It’s easy to build raised beds. Eric shows you how with these simple raised bed plans. Great for vegetables, Eric has 6 of these raised beds. Visit our community site for more info http://gardenfork.tv
Duration : 10 min 23 sec
Cardiomyopathy refers to disease of the heart muscle (the myocardium) without malformation of the heart or its valves. The term cardiomyopathy literally means “sick heart muscle.” There is a breed predisposition to dilated cardiomyopathy in giant breeds, as well as in Doberman pinschers and boxers. Dilated cardiomyopathy is not the most common cause of heart failure in dogs in general. However, this is the most common cause of heart failure in large breeds of dogs. Small breeds are only occasionally affected. The most commonly affected breeds are Boxers, Doberman Pinschers, and Great danes. Occasionally, medium sized breeds, notably Cocker Spaniels and English Springer Spaniels, are also affected. Cardiomyopathy can also develop as a result of some toxins or infections. Heart failure occurs when the blood returning to the heart from the rest of the body cannot be pumped out fast enough to meet the demands of body tissues. Heart muscle disease is one of the potential causes of heart failure. Dilated cardiomyopathy is a condition characterized by a variety of changes in the heart muscle that result in pump failure. As the name implies, the heart chambers are usually dilated or enlarged, and the heart muscle itself is usually thin and weak, contracting with much less vigor than normal. The heart works harder to compensate for the loss of contractility, eventually leading to congestive heart failure. The abnormalities in the heart muscle cells give rise to irregular heart rhythms which may cause sudden death so proper petsafe is necessary.
Dilated cardiomyopathy is by far the most common type in the dog. There is dilation of the chambers of the ventricles of the heart with some increase (hypertrophy) in the heart muscle mass, and a loss of the normal contracting abilities of the ventricles. Dilated cardiomyopathy, or DCM, occurs when the heart muscle is thin, weak, and does not contract properly. DCM most commonly affects large or giant purebred dogs, but it also can be seen in smaller breeds such as cocker spaniels, and in mixed breed dogs. The condition can lead to congestive heart failure, in which fluid accumulates in the lungs, the chest or abdominal cavities, or under the skin. Because of reduced blood flow to the rest of the body, DCM also can result in weakness, fainting, and exercise intolerance. Abnormal heart rhythms, or arrhythmias, frequently accompany DCM, and can complicate the treatment of dogs with this disease. It is also common for dogs with DCM to show signs of both right and left heart failure. These signs can include weakness and exercise intolerance, and difficulty breathing with increased activity. Weight loss is common in dogs with DCM that do not retain fluid. Some animals exhibit signs due to reduced blood flow to tissues, including pale mucous membranes, bluish color to the mucous membranes, and cold feet and legs. Fainting may occur if abnormal heart rhythms are present, or if the heart’s output is severely reduced. Hypertrophic cardiomyopathy is a form of cardiomyopathy, there is a tremendous increase in the mass of the heart muscle in the ventricles, with a resultant decrease in chamber size. Relatively few cases of hypertrophic cardiomyopathy in dogs have been reported, and no significant breed predisposition has been identified. Most of the dogs affected have been male.
Blood and urine tests do not give direct information about heart function, but they allow an understanding of other disorders in the body that may impact on heart function and treatment of heart disease. Chest radiographs (x-rays) provide the best look at the lungs and a view of the size and shape of the heart. In most cases, dilated cardiomyopathy causes tremendous enlargement of the heart. These changes are usually very apparent on x-rays.lectrocardiogram (ECG or EKG) is an assessment of the electrical activity of the heart. It accurately determines the heart rate and to more accurately identify any arrhythmias which might be present. Ultrasound examination (Sonogram, Echocardiogram) uses sound waves which bounce off the structures of the heart and are read on a TV-like monitor. It gives the most accurate determination of the size of each heart chamber, and permits measurement of the thickness of the heart walls. This is seen on the monitor in actual time so the contractions of the heart can be evaluated. Certain measurements can be taken which allow the actual strength of the heart’s contraction to be measured as a number and compared to the normal animal. Ultrasound may not be available in all private veterinary practices because of the additional training needed to learn how to perform the examination and because of the cost of the equipment.
