Check Out Nutritional Advice for Muscle-Building

Despite the fact that you may regularly relate 'getting fit as a fiddle' with losing fat and conditioning up, there are a lot of individuals out there whose principle concern isn't to get thinner, however to put it on. I'm discussing those of you who have been marked 'thin' or 'slender' their entire life, and maintain a strategic distance from the exercise center by all methods in the dread it will bring about losing more weight.

This is a typical misguided judgment, however talking as a matter of fact I can sincerely say that it is conceivable to totally change your body and pick up the solid, conditioned constitution you've generally longed for yet felt you'd never have the capacity to accomplish. On the off chance that you need it anyway, you should to be set up to work for it; bulk does not come quick, regardless of your age, sex or body shape. In any case, on the off chance that you invest the exertion by eating admirably and preparing hard, you can hope to accomplish some phenomenal outcomes.

Sustenance

Sustenance truly is the most essential factor with regards to picking up bulk - all things considered, in the event that you don't expend a larger number of calories than you consume you won't pick up, regardless of how hard you prepare. The development procedure requires a considerable measure of calories, and figuring out how to devour them consistently can be harder than you may might suspect. My recommendation is to eat three expansive suppers, in addition to a few littler ones every day. This implies setting up your sustenance ahead of time so you have sound dinners to eat when you're grinding away or in a hurry.

Protein

Protein is basic for development and the working of new tissue and also the repair of tissue that has been separated (which happens when you work out). The general decide is by all accounts that you require between balanced and a half circumstances your body weight in grams of protein on the off chance that you need to reliably pick up muscle. Notwithstanding, this will fluctuate from individual to individual so you have to find what works best for you. As you put on weight, you should expand your admission likewise. Extraordinary wellsprings of protein incorporate red meat, angle, poultry bosom, eggs, dairy and whey; the last is the base of the greater part of the protein shakes I drink post-exercise.

Protein shakes are an ease choice which work fine as a substitute for one of your 'littler dinners' for the duration of the day. I mix mine with skimmed drain, and eat a banana or a modest bunch of unsalted nuts to go with it post-exercise at the rec center. Refueling instantly subsequent to preparing has worked ponders for me - it's as of now your body is longing for the important supplements expected to make its repairs. As they're fluid, protein shakes are additionally processed less demanding and quicker than entire nourishments, while giving you a fantastic wellspring of protein and carbs. They are additionally adjusted fittingly for a post-exercise dinner, as they contain no fat or different components that may thwart the stomach related process. By getting the essential supplements to the source speedier, your body won't be committed to take from different stores it as of now has.

Starches

Starches regularly get a terrible rep, yet in spite of what Mr Atkins says, carbs are our companions! They are a fundamental macronutrient your body requires with the end goal for it to have the capacity to take advantage of its glycogen stores amid an exercise. In the event that you don't eat enough of them, your body won't have any vitality stores and it will begin to separate muscle.

Go for complex (solid) carbs, for example, cereal, grain and quinoa, and in addition wholegrain other options to rice, pasta and bread. These will furnish your body with heaps of fundamental supplements and discharge their vitality gradually. Since complex starches are separated gradually and have a low-glycaemic file, they are great nourishment sources to eat post-exercise and at breakfast time (the most critical dinner of the day!).

Fats

Fats can't be extensively arranged, in light of the fact that not all sources are made equivalent. It is exhorted that around 20 - 30% of your day by day calorie admission ought to be conveyed from 'solid fats'.

Monounsaturated and polyunsaturated fats are what are known as 'great fats'. These are the ones you ought to consolidate into your eating regimen; prove recommends eating 'sound' fats is in reality bravo! Most 'solid' fats are gotten from plant sources, and incorporate sustenances, for example, angle, soya, tofu, seeds, nuts and plant-based cooking oils.

Immersed and trans fats are the 'terrible fats'; these should make up under 10% of our eating regimen (soaks) and close to 1% for trans fats. It will not shock anyone that these awful fats represent every one of those characteristically 'undesirable' nourishments, for example, frozen yogurt, desserts, chocolate, fricasseed sustenance, spread, high-fat cuts of meat and bundled nibble sustenances. These fats are by and large gotten from creature items and ought to be eaten with some restraint.

Supplements

I wouldn't try sprinkling out on all the favor supplement prevailing fashions that travel every which way; these have a tendency to be a misuse of cash. There are as of now attempted and tried items accessible that do precisely what you require them to, less the robust sticker price. Stick to superb multi-vitamin tablets or mineral supplements that give you 100% of your every day RDA, and in addition whey-based protein powder for protein shakes, et cetera. Creatine is the main other supplement I consolidate in to my eating regimen, as it helps increment unadulterated bulk and recover muscles when you're not working out.

So there you have it, my healthful manual for building. I trust this article will get you on your approach to accomplishing your objectives, and on the off chance that you just remove one things from this, simply recollect change doesn't occur without any forethought. You must keep at it, buckle down and adhere to your schedule. On the off chance that you foul up one day, don't thrash yourself about it or surrender, simply begin once more the following. Try not to squander your cash on costly favor supplements, and certainly don't surrender to the impulse to cheat your way up to the best. Do it my way, do it the correct way, and in the end you'll receive the benefits. Good fortunes

Read More

Free Weights Vs Machines

Presentation:

Amid the development of working out humanity has seen an innovative progress in weight training machines. These days machines are planned and made better then ever. In any case one may ask which is better. That answer will be found in the conclusion segment of this article, however first lets begin with the upsides and downsides between the two!

Machines:

The machines that are discovered today everywhere throughout the world are composed and made better then ever. One must understand that machines simply like free weights are apparatuses that are utilized to shape and manufacture ones body to the most extreme one can accomplish conceivable. Additionally one must be grateful and keen to the machines that are discovered today, take a gander at the machines from the 1960's and 1970's and you will perceive what I mean.

