INTERACTION BETWEEN REISHI 'LING ZHI' MUSHROOM AND WARFARIN

WHAT IS IT?

• Reishi mushroom is commonly known as ‘Ling Zhi’ in Chinese with a scientific name, ‘Ganoderma lucidum’.
• Reishi mushroom is primarily composed of complex carbohydrates called water-soluble polysaccharides, triterpeniods, proteins and amino acids which aids in its beneficial effects.

RATIONALE:

• The polysaccharide content of Reishi mushroom is responsible for possible anticancer and immun0stimulatory effects.
• May also provide hepatoprotective action, antiviral activity, and beneficial effect on the cardiovascular system, rheumatoid arthritis, chronic fatigue syndrome, and diabetes. 

BLOOD THINNING PROPERTIES:

Many references stated that Reishi mushroom has some interactions with anticoagulants where it may enhances the blood thinning properties; to cause bleeding in patient. This interaction is summarized by UpToDate, where the risk associated with concomitant use of Reishi mushroom and warfarin is classified as Category D.

Category D: Consider Therapy Modification

“Data demonstrate that the two medications may interact with each other in a clinically significant manner. A patient-specific assessment must be conducted to determine whether the benefits of concomitant therapy outweigh the risks. Specific actions must be taken in order to realize the benefits and/or minimize the toxicity resulting from concomitant use of the agents. These actions may include aggressive monitoring, empiric dosage changes, choosing alternative agents”

RECOMMENDATION:

Caution is advised in people with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.

References:

1. http://www.reishi.com/what-is-reishi.html

2. http://www.drugs.com/npp/reishi-mushroom.html

3. http://www.uptodate.com.

4. https://my.clevelandclinic.org

Use of Corticosteroid In Acute Asthma in Pregnancy

• Prednisolone has been assigned to pregnancy category C by the FDA.
• Some animal studies have revealed evidence of fetal harm, although data are conflicting
• No controlled data in human pregnancy
• Is only recommended for use during pregnancy when there are no alternatives and benefit outweighs risk

Evidence of Cases Reported

• In the Michigan Medicaid Birth Defects Study involving 229,101 pregnancies from 1985 to 1992, there were 143 first trimester exposures to prednisolone
• A statistically significant increase in the total number of birth defects was found, with eleven cases reported compared with only six cases expected.
• However, no association between prednisolone and the six categories of defects studied (cardiovascular, oral clefts, spina bifida, polydactylies, limb reduction defects/syndactylies, hypospadias) was found

Oral Glucocorticosteroid

• Because of their importance in the treatment of a variety of inflammatory conditions, systemic glucocorticoids have been used fairly extensively during pregnancy
• However, it is difficult to exclude an adverse pregnancy effect due to asthma in studies of patients with asthma symptoms severe enough to require oral glucocorticoids.
• potential gestational risks of oral glucocorticoids must be balanced against the risks to the mother or the infant of inadequately treated disease.
• risks of severe uncontrolled disease are generally considered to be the greater risk, suggesting that oral glucocorticoids should still be used when indicated

Inhaled Glucocorticosteroid

•  In contrast to oral/systemic glucocorticoids, the safety data on inhaled glucocorticoids are reassuring
• One study assessed 84 pregnant women who were managed with or without inhaled beclomethasone after discharge following an asthma hospitalization during pregnancy . Use of this medication significantly decreased the rate of readmission for asthma (12 versus 33 percent), and no adverse events or outcomes were reported

References:

1. www.uptodate.com
2. http://www.drugs.com/pregnancy/prednisolone.html

Anticonvulsant Prophylaxis for Hemorrhagic Stroke

• Early seizure activity occurs in 4-28% of patients with intracerebral hemorrhage; these seizures are often nonconvulsive

