 32
PSH:
Inguinal hernia repair 1997
Ankle fracture ORIF 1999

Family history:
CAD in father (MI age 55)
Stroke in grandfather (mother’s side)

Social history:
Born in Mumbai, India. Moved to US in 1995, employed as a computer programmer. Single, sexually active, uses protection. Some exercise on weekends. No tobacco, no caffeine, social drinker, occasional marijuana use.

Medications:
HCTZ 25mg
Ayurvedic herb tea
Multivitamin daily

Allergies: NKDA
ROS: +decreased appetite +fatigue +thirst
Physical Exam:

PE:
Gen: obese man in NAD
Vital signs:
T: 36.8 BP 136/80 P 78 RR 14
+central obesity, waist: 43”

Laboratory studies:

BMP: 140 | 110 | 18 / 175 Ca: 9.0 Mg: 2.3 Phos: 3.3
4.0| 25 | 1.3\

CBC: 7.8\ 40 | 14.0 / 350
Liver chemistry: 7.9/4.5/1.3/0.1/50/45/80
Lipids:
Total cholesterol: 250
HDL: 39
LDL: 160
Triglycerides: 185
A1c: 6.0%
TSH: 5.05
Total T4: 7.6
HIV: negative
Hepatitis panel: negative

How should we think about DM’s case? Does the combination of his increased waist circumference, high blood pressure, abnormal lipid panel, high random glucose, and elevated A1c indicate that he is at risk for developing type 2 diabetes? His social history is also remarkable for a sedentary lifestyle (employed as a computer programmer) and too little exercise (weekends only). Finally, DM is also relatively young (age 46) so it is important to know whether there are any interventions that could possibly have long lasting positive consequences on his life quality and mortality. However, what is certain is that DM’s metabolic and physiological health information indicate that he has come to a critical juncture in his life, and his behavioral decisions will now have lasting implications. In this paper I will argue that preventing his and others progression to type 2 diabetes can be significantly reduced by creating cost-saving patient performance financial incentives. Let us first create the context for this discussion.

In 2001, Boyle et al. published an estimate of the prevalence and incidence of type 2 diabetes in America. Based on data from both National Health Information Survey (NHIS) and National Health and Nutrition Examination Survey (NHANES) his group estimated that the prevalence of diagnosed diabetes in America in 2000 was 4.0% or approximately 11 million. His group then went on to predict that by the year 2050, there would be approximately 29 million diagnosed cases of diabetes, with a prevalence of 7.2%1. However, the American Diabetes Association (ADA) reported in 2010 that the current number of diagnosed cases of diabetes was 18.8 million, as well as 7 million cases of diabetes undiagnosed2. This report also indicated that the annual incidence of diabetes was 1.9 million cases/year. Holding that incidence constant and taking only diagnosed cases into consideration, this means that our nation would arrive at Boyle’s et al. 2001 estimate of 29 million cases by 2020, or thirty years ahead of his groups’ original prediction. This 2010 report by the American Diabetes Association also estimated that there are approximately 79,000,000 cases of pre-diabetes in America. Boyle et al followed up with a 2010 report3 that adjusted their prior predictions and re-stated the prevalence of diabetes in America by 2050 based on estimates of incidence and mortality to be between 21 and 33%, with a “middle of the road” estimate of 25%. Combining this estimate with a 2008 Pew Research Group report4 US population estimate of 438 million the result indicates that an estimated 109,000,000 Americans will have diabetes by 2050, up from 11 million at the beginning of the century.

I next sought to investigate the cost burden of diabetes. To this end the ADA published a cost analysis in 20075. This analysis reported the annual national burden of diabetes to be at least $174 billion in 2007 dollars (a figure >5.5 times the 2010 NIH total budget). This cost was broken down into medical expenditures ($116 billion or roughly 2/3 of the cost) and lost productivity ($58 billion, 1/3 of the cost). This analysis concluded that half of all annual medical expenditures in diabetes related to inpatient medical care. Also, considering lost productivity, 82% of the total $58 billion of this cost came from reduced work productivity (35% or $20 billion) and early mortality (47% or $27 billion). The report concludes that persons diagnosed with diabetes on average incur healthcare costs of $11,744/person year, of which $6,649 are costs strictly related to diabetes. Also this cost analysis did not estimate lost productivity of disease burden on well persons (e.g. – well person missing work to care for relative with diabetes), the annual burden of Medicare diabetes administration costs, and assumed the annual cost of persons with pre-diabetes to be $0. Thus the actual costs were determined to be higher than the calculated estimate of $174 billion. Therefore, given the predicted incidence and high future prevalence of diabetes combined with the high annual financial burden of the disease I next sought to investigate whether preventive data exist, and if so what measures are either cost effective or cost saving.