Without facilitate farewell, how about we begin - machines help separate one's muscle. What I mean by that is suppose one does straight bar twists for the bicep muscle, while utilizing the free weight, one's front deltoid and lower arms will help with lifting the weight. In any case in the event that one goes on a machine that is made entirely for the bicep muscle, the bicep will entirely take the necessary steps and lift the weight up. This disengagement that ones gets from a machine will influence the muscle to work harder and stricter. However machines have cons as well, cons, for example, not working the stabilizer muscles and not getting the majority of ones normal testosterone creation. General machines help seclude the muscle amass one works out on, yet confines the other muscle bunches as far as development and quality.

Free Weights:

The muscles found in the human body where planned by development to beat the draw of gravity somewhat then to conflict with machines protection. In this manner one's greatest picks up in quality and muscles size will originate from lifting free weights, for example, dumbbells, barbells and straight bars. Lifting free weights will likewise expand ones common testosterone generation which is requirement for muscle development and recuperation. However this all accompanies a cost. When utilizing free weights distinctive muscle gatherings will become possibly the most important factor, in this way making ones exercise less productive. In any case, general the masters exceed the cons when one uses free weights!

Conclusion Which Is Better?:

Neither in light of the fact that both are instruments one needs to develop their bodies to the most extreme they can accomplish conceivable. Hence I suggest one has both machine and free weight practices in their weight-preparing schedules!

Read More

Big changes in the world of VAP?

As you may or may not be aware, the four main professional societies in the US that include large critical care constituencies, AACN, Chest, SCCM and ATS, have created something called a Critical Care Societies Collaborative (CCSC). Its purpose is essentially to give the critical care community a voice in shaping public policy. And, as you can imagine, one of the current-day issues they are tackling is performance measures.

Now, on this web site we have spent a lot of virtual ink talking about quality metrics, particularly where ventilator-associated pneumonia, or VAP, is concerned. Well, I am happy to report that finally, a strong voice in Critical Care medicine is in agreement with what we have been saying: the VAP bundle needs to go! In fact, here is the sum of the recommendations made to the National Quality Forum in a letter dated February 9, 2012, from the CCSC leaders about VAP (emphasis mine):

The Task Force felt that the VAP “care bundle” minimizes the importance of each individual component measure and neglects the fact that many elements of the existing VAP bundle are known to have important effects outside of VAP reduction, including improved patient survival. The task force also notes that one of the components of the VAP care bundle, stress ulcer prophylaxis, may actually increase the risk of VAP.51Therefore, the Task Force would like to make the following recommendations regarding measure gaps related to VAP:(1) Dissolve the VAP care bundle and instead develop a new group of quality measures related to general evidence‐based practices for patients requiring mechanical ventilation (described above.) These potential measure gaps would include care processes known to reduce morbidity and mortality in patients who are ventilated.
(2) Develop measures using the VAP‐specific measure gaps supported by recent guidelines.52,53 These may include measures for the following evidenced‐based practices:
• Orotracheal rather than nasotracheal intubation to prevent VAP54;
• Subglottic secretion drainage to prevent VAP55;
• Elevating the head of bed to 45 degrees to prevent VAP56;
• Oral antiseptic administration to prevent VAP57;
• When empiric antibiotics are used to treat VAP, initial treatment based on qualitative endotracheal aspirates rather than quantitative bronchoscopic aspirates58; and
• No more than an 8‐day course of antibiotics as treatment for uncomplicated VAP.59
All of these VAP prevention strategies are supported by randomized‐controlled trials. However, not all have favorable cost‐benefit profiles, and all have significant barriers, which may make widespread adoption unfeasible. Although we list them all here, we note that all may not be good quality measures.

So, here it is -- the recommendation. But will it be followed? When I was at SCCM, I heard a presentation that talked about some new metrics being developed by the CCSC in collaboration with the CDC, which will likely replace VAP as the focus of mechanical ventilation complications. I am in the process of learning more about these developments even as we speak, and will update my readers on what I learn. Suffice it to say, change is coming to the world of VAP. And it's about time. 

Read More

Teach one thing, or the rule of thirds

When I was a medical student, I did a lot of rotations at the Boston VA in JP. I loved my patients there -- they were patient and kind and stoic. One of the best rotations I did was Hematology, where Lou Fiore was my preceptor. Lou was not only an excellent teacher, but also a terrific doctor and a good human being all around. He used to start our days together by saying, "I'm gonna teach you one thing today." And teach us he did, at least one thing per day. Now I teach. And on occasion I have used the Lou Fiore "I'm gonna teach you one thing today" promise. Well, today is one of those days: I'm gonna teach you one thing.

And here is that thing. I am sure I am not the first one to notice this, but I still think of it as the "Zilberberg rule of thirds." The gist of it is that, for clinical research purposes, one can think of patient populations crudely in thirds: there is one third who are too sick to benefit from any of our interventions, there is one third who are too healthy, so that no matter how we try to tweak, their outcomes will not change, and the middle third, which comprises the "sweet spot" for intervention. So it is a fool's errand to pursue proof of concept studies in either of the bracketing thirds, since it is only the middle third that is likely to show a signal.

Pharmaceutical manufacturers do not always appreciate this trichotomy. Look at Vioxx, for example: when used in patients who were essentially healthy, an unacceptable safety signal arose that drove the drug off the market. Same for SSRIs, where the ill-conceived enthusiasm for treating marginal depression cases seems to be debunking the entire serotonin hypothesis. The flip side is sepsis research: septic shock patients are so far gone that it is difficult for any single therapy to alter their outcomes. Just look at the Xigris story, as well as myriad other therapies that tried and failed. This is the rule of thirds at its most pronounced.

In HEOR the rule of thirds holds as well. To prove cost effectiveness the following questions need to be asked:
1. Is the disease in question prevalent?
2. Is the economic impact of the disease known and substantial?
3. Does the diagnostic/therapy in question alter the course of the disease in such a way as to be significant?
If the answer to any of the questions above is "no," you really need to think carefully about the value proposition.