Treatment

• According to American Heart Association/American Stroke Association (AHA/ASA) 2010 guidelines for the management of spontaneous intracerebral hemorrhage, patients with clinical seizures or electroencephalographic (EEG) seizure activity accompanied by a change in mental status should be treated with antiepileptic drugs
• Patients for whom treatment is indicated should immediately receive a benzodiazepine, such as lorazepam or diazepam, for rapid seizure control.
• This should be accompanied by phenytoin or fosphenytoin loading for longer-term control

Prophylaxis

• Remains uncertain
• In prospective and population-based studies, clinical seizures have not been associated with worse neurologic outcome or mortality.
• 2 studies have reported worse outcomes in patients who did not have a documented seizure but who received antiepileptic drugs (primarily phenytoin)
• 2010 AHA/ASA guidelines do not offer recommendations on prophylactic anticonvulsants
• Suggest continuous EEG monitoring is probably indicated in patients with intracranial hemorrhage whose mental status is depressed out of proportion to the degree of brain injury
• Prophylactic anticonvulsant therapy has been recommended in patients with lobar hemorrhages to reduce the risk of early seizures. One large, single-center study showed that prophylactic antiepileptic drugs significantly reduced the number of clinical seizures in these patients
• AHA/ASA guidelines from 2012 suggest that prophylactic anticonvulsants may be considered for patients with aneurysmal subarachnoid hemorrhage. In such cases, however, anticonvulsant should be limited to the immediate post-hemorrhagic period.
• Routine long-term use is not recommended, but it may be considered in patients with a prior seizure history, intracerebral hematoma, intractable hypertension, or infarction or aneurysm at the middle cerebral artery

Recommendation

• Currently, therefore, there is not enough evidence to justify the routine use of antiepileptic drugs to prevent seizures after stroke (evidence current to 08/2013)

References:

1. http://emedicine.medscape.com/article/1916662-treatment#d9
2. http://www.cochrane.org/CD005398/EPILEPSY_is-there-evidence-to-support-the-use-of-antiepileptic-drugs-for-the-primary-and-secondary-prevention-of-seizures-after-stroke
3. http://stroke.ahajournals.org/content/40/12/3810.full

STORAGE OF EXPRESSED BREAST MILK (EBM)

For Home Use:

Breast Milk	Room Temperature	Refrigerator	Freezer
Freshly expressed into a closed container.	6–8 hrs. (26ºC or lower) If refrigeration is available; store milk there.	No more than 72 hours. Store in back, where it is the coldest.	2 weeks in freezer compartment inside refrigerator (15° C). 3 months in freezer section of refrigerator with separate door (–18°C). 6–12 months in deep freeze (–20°C**)
Previously frozen—thawed (in refrigerator but not warmed).	4 hours or less (ex: the next feeding).	Store in refrigerator 24 hours.	Do not refreeze.
Thawed (outside refrigerator in warm water).	For completion of feeding.	Hold for 4 hours or until next feeding.	Do not refreeze.
Infant has begun feeding.	Only for completion of feeding, then discard.	Discard.	Discard.

**Chest or upright manual defrost deep freezer that is opened infrequently and maintains ideal temperature.

For Hospital Use:

Type	Location	Storage Temperature (degrees celcius)	Duration of Storage
Fresh expressed breast milk.	Room temperature	15-20 degrees	Discard after 4 hours (time from pumping and removal from refrigerator)
Fresh expressed breast milk.	Refrigerator	0-4 degrees	Discard after 48 hours
Expressed breast milk with additives.	Room temperature	15-20 degrees	Discard after 4 hours (time from pumping and removal from refrigerator)
Expressed breast milk with additives.	Refrigerator	0-4 degrees	Discard after 24 hours
Thawed expressed breast milk.	Refrigerator	0-4 degrees	Discard after 24 hours
Frozen expressed breast milk.	Freezer within a refrigerator (one door)	Less than 0 degrees	Discard after 2 weeks
Frozen expressed breast milk.	Freezer attached to refrigerator top, bottom or side (two door)	Less than 0 degrees	Discard after 3-4 months
Frozen expressed breast milk.	Deep freezer	-18 to -20 degrees	Expressed breast milk may be stored in the freezer for up to 12 months