Modern diabetes prevention studies began in 1986 with the China Da Qing study, where 577 Chinese men with impaired fasting glucose were randomized to control, diet, exercise and diet & exercise experimental wings. At a 6 year follow-up, the proportion of individuals with diabetes was significantly lower in the diet & exercise group compared to the control arm (mean 44% vs 66%). The first large scale trial to support the benefit of glycemic control was published 1998, the United Kingdom Prospective Diabetes Study (UKPDS) showed that tight glycemic control in patients with newly diagnosed type 2 diabetes prevented microvascular endpoints (nephropathy, retinopathy, neuropathy) by 25%7. In short 3,867 newly diagnosed type 2 diabetics were randomized either a control group of conventional therapy with the aim of keeping blood glucose levels <270mg/dL versus experimental arms of insulin or sulfonylureas with the aim to keep blood glucose levels <110mg/dL. The UKPDS had a confounding variable worth reporting; in the experimental group sufficient glycemic separation (<110mg/dL) could not be achieved by just one agent thus metformin was added to the experimental group. As well the conventional group (control) had difficulty maintaining consistent blood glucoses of <270mg/dL, thus 80% of the control group received metformin as well. In fact 58% of the total control group patient*years of UKPDS were confounded by metformin use. Mean A1c’s were 7.0% vs 7.9% in experimental versus control, and at 15 year follow up there were no differences in myocardial infarction, stroke, or diabetes related mortality. A trial published in the New England Journal of Medicine (NEJM) 20018, approximately 85,000 female nurses taken from the nurses health study begun in 1976 were followed for 16 years for incident cases of diabetes (of which there were 3300). The study’s finding showed that the RR of diabetes increased sharply depending on BMI at the time of enrollment. BMI’s of >30 had a relative risk of 20.1 (16.6 -24.4), and BMI’s of >35 had RR of 38.8 for acquiring diabetes. This study clearly demonstrated that BMI and bodyweight greatly predicted disease risk. Another NEJM trial published in 20039, by the Diabetes Prevention Program Research Group demonstrated the superiority of diet and exercise compared to metformin or placebo in preventing diabetes. In this trial (DPP), the experimental group consisted of diet and exercise and was formally defined as losing 7% of bodyweight, physical activity >150 minutes per week, and dietary fat constituting <25% of total caloric intake. Both the metformin and placebo group were given information on the importance of exercise, but no requirements. Interestingly, on 50% of those in the diet and exercise group made the weight goal, average follow up was 2.8 years. The trial results clearly showed that diet and exercise prevented new cases of diabetes significantly better than either metformin or placebo. Cumulative incidence rates over follow up were for this study 14% vs. 22% vs. 29% at 3 years. It was shown that the number needed to treat (NNT) to prevent one incident case of diabetes in the diet and lifestyle group was 6.9. Finally, consider that diet, exercise, and weight loss interventions have been shown to persist past the treatment duration. For example, 20-year follow-up of China da Qing study published in the Lancet10 showed that the relative risk of acquiring diabetes of those members of the diet & exercise treatment arm compared to the control arm was 0.57 at 20 years follow up. This finding supports the notion that early diet and exercise interventions have protective effects that outlast their treatment periods. This finding has enormous implications for diabetes prevention. My next step in understanding current methods for diabetes prevention was learning whether or not models exist for predicting absolute risk of acquiring diabetes. One such model from the Framingham Offspring Study11 attempted to assess this risk and created a model for a person’s 8-year risk of acquiring diabetes. This predictor model includes the clinical measurements fasting glucose, BMI, HDL-C, triglycerides, family history, and blood pressure together to create a weighted score with which to predict a person’s risk of diabetes. If patient DM’s clinical data are entered into this model, we arrive at a score of 10 or 20, depending on whether or not his fasting glucose is more or less than 100mg/dL. The uncertainty about this metric creates uncertainty about his true 8-year risk; as it is either <3% or 18%. However, the advent of hemoglobin A1c as a point of care diagnostic tool for diabetes helps to remove doubt regarding risk of diabetes when fasting glucose measurements are not available. I assumed that the risk of diabetes could be reasonably predicted and the diagnosis accurately made by using clinical metrics. Thus, in proposing novel diabetes prevention strategies, I next sought to learn whether or not existing diabetes prevention strategies were cost-effective. A 2010 systematic review by Li12 et al of twenty years of cost effectiveness analyses of diabetes prevention strategies indicated that several cost effective strategies exist, and many are cost saving. This review defined an intervention as cost-effective if it resulted in an inflation adjusted cost-effectiveness ratio of less than or equal to $50,000/QALY. One important prevention strategy that was found to be extremely cost effective (<1,200/QALY) in one analysis and cost saving in all others was the use of angiotensin receptor blockers (ARBs) for type 2 diabetes to prevent hypertension and progression to macrobalbuminuria and renal failure versus either placebo or standard therapy. Thus I propose as a first step toward preventing the morbidity of long term diabetes resulting from hypertension and renal failure is the subsidized provision of ARB’s or ACEi to all diagnosed diabetics. However this idea would only help prevent morbidity after a diagnosis and thus not fully address primary prevention. Given that several of the aforementioned diabetes trials have indicated that diet, exercise and reducing bodyweight is superior to all other primary prevention strategies for preventing type 2 diabetes, I next sought to understand if these interventions are cost effective. To this end the same Li et al. review addressed the cost utility of strict glycemic control (with insulin, sulfonylurea, or metfomin), diet, education, or behavioral modifications. In all other healthcare systems outside the U.S. these measures were highly cost-effective or cost-saving. In the US, strict glycemic control as a prevention strategy costs ~41,384/QALY. However in the CDC cost sensitivity analysis that provided this figure13, cost effectiveness for strict glycemic control depends on age. For example; in age groups 25-34 it was 9,600/QALY, and 35-44 was 18,309/QALY, much less than the average for all age groups. But if one refers back to the DPP trial, strict glycemic control was also achieved in a much more cost-effective manner: diet and exercise. Thus we arrive at the central question in diabetes prevention. If diet, exercise and bodyweight reduction have been shown to be superior to all other preventive strategies for type 2 diabetes, why can’t we achieve this goal? People at risk for type 2 diabetes may not control their diet or exercise because there is no incentive to. The morbidity associated with type 2 diabetes is oftentimes decades away, and thus incentive for good behavior now does not exist. However I believe that positive incentives can create cost-saving behavioral modifications resulting in significant prevention type 2 diabetes. Thus I propose that we can reduce the cost burden of diabetes by providing cash incentives to high-risk individuals between the ages of 25-44. Given that Hemoglobin A1c is a reliable marker of blood glucose control for the previous three months, and that glycemic control (fasting glucose <100mg/dL) is associated with reduced risk of diabetes, I propose cash incentives for hemoglobin A1c’s under 6.0% for high risk individuals (impaired fasting glucose, BMI >32, or diagnosed diabetes). For example as stated earlier, in 2007 the economic cost of diabetes was ~6,649/person. If a patient previously diagnosed with type 2 diabetes can show through lifestyle modifications that his/her A1c is now below 6.0% they are eligible for four quarterly payments of $250 (for the quaterly A1c’s) or $1,000 annually. In this scenario, the economic burden of $6,649 is reduced to $1,000, and the patient benefits directly and tangibly from his/her actions with a cash reward. The payments are made from either Medicaid or insurance. Paying patients for outcomes may at first seem counter-intuitive, however the measure would likely be cost saving in light of cost analysis data suggesting the decreased costs related to A1c’s <6.5% (i.e. reduced diabetes incidence). And if a patient is not able to lower his/her A1c to goal, no payments are made and the system absorbs the cost as would have without the program. A patient (similar to our patient DM) with pre-diabetes would be eligible for “Pay for A1c” program thus averting the cost to the system for each year of prevention (as indicated through A1c). One critical component to the program lies in establishing a correlation between A1c and BMI because although A1c defines diabetes, lowering BMI is what can prevent diabetes. To that end I propose a final step, cash incentive for BMI reduction. Thus for every type 2 diabetic patient whose BMI becomes less than 30kg/m2, a one time payment of $1,000 (the patient cannot go back and forth through the set point of 30 to collect multiple payments). As our century progresses the prevalence of diabetes is projected to grow rapidly, such that the annual cost burden of the disease may become unmanageable. In order to prevent this impending liability to say nothing of the human cost, stronger incentives must be created to modify human behaviors to ways congruent with clinical trial proven lifestyle interventions. First, hypertension medications such as ACEi and ARBs have been shown to be cost saving for preventing morbidity associated with hypertension and diabetic nephropathy (the leading cause of renal failure in the US). Thus subsidized provision of these medications for diabetic patients must be policy. Second, proper diet, exercise, and bodyweight control could be attained with financial rewards to those individuals between the ages of 25 – 44, and defined as high risk (impaired fasting glucose, A1c greater than 6.0%, BMI >30, diagnosed diabetic). Two proposals for achieving these measures are “Pay for A1c” cash incentive and a one time cash outlay for diabetics whose BMI’s are lowered to <30 through their efforts of diet and exercise.