If the dog has a sudden onset of heart failure, rapid administration of the proper drugs is essential to survival. The following drugs may be used at various stages of treatment. Diuretics drugs stimulate the kidneys to remove excess fluid from the body. Furosemide is most commonly used, although others will be selected in certain circumstances. Nitroglycerin drug is called a venodilator; it dilates the veins throughout the body, especially the ones going to the heart muscle. It decreases the amount of blood returning to the heart by allowing some of it to pool in the veins. This takes some of the workload off the heart. This drug can be very useful for treating pulmonary edema, but it is only effective for a few days. Digitalis drug improves heart function in several ways. It regulates excess hormones that have been released, slows the heart rate, and strengthens each contraction of the heart. Enzyme blockers is a relatively new class of drugs which can directly block the compensation system that has gotten out of control. Vasodilators drugs dilate the arteries and/or the veins of the body so that the heart doesn’t have to generate as much pressure to eject blood. They may be used long-term because they continue to be effective, as opposed to the short-term effects of nitroglycerin. Dogs treated with these drugs should be carefully watched for toxity and needs enough rest on pet beds. Loss of appetite, vomiting, diarrhea, and lethargy should be reported to the veterinarian immediately.
Wishbone
http://www.articlesbase.com/pets-articles/dilated-cardiomyopathy-heart-failure-in-dogs-711816.html
According to a new report, “Saudi Arabian Healthcare Market Forecast to 2012”, the Saudi Arabian healthcare market is witnessing rapid growth and will continue to expand exponentially in future. The country’s rapidly increasing population, due to which demand is outpacing supply, can be regarded as the main push for the market. And as the incidences of a number of lifestyle diseases, such as obesity, diabetes and hypertension, in the country amongst the highest in the world, these will significantly boost the healthcare spending in future.
Government plays a central role in providing healthcare services in the kingdom, accounting for around 75% of the total healthcare spending in the country. The government accounted for 67% of the total hospitals and 77% of the total hospital beds in the country in 2006. The government expenditure on healthcare, however, is increasing faster than its total income; as a result, government may resort to cost cutting measures in future.
The report says that due to increasing pressure on the public healthcare system, the government is rapidly promoting the involvement of private healthcare in the country. So big investment will be seen from the private sector in the forecasted period, and according to our estimates, the private sector will account for 62% for all new beds installed during 2006-2012.
However, slump in crude oil prices due to economic recession can hit the nation’s economy. But the fast diversification of the country’s economy into other sectors will provide it a buffer against the severe impact of economic turmoil. Despite some challenges such as shortage of skilled workers, dependency on oil and bureaucratic issues, the market’s future will remain bright with all three sectors – hospital services, pharmaceuticals and medicals devices – expected to show sustained growth.
“Saudi Arabian Healthcare Market Forecast to 2012” gives an extensive and objective analysis on the Saudi Arabian healthcare market. It has segmented the healthcare industry into hospital services, pharmaceuticals and medical devices. It provides analytical and statistical information on these segments, including their market size, demand, supply, segmentation and key players. It also features an analysis on the future directions, supplemented with facts and figures. Thus, the report serves as a useful guide for healthcare companies, government officials, consultants and investors who are planning to enter the Saudi Arab healthcare market.
Our report provides forecast on
- Macroeconomic indicators
- Demographic and healthcare indicators
- Healthcare spending
- Demand for hospital beds
- Pharmaceutical market
- Medical devices market
Key questions answered in the report
- Which factors are driving the Saudi Arabia healthcare market?
- What is the past and present size of the healthcare market?
- What is the role of public and private sectors in providing healthcare?
- What is the total supply and demand for hospital services in Saudi Arab?
- What will be the demand, investment and infrastructure scenario in the hospital services market?
- What is the total size and future outlook of the pharmaceutical market?
- Who are the key players operating in the pharmaceutical market?
- What is the total size and future outlook of the medical devices market?
- What are the key challenges faced by the Saudi Arabia healthcare market?
For More detail Please Visit :- http://www.marketsmonitor.com/Report/IM173.htm
Marketsmonitor
http://www.articlesbase.com/health-articles/marketsmonitor-releases-report-on-saudi-arabian-healthcare-market-forecast-to-2012-717775.html
Bedroom is one of the most desired rooms for retirement. A quiet respite, the space should instantly help you relax and feel at home the moment you enter the room. Bedroom furniture can help you in organizing a space and also fulfilling the needs of a soulful night rest away from the hustle of work and everyday life. Getting a good night sleep is one of the prime concerns when working out a color or furniture scheme for bedrooms.
You get bedroom sets with closets, cabinets and armoires that allow you to stack up extra items. These storage units offer you that extra space to put clothes and other articles conveniently in drawers and shelves. There are armoires that can be used as entertainment centers, and many other viable options. You get dresser and nightstands along with beds as suites where each unit aptly compliments the other. There are bookcases and shelving systems as well to help you stow away the extra stuff lying around. But overall, it helps to work out a theme in-line with your comfort level. Blues, greens and pastels are considered retiring colors, and you could match it all up to harmonize a space with décor articles like paintings, furniture, fabric, accessories and curtains. Work out on relaxing themes and jell it with your personal taste.
