Crenezumab, from Genentech, a unit of Roche Holding AG, ROG.VX +0.26% targets a sticky protein in the brain called amyloid that is thought to contribute to Alzheimer's when it clumps together. The trial also will seek to understand whether the amount of amyloid in one's brain could help predict later cognitive decline—a so-called biological marker. If it works, future trials could potentially use amyloid levels to determine whether a treatment is working rather than waiting to see if patients' memory worsens.

On May 9, the Labor Department also issued a series of frequently asked questions (FAQ) regarding the implementation of the Mental Health Parity and Addiction Equity Act of 2008. While these FAQs do not apply directly to the Affordable Care Act, they are likely to be used to interpret the mental health parity provisions of the ACA. The FAQs clarify that if a plan provides mental health and substance abuse benefits, it may not limit those benefits to inpatient services only. Plans may carve out mental health services and handle them through managed behavioral health organizations as long as standards applied are comparable to and not more stringent than those applied to other services. Indeed, this is the standard that plans must follow generally in applying non-quantitative treatment limitations to mental health and substance abuse services.

For example, many health insurance plans still refuse to cover lifesaving treatment for eating disorders. Others create discriminatory barriers to care, such as imposing stricter prior-authorization requirements for mental health and addiction treatment than for medical benefits. Sadly, as underscored in a recent report by the assistant secretary for planning and evaluation at the U.S. Department of Health and Human Services, levels of care for evidence-based behavioral treatments, such as residential psychiatric services for children, are being eliminated because of uncertainty about what is required.

The most recent National Survey on Drug Use and Health, published last year, found that fewer than half of the 45.9 million adults with a mental illness receive treatment or counseling and that only 10 percent of the more than 23 million people who need help for a substance-use problem received any specialized treatment in 2010. Even more troubling is the fact that people with either disease have shorter life expectancies than most Americans; a 2006 study put the difference at 25 years.

During the decade from 1998 to 2007, the percentage of the general population who used psychotherapy remained stable. Over the same period, however, psychotherapy assumed a less prominent role in outpatient mental health care as a large and increasing proportion of mental health outpatients received psychotropic medication without psychotherapy.

Psychotherapy has traditionally been regarded as a central feature of mental health service in the United States. It is widely viewed as a core clinical activity of psychiatrists, psychologists, social workers, and other mental health care professionals (1). Some evidence suggests that the role of psychotherapy in community treatment has diminished in recent years. According to the National Ambulatory Medical Care Survey, visits to office-based psychiatrists that include psychotherapy declined from 44.4% in 1996-1997 to 28.9% in 2004-2005 (2). Although the survey includes clinical diagnoses reported by the treating physicians, it offers no information about psychotherapy delivered by other mental health specialists and no person-level data on psychotherapy use. As measured by the Medical Expenditure Panel Survey (MEPS), the percentage of Americans treated with antidepressants who also received psychotherapy decreased from 31.5% in 1996 to 19.9% in 2005 (3). There has also been a decrease in employer-sponsored health plans that cover outpatient psychotherapy (4). Over this period, however, Americans have become more comfortable talking with health care professionals about personal problems (5), and concerns about antidepressant-associated suicidality may have led more depressed adults to pursue psychotherapy (6).

There is a paucity of information about recent national trends in use of psychotherapy in the United States. The most recent national profile of psychotherapy use indicated that in 1997 approximately 3.6% of Americans received at least one psychotherapy visit and most of those who received psychotherapy (61%) were also treated with a psychotropic medication (7). The scarcity of data on basic patterns in psychotherapy use contrasts with a relative abundance of information on patterns of psychotropic medication use (8, 9).

Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006 Jul;116(7):1793-801. Review. Erratum in: J Clin Invest. 2006 Aug;116(8):2308.
Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate Improves Glycemia and Inflammatory Parameters in Obese Young Adults. Diabetes Care. 2007 Oct 24; [Epub ahead of print]
Goldfine AB, Silver S, Aldhahi W, Cai D, Tatro E, Lee J, Shoelson SE. Use of Salsalate to Target Inflammation in the Treatment of Insulin Resistance and Type 2 Diabetes, Clinical and Translational Science, 2008 May;1(1):36-43
Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE; for the TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) Study Team. The Effects of Salsalate on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Trial. Ann Intern Med. 2010 Mar 16;152(6):346-357.

Experts who were not involved in the multi-center trial agreed larger trials were needed, and said the impact of the drug on blood glucose levels[—.5% reduction in A1c over three months at the highest tested dose of 4g daily—]was moderate. But they said the findings were exciting because they suggested Type 2 diabetes could be treated by targeting the underlying inflammation....
Since atherosclerosis is also considered an inflammatory state, this approach may also potentially reduce the risk of cardiovascular complications associated with diabetes...
Salsalate sells for less than a quarter a pill, and does not present the opportunity for profit that would attract large pharmaceutical companies to do the research...
The patients continued with their regular Type 2 diabetes treatment regimen throughout the study.

"Then we realized that there were other salicylates, chemically similar to aspirin, that don’t carry the same risk of bleeding.” The drug they’re studying now, salsalate, was widely used not too long ago to treat arthritis, but it got “back-shelved” when other drugs were developed for the treatment of pain and arthritis.
The researchers’ first salsalate studies showed that blood glucose control and glucose metabolism improved in people with diabetes; salsalate also lowered inflammation markers and improved levels of cholesterol and triglycerides in the blood. The second round of studies, investigating whether the drugs could have a beneficial impact on overweight people who do not have diabetes but are at risk for developing it, found that blood glucose levels improved, as did inflammatory markers and other risk factors for disease.

BACKGROUND:
It is commonly assumed that there are clear lines of demarcation between anxiety and depressive disorders on the one hand and psychosis on the other. Recent evidence, however, suggests that this principle may be in need of updating.
METHODS:
Depressive and/or anxiety disorders, with no previous history of psychotic disorder, were examined for the presence of psychotic symptoms in a representative community sample of adolescents and young adults (Early Developmental Stages of Psychopathology study; n = 3021). Associations and consequences of psychotic symptomatology in the course of these disorders were examined in terms of demographic distribution, illness severity, onset of service use, and risk factors.
RESULTS:
Around 27% of those with disorders of anxiety and depression displayed one or more psychotic symptoms, vs 14% in those without these disorders (OR 2.23, 95% CI 1.89-2.66, P < .001). Presence as compared with nonpresence of psychotic symptomatology was associated with younger age (P < .0001), male sex (P < .0058), and poorer illness course (P < .0002). In addition, there was greater persistence of schizotypal (P < .0001) and negative symptoms (P < .0170), more observable illness behavior (P < .0001), greater likelihood of service use (P < .0069), as well as more evidence of familial liability for mental illness (P < .0100), exposure to trauma (P < .0150), recent and more distant life events (P < .0006-.0244), cannabis use (P < .0009), and any drug use (P < .0008).
CONCLUSION:
Copresence of psychotic symptomatology in disorders of anxiety and depression is common and a functionally and etiologically highly relevant feature, reinforcing the view that psychopathology is represented by a network or overlapping and reciprocally impacting dimensional liabilities.