Reference:
1. Boyle JP, Honeycutt AA, Narayan KM, Hoerger TJ, Geiss LS, Chen H, Thompson TJ. Projection of diabetes burden through 2050: impact of changing demography and disease prevalence in the U.S. Diabetes Care. Nov;24(11):1936-40
2. American Diabetes Association
www.diabetes.org/diabetes-basics/diabetes-statistics/
3. Boyle JP, Thompson TJ, Gregg EW, Barker LE, Williamson DF. 2010. Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence. Population Health Metrics. 8:29.
4. Pew Research Center 2008. US Population projections: 2005-2050.
5. Dall T, et al. 2008. Economic costs of diabetes in 2007. Diabetes Care Vol31:3, 596-615
6. Pan XR, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 1997;20(4)537-44.
7. UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. The Lancet, 1998. Vol. 352, 837-853
8. Hu FB et al. Diet Lifestyle, and the Risk of Type 2 Diabetes Mellitus in Women. NEJM 2001; 345;790-797
9. Tuomilehto J et al. Prevention of type 2 Diabetes Mellitus by Changes in Lifestyle among Subjects with impaired glucose tolerance. NEJM 2001 344:1343-1350
10. Li G et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. The Lancet, 371:1783-1789
11. Wilson P WF et al. Prediction of Incident Diabetes Mellitus in Middle-aged Adults: The Framingham Offspring Study. Arch Intern Med. 2007; 167:1068-1074
12. Li R, Zhang P, Barker L, Chowdhury F, Zhang X. Cost effectiveness of interventions to prevent and control diabetes mellitus: A systematic review. Diabetes Care 2010 33:8
13. The CDC Diabetes Cost Effectiveness Group. Cost-effectiveness of intensive glycemic control, intensified hypertension control, and serum cholesterol level reduction for type 2 diabetes. JAMA 2002; Vol.287:19

a must read

http://benbrownmd.wordpress.com/

PP4P

The concept of continuous quality improvement is composed of ten core steps designed to improve a given process. In this context, the process may be defined as optimal type II diabetes management. To this end the results of a recent "Cybertown" quality care medical chart audit designed to assess core markers of diabetes management have revealed two key process shortfalls worth addressing through a CQI framework. First, none of the four patient charts reviewed had recent hemoglobin A1c measurements below the treatment goal 7%. Second, and none had had their urine assessed for microalbumin, the harbinger of cardiovascular disease and diabetic nephropathy. These two factors represent process weaknesses for the patient and physician respectively.

HbA1c measurements are a reliable indicator for the patient's management of his/her blood sugar over time and thus reflect the patient's overall ability to manage the disease outside of the physician's office. As such A1c is more indicative of the patient’s ability to manage his/her disease. By contrast, the measurement of urine microbalbumin through spot semiquantitative dipsticks or albumin/creatinine ratio rests solely upon the physician’s ability to conduct such a measurement at point of care, thus it is a concern dealing with processes internal to the medical management of diabetes. Responsibility to improve this outcome rests largely on the physician. I would like to employ core concepts of CQI informed by my clinical observations to make recommendations for improving this marker of diabetes disease management.

