Month: May 2012

Refining our approach to Clostridium Difficile prevention

May 15, 2012 Infectious Diseases No comments

Laura A. Stokowski, RN, MS; L. Clifford McDonald, MD

Electronic Microscope of Clostridium Difficile.

No Getting Away From Clostridium difficile

Clostridium difficile (C difficile) is in the news again. This time, some of the news is good. In 3 state-led prevention programs, 71 hospitals that focused on prevention of C difficile infection (CDI) were able to cut their aggregate hospital-onset CDI rate by 20% in less than 2 years.[1]

The bad news is that for most of the country, CDI rates are still at an all-time high and remain strongly associated with exposure to healthcare. According to Emerging Infections Program surveillance, in 2010, 94% of CDIs occurred in patients who had received healthcare as an inpatient, outpatient, or both in the preceding 12 weeks.[1] C difficile infection is a rising cause of death in the most vulnerable patients. From 2000-2007, deaths from CDI increased 400% — to 14,000 annually, at a cost of more than $1 billion.

It’s time to reassess the way we think about C difficile.

C difficile infection is not just a frustratingly difficult-to-treat disease. It cannot be dismissed as a “hospital problem” or a “long-term care problem.” It is a healthcare-wide patient safety problem. Like other patient safety problems, resolving CDI requires a multifaceted approach and a commitment to action from both multiple stakeholders and the individuals at the “sharp end” of patient care.

With the conviction that transmission of C difficile is avoidable but that no single action will be sufficient, the Centers for Disease Control and Prevention (CDC) outlined the 6 strategies that have the best chance of eradicating C difficile from healthcare. These strategies involve elements of antibiotic stewardship, testing for C difficile, isolation and infection control procedures, environmental cleaning, and communication[2]:

  1. Prescribe and use antibiotics carefully. About 50% of antibiotics that are given are not needed.
  2. Test for C difficile when patients have diarrhea while taking antibiotics or within several months of taking them.
  3. Isolate patients with C difficile immediately.
  4. Wear gloves and gown when treating patients with C difficile, even during short visits. Hand sanitizer does not kill C difficile, and handwashing may not be sufficient.
  5. Clean room surfaces with bleach or another Environmental Protection Agency (EPA)-approved spore-killing disinfectant after a patient with C difficile has been treated there.
  6. When a patient transfers to another facility, notify the new facility if the patient has CDI.

Food interactions with drugs

May 15, 2012 Drug Interactions, Pharmacokinetics No comments , ,

In outpatient pharmacy the topiest question is that “whether I can take this drug with food? ” “Should I avoid taking drugs with food?”. In China there are few study about the interactions between food and drugs. Today we go along a approach of pharmacokinetics to discuss about the interactions between food and drugs. I found related information from some old pharmacokinetics books – Course they are Chinese pharmacy books.

Firstly we should know that the absorption of drugs is determined by these nine parameters below. They are:

  1. disintegration position in the gastrointestinal tract
  2. absorption position in the gastrointestinal tract
  3. the pH at the disintegration position
  4. the pH at the absorption position
  5. the duration the drug staying at disintegration
  6. the duration the drug staying at absorption position
  7. drug ionized status
  8. the way the drug is absorbed
  9. the drug stability at the staying position in the gastrointestinal tract

First, drugs need to disintegrate before absorbing. According to the Noyes – Whitney Formula, the weak acid drugs’ disintegrating rate increases as the pH rises. By contrary the weak alkali drugs’ disintegrating rate decreases as the pH rises.

After disintegrating, the drug can be absorbed.

For most drugs they are only absorbed when they are in un-ionized status. Because most drugs diffuse across membrane via passive transport.

So when the drug comes to the absorption position of the gastrointestinal tract. The pH of the tract has a huge impact on the un-ionzied or ionized status. Simply, for weak acid drugs the percentage of un-ionzied status decreases as the pH rises. For weak alkali drugs the percentage of un-ionzied status increases as the pH rises.

Two above steps need time. Only the time staying in disintegration position and absorption position is sufficient, the drug disintegrates and is absorbed competely.