Rich evidence has shown that cannabis products exert a broad gamut of effects on emotional regulation. The main psychoactive ingredient of hemp, Δ9-tetrahydrocannabinol (THC), and its synthetic cannabinoid analogs have been reported to either attenuate or exacerbate anxiety and fear-related behaviors in humans and experimental animals.
The heterogeneity of cannabis-induced psychological outcomes reflects a complex network of molecular interactions...The high degree of interindividual variability in the responses to cannabis is contributed by a wide spectrum of factors, including genetic and environmental determinants, as well as differences in the relative concentrations of THC and other alkaloids (such as cannabidiol) within the plant itself.
The present article reviews the currently available knowledge on the herbal, synthetic and endogenous cannabinoids with respect to the modulation of anxiety responses, and highlights the challenges that should be overcome to harness the therapeutic potential of some of these compounds, all the while limiting the [adverse] effects associated with cannabis consumption. In addition the article presents some promising patents on cannabinoid-related agents.

Cannabis has long been known to produce cognitive and emotional effects. Research has shown that cannabinoid drugs produce these effects by driving the brain's endogenous cannabinoid system and that this system plays a modulatory role in many cognitive and emotional processes.
This review focuses on the effects of endocannabinoid system modulation in animal models of cognition (learning and memory) and emotion (anxiety and depression). We review studies in which natural or synthetic cannabinoid agonists were administered to directly stimulate cannabinoid receptors or, conversely, where cannabinoid antagonists were administered to inhibit the activity of cannabinoid receptors. In addition, studies are reviewed that involved genetic disruption of cannabinoid receptors or genetic or pharmacological manipulation of the endocannabinoid-degrading enzyme, fatty acid amide hydrolase (FAAH).
Endocannabinoids affect the function of many neurotransmitter systems, some of which play opposing roles. The diversity of cannabinoid roles and the complexity of task-dependent activation of neuronal circuits may lead to the effects of endocannabinoid system modulation being strongly dependent on environmental conditions. Recent findings are reviewed that raise the possibility that endocannabinoid signaling may change the impact of environmental influences on emotional and cognitive behavior rather than selectively affecting any specific behavior.

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A recent post on the New York Times blog Well looked at what both human and animal studies have found out about the connection between statins and muscle damage. The most recent study, published last year in the Journal of Applied Physiology, found that rats who were given a very high dose of atorvastatin for two weeks had 60% more oxidative stress (an indicator of possible cell damage) than those not given any of the drug. Some of the rats from each group were also made to run on treadmills for as long as possible. Not only did the rats on atorvastatin run a shorter distance than their non-drugged counterparts, but their post-workout oxidative stress was also 226% higher.

Human studies have yielded similar, if less dramatic, results. One study cited in the Well post — published in 2005 in the journal Arteriosclerosis, Thrombosis, and Vascular Biology — found that among healthy people who took atorvastatin for four weeks, 56 genes were expressed differently in leg muscle cells eight hours after vigorous exercise, compared with participants who took a placebo (inactive pill). In particular, genes known to affect muscle building and repair had a lower level of expression in the atorvastatin group. There is also plenty of evidence from patient and doctor reports that statins can lead to muscle fatigue and damage. According to Well, at least 10% of people who take statins will experience some fatigue or weakness, and this number rises to 25% among those who exercise regularly.

Participants with diabetes were stratified by insulin therapy at baseline: group A treated with insulin only; group B treated with insulin and oral hypoglycemic agent; and group C receiving no insulin treatment.
During a mean follow-up of 3.9 years, the researchers found that 4.6% of the cohort without diabetes died, compared with 15, 12.5, and 7.3% of groups A, B, and C, respectively. The hazard ratios (HRs) for all-cause mortality were 4.3, 4.2, and 2.0 for groups A, B, and C, compared with individuals without diabetes. The leading cause of death in groups A, B, and C were ESRD, ESRD and CAD, and CAD, respectively. The HRs for these conditions were at least twice as high as the HRs for all-cause mortality, extending to 17.3, 17.9, and 5.1 in groups A, B, and C, respectively, for ESRD.
"Excess mortality persists among people with young-onset diabetes of long duration, with ESRD and CAD as the leading contributors to mortality," the authors write.

[Excuse me? Don't the numbers, if correctly reported, suggest that insulin-and-drug therapy increases mortality by over two-thirds, and insulin-only therapy more than doubles mortality?—DMM]

Raspberry ketones are on the FDA’s GRAS (generally recognized as safe) list. But in terms of their fat-burning ability, the only research to support this claim dates back years…and that study was done with mice. Not humans. So we really don’t know if this supplement works. And it’s not without some possible serious side effects: increased heart rate and blood pressure, difficulty sleeping, agitation, and maybe hypothyroidism (underactive thyroid). Avoid taking this supplement if you have high blood pressure or thyroid issues. We don’t know enough about it how it affects diabetes control, either....
[Glucocil] is targeted to people with Type 2 diabetes, and its claim to fame is that it can reputedly stabilize postmeal blood glucose levels, decrease carbohydrate absorption, decrease appetite, and promote weight management. Pretty hefty claims for a supplement whose key active ingredient is mulberry leaf extract....
[This supplement also] contains alpha lipoic acid, banaba leaf extract, chromium picolinate, cinnamon bark powder, gymnema sylvestre extract, fish oil, and a few other things thrown in for good measure. Glucocil’s Web site clearly lists the research — but only for each separate ingredient. Nowhere on the site could I find research citing the effectiveness of the actual supplement....As far as mulberry leaf extract goes, a few small studies (mostly done with rats) show some reduction in glucose after ingesting it, but not enough to boast about....
We don’t know if the blend of these ingredients actually live up to Glucocil’s claims of glucose and weight control, nor do we know if the amount of ingredients in this supplement are in the right proportions to be effective. The Web site states that people under the age of 18, pregnant women, and people with liver and kidney problems should not take Glucocil. Also, they state that if you take insulin and don’t have cardiovascular, liver, or kidney problems, you can “consider” taking Glucocil. Side effects include “minor GI discomfort,” such as gas and loose stools.