During my experience in the clinic this week, none of the patients with medical histories remarkable for diabetes had their urine assessed for microalbumin during their visit. One core concept in CQI states: Brainstorm potential change strategies for producing improvement. Thus the most direct strategy for having all patients with diabetes screened for microalbumin is to emphasize the importance of microalbumin in the clinical setting whether by mandate, incentive, or education. However, I believe that mandating spot urine assessments for clinic visits once yearly takes away from physician autonomy and creates excess regulation and confusion. Likewise, providing financial incentive for discovery of new onset microalbuminuria is a perverse incentive and may be subject to abuse. Thus the best way to emphasize the importance of microalbumin is through proper physician education that presents the most up to date clinical data on the risks of not treating microalbuminuria. For example, in the clinic every patient had his/her blood pressure checked. Why? Because the clinical importance of blood pressure maintenance is indisputable and widely known. Then it follows that if yearly urine testing is an important clinical measure of diabetes management, so too should evidence be strongly presented for it. This is the best solution for proper practice change.

In the case of hemoglobin A1c, the fact that none of the patient charts reviewed had a most recent A1c less than 7% is indicative of the fact that managing a chronic disease is difficult. Furthermore, it may also indicate that current incentives for maintaining proper A1c may be inadequate to produce the behavior changes necessary to lower A1c to goal for a given patient. In light of this, I propose a mechanism of incentive called, Pay Patient 4 Performance (PP4P), a step forward from the P4P movement in which physicians were reimbursed for meeting healthcare goals at point of care. In PP4P both the burden of management and temptation to “cherry pick” patients no longer befalls the physician. Instead it is the patient who stands to be rewarded financially if his/her A1c is within goal, and it is the patient who takes responsibility for his/her own health. For example, assume that there is a yearly cost savings to having a patient adequately manage their blood sugars as indicated through serial A1c’s within goal. Let us assume that this figure, $X per capita ($X/c), comes about from reducing the burden on the system through staving off the expensive consequences of late stage diabetes; dialysis, laser photocoagulation, amputation, and cardiovascular disease. Thus for every year that a patient delays these financial burdens to the system, they are allowed to share in the cost savings to the system through direct financial reward for that year. My proposal, PP4P, seeks to reward patients for reducing present demand on health costs by awarding them financially with a fraction of the savings to the system. With this system, the patient can realize the benefit of their actions in the present by receiving a reward now instead of having the benefits of prevention remain in future and difficult to conceptualize (i.e. delayed morbidity). As well, this system empowers the patient to take responsibility for their health and relieves the physician of the ethical quandaries of deselection that abounded in P4P (dismissing patients who do not meet goal A1c).

alzheimers write up discussion

Alzheimer’s dementia is an irreversible and progressive degenerative neurologic disorder that is insidious in onset and ultimately fatal. Alzheimer’s is most commonly associated with old age, and it is estimated that between 20-40% of those older than 85 have some form of this disease. I would like to briefly review the clinical presentation, pathology, and current efforts at treatment for this tragic disease.

Alzheimer’s first manifests through declarative memory impairment; patients will typically have word finding difficulties as well as problems naming common objects or names. Long-term memories from decades past are preserved (wedding dates, names of children) and a profound anterograde amnesia takes hold. However, motor task skills and basic social skills are normally preserved during this period, as are language and visuospatial skills. Patients are often disoriented, and although they are capable of spontaneous speech they can be wildly tangential. As the dementia progresses language skills inevitably regress. 10% of patients can demonstrate a phenomenon termed Capgras syndrome a delusional disorder characterized by the belief that their caretaker has been replaced by an imposter. Another characteristic of Alzheimer’s dementia is anosognosia, the patient lacks insight into their own dementia. As a result of this the patient’s may confabulate details or simply display a pleasant disorientation. Patients may wander, especially at night, and may become lost. Patients’ may also display a masked expressionless face, normally characteristic of Parkinsonism. Unfortunately as the disease progresses the dementia strips the patient of basic functioning and they can become rigid, bed bound, incontinent, and agitated. Death normally results from malnutrition, infection, or pulmonary embolus. The average time from onset of symptoms to death is between 8 to 10 years, however it can be as soon as 1 year and as long as 25 years.

The characteristic post mortem pathologies of Alzheimer’s patients are extracellular neuritic plaques and intracellular neurofibrillary tangles. The plaques are composed of aggregates of a transmembrane protein beta-amyloid. The intracellular neurofibrillary tangles are composed of twists of mictrotubules and their associated stabilizing protein Tau (except in this case the Tau is abnormally hyperphosphorylated, a state believed to contribute to its pathological effect). The current belief is that as these proteins accumulate they interfere with normal cellular functioning and eventually become toxic. On autopsy, brains of Alzheimer’s patients have greater plaque and tangle burdens in the hippocampus, tempo-parietal cortex and nucleus basalis of Meynert; neuroanatomical locations that accurately reflect the deficits during life.

Unfortunately there are no treatments that can improve, reverse, or halt the course the disease. Current treatments available for patients diagnosed with Alzheimer’s are primarily symptomatic. Acetylcholinesterase inhibtors such as donepezil, rivastigmine, and galantamine exert their effect by improving neurotransmission in the nucleus basailis of Meynert but their efficacy is limited. Memantine, an NMDA receptor antagonist blocks pathological glutamate excitotoxicity in hippocampal neurons and has been shown to have a small but significant effect in improving cognition, however side effects such as hallucination and agitation have been described. Finally, the well-known anti-oxidant Vitamin E (alpha tocopherol) has been shown to have a modest but measurable effect in delaying clinical endpoits in trials, and has been recommened as a treatment for those patients without heart disease.

post ERCP complication summary

Expanded Discussion

This patient presents to the ER with abdominal symptoms less than one week since ERCP guided biliary stricture stenting. These symptoms likely may be related to well-described complications of ERCP, and I would like to review them here. It is helpful to think of the ERCP complications from three perspectives; severity, timing, and etiology.