Some of you will bring up the inter-individual differences, the heterogeneous treatment effect, etc. And yes, these are supremely important. However, though the framework I propose here is simplistic, we have to start somewhere. To be sure, there is a more nuanced approach to this beast, but generally, one will not go wrong by asking these questions before committing huge resources to a project, particularly if the answer to question 2 or 3 is a resounding "no." So, even in health economics it behooves one to know the Zilberberg rule of thirds: choose the right population where the diagnostic/therapeutic advance and its costs can be justified by a substantial gain in the outcomes.

And that is your one thing for today.    

Read More

Marie Curie, Geiger counters and mass hysteria: more in common than meets the eye

What do Marie Curie, a Geiger counter and mass hysteria have in common? Well, to answer this question we need to go Sir Arthur Eddington, who was a British astrophysicist and philosopher of science at the turn of the 20th century. He came up with what is frequently referred to as the Eddington parable, which has nothing to do with the stars specifically and everything to do with how we make scientific progress. Here it is for your reading enjoyment, as told in this editorial (available by subscriptionby Diamond and Kaul, two highly respected clinician-researchers:

Let us suppose that an ichthyologist is exploring the life of the ocean. He casts a net into the water and brings up a fishy assortment. Surveying his catch, he [concludes that no] sea-creature is less than two inches long. An onlooker may object that the generalization is wrong. "There are plenty of sea-creatures under two inches long, only your net is not adapted to catch them." The ichthyologist dismisses this objection contemptuously: "Anything uncatchable by my net is ipso facto outside the scope of ichthyological knowledge, and is not part of the kingdom of fishes which has been defined as the theme of ichthyological knowledge. In short, what my net can't catch isn't fish”.

Suppose that a more tactful onlooker makes a rather different suggestion: "I realize that you are right in refusing our friend's hypothesis of uncatchable fish, which cannot be verified by any tests you and I would consider valid. By keeping to your own method of study, you have reached a generalization of the highest importance—to fishmongers, who would not be interested in generalizations about uncatchable fish. Since these generalizations are so important, I would like to help you. You arrived at your generalization in the traditional way by examining the fish. May I point out that you could have arrived more easily at the same generalization by examining the net and the method of using it?"

So,you see my point? Tools determine knowledge. Period.

  

Read More

Physician Payment Sunshine Act: More marginal thinking

It never ceases to amaze me how we gravitate to the margins in our thinking: margins seem to have a centrifugal force that is nearly impossible to overcome in today's political discourse. Yet the truth almost always lies at the center, the place that does not generate Op-Eds or produce votes.

I have said this before, and I will say it again: industry-physician relationship is not all bad or all good, there is no one within this relationship that is all bad or all evil, and it does not always benefit or always harm patients! The truth, of course, is somewhere in the middle. Contrary to Stossel's thesis, there is plenty to worry about with respect to corruption promoted by the big money exchanging hands between Pharma and doctors. On the other hand, just because there are instances of corruption and its consequences, not all interaction, financial or otherwise, is counterproductive. I am the first to admit that the much-touted innovation in medicine is rare, and we have largely given up its pursuit in favor of predictable markets and returns. Yet without a robust and transparent collaboration between industry and practitioners there is not only little hope of innovation, but any innovation that may stand a chance is likely to be irrelevant.

Yes, I agree with Stossel that the new reporting regulation is overly punitive and will inevitably result in undue administrative burden. But it would be disingenuous of me to disagree with the fundamental idea that there needs to be at least some degree of transparency in the financial dealings between industry and clinicians, if only to avoid the appearance by the docs of serving two masters.

As in everything in life, the devil is in the details. And it is these details that get buried by the gravitational pull of peripheral thinking and discourse. The solution? How about we stop paying attention to these marginal fallacies and start putting our heads together for real to solve these significant problems? How about we start a rational discussion about what is best for the people and not for the corporations or the economy or reputations? The discussion has been subverted by extremism. It is time to give in to the centripetal pull of reason.      

Read More

3 ways to sink a new drug

I don't just rant about methods and evidence -- in my work life I also rant about health economics and outcomes! This is why I was so interested in this post by the health economist Ulf Staginnus called
"New Models for Market Access." I want to give a hat tip to Healtheconomics.com for pointing me here.

The thesis of the article is that we need to refocus our discussion from market access to true innovation in the biopharma sector. There are some priceless quotes here, like this one, for example:

It is amusing, at least to me, to see the continued flood of articles, consultant presentations, blogs, congress announcements, workshops, summits, reorganizations, speeches, etc. all over the place, basically suggesting how the industry just needs to throw a few more people with fancy titles here and there, coupled with slight organizational changes, onto the problem and involve stakeholders and—guess what?!—actually talk to patients and perhaps even payers and all of a sudden, like Alice in Wonderland, everything will be good, after all.

The uncomfortable truth is, it won't be. All this “noise” is only good for one thing, paying the bills of the consultants, which is fine, too, as I have been one myself so I can understand. But it will not address the problem the research-based pharmaceutical industry and its employees are facing. Without a substantial increase in R&D productivity, the pharmaceutical industry's survival (let alone its continued growth prospects), at least in its current form, is in great jeopardy.

Don't you love it? It is hard to disagree. He also calls for more of a focus on the long-term returns than the short-term (duh!), as well as more internal honesty, or having the courage to stand up to the pathologic internal enthusiasm about a late-stage product that will obviously go nowhere. And all of this is on target.

He has this to say about health economics and outcomes and such:

Of course, you need experience in areas such as HE, outcomes research, pricing, economics, policy, advocacy, etc. and all needs to work in sync and early on and with the payer in mind and, yes, most people have understood that by now. So the problem is essentially not in the capabilities, although some are more advanced than others, but rather in the company cultures.