Federal regulators have warned Johnson & Johnson that it could face fines and other sanctions for selling faulty insulin pumps and delaying disclosures of serious injuries to diabetics who were using its OneTouch Ping and 2020 pumps. The FDA ordered the Animas Corp. unit of J&J to explain why it kept selling pumps known to fail and also to submit a plan to rectify a failure to promptly report cases in which its device might have caused or contributed to death or serious injury....
In the issue with the Animas insulin pumps, some pump keypads for controlling how much insulin is injected were deteriorating prematurely, leading to failures. "We decided to go with a new keypad because it's more durable," [spokesperson Caoline] Pavis said.
But while Animas was lining up the new keypad supplier, it was still selling the older ones. The FDA demanded documents about the company's decision to do that.

• High blood glucose makes your blood “sludgy,” slowing circulation so cells can’t get the oxygen and nutrients they need. Margaret commented, “I can tell if my sugars are high in the morning, because ‘groggy’ doesn’t begin to describe it. ‘Drugged’ is how it feels.”
• Low sugars levels also cause fatigue, because when blood sugar is low, there is not enough fuel for the cells...
• [With vascular inflammation caused by igh blood glucose,] immune cells called monocytes come into the brain, causing fatigue....
• [P]eople with diabetes are more likely than others to have thyroid problems. If your thyroid level is low, you are likely to feel tired, sleepy, and depressed.
• Low testosterone levels, especially in men. Men with diabetes are much more likely to have low testosterone.
• Infections: People with diabetes often have infections they don’t know about. Infections take energy to fight, which can cause fatigue and raise blood sugar levels. A common source is urinary tract or “bladder” infections. They often hurt, but sometimes have no symptoms, except for the fatigue. Silent dental infections and vaginal infections are also common and fatiguing.
• Undiagnosed heart disease : If you get tired after tasks that you used to sail through, it could be time to for a heart check-up....
• Many drugs for diabetes, blood pressure, depression, pain, and other issues can cause fatigue. Read labels, ask your doctor or pharmacist....
• Some people are too wound up or too busy to sleep. Or they’re up to use the bathroom all night, or they have obstructive sleep apnea (OSA), which can wake them up many times an hour....
• [Rotating shifts or working nights] can cause fatigue directly by messing with your body clock or indirectly by disrupting sleep.
• Depression is very common with diabetes. Most depressed people feel fatigued, even if they don’t feel sad. Even at low levels, depression can sap your motivation....
• Doing too much: If you’re ripping and running all day, not taking breaks or even stopping to breathe much, you are courting fatigue....
• Stress: In small doses, psychological or physical stress can give you energy, but if it goes on too long, it will wear you out...
• Too much carbohydrate — especially refined carbs — can make anyone tired, especially with diabetes. Kat wrote, “now that I am eating a higher protein/fat, lower-carbohydrate diet, I have shaken off that really sleepy/extreme fatigue that I used to have every day.”
• According to WebMD, too much caffeine can cause fatigue through a rebound effect. They also say that dehydration, or not drinking enough liquid, is a major cause of fatigue.
• Being out of shape or having weak muscles: Not moving our bodies contributes to fatigue. Of course, it’s hard to exercise when you’re fatigued.

Scientists have proven that cannabis does have medical usefulness, and the more we learn the more intriguing these discoveries become. Since the early 1980s, medical researchers have published about how cannabis relieves pressure in the eye, thus easing the symptoms of glaucoma, a disease that causes blindness. THC is also "neuroprotective," meaning in essence that it prevents brain damage. Some studies have suggested that cannabis could mitigate the effects of Alzheimer's for this reason.
At the same time, we know that THC interferes with memory, and it's still uncertain what kinds of long-term effects the drug could have on memory functioning. No one has been able to prove definitively that it does or does not erode memory strength over time.
[Article strength: quite specific about potentially adverse effects on brain and body before the cautious statement above about neuroprotective effects.
Weaknesses: Ignores action of other cannabinoids and cannabinols. Sets up a false opposition insofar as the short-term memory effects seem to be about memory formation, not memory retention or loss. No citations.—DMM]

I may say some nasty and completely true things about the medical establishment.
I only started paying attention [to the ACCORD study] when the intensive blood sugar control arm was canceled. The more I found out about it, the angrier I got...ACCORD is a great example of most of what is wrong with American medicine, and with the way our media covers it....
From the beginning, ACCORD was a drug trial. The study called for participants to receive diet and exercise counseling if they wanted it, but set no guidelines for the counseling. There was no self-management group. It was all, repeat all, about the drugs.[Encouraging participating doctors to unsystematically and aggressively prescribe multiple drugs all but guaranteed drug interactions and adverse effects.]
In February, NHLBI stopped the intensive blood sugar control arm because more of the participants in that group were dying than in the normal care group.
Then came the outrageous part: NHLBI and media dummies came out saying that the intensive group’s blood sugars had been too low....
What kind of madness is this? You throw scads of drugs at sick people, treating only their numbers, not their bodies and lives as a whole. Then, when they die, you say it couldn’t have been the drugs. It must be the numbers. And you tell people with diabetes to get their blood sugars up.
You better believe that if ACCORD had shown a 10% decrease in cardiac deaths from intensive blood glucose management with drugs, those drugs would have become standard therapy for every person with Type 2 in the country. Nobody in the media would have said, “It wasn’t the drugs.” The drug companies would have made billions. That was the goal of the trial.