References:

1. Maternity breast milk: Safe management <http://www.health.nsw.gov.au/policies/>

2. <https://www.breastfeeding.asn.au/bf-info/breastfeeding-and-work/expressing-and-storing-breastmilk>

3. Expressed breast milk; Safe management, Alberta Health Services

WHO SHOULD NOT RECEIVE EXPRESSED BREAST MILK (EBM)

Human milk contains antibodies and other protective factors, but in the case of certain pathogens, it may also pose a possible risk of infection for the infant. The benefits for the infant to continue receiving EBM must be considered against the possible severity of the disease. It would be wise if the breast milk that is to be given to infants are tested for pathogens and the risks that the milk could expose are being elucidated first, before consumption. Here are some measures that could done to reduce the risk of infants receiving milk that is dangerous to them:

Risk Assessment of the Source (non-birth) Mother:

An assessment of the clinical status of the source mother at the time of breast milk collection/expression or feeding with regard to:

• the presence of fever
• the presence of rash (including vesicles on the breast), and
• the presence of mastitis, breast abscess or bleeding nipple.

Checking the source mother’s antenatal serology for previous results, e.g. syphilis, hepatitis C (HCV) antibodies, hepatitis B (HBV), and Human Immunodeficiency virus (HIV) antibodies.

Checking for a history of HBV vaccination.

Checking medications prescribed to the source mother.

Where recent serological results are lacking, discussing risk factors for blood borne viruses (HIV, HBV and HCV) and syphilis in the source mother. These include:

• Injecting drug use
• Birthplace or previous residence or travel in a country with high prevalence of HIV or other blood borne viruses (as identified by an appropriate specialist)
• Tattoo or piercing
• History of syphilis (including date and treatment)
• Blood transfusion history or possible iatrogenic exposure to a blood borne virus, and
• Unprotected sex with a partner who has or is at risk of having a blood borne virus

Serological & Breast Milk Screening:

Testing should be expedited, in order to inform appropriate treatment to the baby, should it be required. It is recommended that at the time of the exposure the following should be collected from the source mother and the mother of the exposed baby:

Blood	HIV RNA NAT, HIV proviral DNA (if available) and HIV antibody/ antigen test. However this information will be unlikely to be available in time to guide initiation of prophylactic therapy of the baby.
	HCV antibody test, HCV RNA test
	HBV surface antigen, HBV core antibody
Breast Milk	Cytomegalovirus (CMV) NAT (if baby is less than one month of age, or has underlying immune deficiency illness)

References:

1. Maternity-breast milk: Safe management <http://www.health.nsw.gov.au/policies/>

2. <https://www.breastfeeding.asn.au/bf-info/breastfeeding-and-work/expressing-and-storing-breastmilk>

3. Malaysian Dietary Guideline

What is Typhoid?

WHAT IS IT?

Typhoid fever is an infectious disease characterized by severe systemic illness with fever and abdominal pain. It is also known as enteric fever. The term "enteric fever" is a collective term that refers to both typhoid and paratyphoid fever as they clinically indistinguishable diseases. The organism classically responsible for the enteric syndrome is Salmonella enterica serotype Typhi (formerly known as S. typhi). The illness is characterized by a very high fever, sweating, gastroenteritis, and diarrhea and it is easily spreads through contaminated food and water supplies and close contact with others who are infected.

HOW TYPHOID FEVER SPREADS?

Salmonella Typhi lives only in humans and it is commonly transmitted through the fecal-oral route. Persons with typhoid fever carry the bacteria in their bloodstream and intestinal tract, then spreads them to other persons. Typhoid fever can be spread through various ways:

• Eat food and drink beverages that have been handled by a person who is shedding the bacteria.
• Consume/use tainted food or water that has been contaminated with the bacteria. Including use the water to wash the food.
• Poor sanitation/ fails to wash hands after using the bathroom.