First, consider the severity of a potential complication. They are normally classified as mild, moderate, or severe. This classification is assigned depending on the need for hospitalization. Normally mild complications result in hospitalizations of less than 3 nights. Moderate severity complications normally require between 4 to 10 nights of hospitalization, and severe complications usually require ICU admissions or hospitalizations greater than 10 nights. Unfortunately, fatalities have been attributed to post-ERCP complications as well. In terms of etiology, there are complications arising directly from the procedure, so called “focal”, and those related generally to all procedures themselves, called “nonspecific”. The four most common focal complications of ERCP are pancreatitis, bleeding, perforation, and infection. Common nonspecific complications include medication adverse events, contrast allergies, cardiopulmonary complications, and electrosurgical hazards. One must next consider the timing of the complication. These are subdivided into immediate, early, delayed, and late. Immediate complications are those that are said to have happened during the procedure itself. Early complications normally arise within the recovery period, normally a day. Delayed complications manifest themselves within 30 days in the case of focal complications and within 3 days in the case of nonspecific complications. Finally late complications manifest themselves months to years later.

Given this perspective into the classification of ERCP complications let us now more fully described both focal and non-specific complications. Pancreatitis, the most frequent adverse event ranges from 2 -5% but it is important to remember that post procedure hyperamylasemia is seen in 75% of patients. Several treatments are currently being investigated including NSAIDs, glucocorticoids, allopurinol, IL-10, pentoxifylline, PAF, octreotide, anti-oxidants, and anti-metabolites, however none are currently recommended. With respect to bleeding, half of all cases have been found to follow sphincterotomy with an overall incidence ranging from 1 to 5% depending on the study. Of all cases of bleeding (226) in a review of 16,855 patients, severe bleeding (defined as transfusion of 5 or great units of blood or surgical/angiography intervention) was described in 66 episodes (29%). Post ERCP infection normally results from instrumentation of obstructed biliary or pancreatic systems. The recommended way to maximally reduce the incidence of infection/sepsis/cholangitis (currently estimated at ~1.5%) is a complete drainage of an obstruction. Finally, GI perforations during ERCP are subdivided into retroperitoneal, bowel wall, or bile duct perforations. Bowel wall perforations normally occur in the esophagus, stomach, duodenum, or jejunum with an estimated of incidence of between 0.5 to 2% and require surgical intervention in their management or stenting. Biliary perforations can be effectively treated with transhepatic drains to nasobiliary tube and are preferable to internal biliary stents because they do not permit adequate bile drainage.

References:

1. Loperfido S, Costamagna G. 2010. “Overview of indications for and complications of ERCP and endoscopic biliary sphincterotomy.” www.uptodate.com

2. Loperfido S, Costamagna G. 2010. “Post ERCP bleeding.” www.uptodate.com

3. Loperfido S, Costamagna G. 2010. “Post ERCP perforation.” www.uptodate.com

4. Loperfido S, Costamagna G. 2010. “Post ERCP pancreatitis.” www.uptodate.com

5. Fauci, Braunwald, Kasper, Hauser, Longo, Jameson, Loscalzo. “Chapter 285: Gastrointestinal Endoscopy”. Harrison’s Principles of Internal Medicine 17^th Edition. McGraw Hill 2008.

quick hit cardio notes...

triad of right heart infarction
1. increased CVP
2. clear lungs
3. hypotension
don't give nitro, dont give bb if brady
1. fluids
2. dobutamine

Diabetic w/triple vessel diesase + cabg
50% stenosis in left main is enough for intervention

enhanced external counterpulsation- variable tourniquets in lower extremities that rapidly inflate during diastole helps coronaries perfuse and reduces angina

loud S1? could be mitral stenosis

evolution of mitral stenosis:
pulmonary edema w/mitral stenosis in 20's
develop pulmonary htn
develop fatigue and decreased CO

cardiomyopathy? think increased risk of embolic phenomenon

diagnosing AHI/OSA

osa most prevalent sleep disturbance 2-26%
gold standard for diagnosis - in lab polysomnography

STOP questionnaire

S - do you snore loudly
T - do you feel tired (fatigue)
O - observed not breathing
P - treated for HTN

2 or more associated with risk of OSA

now BANG four more questions

BMI >35
Age 50
Neck circumfrence >40
Gender: male

now >3 in STOPBANG associated with sleep apnea/OHS?OSA

medicine away week 3 some more notes TRICC summary

3 types of aspergillus infection

1. aspergilloma (ball) - seen in COPD, TB, sarcoid, needs a cavity to grow in, treating with abx not really effective because ball ~avascular low circulation, just keep it in

2. allergic bronchopulmonary aspergillosis (ABPA) - immune reaction high titers of IgE, reaction to aspergillosis

3. disseminated aspergillosis

patient is tachycardic and the nurse calls you...

get ekg- if sinus tachycardia the major causes are...

1. fever

2. pain

3. dehydration

4. pulmonary embolism

typical a-flutter has inverted p waves in the inferior leads

TRICC trial - transfusion trial in critical care (liberal vs restrictive transfusion)

canadian study -

admitted direct to ICU euvolemic and hgb >9

wings

1. keep hgb 10-12

2. transfuse <7

endpoints 30 day mortality, hospital mortality

6451 patients screened - ~860 enrolled

RESULTS

no sig difference in overall mortality at 30 days

decreased mortality in less critically ill patients APACHE <20

no sig difference in older patients or patients w/cardiac disease

in hospital mortality sig lower in restrictive group overall

"a restrictive strategy is at least effect, possibly superior to critically ill patients except myocardial infarction /unstable angina"