Apart from organizing a space, bedroom furniture can be fashioned in the most appealing manner to allow a collage of art and function. You get beds in different materials—leather, wood, wrought iron and a combination that allows you to invest in comfort within your budget. A storage bed, for instance, is great for storing extra linen, sheets and pillows. A leather bed bestows a room with a suave modern looks that is all great; but you must match it up with some great modern furniture pieces or even think out of the box and create an interesting fusion of old and new to infuse your bedroom with a great harmonizing balance and energy.
You get modern beds in different styles. On basics of modern interior design, the trend follows easy lines, open spaces and muted, textured colors and shades. Tones towards the bolder versions are here, but there are beiges and browns too for a serene ambience. You can add depth to any color, and add pieces and accessories in complimenting shades and tones to further accentuate the overall décor. Hang paintings in complimenting frame colors and retiring tones, wall papers are great too, and textured designs can help you personalize a space to suit your taste. Planning helps in fashioning bedroom furniture that compliments the overalls in the most harmonizing way. Measure the space and evaluate your storage needs on a practical level. Also, it is important to have some space around for you to move about in the room.
There are different kinds of beds available, some of the most popular ones being listed here,
Types of beds
Trundle Bed : Trundle bed is normally a pair of beds. One of the beds is slightly smaller than a twin bed, which is on rollers or casters so that it may be put under the upper twin bed for storage. Designed to be used for extra guests when needed, trundle beds allow you to use the extra bed/s separately without occupying extra space.
Sleigh Beds : A classic sleigh bed looks modern and comes with headboards and footboards. Sleigh beds can be opted for along with a set of side drawers for more storage space.
Platform bed : Bedroom platform beds come without springs. The bed is actually designed to be elevated on the legs or the support frame. Great for comfort and has a clean, neat and simple appeal, good for avoiding stuffy looks.
Sofa beds : Sofa bed is a versatile piece of furniture. It can be used in the day time as a chic sofa and converted into a bed with the help of easy click-clack mechanism. These days you get sofa beds in the most fashionable designs to suit the urbane lifestyle. A great combination of function and style, it is a great solution for smaller spaces too.
Child Bed/ Bunk Bed : Child bed is designed at a level lying very low to the ground, so that the child can climb up and down safely. Look out for safety features—rounded edges and other available features that make the beds safe. Bunk beds are twin beds fashioned to accommodate two kids. Arranged one on top of the other, the upper bed can be accessed with the help of a ladder. There are many different designs and styles available that allow room for storage and study. Designer kid’s bunk bed suites are great for scheming up a room in different color schemes and styles.
Amanda Somers
http://www.articlesbase.com/home-improvement-articles/indoor-furniturebedroom-676606.html
Bedroom is one of the most desired rooms for retirement. A quiet respite, the space should instantly help you relax and feel at home the moment you enter the room. Bedroom furniture can help you in organizing a space and also fulfilling the needs of a soulful night rest away from the hustle of work and everyday life. Getting a good night sleep is one of the prime concerns when working out a color or furniture scheme for bedrooms.
You get bedroom sets with closets, cabinets and armoires that allow you to stack up extra items. These storage units offer you that extra space to put clothes and other articles conveniently in drawers and shelves. There are armoires that can be used as entertainment centers, and many other viable options. You get dresser and nightstands along with beds as suites where each unit aptly compliments the other. There are bookcases and shelving systems as well to help you stow away the extra stuff lying around. But overall, it helps to work out a theme in-line with your comfort level. Blues, greens and pastels are considered retiring colors, and you could match it all up to harmonize a space with décor articles like paintings, furniture, fabric, accessories and curtains. Work out on relaxing themes and jell it with your personal taste.
Apart from organizing a space, bedroom furniture can be fashioned in the most appealing manner to allow a collage of art and function. You get beds in different materials—leather, wood, wrought iron and a combination that allows you to invest in comfort within your budget. A storage bed, for instance, is great for storing extra linen, sheets and pillows. A leather bed bestows a room with a suave modern looks that is all great; but you must match it up with some great modern furniture pieces or even think out of the box and create an interesting fusion of old and new to infuse your bedroom with a great harmonizing balance and energy.