And this, I think, is where I have to disagree with him. In my experience there are glaring deficits in the approach to HEOR within biopharma, though of course there are exceptions to the rule. It starts with the fact that disease burden, and especially its costs, are initially assessed through less than, shall we say, rigorous methods. I have seen this critical information get pieced together through market "research", where 5-10 "thought leaders" are asked for their opinions, and the quantification is based on this tiny non-representative sample of nothing more than guesses. This is a shame because the data usually exist which can give a much more bona fide estimate of the extent of the problem.

The second problem is that articulating the value proposition of a nascent technology is usually an afterthought. In fact it is self-evident that drug pricing must be fed using the information on the burden of disease, and the impact the new technology can make in mitigating such burden. Unfortunately, time and time again I see companies backing into a price simply in reaction to what their Boards perceive the returns should be. And frequently this is based on the overly optimistic market projections flowing from, you guessed it, market "research."

So, the direct result of all this short-sightedness and business as usual is that even innovative useful products are driven into oblivion because there is no realistic look at what the technology is worth or where best to use it. And fixing the problem after the drug or device is on the market is a much bigger challenge for several reasons. First, the acquisition costs of new technologies are bound to be higher than of those already in use. This puts them at a disadvantage in that they get niched into populations that have much greater burdens of illness and therefore less of a chance of doing well. In other words, they are used as a last ditch therapy, which very rarely ends well. Ironically, these are usually not the populations who were studied in the pre-approval studies, and thus the use turns out to be off-label. But here is the real problem: When these technologies are in the "kitchen sink" category, they will almost always end up looking worse in terms of the outcomes than their older counterparts. And to the untrained eye, or an eye who does not have the time to discern the truth, particularly in the setting of perceived high expenses on the new product, this rings the death toll for the drug. But the reality, of course, is that the abysmal outcomes are the result of confounding by indication, where the drug was inappropriately given to those patients who were very unlikely to benefit from in the first place. But you see how this early lack of attention to the articulation of appropriate populations and health economic data can snowball into failure of a promising therapy.

So, if you want your drug to fail, do the opposite of what I recommend below. In other words DO NOT
1. Develop your market understanding
Do it not from the opinions of a handful of "experts" -- experts will rarely tell you the truth. Instead, do epidemiology studies to understand your population and its subpopulations so as to get the most reasonable idea of the disease.
2. Start thinking about the value proposition early 
At the end of a successful Phase 2 program is a good time to do this. The surprise to most companies is how little HEOR studies cost in comparison with their clinical trials program. Yet, as you can see from above, this drop in the ocean can make or break a product.
3. Focus on transparent pricing methods
When pricing the technology, be very very sure that you have all of the ducks in a row, meaning:
                    a. do understand your market 
                    b. do understand the burden and costs of the disease
                    c. do understand how your product impacts these costs
                    d. do price the product to reflect this balance
It is truly embarrassing to have to admit that your price reflects nothing more than the greed of your investors. Trust me, you will not score points with your customers.

Staginnus makes one other important point which I generally agree with:

And let's face it, if you need a major workshop and intensive external “coaching” to help define the value of your product … well, there actually is little to none. If it was really good, it would have been obvious from the start. So maybe we ought to stop beating around the bush and move on if there is nothing to be done anymore. 

There is a nuance here, however, as in most things. Given what I have said above, products are more likely to gut than sell themselves. So, while I agree that you do not need a throng of consultants in suits and hair gel to pollute your offices, you do need to understand how to articulate this value, even when it appears obvious.

          

Read More

When end of life is not

Twenty years ago, I helped save a man's life.

So begins this New York Times essay by Peter Bach, MD, where he talks about the inadequacy of resource use at the end of life as a policy metric. Now, I am not very fond of policy metrics, as most of you know. So, imagine my surprise when I found myself disagreeing vehemently with Peter's argument. Well, to be fair, I did not disagree with him completely. I only disagreed with the thesis that he constructed, skillfully yet transparently fallaciously (wow, a double adverb, I am going to literary hell!) Here is what got me.

He describes a case of a middle-aged man who was experiencing a disorganized heart rhythm, which ultimately resulted in dead bowel and sepsis. The man became critically ill, the story continues, but three weeks later he went home alive and well. This, Dr. Bach says, is why end of life resource utilization is a bad metric: if this guy, who had a high risk of dying, had in fact died in the hospital, the resources spent on his hospital care would have been considered wasted by the measurement. And I could not agree more that lumping all terminal resource use under one umbrella of wasteful spending is idiotic. Unfortunately, knowingly or not, Peter presented a faulty argument.

The case he used as an example is not the case. Indeed it is a straw man constructed for the cynical purpose of easy knock-down. When we talk about futile care, we are not referring to this middle-aged (presumably) relatively healthy guy, no. We are talking about that 95-year-old nursing home patient with advanced dementia being treated in an ICU for urosepsis, or coming into the hospital for a G-tube placement because of no longer being able to eat or drink. We are talking about patients with advanced heart failure and metastatic cancer, whose chances of surviving for the subsequent three months are less than 25%. And yes, we are also talking about some middle-aged guy with gut ischemia, sepsis and worsening multi-organ failure whose chances of surviving to hospital discharge are close to nil; but in his case, instead of being clear from the beginning, the situation evolves.

So, yes, the costs of end of life care, and specifically hospitalizations, are staggering. But more importantly, among patients with terminal illnesses like metastatic cancer, advanced heart failure and dementia, hospitalizations and heroic interventions at the end of life cause unnecessary pain and suffering, and without much, if any, benefit in return. Their families and caregivers suffer as well, and many studies suggest that these caregivers are not interested in prolonging suffering, provided they are aware of the prognosis. Unfortunately, just as many studies suggest that communication between doctors and patients' families about these difficult issues is less than stellar.