ID lecture

the sanford guide to antimicrobial therapy- use to guide choice of antimicrobial

antibiogram - for hospital gives readout of major susceptibility for the hospital you're in

antibiotics ppx for surgery need to know three things

1. drug of choice

2. pre-operative timing- give abx within 60 minutes (2hrs w/vancomycin*) to right before skin incision - all needs to be in if you're going to use tourniquet

3. where indication

*b/c longer half life ~6hours and need to infuse slow (red man syndrome)

abx administration delegated to anesthesiologist

post op abx - no indication for this but standards allow for up until 24hours, limit to one dose post op.

surgery goes >2 half lives the drug should be readministered

staph epi most common hosp acquired infection since 2000

cephalosporins – beta-lactam antibiotics that cover a broad range of organisms that are resistant to beta lactamases

drug resistance to vancomycin and cephalosporins increasing

now, we have fifth generation -

ceftobiprole (Zeftera) - currently approved in Canada, currently under FDA review

volume of distribution equal to ECF, renally cleared half life 3-4hrs

current dosing is 500mg IV q8h (q12 in gram+, foot infections)

shown to be as effective as vanc + ceftazidime in copmlicated skin infx (cSSSIs, Clin Infect Dis. 2008;46(5):647-55)

adverse effects

dysgeusia, nausea, headache

binds penicillin binding protein 2a (this is the one that makes staph resistant to beta-lactam aka MRSA)

binds penicillin binding protein 2x - this is the one that makes s. pneumoniae resistant to penicillin

has activity against enterobacteriaceae and enterococci

ceftaroline fosamil -still under review by FDA

dose is 600mg iv q12hr, converted from prodrug in serum, renally excreted half life ~2.5hrs

not strongly plasma protein bound

binds penicillin binding protein 2a (this is the one that makes staph resistant to beta-lactam aka MRSA)

binds penicillin binding protein 2x - this is the one that makes s. pneumoniae resistant to penicillin

activity against gram + (mrsa, visa/vrsa, and macrolide resistant s. pyo)

not good for psuedomonas or ESBL (exteded spectrum beta lactamase producers)

covers gram negative (h. influenza, moraxella, enterobacteriaceae) but resistance has a tendency to form in enterobacteriaceae

synergistic w/tobramycin vs. MRSA, hVISA

Safety- similar to other cephalosporins, side effects -mild transaminitis, urine discolor/odor, calcium oxalate crystals,

on the other side-

NDM-1 - first discovered in 2008

new dehli metallo beta lactamase a transmissable genetic element (plasmid) described in dec2009 in patient w/klebsiella (but can be found in all enterobacteriaceae) pneumonia/uti in india found to be resistant to all tested anti-microbials except colistin-> now reported in asia, europe, north America

wow!

http://www.youtube.com/watch?v=h2OfQdYrHRs

more medicine clinic notes a-fib

a-fib normally irregularly irregulary

a-fib w/complete block has normal rhythm because AVnode takes ove and rhythm is junctional

Afib types

Paroxysmal

Non-paroxysmal

Persistent

Permanent

Atrial remodeling is

Cellular - interstitial fibrosis (increased ACE and TGFbeta)

Molecular remodeling - ^HR --> ^Ca concentration --> increased Ca channel formation --> decreased contractile strength --> atrial dilation and fib...

A-fib and decompensation must cardiovert!

Rate vs rhythm control no difference in outcomes, women

internal medicine part #2, more clinical notes

adding amiodarone to someone on coumadin? look for ^^^in INR

classic digitalis toxicity - supraventricular arrhythmia + heart block

Diabetic and Cr >2? no metformin (lactic acidosis) no ACEi (hyperkalemia)

repleting K? check Mg, if not normal K will not rise appropriately.

whats the mechanism behind that?

Mg is bound to ATP, low Mg, low ATP activity--> especially in the thick ascending limb where tonic ATP activity inhibits K efflux into tubular lumen. IF Mg is low then the normally ATP inhibited K channels open and K is lost in urine- and refractory to repletion.

multifocal atrial tachycardia most often associated w/COPD

Stroke patient discussion.

This patient presented with signs and symptoms consistent with a potentially catastrophic L MCA stroke that could have left her hemiplegic and aphasic. Fortunately she recanalized secondary to thrombolytic therapy in the emergency room and later in ICU and recovered her neurological function to near baseline. This is not the outcome of many strokes and far more patients while regaining some prior neurological function are still nevertheless often left with some kind of permanent disability for the remainder of their lives. And although prevention of stroke is key, one must also consider what can be done for patients who have already suffered infarction of cortical tissue. While it is known that the CNS does retain some plasticity, normally infarcted cortical tissue does not regenerate to any significant extent in the context of a cortical stroke as suffered by Ms. X. I would like to discuss current avenues that are being investigated for stimulating endogenous neurogenesis and eventual cortical tissue genesis as a potential post-stroke therapy designed to regain functions currently considered permanently lost.

The CNS tissue is mainly composed of terminally differentiated neurons and glial cells. However, it has been widely identified that there are two regions in the CNS that harbor proliferating neural stem cells, the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. Under normal conditions the SVZ cells continuously migrate into the olfactory bulb in a process termed the rostral migratory stream where a small portion integrate into bulbar circuitry presumably for continued olfaction and odor discrimination. The SGZ neural progenitors predominantly give rise to the dentate gyrus granular layer neurons, and via their incorporation into this structure it is thought they are a vital component to ongoing adult learning and memory.