You get modern beds in different styles. On basics of modern interior design, the trend follows easy lines, open spaces and muted, textured colors and shades. Tones towards the bolder versions are here, but there are beiges and browns too for a serene ambience. You can add depth to any color, and add pieces and accessories in complimenting shades and tones to further accentuate the overall décor. Hang paintings in complimenting frame colors and retiring tones, wall papers are great too, and textured designs can help you personalize a space to suit your taste. Planning helps in fashioning bedroom furniture that compliments the overalls in the most harmonizing way. Measure the space and evaluate your storage needs on a practical level. Also, it is important to have some space around for you to move about in the room.
There are different kinds of beds available, some of the most popular ones being listed here,
Types of beds
Trundle Bed : Trundle bed is normally a pair of beds. One of the beds is slightly smaller than a twin bed, which is on rollers or casters so that it may be put under the upper twin bed for storage. Designed to be used for extra guests when needed, trundle beds allow you to use the extra bed/s separately without occupying extra space.
Sleigh Beds : A classic sleigh bed looks modern and comes with headboards and footboards. Sleigh beds can be opted for along with a set of side drawers for more storage space.
Platform bed : Bedroom platform beds come without springs. The bed is actually designed to be elevated on the legs or the support frame. Great for comfort and has a clean, neat and simple appeal, good for avoiding stuffy looks.
Sofa beds : Sofa bed is a versatile piece of furniture. It can be used in the day time as a chic sofa and converted into a bed with the help of easy click-clack mechanism. These days you get sofa beds in the most fashionable designs to suit the urbane lifestyle. A great combination of function and style, it is a great solution for smaller spaces too.
Child Bed/ Bunk Bed : Child bed is designed at a level lying very low to the ground, so that the child can climb up and down safely. Look out for safety features—rounded edges and other available features that make the beds safe. Bunk beds are twin beds fashioned to accommodate two kids. Arranged one on top of the other, the upper bed can be accessed with the help of a ladder. There are many different designs and styles available that allow room for storage and study. Designer kid’s bunk bed suites are great for scheming up a room in different color schemes and styles.
Amanda Somers
http://www.articlesbase.com/home-improvement-articles/indoor-furniturebedroom-676606.html
Bedroom is one of the most desired rooms for retirement. A quiet respite, the space should instantly help you relax and feel at home the moment you enter the room. Bedroom furniture can help you in organizing a space and also fulfilling the needs of a soulful night rest away from the hustle of work and everyday life. Getting a good night sleep is one of the prime concerns when working out a color or furniture scheme for bedrooms.
You get bedroom sets with closets, cabinets and armoires that allow you to stack up extra items. These storage units offer you that extra space to put clothes and other articles conveniently in drawers and shelves. There are armoires that can be used as entertainment centers, and many other viable options. You get dresser and nightstands along with beds as suites where each unit aptly compliments the other. There are bookcases and shelving systems as well to help you stow away the extra stuff lying around. But overall, it helps to work out a theme in-line with your comfort level. Blues, greens and pastels are considered retiring colors, and you could match it all up to harmonize a space with décor articles like paintings, furniture, fabric, accessories and curtains. Work out on relaxing themes and jell it with your personal taste.
Apart from organizing a space, bedroom furniture can be fashioned in the most appealing manner to allow a collage of art and function. You get beds in different materials—leather, wood, wrought iron and a combination that allows you to invest in comfort within your budget. A storage bed, for instance, is great for storing extra linen, sheets and pillows. A leather bed bestows a room with a suave modern looks that is all great; but you must match it up with some great modern furniture pieces or even think out of the box and create an interesting fusion of old and new to infuse your bedroom with a great harmonizing balance and energy.
You get modern beds in different styles. On basics of modern interior design, the trend follows easy lines, open spaces and muted, textured colors and shades. Tones towards the bolder versions are here, but there are beiges and browns too for a serene ambience. You can add depth to any color, and add pieces and accessories in complimenting shades and tones to further accentuate the overall décor. Hang paintings in complimenting frame colors and retiring tones, wall papers are great too, and textured designs can help you personalize a space to suit your taste. Planning helps in fashioning bedroom furniture that compliments the overalls in the most harmonizing way. Measure the space and evaluate your storage needs on a practical level. Also, it is important to have some space around for you to move about in the room.
There are different kinds of beds available, some of the most popular ones being listed here,
Types of beds
Trundle Bed : Trundle bed is normally a pair of beds. One of the beds is slightly smaller than a twin bed, which is on rollers or casters so that it may be put under the upper twin bed for storage. Designed to be used for extra guests when needed, trundle beds allow you to use the extra bed/s separately without occupying extra space.
Sleigh Beds : A classic sleigh bed looks modern and comes with headboards and footboards. Sleigh beds can be opted for along with a set of side drawers for more storage space.