Finally, the drug stability in the staying position of the gastrointestinal tract is important. If the drug stability is weak, the drug disappears.

So when patients inqury whether they can take drugs with food. Pharmacists could answer them according to above theory I wrote. I think food has interactions with drugs via changing the nine parameters. While the nine parameters are changed, the bioavailablity changes.

Above is my own opinion.

Food and drug interactions with emerging oral anticoagulants

May 15, 2012 Anticoagulant Therapy, Drug Interactions, Therapeutics No comments , ,

Food Interactions With Anticoagulant Drugs.

By Michael O’Riordan

June 8, 2010 (Maywood, Illinois) — A new review warns physicians to be aware of the potential for drug and dietary interactions with the emerging oral anticoagulants [1]. At present, there are few documented interactions with the new drugs, including dabigatran (Pradaxa, Boehringer Ingelheim), rivaroxaban (Xarelto, Johnson & Johnson), and apixaban (Bristol-Myers Squibb/Pfizer), but considering the extensive food and drug interactions with warfarin, caution should be taken with the new agents, according to researchers.

“Many unknowns remain as to how the new oral anticoagulants will behave in the real-world patient population,” write authors Drs Jeanine Walenga and Cafer Adiguzel (Loyola University Medical Center, Maywood, IL) in the June 2010 issue of the International Journal of Clinical Practice. “As evaluations of the new oral anticoagulants continue, the issue of drug interactions needs to be properly evaluated, particularly as some of the interacting drugs are used to treat potentially life-threatening conditions.”

One recent study reported by heartwire showed that the safety of warfarin, a vitamin-K antagonist, can be compromised by many popular herbal and nonherbal supplements. In fact, eight of the 10 most widely used supplements interact with warfarin, and many of these are associated with significant changes in the international normalized ratio (INR). Cranberry, garlic, ginkgo, and saw palmetto have been linked to increased rates of bleeding, whereas others have been shown to cause changes in prothrombin times, which would result in a need to alter warfarin doses.

Little Known About Food, But Caution Still Needed

In their review, Walenga and Adiguzel note that the new and emerging oral anticoagulants have a “rapid onset of action and a predictable anticoagulant effect,” but little is known about potential interactions with food. They point out the various physiological parameters can alter the pharmacokinetics of orally administered drugs, such as changes in gastric pH balance and intestinal motility and binding, and these can be affected by eating and taking the drugs at the same time.

Regarding drug interactions, dabigatran is contraindicated with quinidine, a drug used to treat cardiac arrhythmias and malaria. Caution should also be used when dabigatran is prescribed in combination with inhibitors or inducers of P-glycoprotein (P-GP), such as amiodarone, clarithromycin, and rifampin. Rivaroxaban, as well as possibly apixaban, is contraindicated with drugs that inhibit both cytochrome P450 3A4 (CYP3A4) and P-GP pathways, such as azole antimycotics, ritonavir, and clarithromycin, among others. Caution should be exercised prescribing rivaroxaban with a drug that inhibits either the CYP3A4 only or P-GP pathway only.

One over-the-counter supplement that the reviewers highlight as a possible problem with the new oral anticoagulants is St John’s wort, a herb taken frequently for depression. St John’s wort is known to reduce the anticoagulant effect of warfarin.

There is also risk of bleeding when using the new oral anticoagulants in combination with an antiplatelet agent, such as clopidogrel, or nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin.

“In addition to drug and food interactions, it is equally important to consider liver, kidney, and other common disease states that the US population experiences, particularly if these patients have been excluded from clinical trials,” write Walenga and Adiguzel. Although dabigatran and rivaroxaban are contraindicated in patients with severe liver impairment, they might inadvertently be given to patients in whom clinical symptoms are not pronounced, a population that has not been extensively studied.

The reviewers recommend clinicians use caution with the new drugs in older patients, particularly since this population often has long-term comorbid conditions.