WHAT ARE THE SYMPTOMS OF TYPHOID FEVER?

First week:

• Rising ‘stepwise’ fever and bacteremia
• Chills and rigors
• Relative bradycardia
• Pulse temperature

Second week:

• Abdominal pain develops
• ‘Rose spots’ (faint salmon coloured macules on the trunk and abdomen) may be seen

Third week:

• Hepatosplenomegaly
• Intestinal bleeding
• Perforation due to ileocecal lymphatic hyperplasia of the Peyer’s patches
• Secondary bacteremia
• Peritonitis
• Septic shock/ altered level of consciousness

WHY IS IT DANGEROUS?

Typhoid Fever if untreated properly, could leads to many serious complications and fatal. For example, in the United States, an estimated 5,700 cases of typhoid fever occur annually, mostly among travelers. An estimated 21 million cases of typhoid fever and 200,000 deaths occur worldwide.Without therapy, the illness may last for 3 to 4 weeks and death rates range between 12% and 30%. This situation could be worsened in the endemic countries where the burden of the disease is higher such in second and third world countries.

HOW CAN WE AVOID TYPHOID FEVER?

Two basic actions can protect you from typhoid fever:

1. Avoid risky foods and drinks:

• If you drink water, buy it bottled or bring it to a rolling boil for 1 minute before you drinkit.
• Bottled carbonated water is safer than uncarbonated water.
• Ask for drinks without ice unless the ice is made from bottled or boiled water.
• Avoid popsicles and flavored ices that may have been made with contaminated water.
• Eat foods that have been thoroughly cooked and that are still hot and steaming.
• Avoid raw vegetables and fruits that cannot be peeled. Vegetables like lettuce are easilycontaminated and are very hard to wash well.
• When you eat raw fruit or vegetables that can be peeled, peel them yourself. (Wash your hands with soap first.) Do not eat the peelings.
• Avoid foods and beverages from street vendors. It is difficult for food to be kept clean Onthe street, and many travelers get sick from food bought from street vendors.

2. Get vaccinated against typhoid fever:

• If you are traveling to a country where typhoid is common, you should consider being vaccinated against typhoid.
• Remember that you will need to complete your vaccination at least 12 weeks (dependent upon vaccine type) before you travel so that the vaccine has time to take effect.
• Typhoid vaccines lose effectiveness after several years; If you were vaccinated in the past, check with your doctor tosee if it is time for a booster vaccination.

DOES THE DANGER ENDS WHEN THE SYMPTOMS DISAPPEAR?

Even if your symptoms seem to go away, you may still be carrying Salmonella Typhi. If so, the illness could return, or you could pass the disease to other people. In fact, if you work at a job where you handle food or care for small children, you may be barred legally from going back to work until a doctor has determined that you no longer carry any typhoid bacteria. If you are being treated for typhoid fever, it is important to do the following:

• Keep taking the prescribed antibiotics for as long as the doctor has asked you to take them.
• Wash your hands carefully with soap and water after using the bathroom, and do not prepare
• Or serve food for other people. This will lower the chance that you will pass the infection on to someone else.
• Have your doctor to perform a series of stool cultures to ensure that no Salmonella Typhi bacteria remain in your body.