Platform bed : Bedroom platform beds come without springs. The bed is actually designed to be elevated on the legs or the support frame. Great for comfort and has a clean, neat and simple appeal, good for avoiding stuffy looks.
Sofa beds : Sofa bed is a versatile piece of furniture. It can be used in the day time as a chic sofa and converted into a bed with the help of easy click-clack mechanism. These days you get sofa beds in the most fashionable designs to suit the urbane lifestyle. A great combination of function and style, it is a great solution for smaller spaces too.
Child Bed/ Bunk Bed : Child bed is designed at a level lying very low to the ground, so that the child can climb up and down safely. Look out for safety features—rounded edges and other available features that make the beds safe. Bunk beds are twin beds fashioned to accommodate two kids. Arranged one on top of the other, the upper bed can be accessed with the help of a ladder. There are many different designs and styles available that allow room for storage and study. Designer kid’s bunk bed suites are great for scheming up a room in different color schemes and styles.
Amanda Somers
http://www.articlesbase.com/home-improvement-articles/indoor-furniturebedroom-676606.html
Personal Injury Law Firms experienced in negligence, malpractice and other types of personal injury actions have taken note of recent product liability actions involving the drug, Duragesic.
Duragesic® is the trade name for a pain-medication patch containing fentanyl, a potent opioid analgesic. Duragesic is a transdermal system-the medicine, fentanyl, is absorbed through the patient’s skin and into the bloodstream, providing pain relief for up to three days (72 hours) from a single patch application.
Duragesic is prescribed in five dosage strengths: 12, 25, 50, 75 and 100 mcg of fentanyl per hour. The 50, 75, and 100 ug/h doses are only prescribed for patients who are already on and tolerant to opioid therapy, and require continuous opioid administration. Moreover, the Duragesic label warns that 12 mcg/hour as an initiating dose has not been systematically evaluated; therefore, Duragesic should be used only in patients who are opioid-tolerant.
Fentanyl was found to be a good choice for transdermal application because of its physicochemical properties and high analgesic potency. However, Fentanyl is not without its serious adverse effects. Pharmacologically, fentanyl acts on the central nervous system causing analgesia, sedation, severe respiratory depression, muscle rigidity, seizures, coma, and hypotension. Adverse reactions include mood changes, euphoria, dysphoria, drowsiness, constricted pupils, nausea, and vomiting. The most serious side effect of fentanyl overdose is hypoventilation (respiratory depression), which can be fatal.
Development of Duragesic
Currently, only eleven transdermally administered drugs are on the market; seven of which were developed by ALZA. In 1981, ALZA responded to a plea from a White House-created committee of scientists and physicians to develop more potent analgesics with alternative delivery systems for critically ill and dying patients who were suffering from intractable pain. ALZA began work on a project to develop a fentanyl transdermal patch in late 1982.
In early 1983, ALZA representatives met with agents from the DEA to discuss the handling of fentanyl. Among other issues, the DEA expressed concern that the dosage be kept to an absolute minimum, because of the potential for overdose and abuse.
In 1991, ten years after ALZA proposed the development of a transdermal fentanyl patch, Duragesic was made available for sale in the United States. Originally, Duragesic was approved to treat acute, postoperative and moderate-to-severe pain. However, due to the slow onset of drug levels from the transdermal delivery and three day maintenance of drug levels with Duragesic, the system was more suited for treatment of chronic pain conditions, in particular, cancer patients. By 1998, the World Health Organization (WHO) recommended transdermal fentanyl for treatment of cancer pain in stable patients.
Since receiving FDA approval in 1990, ALZA and Janssen aggressively sought the expansion of Duragesic use beyond cancer patients. For example, transdermal fentanyl has been used to treat rheumatologic pain and severe back pain.
The FDA has also approved an expansion of Duragesic to treat pediatric patients.
Janssen’s most recent advertising campaign to expand the use of Duragesic was thwarted by the FDA. In the late 1990s, the company sent a document called Top Ten List to doctors urging physicians to switch their patients to Duragesic patches rather than use more traditional type pain relievers. Among the reasons listed is the phrase “It’s not just for end stage cancer any more!” However, in 2000, the Department of Health and Human Services wrote a letter to Janssen informing the company that its promotional pieces concerning the “Broadening of indication” for Duragesic were misleading and contained misrepresentations. The government agency responded, “The suggestion that Duragesic can be used for any type of pain management promotes Duragesic for a much broader use that is recommended by the PI, and thus, is misleading.”
Currently, Duragesic is the most widely prescribed transdermal medication. From 2002 to 2003, the total number of fentanyl patch prescriptions within the United States rose from 4.5 million to 5.4 million-a twenty percent increase. And the resulting sales figures for Duragesic have been enormous: total annual sales in the United States have reached one and a half billion ($1,500,000,000.00) dollars annually.