So, let me play the devil's advocate and pretend that I support end of life resource utilization as a quality metric. If I did, I certainly would not be interested in depriving Dr. Bach's middle-aged acutely ill patient of the chance to survive. In fact, my aim would be to make sure that we align resource use with where it can do most good, and turn away from interventions that are apt merely to prolong dying.        

Read More

Lessons from Xigris

I have been wanting to write for a while about the demise of Xigris, but work and other commitments have stalled my progress. But it is time.

Here is my disclosure: I have received research funding from BioCritica, a daughter company of Eli Lilly, the manufacturer of Xigris. I also happen to know well and hold in high esteem the depth of knowledge and integrity of several colleagues who worked on Xigris internally at Lilly.

But on to the story. Xigris has had a short and bumpy life. When the PROWESS study, the Phase III Xigris trial, was first published in the NEJM in 2001 [1], it was the first therapy to succeed in sepsis, reducing mortality by 6% from about 31% to about 25%, yielding the number needed to treat of 16. This was huge, as so many trials to date had failed, and no progress had been made in sepsis management for years. These data opened the door to the FDA approval, despite a hung advisory committee, where equal numbers of members voted for and against approval. The controversy centered on concerns for bleeding complications, as well as some protocol changes during the trial and a switch in the manufacturing process. The latter concern was allayed by the Agency's detailed analysis and the finding of equivalence. There was a signal in a subgroup analysis that the drug might have been most effective among the most ill patients with a high probability of death, but not in their less ill counterparts. And despite the fact that the pivotal trial was not specifically performed in these patients, the approval for use specified just such a population.

So, despite the controversy, the drug was approved, though several post-marketing commitment studies were mandated. ENHANCE [2, 3] was an international study whose findings broadly confirmed the safety and efficacy of the drug, while the ADDRESS study [4], done in patients at low risk for death, was terminated early for lack of efficacy.

It seemed that PROWESS ushered in an era of positive results in sepsis. Shortly after its publication, other studies on the use of early goal-directed therapy [5], low-dose steroids [6] and tight glucose control [7] appeared in high impact journals, and the years of failure in sepsis management seemed to be over.  

In the meantime, and amid further controversy [8], Lilly supported the creation of the Values, Ethics and Rationing in Critical Care (VERICC) Task Force [9, 10], in addition to giving funding for the international Surviving Sepsis Campaign (SSC), which has resulted in the evidence-based practice guideline for sepsis management [11, 12] and an implementation program for the sepsis bundles, jointly sponsored by the SSC and the Institute for Healthcare Improvement [13]. The latter 2-year program enrolled over 15,000 patients world-wide, and achieved a doubling of bundle compliance from 18% to 36% with a concurrent drop in adjusted mortality of 5%. Because of several methodological issues and the lack of transparency about what it took to implement the bundle, it has never been clear to me a). whether there was causality between the bundle and mortality, and b). whether this effort was cost-effective.

But that aside, Xigris continued to stir up controversy, and there were still safety concerns. Some very well done observational studies, however, continued to confirm its effectiveness and safety in the real world setting [14]. Yet the final trial, PROWESS-SHOCK (done because of fears of an increase in bleeding complications), where patients in septic shock received Xigris as a part of their early management, brought doom. It was this study, whose preliminary results appeared in the press release from October 25, 2011, that prompted Lilly to pull the drug off the world market, since no difference in the 28-day mortality was detected between placebo and Xigris arms. Ironically, the preliminary reports indicate that no excess bleeding was noted in the treatment arm.

So, after roughly 10 years and millions of dollars, Xigris disappeared. But what can we learn from its story? There are many lessons that we should carry away, some about the way we do research, some about marketing practices, but all of them are about the need for a higher level of conversation and partnership. The biggest elephant in this room is whether a manufacturer should be allowed to fund guideline development. It is a complicated issue, particularly given our native proneness to cognitive bias, but in my opinion yes. This certainly cannot be done in a quid pro quo way. Perhaps this is naïve but should it not simply be a question of good data? And why wouldn't a manufacturer give money for the development of sensible guidelines without strings attached when the data are good?

Unfortunately, to me, Xigris is the poster child for how broken our research enterprise is, as I have discussed in this JAMA commentary [15]. Until all stake holders start talking to each other and arriving at common, useful and achievable goals, this is a story that will repeat itself again and again. The fact that regulatory trials, with all of their expensive and flashy internal validity, concern themselves only with statistical issues and care nothing about what happens in the real world is a travesty on many levels. The fact that it costs nearly $1 billion to bring a drug to market means that only big Pharma can bankroll such a gamble, and in return must demand big profits. The fact that this $1 billion fails to bring us studies that help clinicians and policy makers understand fully how to optimize the use of a drug once it is on the market is inexcusable. What we need is more intellectually honest discussions leading to novel pragmatic ways to answer the relevant questions in a timely manner and without bankrupting the system.

So, does the obvious financial interest mean that manufacturers should stay out of these discussions? I happen to think that they need a prominent place at the table. I actually think that the current fiasco is largely the result of too little interaction and too little cross-pollination of ideas: when we all sit around the table a nod in agreement, there is little progress. Deeper and novel understanding is built on disagreement and debate. Therefore, to leave the manufacturers out would invite further irrelevance. The bottom line is that we are all conflicted, and, according to the editors of PLoS, non-financial conflicts of interest, though more subtle and difficult to discern, may present an even bigger threat to much of what we do [16]. Elbowing out a party with an obvious conflict may have the unintended consequence of leaving some of the more insidiously conflicted others to run the show. And although we can argue whether profit is the healthiest driver for performance in healthcare, the reality is that our entire healthcare "system" is built around profit-making. Therefore it is disingenuous to single out one player over others.

On the positive side, the halo effect around Xigris brought a ton of attention to sepsis and its management. As Wes Ely conjectured in this piece, our improved understanding of sepsis (largely due to all the attention Xigris brought to it, in my opinion), is probably what rendered the drug useless in PROWESS-SHOCK. So, after all the hype, the noise and the hoopla, what is left is a company less one drug and hundreds of millions of dollars, and a disease area with a whole lot of what amounted to public health investment, with a vastly improved understanding of the disease state. How much is this benefit worth?