Statin use in postmenopausal women is associated with a significantly increased risk of diabetes mellitus.
New data from the Women's Health Initiative (WHI) [indicates risk of diabetes is higher than previous studies have suggested: 48% increased risk]....
Recently published data reported the potential risk of diabetes with statin therapy. Dr. Kausik Ray (St. George's University of London, UK) and colleagues published a meta-analysis of [five trials testing high-dose statin therapy,] and found a significant increase in risk of diabetes with higher doses of the lipid-lowering drugs. A meta-analysis published in The Lancet in 2010 by Dr. Naveed Sattar (University of Glasgow, UK) also showed that statin therapy was associated with a 9% increased risk of diabetes.
[The present study produced an unadjusted risk model associating statin use at baseline] with a 71% (95% CI 1.61–1.83) increased risk of diabetes. After adjusting for potential confounding variables, the risk...declined to 48% (95% CI 1.38–1.59). The association was observed for all types of statins.
Dr. Kirsten Johansen,[ Editor of the Archives of Internal Medicine, noted that previous meta-analyses show no benefit of statins on all-cause mortality in the setting of primary prevention]...
[S[tatins are used with increasing frequency, including in primary prevention, and—based on the JUPITER trial—in patients with normal LDL cholesterol, but elevated C-reactive protein (more than 2.0 mg/L). In the present study, baseline statin therapy was associated with a significant 46% and 48% increased risk of diabetes in women with CVD and without CVD, respectively.
Just 7% of women in the WHI study were taking statins in the analysis, but today that number would be significantly higher, making the potential risk of diabetes at the population level much more widespread.

Millions of women over age 50 on statin drugs are at a significantly increased risk of developing diabetes, according to a new study from UMass Medical School published online Monday, Jan. 9, in the Archives of Internal Medicine. Senior author Yunsheng Ma, MD, PhD, associate professor of medicine and an epidemiologist at UMMS, said the study found that postmenopausal women on statin drugs showed a 48 percent increased rate of diabetes compared to those not on the cholesterol-lowering medications....
According to surveys by the National Center for Health Statistics, the rate of Americans over age 45 taking statins has increased tenfold over the last 20 years: from 2 percent in the period from 1988 to 1994, compared to 25 percent from 2005 to 2008, the most recent years for which figures are available. The federal data also shows that figure jumps to 50 percent of men ages 65 to 74 taking statins, while 39 percent of women age 75 and older are doing so.

The problems I have described are not new, and they have been described on many previous occasions. They could be fixed, without taking research out of the hands of industry altogether, but to do so would require that the drug companies recognised the scale of this scandal, and campaigned themselves for more effective regulation: demanding full mandatory publication of all trial data from themselves and their competitors, for example.
Instead we see inertia, and the failure of regulators to engage adequately with these serious problems. In medicine, bad information leads to bad decisions: we prescribe one drug where an alternative would have been more effective, or had fewer side effects; or we prescribe an expensive drug, unnecessarily, when a cheaper alternative was equally effective, and so we deprive the community of limited healthcare resources. This is dangerous and absurd. Doctors who are making treatment decisions need access to good quality trial data, presented transparently, and all of it, not just the positive findings that drug companies choose to share.

There is no excuse for companies witholding data from academics and doctors. But most revealing, as ever, are the deeprooted flaws this story exposes in our rather ad hoc systems for gathering, analysing, and disseminating evidence on risks and benefits of treatments.
This drug has been on the market since 1999, and it has seen billions of dollars of sales every year. There has been plenty of real patient experience of this treatment, but we have failed to capture it for analysis. Most of the trials included in these meta-analyses weren’t specifically designed to look at heart problems, and so the data on these, collected incidentally, is unpredictably inaccurate.
In an ideal world, for every patient, wherever possible, we could be gathering anonymised outcome data and comparing this against medication history, making exceptions only for those who put their anxieties about privacy above the lives of others (I will have this argument with you any time). In an ideal world, wherever a patient is given any treatment, and there is genuine uncertainty about which treatment is best, they would be simply and efficiently randomised to one treatment, and their progress monitored. In an ideal world, these notions would be so routinely embedded in our notion of what healthcare looks like that no patient would be bothered by it.
This isn’t fanciful, or difficult, or disproportionately expensive. Instead we have unsatisfactory hotchpotch of incomplete monitoring systems and unforgivable secrecy.

[The suppressed report] dared to challenge the prevailing policy view that all drug use is harmful misuse. "An enormous variety was found in the types of people who use cocaine, the amount of drug used, the frequency of use, the duration and intensity of use, the reasons for using and any associated problems."
Experimental and occasional use were by far the most common types of use, it said, and compulsive or dysfunctional use, though worthy of close attention, were much less common.
It then descended into outright heresy. "Occasional cocaine use does not typically lead to severe or even minor physical or social problems … a minority of people … use casually for a short or long period, and suffer little or no negative consequences."
And finally: "Use of coca leaves appears to have no negative health effects and has positive, therapeutic, sacred and social functions for indigenous Andean populations."
At the point where mild cocaine use was described in positive tones the Americans presumably blew some kind of outrage fuse. This report was never published because the US representative to the WHO threatened to withdraw US funding for all its research projects and interventions unless the organisation "dissociated itself from the study" and cancelled publication. According to the WHO this document does not exist, (although you can read a leaked copy atwww.tdpf.org.uk/WHOleaked.pdf).
Drugs show the classic problem for evidence-based social policy. It may well be that prohibition, and distribution of drugs by criminals, gives worse results for the outcomes we think are important, such as harm to the user and to communities through crime. But equally, we may tolerate these outcomes, because we decide it is more important that we declare ourselves to disapprove of drug use. It's okay to do that. You can have policies that go against your stated outcomes, for moral or political reasons: but that doesn't mean you can hide the evidence.

in the US, where many are still unable to afford healthcare, clinical trials are frequently marketed as a way to access doctors appointments, scans, blood tests, and treatment for free. One study compared insurance status among people who either agreed or refused to participate in a clinical trial: participants are a diverse population, but notably they were 7 times more likely to have no health insurance than those who declined. Another looked at strategies to improve targeted recruitment among latinos, a group on average with far lower wages and poorer healthcare: 96% agreed to participate, a rate far higher than anyone would normally expect.
In large clinical trials such as these, a drug has usually been identified as being broadly safe – it may even be licensed already – and the study is designed to measure how effective the drug is, or give better guidance on the balance between benefits and risks.
“First in man” studies are different: here the risks are greater, and the picture is more stark. A drug, which has only been previously tested in animals, is given to a small number of healthy and disease-free people, mostly men, often unemployed, who then undergo painful, embarrassing, and risky procedures, in exchange for money.
This is a relatively new phenomenon. Up until the 1970s studies like these were conducted on prisoners, who are captured, compliant, stigmatised and in need of money. When concerns were raised about their ability to give meaningful and uncoerced consent, paid volunteers made a ready alternative.
This strange new profession has only recently begun to be formally documented in the work of anthropologists like Robert Abadie in his book “The professional guinea pig”. The industry refers to these participants with the oxymoron “paid volunteers”, and there is a universal pretence that they are not paid for their work, but merely reimbursed for their time and travel expenses....
Payment is often around $200 to $400 a day, studies can last for weeks or more, and participants will often do several studies in a year. Money is central to the process, and payment is often back-loaded so that you only receive full payment if you complete the study, unless you can prove your withdrawal was due to serious side effects. Participants are generally those with few economic alternatives, especially in america, and are frequently presented with lengthy and impenetrable consent forms which are hard to navigate and understand....
Plainly there is a need for drugs to be tested in humans, and although many of those participating in “first in man” studies have lives where the scale of the payment is hard to resist, they do participate of their own free will.
But equally, we should not allow ourselves to ignore what happens in healthcare today. In the US, in particular, the reality is stark: poor people participate in early tests so that rich people can have better drugs.