And in 2005, Duragesic sales generated two point one billion ($2,100,000,000.00) dollars worldwide.
Duragesic Defects:
Package Leak-Subsequent Recalls
The design/manufacturing defect most applicable to our case is an improper sealing of one edge of the Duragesic patch, resulting in millions of patches being recalled. During 2004, ALZA (through Janssen) initiated two large Class I recalls of Duragesic for this exact reason. The first was February 17, 2004 at which time Duragesic Control No. 0327192 (75 mcg/hr) was pulled from the market. The cited reason was a potential seal breach on one edge of the patch, which could result in fentanyl leaking from the patch. This recall included about 440,000 patches.
On April 5, 2004, Janssen expanded its recall of Duragesic to include 2.2 million patches (Control Numbers 0327192, 0327193, 0327294, 0327295, and 0330362). Again, the reason cited was the potential for a breach of the seal, which would result in fentanyl leakage. Janssen sent a “Dear Healthcare Professional” letter to inform of the expanded recall.
A leak of fentanyl from a Duragesic patch could cause patients to receive either too much or too little of the drug. If the fentanyl seeps out of the patch before its application to the skin, patients may receive too little medication to adequately treat their pain. In this situation, patients used to a specific does may experience withdrawal effects including sweating, sleeplessness, and abdominal discomfort.
Conversely, fentanyl leaks that occur while the patch is on the skin expose patients to a potentially life-threatening overdose of fentanyl. Duragesic is designed to deliver only a controlled amount of fentanyl into the patient’s skin. Patients wearing a defective patch that leaks fentanyl directly onto the skin will receive too much of the medication. If this occurs, patients could experience minor complications such as sedation, drowsiness, and nausea. Fentanyl overdose may result in more serious complications, including fatal hypoventilation (respiratory depression) or cardiac arrest.
When Jansen placed Duragesic on the market in 1991, reports of toxicity due to fentanyl overdosing were fairly common. In fact, one study in California of 112 deaths associated with fentanyl concluded that the general availability of the drug may be responsible for the high incidence of overdoses.
Furthermore, in a recent Duragesic lawsuit filed against Johnson & Johnson, Janssen, and ALZA, the plaintiffs alleged that “despite knowing of this defect, the defendants (Johnson & Johnson, Janssen, ALZA) took inadequate steps to advise physicians, hospitals, nursing Homes and other health care professionals of the defect and the significant damages to users of the Duragesic patches.”
Heat-Induced Overdose
ALZA and Janssen’s knowledge of the overdosing potential caused by external heat dates back to 1986, when ALZA did lab testing on a nitroglycerin-delivering patch using the same co-polymer membrane used in Duragesic patches. ALZA subsequently did lab testing on Duragesic in 1988-that showed that a five degree Centigrade increase in temperature doubled Duragesic’s release rate. Dr. Curtis Wright, the FDA Medical Review Officer, was quite concerned in 1989 and again in 1990 that ALZA had not responded to his request for more information on the effects of external heat. After Duragesic hit the market in April of 1991, ALZA and Janssen learned of six reports from healthcare providers that external heat appeared to increase blood fentanyl levels in patients in the hospital setting and at home.
However, the first time Janssen or ALZA made an effort to warn of the effects of external heat came in a January 17, 1994 “Dear Doctor” letter with an attached proposed labeling revision. The labeling contained a new heat warning, which was buried at page 10 of the attachment, but no mention was made in the letter itself to alert physicians that external heat applied to the patch was potentially life-threatening.
GOVERNMENT REGULATION
In 2004, the FDA influenced Janssen and ALZA to issue two Class I Recalls of Duragesic, “due to improper sealing of one of their edges,” which could result in a life-threatening overdose of fentanyl. Yet, this was not the first time the FDA encountered problems with the companies’ handling of Duragesic. In fact, prior to the recalls in 2004, the FDA has required Duragesic labeling revisions 13 times.
And, as recently as July 2005, the FDA issued a Public Health Advisory concerning the use of Duragesic Patches in response to reports of deaths in patients using the patch.
Beginning in 1994, the FDA sent ALZA a “warning letter” identifying certain violations and deviations from Good Manufacturing Practices (GMP) regulations under the Food and Drug Act. This prompted the company to issue a letter to all health care professionals warning of Duragesic misuse.