Prevention/delay of type 2 diabetes

May 14, 2012 Diabetes, Therapeutics No comments , ,

RCTs have shown that individuals at high risk for developing type 2 diabetes (those with IFG, IGT, or both) can significantly decrease the rate of onset of diabetes with particular interventions (2026). These include intensive lifestyle modification programs that have been shown to be very effective (∼58% reduction after 3 years) and use of the pharmacologic agents metformin, α glucosidase inhibitors, orlistat, and thiazolidinediones, each of which has been shown to decrease incident diabetes to various degrees. Follow-up of three large studies of lifestyle intervention has shown sustained reduction in the rate of conversion to type 2 diabetes, with 43% reduction at 20 years in the Da Qing study (41), 43% reduction at 7 years in the Finnish Diabetes Prevention Study (DPS) (42), and 34% reduction at 10 years in the U.S. Diabetes Prevention Program Outcome Study (DPPOS) (43). A cost-effectiveness model suggested that lifestyle interventions as delivered in the DPP are cost-effective (44), and actual cost data from the DPP and DPPOS confirm that lifestyle interventions are highly cost-effective (45). Group delivery of the DPP intervention in community settings has the potential to be significantly less expensive while still achieving similar weight loss (46).

Based on the results of clinical trials and the known risks of progression of prediabetes to diabetes, persons with an A1C of 5.7–6.4%, IGT, or IFG should be counseled on lifestyle changes with goals similar to those of the DPP (7% weight loss and moderate physical activity of at least 150 min per week). Regarding drug therapy for diabetes prevention, a consensus panel felt that metformin should be the only drug considered (47). For other drugs, issues of cost, side effects, and lack of persistence of effect in some studies (48) require consideration. Metformin was less effective than lifestyle intervention in the DPP and DPPOS but may be cost-saving over a 10-year period (45). It was as effective as lifestyle in participants with a BMI of at least 35 kg/m2 (20), and in women with a history of GDM, metformin and intensive lifestyle led to an equivalent 50% reduction in the risk of diabetes (49). Metformin therefore might reasonably be recommended for very-high-risk individuals (those with a history of GDM, the very obese, and/or those with more severe or progressive hyperglycemia). Of note in the DPP, metformin was not significantly better than placebo in those over age 60 years.

Recommendations.

  • Patients with IGT (A), IFG (E), or an A1C of 5.7–6.4% (E) should be referred to an effective ongoing support program targeting weight loss of 7% of body weight and increasing physical activity to at least 150 min per week of moderate activity such as walking.

  • Follow-up counseling appears to be important for success. (B)

  • Based on the cost-effectiveness of diabetes prevention, such programs should be covered by third-party payers. (B)

  • Metformin therapy for prevention of type 2 diabetes may be considered in those with IGT (A), IFG (E), or an A1C of 5.7–6.4% (E), especially for those with BMI >35 kg/m2, age <60 years, and women with prior GDM. (A)

  • At least annual monitoring for the development of diabetes in those with prediabetes is suggested. (E)

Testing for diabetes in asymptomatic patients

May 13, 2012 Diabetes No comments , ,

In last post we talked about the categories of increased risk for diabetes (prediabetes).

Now we will talk about how to identify the people at risk for diabetes.

For many illnesses, there is a major distinction between screening and diagnostic testing. However, for diabetes, the same tests would be used for “screening” as for diagnosis.

Why the screening for diabetes is significant. Because diabetes may be identified anywhere along a spectrum of clinical scenarios ranging from a seemingly low-risk individual who happens to have glucose testing, to a higher-risk individual whom the provider tests because of high suspicion of diabetes, to the symptomatic patient.

Here in this post we primarily discuss the testing for diabetes in those without symptoms. The same assays used for testing for diabetes will also detect individuals with prediabetes.

Prediabetes and diabetes meet established criteria for conditions in which early detection is appropriate. Both conditions are common, increasing in prevalence, and impose significant public health burdens. There is a long presymptomatic phase before the diagnosis of type 2 diabetes is usually made. Relatively simple tests are available to detect preclinical disease. Additionally, the duration of glycemic burden is a strong predictor of adverse outcomes, and effective interventions exist to prevent progression of prediabetes to diabetes (see section IV. PREVENTION/DELAY OF TYPE 2 DIABETES) and to reduce risk of complications of diabetes (see section V.I. PREVENTION AND MANAGEMENT OF DIABETES COMPLICATIONS).