Researchers at Salk Institute for Biological Studies in the US found proteins that control the body's biological rhythms, known as cryptochromes also interact with metabolic switches that are targeted by certain anti-inflammatory drugs....

The [finding suggests that serious adverse] effects of current drugs might be avoided by considering patients' biological rhythms when giving drugs...

Glucocorticoids are steroid hormones that occur naturally in the body and help control the amount of sugar in a person's blood, so that nutrient levels rise in the morning to fuel daily activities and fall again at night. They function in cells by interacting with glucocorticoid receptors, molecular switches on the outside of the nucleus, which play a role in regulating inflammation. They are used as anti-inflammatory drugs for diseases like allergies, asthma and rheumatoid arthritis as well as used to treat inflammation in cancer patients.

However, the steroids can disrupt a person's normal metabolism, resulting in dangerous side effects, including excessively high blood sugar levels, insulin resistance and diabetic complications.

Nature, Dec 2012

biochemical B12 deficiency was greatest for people with type 2 diabetes taking metformin compared with those with type 2 diabetes but not taking metformin and those without diabetes.

Biochemical B12 deficiency was revealed in 5.8 per cent of patients with diabetes that took metformin as compared to 2.4 per cent of those who did not take metformin and 3.3 per cent of people that did not have diabetes.

In the US, it is currently believed that adults with type 2 diabetes that are over 50 should take 2.4 µg of synthetic vitamin B12 daily either in supplement form or in fortified food.

Researcher Godfrey Oakley commented "It is important to conduct further research to learn how much B12 is needed to correct the deficiency and to determine whether or not raising serum B12 levels improves the clinical picture for persons taking metformin who have low serum B12 concentrations."
Archives of Internal Medicine, Oct 2011

[Diabetes mellitus] has reached epidemic proportions in the US and more recently worldwide. The morbidity and mortality associated with diabetes is anticipated to account for a substantial proportion of health care expenditures. Although there are several drug treatments currently available, the need for new herbal agents for treatment of diabetes are required. The treatment goals for patients with diabetes have evolved significantly over the last 80 years, from preventing imminent mortality, to alleviating symptoms, to the now recognized objective of normalization or near normalization of glucose levels with the intent of forestalling diabetic complications. The present review stated several findings from an extensive literature search of natural plants that have been assessed for the anti diabetic activity over past 80 years. An attempt has been made to summarize the information in order to highlight those chemical entities and plant species which are of worthy for further investigation as leads to the drug developments. Over 100 plant species from wide range of families containing various chemical classes of compounds have been cited here which are worthy for the researchers and the industrialist concerned to diabetes.

Ninety-seven 7-17 year-olds with OCD completed 12 weeks of treatment with either CBT, the SSRI sertraline, the combination treatment, or a placebo. Independent evaluators, blind to their treatment status, assessed each patient every four weeks. Patients in the study were typical of patients seen in clinical practice. For example, while industry-sponsored trials commonly exclude patients with more than one condition, 80 percent of study participants had at least one additional psychiatric disorder.

Combining sertraline and CBT was more effective than treatment with just one or the other. CBT alone did prove superior to sertraline, which, in turn, was better than a placebo. By the end of the trial, the remission rates were 53.6 percent for combined treatment, 39.3 percent for CBT, 21.4 percent for sertraline, and 3.6 percent for placebo.

CBT alone was more effective in the University of Pennsylvania site than at Duke University site, but the combination treatment was equally effective at both sites, suggesting that it may be less susceptible to setting-specific variations. The strong showing of CBT at the University of Pennsylvania led the researchers to recommend it as "a first line option" for initial treatment. They point out, however, that "only a small minority" of children and adolescents with OCD receives such state-of- the-art care.

Data Tables with government assistance as a variable:
* Adult (age 18 and older) mental health treatment/counseling, 2000 & 2001 (PDF format) -- Number and percent of (1) any mental health treatment, (2) inpatient, outpatient, and prescription medication treatment, and (3) unmet need for mental health treatment/counseling by socioeconomic demographics & geographic variables, family income, government assistance, and any illicit drug use (Tables 8.35A - 8.40B).
* Substance use by adult mental health treatment/counseling , 2000 & 2001 (PDF format) -- Number & percent of past year users of any illicit drugs, marijuana, nonmedical use of prescription-type drugs, cigarettes, & alcohol by receipt & perceived need for mental health treatment/counseling by sociodemographics, government assistance, and geographic variables

1999-2007:
Researchers had known opioids were involved in pain tolerance, but these studies were amongst the first to show they can be involved in the brain’s placebo response to pain.

2011:
* By binding to CB1, rimonabant must have blocked the action of the brain’s own cannabinoids, which the brain apparently is able to produce in order to effectively combat pain in this instance.

* The study is the first to prove that the placebo response to pain involves the cannabinoid system, specifically CB1, the receptor to which the brain’s own natural cannabinoids bind. It’s also the receptor bound to by THC, the main psychoactive ingredient in cannabis.
* This study tested 82 people, large enough for meaningful results but not especially large or diverse, considering the wide variety of responses seen in placebos. Future studies are needed to fully understand the effect, which involves more neurotransmitters than just opioids and cannabinoids.

There is no certain way of knowing how many Vietnam veterans have died through suicide, motor vehicle "accidents," or illnesses. The available evidence, both anecdotal and scientific, however, suggests elevated mortality rates from suicides, motor vehicle accidents, and certain cancers for Vietnam veterans. In some cases the data suggests mortality rates are "significantly elevated."