References

[1] Bernard GR, Vincent JL, Laterre PF, et al: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344:699–709
[2] Bernard GR, Margolis BD, Shanies HM, et al. Extended Evaluation of Recombinant Human Activated Protein C United States Trial (ENHANCE US). A Single-Arm, Phase 3B, Multicenter Study of Drotrecogin Alfa (Activated) in Severe Sepsis. Chest 2004;125:2206-16
[3] Vincent JL, Bernard GR, Beale R et al.
Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: further evidence for survival and safety and implications for early treatment. Crit Care Med 2005;33: 2266-77
[4] Abraham E, Laterre P-F, Garg R, et al. Drotrecogin Alfa (Activated) for Adults with Severe Sepsis and a Low Risk of Death. New Engl J Med 2005;353:1332-1341
[5] Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-1377
[6] Annane D, Seville B, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-871
[7] van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients.  N Engl J Med 2001;345:1359-1367 

      [8] Eichacker PQ, Natanson C, Danner RL. Surviving Sepsis – Practice Guidelines, Marketing Campaigns and Eli Lilly. N Engl J Med 2006;355:1640-2 

      [9] Sinuff T, Kahnamui K, Cook DJ, et al. Rationing critical care beds: A systematic review. Crit Care Med 2004;32:1588-97

      [10] Truog RD, Brock DW, Cook DJ, et al. Rationing in the intensive care unit. Crit Care Med 2006;34:958-63

      [11] Dellinger RP, Carlet JM, Masur H, et al: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. 2004;32:858-73 

      [12] Dellinger RP, Levy MM, Carlet JM, et al: Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296-327. Erratum in Crit Care Med 2008;36:1394-96

      [13] Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2010;38:367-74

      [14] Lindenauer PK, Rothberg MB, Nathanson BH, et al. Activated protein C and hospital mortality in septic shock: A propensity-matched analysis. Crit Care Med 2010;38:1101-7

      [15] Zilberberg MD. The clinical research enterprise: Time for a course change? JAMA 2011;305:604-5 

      [16] The PLoS Medicine Editors (2008) Making Sense of Non-Financial Competing Interests. PLoS Med 5(9): e199. doi:10.1371/journal.pmed.0050199

Read More

Massachusetts' unwinnable gamble

It is ironic how, just a few days following the startling (?) confirmation by the Robert Wood Johnson Foundation-funded research that an ounce of prevention is indeed worth a pound of cure, the Massachusetts legislature with reckless abandon ushered in yet another mechanism for the erosion of public health: legalized gambling. Really, I have nothing against a little gambling. The issue is that this legislative move does not just open the door to a trickle of small local gambling operations. No, what it does is turn the crank to open a fire hose of "big box" gambling establishments descending upon our state. And it is not just anywhere in the state: it is in the Western part, far removed from the back yards of the legislators who are salivating over the projected licensing and tax revenues.

But I don't want to get into the NIMBY aspect of this misguided bill. I would rather stick to the real issue: selling us out to raise short-term revenue. The move projects 15,000 new jobs (menial with no benefits mostly), $40 million annually in tax income, on top of $85 million licensing fees from each of the three casinos, all this in addition to construction investment and the like. Already the bill allocates $50 million to overhauling healthcare reimbursements in the state. As well, there is a $25 million provision to shore up research into and prevention of problem gambling. And even people who are in staunch opposition to legalizing gambling seem appeased by this provision, which they say makes it the best bill of its kind. But we still have to ask, if prevention is better than cure, why settle for good mitigation strategies when we have the best prevention available to us already: keep casinos out!

Some of you will probably say that I am naive. After all, reason fades when we are talking about such big bucks for the state coffers. Well, just because this kind of a trade-off is something we have come to expect from our politicians does not mean that we should tolerate it. Others will bring up the old free will argument. No, I am not against people exercising their personal decision making, but haven't you read "Nudge?" We are all deeply flawed human beings, and in the face of temptation we fail miserably! And since we know that casinos increase the risk of problem gambling, why not just steer clear of them altogether? This is simply not a winnable gamble.

I hope that some of you are hearing echoes of the food-obesity debate. We deem it an individual rather than a societal problem, and look how well we have done mitigating the obesity epidemic! There is no rocket science here, and it is disingenuous to say that we do not understand the causes of obesity. Human physiology has not changed over a couple of generations, no. What has changed is our constant access to high-calorie cheap concoctions that pass for food; what has changed is our limited access to physical activity; and what has changed is the degree to which we as a society are willing to sign on to corporate and political propaganda designed to get votes and make money at the expense of our health.

So, am I shocked that this casino bill is likely to become law? Not at all. Am I surprised that the public is allowing this to happen in a pathetic perversion of personal freedom? Of course not. Am I going to shut up about what a mistake this is? You bet I am not. And in a decade I will say "I told you so." But I am sure that then, not unlike now, no one will be listening.              

Read More

ONLY kills cancer cells ?

SUPPOSED TO BE BETTER THAN CHEMO!!! PLEASE READ BELOW THEN SHARE AROUND.

Just cut 2-3 thin slices of lemon in a cup/container and add drinking water will become "alkaline water", drink for the whole day, just by adding drinking water.

Take it as drinking water everyday is good for everybody.
The surprising benefits of lemon!
I remain perplexed!
================================
Institute of Health Sciences, 819 N. L.L.C. Charles Street Baltimore , MD 1201.
This is the latest in medicine, effective for cancer!
Read carefully & you be the judge

Lemon (Citrus) is a miraculous product to kill cancer cells. It is 10,000 times stronger than chemotherapy.