References:

1. <www.uptodate.com>

2. Centers for Disease And Prevention Control

3. <http://www.medicalnewstoday.com/articles/156859>

4. Bulletin of World Health Oragnization 2004; 82; 346-352

Isosorbide Dinitrate VS Isosorbide Mononitrate

Isosorbide Dinitrate (ISDN) 

• is an intermediate acting nitrate approved for prevention of angina pectoris.
• ISDN is available in immediate release (Ex: Isordil®) and extended release (Ex: DilatrateSR ®) forms. ISDN has an extensive first pass metabolism in the liver, produces two major metabolites (Isosorbide 2 mononitrate & Isosorbide 5 Mononitrate) with half-lives of 2 & 4 hours respectively. 
• Due significant first pass metabolism, ISDN has a half-life of about 1 hour. 
• Normally it is doses in 3 to 4 doses daily. 
• In a study done on patient with TDS dose of ISDN with a 14 hours free interval, the exercise capacity improved after the first dose.

Isosorbide Mononitrate (ISMN)

• active metabolite of ISDN and is primarily used in the management of chronic stable angina. 
• ISMN does not undergo first pass metabolism, hence it has higher bioavailability and a longer half-life (4-6 hours) than ISDN. 
• ISMN is available as an immediate release form (Ex: ISMO® and Monoket®) which is typically given in 2 doses daily 7 hours apart to minimize tolerance and sustained released form (Ex: Imdur®) which can be given once daily. 
• It is primarily used in the management of chronic stable angina. However, it is not approved by the FDA to be used in treating heart failure.

INDICATION

• For management of angina pectoris, ISMN may be preferred because of its ease of administration as a once daily formulation. 
• Better adherence can lead to a decrease in chest pain episodes. 
• Although the pharmacokinetic parameters of ISDN extended release are not well defined, it also has been given in a single daily dose for prevention of angina.
• For heart failure, ISDN has been more extensively studied than ISMN and is recognized in the American College of Cardiology/American Heart Association guidelines for treatment of heart failure. 
• On the other hand, FDA does not approve the use of ISMN in treating heart failure.

TOLERANCE

• Development of nitrate tolerance and clinical rebound should be considered with long term nitrate use. 
• Nitrate tolerance may develop within 1 to 2 days, resulting in decreased angina control. It is induced by nitrate regimens that produce continuous therapeutic levels. 
• Dose adjustments allowing a low nitrate period have been devised to reduce development of nitrate tolerance. 
• Unfortunately, breakthrough angina, or clinical rebound, can occur during the nitrate free intervals used in some dosing strategies. 
• For immediate release form of ISDN, a 14 hours drug free interval has been recommended, and for sustained release forms, a greater than 18 hours drug free period is recommended.
• According to Medscape (2010), for immediate release ISMN, given in 2 doses, on awakening and 7 hours later each day has been shown to prevent development of tolerance without inducing clinical rebound in a well-designed clinical trial. 
• Waller (1999), for once daily formulations of ISMN, it delivers high plasma nitrate concentrations that improve exercise tolerance in patients with angina for at least 12 h after dosing. 
• During the remainder of the dosage interval, plasma nitrate concentrations fall but are sufficient to protect against coronary artery spasm overnight. For example, Elantan is a sustained-release capsule formulation of ISMN for once-daily dosing. 
• This capsule contains pellets which release 30% of the dose immediately, while 70% is released slowly to maintain the therapeutic response. 
• The pharmacokinetic profile of this formulation prevents the development of tolerance, while also conferring long-term anti-anginal efficacy.

ADHERENCE/COMPLIANCE

• Another consideration in the selection of an isosorbide regimen is patient adherence. 
• The COMPASS (Compliance with Oral Mononitrates in Angina Pectoris Study) demonstrated that once daily dosing of ISMN resulted in better patient adherence (fewer missed doses) and a greater decrease in chest pain episodes than did ISMN given twice daily at 8 AM and 2 PM. 
• If adherence is a concern, off label ISMN could be considered in place of ISDN in management of heart failure.

References:

1. <www.medscape.com>

2. <http://www.ncbi.nlm.nih.gov/pubmed/10499557>

3. <http://www.drugs.com/monograph/isosorbide-dinitrate-mononitrate.html>

4. Thadani U. Nitrate therapy and the development of tolerance. Arch Fam Med. 1993:2;880885