Depressed people consistently see the world around them more realistically than mentally healthy people who are biased toward optimism. Depression makes leaders more realistic and empathetic, and mania makes them more creative and realistic. The same, to a lesser but important degree, goes for people who are neither depressed nor manic, but not mentally healthy either—those with abnormal personalities [such as dysthymics]—a little depressed, low in energy, needing sleep—and the hyperthymic—always upbeat, sleep little, high libido....<br />
Kennedy as mentally ill and Nixon as normal? I define mental health as the absence of mental illness and being within the normal range of personality traits]; Nixon’s biography, looking for the 4 objective markers of mental illness, supports that conclusion. People ascribe mental abnormality to Nixon because they don't like his behaviours; that reflects psychological stigma,] stigma against mental illness, which is really very deep-rooted in our society.

[Among nearly 12,000 US nurses with a history of heart disease or stroke, regular coffee drinkers were no more likely to die than non-drinkers during a study spanning over 20 years for some subjects. No link was found between coffee intake and risk of death from heart attack, stroke or any other cause—even among women who drank 4 or more cups a day]. <br />
[The long-running Nurses' Health Study began tracking more than 100,000 female nurses in 1976. The new research focuses on 11,697 women who developed heart disease or had a stroke from 1976 to 2002.] Of those women, 62% continued to drink [unde]caffeinated coffee after their diagnosis. <br />
Overall, 1159 women had died by 2004. That risk was no greater among coffee drinkers than non-drinkers, including women who drank at least four 4 cups a day.... <br />
Some research [links coffee to increased blood pressure in those who metabolize caffeine slowly; the reverse pattern shows] in people who quickly process caffeine—more coffee, lower heart risks.

"Patients that adhere to their medications are likely to have improved health and increased quality of life".... <br />
[Pharmacy and medical claims from a 1.3 million-member commercial medical plan identified individuals continuously enrolled between 2007 and 2009] who had either two separate office visits for diabetes or a diabetes-related hospitalization in 2008 and with a DM medication supply or a diagnosis of diabetes with microvascular disease. All medical and pharmacy claim costs were added up to determine the total cost of care. <br />
[Of 15,043 members followed for one year], 73.9% (11,108 members) were adherent to their medication and 26.1% (3,935 members) were non-adherent. While those individuals adherent to DM medication had higher pharmacy costs which led to an increase in the overall total cost of care ($572), those adhering to medications were found to have a 31% lower risk of hospitalization and significantly lower overall medical costs ($1,010) than the non-adherent group.

[In 200 healthy, middle-aged volunteers, three portions of whole-grain foods per day lowered systolic blood pressure 5-6 mmHg, comparable to the effect of common hypertension drugs.] <br />
Some of the study-participants were given three servings of whole-grain foods each day, in the form of wheat, or both wheat with oats, while the rest received refined cereals and white bread (made of refined flour). <br />
[Both groups] were encouraged to eat what they normally ate apart from consuming their apportioned servings.... <br />
"We observed a decrease in systolic blood pressure of 5-6 mm Hg in the volunteers who ate the whole-grain foods, and this effect is similar to that you might expect to get from using blood pressure-lowering drugs.<br />
<br />
"This drop in systolic blood pressure could potentially decrease the incidence of heart attack and stroke disease by at least 15 and 25% respectively. <br />
"It's also good news for the food industry and especially for Scottish food producers."

5.6% of hospital patients in the US contract some form of health care-associated infections [(HAIs)—1.7 million preventable infections resulting] in over 99,000 deaths each year.<br />
[Hospital-born outbreak hijacks resources that could] be funnelled into research or providing better primary healthcare....[I]mmunocompromised children, such as cancer patients, premature babies and transplant patients...are particularly vulnerable to the horrors of HAIs[: "Precise definitions need to be established and] rigorous research needs to be performed…the expectation that adult criteria can be used to define, track and eliminate HAI in children is problematic"... <br />
HHS Secretary Kathleen Sebelius was joined by leaders of major hospitals, physicians, nurses and patient advocates when she announced the Partnerships for Patients initiative which hopes to avoid 60,000 deaths caused by preventable hospital injuries and complications, as well as save up to $35 billion, including $10 billion in Medicare.

Not mentioned in this piece is another reason to be cautious about red yeast rice extract—it IS a statin, specifically the one known pharmaceutically as lovastatin, and is therefore not really a statin alternative. It should probably be a avoided by anyone who has shown a sensititivity to statins, or wishes to avoid them on whatever principle. (This is a rare case of a drug having been developed in the laboratory before being "discovered" in nature.)—DMM

Between medicines, monitoring equipment, and medical co-pays, managing diabetes can be expensive. So the announcement that two popular retail chains — Meijer and Publix — have introduced programs providing free generic metformin to people with Type 2 diabetes may come as welcome news.<br />
<br />
As part of a healthy-living initiative to provide certain medicines at no cost to shoppers, Meijer will supply generic immediate-release metformin in tablet strengths of 500 milligrams, 850 milligrams, and 1,000 milligrams. Up to 100 tablets are covered per prescription fill, and refills are also free. The Publix Pharmacy Diabetes Management System provides no-cost generic immediate-release metformin in tablet strengths of 500 milligrams, 850 milligrams, and 1,000 milligrams. Up to 90 tablets are provided per prescription fill, and refills are free.<br />
<br />
For more information about these programs, see the Meijer and Publix Web sites. And to learn more about metformin, click here.

Metformin has a long track record for being safe and causing relatively few serious side effects—plus, it also works! Chances are, if you have Type 2 diabetes and need to start on medication, your health-care provider will recommend you take metformin....<br />
Metformin works by: <br />
* Reducing the amount of glucose released by your liver (and your liver regularly releases glucose) <br />
* Helping the insulin in your body work better (i.e., increasing insulin sensitivity). <br />
Metformin doesn’t cause your pancreas to secrete insulin, as do sulfonylureas, so it’s very unlikely that you will experience hypoglycemia (low blood glucose) with metformin alone; however, if you take a sulfonylurea or insulin along with metformin, you may get hypoglycemia. <br />
Side effects are usually temporary, and consist of gas, nausea, vomiting, and/or diarrhea. Some people have side effects, some never do. And if you can “stomach” metformin for the first month or so, you may end up losing weight...