Why do we not know about that? Because there are laboratories interested in making a synthetic version that will bring them huge profits. You can now help a friend in need by letting him/her know that lemon juice is beneficial in preventing the disease. Its taste is pleasant and it does not produce the horrific effects of chemotherapy. How many people will die while this closely guarded secret is kept, so as not to jeopardize the beneficial multimillionaires large corporations? As you know, the lemon tree is known for its varieties of lemons and limes.

You can eat the fruit in different ways: you can eat the pulp, juice press, prepare drinks, sorbets, pastries, etc... It is credited with many virtues, but the most interesting is the effect it produces on cysts and tumors.

This plant is a proven remedy against cancers of all types. Some say it is very useful in all variants of cancer. It is considered also as an anti microbial spectrum against bacterial infections and fungi, effective against internal parasites and worms, it regulates blood pressure which is too high and an antidepressant, combats stress and nervous disorders.

The source of this information is fascinating: it comes from one of the largest drug manufacturers in the world, says that after more than 20 laboratory tests since 1970, the extracts revealed that: It destroys the malignant cells in 12 cancers including colon, breast, prostate, lung and pancreas ...

The compounds of this tree showed 10,000 times better than the product Adriamycin, a drug normally used chemotherapeutic in the world, slowing the growth of cancer cells. And what is even more astonishing: this type of therapy with lemon extract only destroys malignant cancer cells and it does not affect healthy cells.

Institute of Health Sciences, 819 N. L.L.C. Cause Street, Baltimore, MD1201

SEND TO EVERYONE ... ! ! ! ! !

Read More

Take note...don't always sleep late!!!!!!!

                                                                                                                 

Good rest and sound sleep is very important... if u don't sleep well,
The toxins in your body will accumulate... Affecting your health and your mood...

The main causes of liver damage are:
1. Sleeping too late and waking up too late are the main cause..
2. Not urinating in the morning.
3. Too much eating.
4. Skipping breakfast.
5. Consuming too much medication.
6. Consuming too much preservatives, additives, food coloring, and artificial sweetener. 




7. Consuming unhealthy cooking oil. As much as possible reduce cooking oil use when frying, which includes even the best
Cooking oils like olive oil. Do not consume fried foods when you are tired, except if the body is very fit.
8. Consuming overly done foods also add to the burden of liver. Veggies should be eaten raw or cooked 3-5 parts. Fried
Veggies should be finished in one sitting, do not store.

We have to adopt a good daily lifestyle and eating habits. Maintaining good eating habits is very important for our body to absorb and get rid of unnecessary chemicals.

Because….
 
Evening 9 - 11pm: is the time for eliminating unnecessary/ toxic chemicals (de- toxification) from the antibody system (lymph nodes). This time duration should be spent by relaxing or listening to music. If during this time a housewife is still in a un relaxed state such as washing the dishes or monitoring children doing their homework, this will have a negative impact on her health.

Night at 11pm - 1am: The de-toxification process in the liver, and ideally should be done in a deep sleep state.
 
Early morning 1 - 3am: de-toxification process in the gall, also ideally done in a deep sleep state.

Early morning 3 - 5am: de-toxification in the lungs. Therefore there will sometimes be a severe cough for cough sufferers during this time. Since the de-toxification process had reached the respiratory tract, there is no need to take cough medicine so as not to interfere with toxin removal process.

Morning 5 - 7am: de-toxification in the colon, you should empty your bowel.

Morning 7 - 9am: Absorption of nutrients in the small intestine, you should be having breakfast at this time. Breakfast should be earlier, before 6:30am, for those who are sick. Breakfast before 7:30am is very beneficial to those wanting to stay fit. Those who always skip breakfast, they should change their habits, and it is still better to eat breakfast late until 9 -10am rather than no meal at all. Sleeping so late and waking up too late will disrupt the process of removing unnecessary chemicals.
 
Midnight to 4am is the time when the bone marrow produces blood.

Therefore, have a good sleep and don't sleep late.

Sharing Is Caring!

Read More

An open letter to my past and future students

As most of my readers know, I teach Public Health graduate students and the University of Massachusetts, sometimes on campus, and sometimes online. This is an open letter to all of my past and future students. 

First, I want to thank everyone in my June course who took the time to complete the evaluation -- the feedback is very helpful to me. I also want to thank the whole class (and all my previous and future classes) for the privilege of learning together with you. Looking at this and previous rounds of evaluations made me realize that I need to make a public statement that all students contemplating taking my courses can read before they commit.

My evaluations tend to be bimodal -- a peak around "love", a (smaller, thankfully) peak around "hate", and mostly a trough in between. Oddly, the reasons for the love and the hate are the same: not too much structure, not too much interim formal performance evaluations, a lot of opportunities for discussions and questions. Everyone seems to appreciate my effort to make the material interesting and relevant, but a substantial number do not seem to like it.

I am actually fascinated by the convergence of the reasons for liking and disliking. By way of inference, I am going to suggest that where you fall out on the teaching should tell you more about your learning style than how I teach. To clarify, let me spell out my philosophy of teaching.

Whether I teach on campus or online, I limit my classes to graduate students. The reason for this is not that I do not think that undergrads cannot handle the material. Rather it is because I believe nothing replaces time with a topic to develop a depth of understanding and discussion about it. So, I view my classes as incubators of ideas. I do not see myself as the oracle delivering answers. My role is to get you excited about the questions. Furthermore, it is not my questions that should excite you, but the questions that you come to at the limits of your knowledge seen through the prism of the class material and discussions.

To be sure, I realize that this not a comfortable place for many. Most of us glide through an educational system that convinces us that there is a single correct answer, and, after teaching us to parrot it compliantly, punishes us if we stray. So, swimming in the sea of questions, seemingly answering them only to realize that the answers lead to further questions is disquieting. Yet it is at this edge that we gain access to the next level of understanding of our universe. Here, the feedback is not about an arbitrary letter, but about the exuberance of ideas, discussion generated and the richness of asking the questions.