In the late 1990s, the Department of Health and Human Services warned Janssen that its promotional materials to expand the use of Duragesic were in direct violation of the Federal Food, Drug, and Cosmetic Act and contained misrepresentations as to the safety and efficacy of the product. The agency determined that the promotional pieces were “false or misleading because they contain misrepresentations of safety information, broaden Duragesic’s indication, contain unsubstantiated claims, and lack fair balance.”
Following Janssen’s “voluntary” recall of Duragesic in 2004, the FDA issued a “Safety Alert” warning that the recall was “due to a potential leak in the product seal,” which could result in skin exposure to fentanyl. The warning adds that “skin exposure to any leaked medication from a DURAGESIC patch may cause nausea, sedation, drowsiness, or potentially life-threatening complications.” Govt Regulation 6. Janssen also wrote a letter to “Healthcare Professional[s]” informing them of the expanded recall in April 2004.
Furthermore, on September 2, 2004 the FDA issued Janssen another “warning letter.” This letter states that the latest Duragesic promotional pieces make “false or misleading claims about the abuse potential and other risks of the drug, including unsubstantiated effectiveness claims for Duragesic.” The letter states, “By suggesting that Duragesic has a lower potential for abuse compared to other opioid products, the file card could encourage the unsafe use of the drug, potentially resulting in serious or life-threatening hypoventilation.”
The Duragesic product label was again updated in June 2005 to add new safety information in several areas of labeling, and Janssen issued another “Dear Healthcare Professional” letter about these changes. Under a section entitled “Hypoventilation (Respiratory Depression),” the letter warns that “Serious or life-threatening hypoventilation may occur at any time during the use of DURAGESIC® especially during the initial 24-72 hours following initiation of therapy and following increases in dose.” Janssen also warns of a “potential for temperature-dependant increases in fentanyl released from the system resulting in possible overdose and death.” Therefore, the letter instructs all patients to avoid exposing Duragesic to “direct external heat sources, such as heating pads or electric blankets, heat lamps, saunas, hot tubs, and heated water beds, etc., while wearing the system.”
Finally, on July 15, 2005 the FDA issued a “Public Health Advisory” concerning the use of Duragesic Patches in response to reports of deaths in patients using the patch. The FDA stated it is conducting an investigation into the deaths related to fentanyl overdose in patients using Duragesic. According to the FDA, “Some patients and health care providers may not be fully aware of the dangers of this very strong narcotic painkiller. Therefore, FDA is issuing this public health advisory to alert patients and their caregivers and health care professionals by highlighting the following important safety information.”
MEDICAL LITERATURE
Fentanyl Overdose
Since Duragesic hit the marketplace in 1991, studies have shown continued high numbers of overdoses involving transdermal delivery of fentanyl. The most serious side effect is respiratory depression, which can be fatal. One study, published in 1991, examined 112 fentanyl-related deaths in the Eastern United States, mostly in California. Fentanyl deaths appeared to occur rapidly, “probably the result of acute respiratory depression.” While acknowledging the extreme potency of fentanyl, the author suggests that “the incidence of fentanyl-related deaths is probably determined by the general availability of the drug, rather than the relative potency of the analogs.”
In a study published in 2000, the Los Angeles County Department of the Coroner analyzed 25 cases involving fentanyl-related deaths. The author notes that the Los Angeles County Coroner’s Office evaluates nearly one case each month involving fentanyl patch-related death. Another study that same year identified 61 cases of transdermal drug overdoses in a Regional Poison Information System over a five-year period.
Head-Induced Overdose
Heat is expected to increase skin permeability, metabolism and elimination of fentanyl. If drug release from the system is much faster than permeation through the skin, the skin controls the transdermal absorption rate into the patient’s systemic circulation, rather than Duragesic’s special rate control membrane.
Several case reports have described the development of life-threatening overdose caused by a heating pad or rise in body temperature. Frolich et al. reported a narcotic overdose in a patient that was using a warming blanket to relieve pain following surgery. Medical Literature 17, see M.A. Frolich et al., Opioid Overdose in a Patient Using a Fentanyl Patch During Treatment with a Warming Blanket, 93 ANESTH. ANALG. 647-48 (2001) (unable to obtain hard copy). The increase in absorption may account for other heat-related toxicity associated with transdermal fentanyl. G. Newshan, Heat-Related Toxicity with the Fentanyl Transdermal Patch, 16 J. PAIN SYMPTOM MGMT. 277-78 (1998) (unable to obtain hard copy).
One study, in 2003, examined the effect of heat on transdermal fentanyl absorption. The authors concluded that increases in skin temperature may result in increased systemic absorption of fentanyl. Therefore, warming blankets and heating pads should not be either used in conjunction with, or placed over Duragesic patches.