Type 2 diabetes is frequently not diagnosed until complications appear, and approximately one-fourth of all people with diabetes in the U.S. may be undiagnosed. The effectiveness of early identification of prediabetes and diabetes through mass testing of asymptomatic individuals has not been proven definitively, and rigorous trials to provide such proof are unlikely to occur. In a large randomized controlled trial (RCT) in Europe, general practice patients between the ages of 40 and 69 years were screened for diabetes and then randomized by practice to routine care of diabetes or intensive treatment of multiple risk factors. After 5.3 years of follow-up, CVD risk factors were modestly but significantly more improved with intensive treatment. Incidence of first CVD event and mortality rates were not significantly different between groups (16). This study would seem to add support for early treatment of screen-detected diabetes, as risk factor control was excellent even in the routine treatment arm and both groups had lower event rates than predicted. The absence of a control unscreened arm limits the ability to definitely prove that screening impacts outcomes. Mathematical modeling studies suggest that screening independent of risk factors beginning at age 30 or age 45 years is highly cost-effective (<$11,000 per quality-adjusted life-year gained) (17).

Recommendations for testing for diabetes in asymptomatic, undiagnosed adults are listed in Table 4. Testing should be considered in adults of any age with BMI ≥25 kg/m2 and one or more of the known risk factors for diabetes. There is compelling evidence that lower BMI cut points suggest diabetes risk in some racial and ethnic groups. In a large multiethnic cohort study, for an equivalent incidence rate of diabetes conferred by a BMI of 30 kg/m2 in whites, the BMI cutoff value was 24 kg/m2 in South Asians, 25 kg/m2 in Chinese, and 26 kg/m2 African Americans (18).Disparities in screening rates, not explainable by insurance status, are highlighted by evidence that despite much higher prevalence of type 2 diabetes, non-Caucasians in an insured population are no more likely than Caucasians to be screened for diabetes (19). Because age is a major risk factor for diabetes, testing of those without other risk factors should begin no later than age 45 years.

Either A1C, FPG, or the 2-h OGTT is appropriate for testing. It should be noted that the tests do not necessarily detect diabetes in the same individuals. The efficacy of interventions for primary prevention of type 2 diabetes (2026) has primarily been demonstrated among individuals with IGT, not for individuals with isolated IFG or for individuals with specific A1C levels.

The appropriate interval between tests is not known (27). The rationale for the 3-year interval is that false negatives will be repeated before substantial time elapses, and there is little likelihood that an individual will develop significant complications of diabetes within 3 years of a negative test result. In the modeling study, repeat screening every 3 or 5 years was cost-effective (17).

Because of the need for follow-up and discussion of abnormal results, testing should be carried out within the health care setting. Community screening outside a health care setting is not recommended because people with positive tests may not seek, or have access to, appropriate follow-up testing and care. Conversely, there may be failure to ensure appropriate repeat testing for individuals who test negative. Community screening may also be poorly targeted, i.e., it may fail to reach the groups most at risk and inappropriately test those at low risk (the worried well) or even those already diagnosed.

The recommendations are:

  • Testing to detect type 2 diabetes and assess risk for future diabetes in asymptomatic people should be considered in adults of any age who are overweight or obese (BMI ≥25 kg/m2) and who have one or more additional risk factors for diabetes. In those without these risk factors, testing should begin at age 45 years.
  • If test are normal, repeat testing at least at 3-year intervals is resonable.
  • To test for diabetes or to assess risk of future diabetes, the A1C, FPG, or 2-h 75-g OGTT are appropriate.
  • In those identified with increased risk for future diabetes, identify and, if appropriate, treat other CVD risk factors.

Criterias for testing diabetes in asymptomatic adult individuals:

  • physical inactivity

  • first-degree relative with diabetes

  • high-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander)

  • women who delivered a baby weighing >9 lb or who were diagnosed with GDM

  • hypertension (blood pressure ≥140/90 mmHg or on therapy for hypertension)

  • HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82 mmol/L)

  • women with PCOS

  • A1C ≥5.7%, IGT, or IFG on previous testing

  • other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)

  • history of CVD