I cannot tell you how much I love the learning environment that we create together. I gain something from each and every one of you, and I hope that each of you walks away with at least one idea that is new. What I suggest to you if you are a potential student considering taking a course with me in the future is to contemplate the boundaries of your own comfort zones in learning. If you like the feeling of vertigo that you get when old dogmatic answers are shattered and uncertainty reigns, take my classes. If you are worried about how it might feel, but curious to try, I will meet you where you are and help you weave a net to cradle your fall. But if you know that uncertainty cripples you, that you would rather have a map for every step of the way, my classes may be the wrong stop along your educational path at this time. But perhaps sometime in the future?

Again, thanks to everyone for enriching my learning. I miss you and look forward to future opportunities for exchanging ideas.                    

Read More

Clinician as the Politbureau of medicine?

Do you think that medicine in the US is centralized? I do, but not in the way that we generally understand centralization. And furthermore, it is this centralization that I believe is making the idea of shared decision making so intimidating to some. Here is what I mean.

If you read management texts, centralization refers to an organization that is run predominantly top-down. In other words, a couple of oligarchs at the top of the ladder make all the decisions without consulting anyone below. In this way all the power is concentrated in the hands of the few. In an antithesis to this, in a decentralized organization, grassroots input and initiatives are incorporated into the fabric of the organization. And while in the times of a great crisis, when rapid decisions are necessary, the benefits of centralization may outweigh its risks, during normal day-to-day operations, such unilateral power can result in obviously negative consequences, from discontent among the employees to making the wrong choices. Furthermore, as organizations grow in size, it gets that much more difficult to run them effectively within the centralized paradigm.

Now, let us look at medicine. The traditional model of the doctor-patient relationship relies on the clinician to know what is right for the patient: take this pill and don't worry about the side effects, dear. Now, clearly, when someone shows up to the emergency room in septic shock, there is very little room for a democratic process; we want the doctor to do rapidly what needs to be done to save the patient. But this is a catastrophic exception to the rule of what modern medicine cares for. From pre-diabetes to pre-hypertension to "borderline cholesterol" to osteopenia to mild depression, these are the "diseases" that are prevalent in the office of the 21st century. None of these is particularly urgent or life-threatening. And if we are honest with ourselves, even a devastating diagnosis of cancer does not demand an instantaneous intervention: in the vast majority of cases there is ample time for discussion and contemplation. So, the centralized approach is the wrong way to go. Thus enter the robust discussion about shared decision making. 

Another reason that centralization of medical decisions is crumbling is the expanding patient panels that clinicians need to engage with in order to stay solvent, all within the context of increasing compliance and regulatory burdens along with decreasing reimbursements. Without an equal growth in one's cognitive ability to multi-task, this escalating imbalance is creating a rising risk for unilateral decisions to be plain wrong.

So, in my mind, this is yet another argument for all parties to embrace shared medical decision making to the extent we as patients are willing and able to do so. Because what is the alternative?          

Read More

Why patient lab data should be liberated, with a few caveats

I am admittedly not an expert on health IT, but I am a firm believer in the empowerment of patients to be the driver of her/his health decision making. So this whole discussion about lab data being available directly to the patient is of great interest to me. But it does seem like yet another instance of the two sides coming together not to listen to each other but to be heard by the other side. And as well know, this works so well for any relationship!

Each side's view is represented roughly thusly:
Patients -- these are my data and I have the right to access them as soon as they are available.
Doctors -- we are worried that the sheer volume, complexity and irrelevance of (much) of the data will make it confusing and unnecessarily alarm the patient
Both arguments are valid, of course. But it is important to ask what lurks below the visible portion of each iceberg.

Let's take the patient view. Why do I want immediate access to my data? Well, obviously, because it is mine, it represents the results of testing on my body, and the record should belong to me. I should be able to access it freely whenever I damned well please. I am also more than a little exasperated with having to wait sometimes days to hear from my doctor's office about a result that has been available for a while, but was buried under the reams of paperwork on the MD's desk or his/her assigning a low priority to my data. And I am most exasperated when my lab results get lost or otherwise never make it to me at all. Perhaps if I have direct and unfettered access, this will make thing more efficient for me as an individual.

The doc's view, on the other hand, is that the patient does not necessarily understand what the notation of "low"connotes in reference to, say, total bilirubin, or how to interpret the RDW data. Even more importantly, what if there is an outrageously abnormal value for some important test? Surely the patient will desire an immediate explanation of it and its implications.

So, clearly, both sides have valid concerns. I do think that those of access predominate, as ethically it just makes sense. But for a non-medical person, looking at a lab sheet is like trying to read information about yourself in Chinese: your success in understanding is largely dependent on your ability to read and understand Chinese. So, before that horse leaves the barn, we should think through how to execute this most sensibly. For example, perhaps it is not sensible to have the lab computer directly vomit all of the inane values that no one really looks at right to the patient's account. And backing up a step, perhaps it is time for our lab use to be driven not by the lab equipment packages and processes, but to test only for factors that are of value. If I want to know the patient's creatinine, maybe the other 6 components of the Chem-7 should not be run, or at least not reported. And obscure values like the ones I mentioned above, e.g., RDW, MCHC, etc., should only be available when the situation actually makes them useful, and not just distracting.

I can see a potential positive unintended consequence of this development as well: maybe clinicians will be less trigger-happy ordering all kinds of labs for all kinds of oblique reasons. Maybe, just maybe, this apprehension about the patient's access to all the labs will result in more Bayesian thinking in the office and a lot less shot-gunning. Finally, it will not be all patients that choose to access their data. Let us hope that the selection bias does its job and assures that only those who are truly ready to be educated and empowered decide to do so.

All in all, I am looking forward to the liberation of my lab data. What I worry about is all the calls I will be getting from friends and family to help them understand them. All the same, I will do my part for the education and empowerment that absolutely needs to happen for this to be a successful and meaningful change.        

Read More