In an experimental model of stroke termed transient middle cerebral artery occlusion (tMCAO), focal ischemic injury has been found to increase SVZ proliferation for up to four months post insult. In this condition, the normal rostral migratory stream is disrupted and SVZ cells migrate toward areas of focal ischemia directed by inflammatory cytokines and tunneling with the aid of matrix metalloproteinases. Although many of these neuroblasts will migrate to areas of injury, for example the striatum, unfortunately few will terminally differentiate and incorporate to recreate viable neuronal tissue. The reason for this lack of functional incorporation and thus its utility as a therapy for stroke is unknown. Current hypotheses abound and several regulatory factors have been identified experimentally. One may involve inflammatory mediators secreted by astrocytes and microglia that pose as inhibitors to the process of functionally integrating into these cells into existing neural circuits. Also SVZ neurogenesis has been found to globally decrease with advanced age, the mechanism not thought to be intrinsic to the neural progenitor cell, instead largely as a result of an aged cell microenvironment, termed “niche”. Many other soluble factors have been found to modulate both SVZ and SGZ proliferation, survival, and neuronal differentation and are the subject of many current investigations as potential therapeutics for post stroke neuronal regeneration; brain-FGF, heparin binding EGF, VEGF, BDNF, EPO, glutamate, 5-HT, and NO. As well, neuroendocrine states have been shown to modulate endogenous progenitor proliferation in post stroke states as it has been identified that adrenal steroids are inhibitors of SVZ and SGZ progenitor cell mitoses. Another promising avenue for investigation is serotonin’s positive effect on neurogenesis, a mechanism observed in rodents treated with SSRI’s. To this end clinical trial NCT00967408 is currently investigating the functional outcomes of stroke patients treated with escitalopram in an acute setting. The results of this trial are eagerly being awaited; treating stroke patients with SSRI may prove to be as important to recovery as administration of statin.

Central to any cellular therapy for CNS regeneration is the cellular microenvironment, one in which astrocytes and microvasculature play key roles. In several basic science investigations, astrocytes have been shown to promote neuroblast proliferation and differentiation. Additionally, soluble brain endothelial factors positively regulate SVZ/SGZ cells, and that microglia (mentioned previously) may actually be inhibiting neurogeneiss by means of upregulation of inflammatory mechanisms leading to reactive gliosis. However it is important to realize that even though increasing neural progenitor cell proliferation has potential as stroke therapy, many cell mechanisms must be regulated. For example Columbia’s own Doetsch et al found that EGF receptor expression in SVZ may actually contribute to glioma formation, and isolated BDNF infusions into mouse hippocampi induce limbic seizure in 25% of cases. These findings illustrate that controlled neurogenesis is an elegant process and will be more complicated to modulate than merely a crude exogenous cell graft.

Adult CNS regeneration as a therapy has complications, even if endogenous neural progenitors proliferate in response to ischemia and can spontaneously migrate to peri-infarcted cortical areas, restoration of function depends on new neural connections being appropriately formed, and in the case of a cortical stroke of the precentral gyrus, UMN neurons have very long connections. Amazingly, patial restoration of corticospinal neuronal connection of this length have been demonstrated in mice by Chen et al, an exciting prospect, but have yet to be scaled up to primate models a key step for translating this phenomenon into clinical medicine. A separate problem revolves around whether or not progenitors differentiate into the proper subtype of neuron; because it has been observed that these cells do not appear to differentiate into neocortex. Furthermore this is compounded by the observation in mice that neural progenitors have not yet been shown to integrate into peri-infarcted cortical circuits. In contrast neural progenitor differentiation into striatal structures has been demonstrated, but functional restoration from this incorporation has not yet been reported.

Although no regenerative therapy exists for neurological dysfunctions as a result of stroke there are novel therapies on the horizon involving both endogenous stem cell proliferation and exogenous stem cell graft. Before these therapies can safely enter clinical medicine the cellular mechanisms of migration and cortical circuit integration must be more fully described. The field must reliably demonstrate how to substantially increase the small pool of endogenous neural precursors in order to adequately mount the task of replenishing large areas of cell loss from cortical infarcts that may lead to functional recoveries. Mechanisms of migration and functional integration into existing circuits are still imprecise and require further illumination. Discoveries found in mouse models must be scaled up to primate models to more closely approximate human physiology. Despite these unknowns, many clinical trials are underway attempting to demonstrate clinical efficacy of cell therapy in stroke. If resources are continually invested in unearthing the biology of neural progenitors, the employment of cell therapy for regenerative treatment for the disabilities wrought by stroke may one day be a standard of care in clinical medicine.

References

1. Effects on Clinical and Functional Outcome of Escitalopram in Adult Stroke Patients http://www.clinicaltrials.gov

2. Chen J, Magavi SS, Macklis JD. 2004. Neurogenesis of corticospinal motor neurons extending spinal projections in adult mice. Proc Natl Acad Sci USA 101:16357-62

3. Doetsch F et al. 2002. EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 36: 1021-34

4. Erlandsson et al. 2010. Immunosuppresion promotes endogenous neural stem and progenitor cell migration and tissue regeneration after ischemic injury. Exp Neurol epub ahead of print

5. Kernie, Steven G., Parent J M. 2010. Forebrain neurogenesis after focal ischemic and traumatic brain injury. Neurobiology of Disease 37:267-274

6. Lichtenwalner R J, Parent J M. 2006. Adult neurogenesis and the ischemic forebrain. Journal of Cerebral Blood Flow & Metabolism 26:1-20.

7. Martin JH. Neuroanatomy: text and atlas 3^rd edition. McGraw Hill 2003

8. Scharfman HE, Goodman JH, Sollas AL, Croll SD. 2002. Spontaneous limbic seizures after intrahippocampal infusion of brain-derived neurotrophic factor. Exp. Neurol 174:201-14

9. Hung CW et al. 2010. Stem cell-based neuroprotective and neurorestorative strategies. Int J Mol Sci, 5:11(2039-55)

How could an undocumented MS patient get care?