In 2010, basic Medicare Part D coverage works like this:<br />
<br />
* You pay out-of-pocket for monthly Part D premiums all year.<br />
* You pay 100% of your drug costs until you reach the $310 deductible amount.<br />
* After reaching the deductible, you pay 25% of the cost of your drugs, while the Part D plan pays the rest, until the total you and your plan spend on your drugs reaches $2,800.<br />
* Once you reach this limit, you have hit the coverage gap referred to as the “donut hole,” and you are now responsible for the full cost of your drugs until the total you have spent for your drugs reaches the yearly out-of-pocket spending limit of $4,550.<br />
* After this yearly spending limit, you are only responsible for a small amount of the cost, usually 5% of the cost of your drugs.

Got Drugs? General disposal guidelines, and links to Take-Back sites mid-day Saturday, April 30th.

The treatment goals for patients with diabetes have evolved significantly over the last 80 years, from preventing imminent mortality, to alleviating symptoms, to the now recognized objective of normalization or near normalization of glucose levels with the intent of forestalling diabetic complications....

From a clinical perspective, type 2 diabetes is a cardiovascular disease, an observation that is supported by a range of epidemiologic, postmortem, and cardiovascular imaging studies. Vascular wall dysfunction, and particularly endothelial dysfunction, has been posited as a "common soil" linking dysglycemic and cardiovascular diseases. Vascular wall dysfunction promoted by environmental triggers (e.g., sedentary lifestyle) and metabolic triggers (chronic hyperglycemia, obesity) has been associated with the upregulation of reactive oxygen species and chronic inflammatory and hypercoagulable states, and as such with the pathogenesis of type 2 diabetes, atherosclerosis, and cardiovascular disease.

Diabetes drugs metformin, gliclazide and repaglinide proved more effective than other treatments in lowering the risks of cardiovascular disease and death, according to a study of more than 100,000 Danish people older than 20. Glimepiride, glibenclamide, glipizide and tolbutamide were linked to a higher risk of all-cause mortality as well as to a higher risk of heart attack, stroke and cardiovascular death, the study found.

Investigators examined the incidence and clinical predictors of new-onset type 2 diabetes [in 3 large randomized trials involving atorvastatin. In the TNT (Treating to New Targets) trial, 9.24% of 3,798 patients on 80 mg of atorvastatin and 8.11% of 3,797 patients on 10 mg developed new-onset DM2]. In the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial, 6.40% of 3,737 patients [on atorvastatin 80 mg/day and 5.59 percent of 3,724 patients on simvastatin 20 mg/day developed new-onset DM2]. In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, new-onset [DM2 was seen in 8.71% of 1,905 patients on atorvastatin 80 mg/day and in 6.06% of 1,898 placebo patients. Baseline fasting blood glucose, body-mass index, hypertension, and fasting triglycerides were independent predictors of new-onset DM2 in each trial. High-dose atorvastatin treatment] is associated with a slightly higher risk of type 2 diabetes.

In theory, a person prone to asthma should not be prone to diabetes.... <br />
[L]ead author Juhn noted that although people with asthma have a more allergy-prone immune profile, it is balanced by [the counter-regulatory Th1 immune profile underlying pro-inflammatory conditions like] coronary artery disease and diabetes. He [originally posited] "an inverse relationship" between asthma and those types of pro-inflammatory conditions. <br />
[Instead, some 138 asthmatics] per 100,000 had diabetes, compared to 104 for people without asthma; the rate for coronary heart disease was close to 189 per 100,000, versus 134 among non-asthmatics. <br />
[Patients from the 1960s through the 1980s] did not have access to many medications available today...Treatment 40 years ago was very "steroid heavy," which could have contributed to weight gain—a known risk factor for diabetes and heart disease..."Sometimes treatment can be part of the problem"...

[In all men and in women over] 65, aspirin can prevent a 1st or 2nd heart attack and reduces overall heart-disease risk. [Aspirin can prevent or protect against a 1str stroke in women, depending on age, and in women under 65 can prevent] a 2nd heart attack.<br />
[Adverse effects range from stomach upset to bleeding in the brain if given DURING a stroke. [Don't combine aspirin with ibuprofen without medical advice]....<br />
Aspirin therapy is [contraindicated with bleeding or clotting disorder, asthma, stomach ulcers or heart failure. Too much aspirin can cause tinnitus] and hearing loss. <br />
[Daily low-dose aspirin therapy—81 mg or one baby aspirin a day—is usually protective. Heart attack symptoms—severe chest pain, difficulty breathing, profuse sweating, pain radiating] to the back, jaw, throat or arm, indigestion or heartburn, anxiety, extreme weakness, dizziness, irregular heartbeat—[call for chewing 4 baby aspirin and calling 911. <br />
Chewing helps rapid absorption that can heart prevent damage.]

Alzheimer's disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer's disease are expected to triple over the next 50 years....Here, we demonstrate that the active component of marijuana, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) aggregation, the key pathological marker of Alzheimer's disease. Computational modeling of the THC−AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer's disease, THC is a considerably superior inhibitor of Aβ aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.

The Senate Finance Committee accused GlaxoSmithKline of knowing about the drug's risks well before they became public. The report also criticized the FDA for letting clinical trials continue, despite 83,000 heart attacks from 1999 to 2007 that the FDA linked to rosiglitazone. GlaxoSmithKline maintains the drug is safe and that the Senate report did not consider scientific evidence or the company's efforts to make known its concerns to the parties involved. However, the FDA still recommends patients continue taking it unless their doctor tells them otherwise. <br />
[A 2010] retrospective study of 227,571 elderly American patients, comparing roziglitazone to pioglitazone, the other thiazolidinedione marketed in the [US, associated rosiglitazone] with "an increased risk of stroke, heart failure, and all-cause mortality and an increased risk of the composite of AMI, stroke, heart failure, or all-cause mortality in patients 65 years or older." The number needed to harm with roziglitazone was 60.

"In Type 1 diabetes, your pancreas isn't making insulin. In Type 2 diabetes, your tissues are insensitive to insulin because of problems in the insulin receptor. Type 3 is where that insulin receptor problem is localized in the brain....[Some older] individuals start to have less effective insulin signaling, including in the brain"[, making the brain more vulnerable to large sticky plaques of amyloid beta protein,] a hallmark of Alzheimer's...<br />
[Short strands of the protein, known as] ADDLs, attack memory-forming brain cells...[In lab tests, insulin blocked the effects of ADDLs in rat nerve cells, an effect amplified by a drug that] increases insulin sensitivity. <br />
Several studies have found that diabetics have a higher risk of getting Alzheimer's... <br />
[Earlier research reports] diabetics who take insulin plus a range of anti-diabetic medications, including an older pill known as a sulfonylurea], have a lower risk of developing Alzheimer's than diabetics who only take insulin.

Images of attractive acquaintances were not very effective painkillers, but gazing at the faces of significant others and playing the word game reduced reported pain on average between 36 and 44% and high pain between 12 and 13%. <br />
Only photos of loved ones, however, sparked activity in reward centers within the amygdala, hypothalamus and medial orbitofrontal cortex. The faces of romantic partners also decreased activity in major pain-processing areas, such as the left and right posterior insula. Because the reward centers did not flutter in response to the distracting word game, the researchers argue that the salve of romantic affection is not mere distraction—it is a bliss as potent as that of drugs such as cocaine, which invigorate the same pleasure pathways.

[Muscle cramps are likely related to] poor flexibility, muscle fatigue, and/or doing new physical activities. [A]thletes are more likely to get cramps in the preseason when less conditioned and more subject to fatigue. Cramps often develop near the end of unaccustomed intense or prolonged exercise or during the night following the activity...
[C]ramps can also be related to dehydration and depletion of electrolytes (sodium, potassium, magnesium, and calcium) lost through sweating...[M]any people with diabetes already have low blood levels of magnesium...[P]otassium and sodium can also become unbalanced during periods of uncontrolled hyperglycemia when water losses through urine are usually greater. Finally, cramps in people with diabetes also may occur as a side effect of certain drugs (e.g., lipid-lowering agents, antihypertensives, beta-agonists, insulin, oral contraceptives, and alcohol).

In a study of bupropion for ADHD, a rise of systolic blood pressure by 6 mm Hg and of heart rate by 7 beats per minute (both statistically significant) were ...
en.wikipedia.org/wiki/Bupropion....there are possible side effects with Wellbutrin® (bupropion hydrochloride). ... A rapid heart rate (tachycardia) -- up to 10.8 percent of people ...
depression.emedtv.com/wellbutrin/wellbutrin-side-effects.html....Pharmacologic Treatment of Depression in Patients With Heart ....by SP Roose - 2005 - Cited by 28 - Related articles
TCAs routinely increase heart rate by 11%, induce orthostatic hypotension, .... The cardiovascular effects of bupropion treatment were documented in 36 patients ... Flecainide-induced ventricular tachycardia and fibrillation in patients ...www.psychosomaticmedicine.org/cgi/content/full/67/....How does bupropion increase a person's heartrate?... elevated heartbeat in the upper intake portion of the heart) is a ...www.answerbag.com › Categories › Health & Fitness

Clinicians should be aware of the risk of serotonin syndrome when the patient receives not only a combination of 2 antidepressants, but also the single potent serotonergic agent [!?] venlafaxine.
- Ann Pharmacother 2003 Feb;37(2):209-11 -- Serotonin syndrome induced by low-dose venlafaxine. -- Pan JJ, Shen WW....Bupropion had an effect on the pharmacokinetics of venlafaxine.
- J Clin Psychiatry 2002 Mar;63(3):181-6 -- Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects. -- Kennedy SH, McCann SM, Masellis M, McIntyre RS, Raskin J, McKay G, Baker GB.

There was a clinically significant benefit in 14 (78%) of 18 partial responders or nonresponders, and 33% (N = 6) achieved a full response (chi2= 8.06, df = 2, p = .017). Sexual dysfunction, particularly a decrease in orgasmic delay, was also significantly improved with combination therapy (men: paired t = -2.1, df = 6, p = .08; women: paired t = -3.0, df = 7, p = .02). Plasma monitoring of drugs and their metabolites revealed a statistically significant increase in venlafaxine levels (F = 6.89, df = 4,24; p = .001) accompanied by a decrease in O-desmethylvenlafaxine (F = 14.26; df = 4,24; p < .0005) during combined treatment with bupropion SR. There were no statistically significant changes in plasma levels of SSRIs (paroxetine and fluoxetine) during the trial. CONCLUSION: Bupropion had an effect on the pharmacokinetics of venlafaxine but not those of the SSRIs.

See physician always: Abnormal speech, bleeding / irritated gums, chest pain, depression, difficulty breathing, dry skin, ear pain, hair loss, excessive salivation, loss of strength, migraines, problem urinating, seizures, sensitivity to sun, soft stools, stomach irritation, suicide attempts, taste disorders, tongue discoloring, thyroid changes, tremors, problems with vision, and /or vomiting

See physician if severe: Anxiety, constipation, delayed orgasm, dizziness, dry mouth, itching, loss of appetite, nausea, nervousness, sedation, sleepiness / sleeplessness, sweating, tingling hands / feet, unusual dreams, weight loss, and / or weakness.

See physician NOW: Skin rash or vomiting.

Stop taking and see physician NOW: Seizures.

'Diabetes is associated with increased risk for Alzheimer's disease (AD), but a new study of metformin suggests that diabetes treatments might bear some of the blame...[M]etformin increased insulin's reduction of intracellular and extracellular beta-amyloid accumulation, but metformin by itself actually increased levels of the Alzheimer's-linked peptides...[Obervation] in vitro and in animal models of AD raises the specter of a wave of new Alzheimer's cases in diabetic patients who have been taking metformin for years. It is the most popular antidiabetic drug in the United States and one of only two oral antidiabetics on the World Health Organization List of Essential Medicines (along with glibenclamide). In 2006, there were 35 million prescriptions for generic metformin filled in the United States...[A]lthough this was an animal study, the findings are worrisome enough that physicians should promptly follow up any complaints of cognitive decline in patients taking metformin.'

Obesity...tends to cause chronic, low-grade inflammation[, which] Dr. Shoelson believes makes insulin less effective. Most people are able to produce more insulin to overcome this problem, but those with genetic risk factors for diabetes aren't able to do so, and they develop the disease. Using salsalate to reduce inflammation could break this chain. In [small studies] the drug significantly lowered spikes in blood sugar....[Results from a placebo-controlled study of 100 diabetics] were promising enough to convince the NIH to fund a yearlong trial with more than 400 patients....Since salsalate already is sold as an inexpensive, generic arthritis medicine, pharmaceutical companies have little financial incentive to fund research....Salsalate carries a safety warning, shared by many painkillers, that it may increase the risk of heart attacks and strokes. But the drug works differently than the other painkillers in the class, and there is no clear evidence that it shares that risk.