The course that Ms. X’s case has taken is non-reassuring in that she has not regained any of her lost function and now receives IVIG a treatment that has not shown efficacy in SPMS, her presumptive diagnosis. However, what has further complicated her care is her citizenship status: she is undocumented, and currently receives care under emergency Medicaid. My understanding of Medicaid is quite limited so I wanted to expand on this subject and attempt a greater understanding of the legal complications to her care.

Medicaid, enacted in 1965, is a federally funded program that provides assistance to acquiring healthcare to those individuals with low incomes¹. The program assumes the cost of medical care by reimbursing on a state level certain medical expenses that fall within its sphere. The burden of cost shared by each state varies; those states with higher per capital incomes are less well reimbursed for the cost of the care they provide, and poorer states with less per capital income are federally reimbursed more substantially. Currently New York States federal medicaid match rate is 50%², shifting the burden of health care onto state coffers. Guidelines for states to administer entitlements vary, but most states do not offer benefits for adult men and non-pregnant women who are not disabled. In fact beneficiary populations are normally subdivided into categorically needy, medically needy, special groups, waiver populations, and children¹.

Categorically needy are pregnant women, women with children less than 6, income below 133% of poverty level ($29,326.50 for family of four)³, those living in medical institutions, and the impoverished elderly who are eligible for supplemental security income (SSI). The medically needy are individuals who may have limited financial resources and states may chose to expand and widely vary in what they cover. Certain individuals who variably qualify may nonetheless be unable to get care, and so Medicaid reserves the following special groups, those who lose Medicaid coverage because of work but are still below 200% of federal poverty line, those with TB, women with breast/cervical cancer not otherwise eligible for Medicaid but who have no insurance. Many states engage in cost experimentation and pilot studies and in these circumstances a “waiver” may be acquired to access care. Centers for Medicaid and Medicare Services (CMS) regularly reviews these waivers. Finally there is SCHIP, the state children’s health insurance program designed to provide care for children whose parents do not meet income criteria for Medicaid. Benefits provided by Medicaid include hospital services and long term nursing care. “The bulk of long term care is provided by medicaid⁴.”

However, what about Ms. X? How is she able to access care? Immigrants and undocumented individuals are generally ineligible for Medicaid, however Ms. X is eligible for emergency treatment under Emergency Medicaid and Emergency Medical Treatment and Labor Act (EMTALA)⁵. These laws require anyone who shows up on the doorstep of the emergency room the right to receive care and be stabilized. However what about Ms. X’s case, she is overall medically stable and being treated for a chronic neurodegenerative disease. How was her care able to be arranged? The New York City Health and Hospitals Corporation has a program called HHC Options which has the ability to provide care for everyone regardless of legal status and ability to pay⁶. This would include access to city hospitals, including her current residence where she is receiving long term care at the skilled nursing facility XYZ. Although it is not clear how her care is arranged I believe this program may in fact be her lifeline. As the social burden in New York and America continually increases, tax funded city programs like this will face mounting financial stressors. But it is critical that they be maintained so that the rare cases like Ms. X do not end in tragedy. Currently Ms. X is getting by with very little help and is not a great burden on taxpayes, and she has no good options. First she is unfortunately afflicted with a crippling and unremitting neurodegenerative disease. Second, she has little support from family members, only a sister that has been a regular caretaker. And third, she is undocumented, a status that severely limits her access to care, keeping her the institutionalized. But although the system where she subsides may at times be inefficient she is nevertheless receiving some standard of care (more than if she were in her home country).

References:

1. Baldor R. Medicaid. http://www.uptodate.com/

2. Comparison of State Medicaid Costs. 2002. http://www.leg.state.vt.us

3. Human Health Services. 2009 Federal Poverty Guidelines http://aspe.hhs.gov/poverty/09poverty.shtml

4. Baldor, RA. Managed Care Made Simple, 2nd ed, Blackwell Science, Cambridge, MA 1998.

5. Kaiser Family Foundation: Kaiser Commission Medicaid and the Uninsured: Medicaid and SCHIP eligibility for immigrants. 2006

6. http://www.nyc.gov/html/hhc/downloads/pdf/hhc-options-06-2009-eng.pdf

Charles Bonnet b1720 Swiss naturalist

Charles Bonnet was a swiss lawyer turned naturalist. He was the first to describe the phenomenon of visual release hallucinations in his aging father in the 18th century. The tonic inhibition of the visual cortex by visual input from the environment when removed creates a denervation hypersensitivity that can occur anywhere along the visual pathway (from the granular layer to higher order integration areas), thus excessive cortical activity about the occipital lobe and beyond originally inhibited is now "released" and the patient experiences a wide ranging assemblage of visual hallucinations.

This above picture was a drawing by a patient described in this case report who also experienced these visual hallucinations.

Later in his life, Bonnet set out to the Swiss countryside to write. In my opinion his intuition regarding the nervous system as a modifiable feedback loop with the environment first, correctly identified the chief mechanism believed to underlie the development of memory in organisms, that repeated environmental stimuli create nerve approximations that are favored because that have less resistance (or could be said to be more likely to refire). And second, created the central dogma for approaching an understanding of how nervous tissue functions (much the way Newton reorganized bodies in motion) Genius!!!

The following excerpt is taken from his 1760 essay on the faculties of the heart Essai analytique sur les facultes de l'ame (i think).

"All knowledge originates in sensations; sensations follow vibrations in the nerves appropriate to each; the nerves are made to vibrate by external physical stimulus. A nerve once set in motion by a particular object tends to reproduce that motion; so that when it a second time receives an impression from the same object it vibrates with less resistance. The sensation accompanying this increased flexibility in the nerve is, the condition of moemory. That which puts [the mind] into activity is pleasure or pain. When the active element of the mind is applied to the acquisistion and combination of sensations, those abstract ideas are formed which, though generally distinguished from , are thus merely sensations in combination only."