However, as of 2003, the Duragesic label warned that serum fentanyl concentrations may “theoretically” increase by one third in patients with a body temperature of 40 degrees Celsius because of accelerated drug release and increased skin permeability. The current label warns of a “potential for temperature-dependent increases in fentanyl release from the system.”
Mathew A. Passen
http://www.articlesbase.com/personal-injury-articles/duragesic-product-liability-personal-injury-lawsuits-723732.html
Personal Injury Law Firms experienced in negligence, malpractice and other types of personal injury actions have taken note of recent product liability actions involving the drug, Duragesic.
Duragesic® is the trade name for a pain-medication patch containing fentanyl, a potent opioid analgesic. Duragesic is a transdermal system-the medicine, fentanyl, is absorbed through the patient’s skin and into the bloodstream, providing pain relief for up to three days (72 hours) from a single patch application.
Duragesic is prescribed in five dosage strengths: 12, 25, 50, 75 and 100 mcg of fentanyl per hour. The 50, 75, and 100 ug/h doses are only prescribed for patients who are already on and tolerant to opioid therapy, and require continuous opioid administration. Moreover, the Duragesic label warns that 12 mcg/hour as an initiating dose has not been systematically evaluated; therefore, Duragesic should be used only in patients who are opioid-tolerant.
Fentanyl was found to be a good choice for transdermal application because of its physicochemical properties and high analgesic potency. However, Fentanyl is not without its serious adverse effects. Pharmacologically, fentanyl acts on the central nervous system causing analgesia, sedation, severe respiratory depression, muscle rigidity, seizures, coma, and hypotension. Adverse reactions include mood changes, euphoria, dysphoria, drowsiness, constricted pupils, nausea, and vomiting. The most serious side effect of fentanyl overdose is hypoventilation (respiratory depression), which can be fatal.
Development of Duragesic
Currently, only eleven transdermally administered drugs are on the market; seven of which were developed by ALZA. In 1981, ALZA responded to a plea from a White House-created committee of scientists and physicians to develop more potent analgesics with alternative delivery systems for critically ill and dying patients who were suffering from intractable pain. ALZA began work on a project to develop a fentanyl transdermal patch in late 1982.
In early 1983, ALZA representatives met with agents from the DEA to discuss the handling of fentanyl. Among other issues, the DEA expressed concern that the dosage be kept to an absolute minimum, because of the potential for overdose and abuse.
In 1991, ten years after ALZA proposed the development of a transdermal fentanyl patch, Duragesic was made available for sale in the United States. Originally, Duragesic was approved to treat acute, postoperative and moderate-to-severe pain. However, due to the slow onset of drug levels from the transdermal delivery and three day maintenance of drug levels with Duragesic, the system was more suited for treatment of chronic pain conditions, in particular, cancer patients. By 1998, the World Health Organization (WHO) recommended transdermal fentanyl for treatment of cancer pain in stable patients.
Since receiving FDA approval in 1990, ALZA and Janssen aggressively sought the expansion of Duragesic use beyond cancer patients. For example, transdermal fentanyl has been used to treat rheumatologic pain and severe back pain.
The FDA has also approved an expansion of Duragesic to treat pediatric patients.
Janssen’s most recent advertising campaign to expand the use of Duragesic was thwarted by the FDA. In the late 1990s, the company sent a document called Top Ten List to doctors urging physicians to switch their patients to Duragesic patches rather than use more traditional type pain relievers. Among the reasons listed is the phrase “It’s not just for end stage cancer any more!” However, in 2000, the Department of Health and Human Services wrote a letter to Janssen informing the company that its promotional pieces concerning the “Broadening of indication” for Duragesic were misleading and contained misrepresentations. The government agency responded, “The suggestion that Duragesic can be used for any type of pain management promotes Duragesic for a much broader use that is recommended by the PI, and thus, is misleading.”
Currently, Duragesic is the most widely prescribed transdermal medication. From 2002 to 2003, the total number of fentanyl patch prescriptions within the United States rose from 4.5 million to 5.4 million-a twenty percent increase. And the resulting sales figures for Duragesic have been enormous: total annual sales in the United States have reached one and a half billion ($1,500,000,000.00) dollars annually.
And in 2005, Duragesic sales generated two point one billion ($2,100,000,000.00) dollars worldwide.
Duragesic Defects:
Package Leak-Subsequent Recalls
The design/manufacturing defect most applicable to our case is an improper sealing of one edge of the Duragesic patch, resulting in millions of patches being recalled. During 2004, ALZA (through Janssen) initiated two large Class I recalls of Duragesic for this exact reason. The first was February 17, 2004 at which time Duragesic Control No. 0327192 (75 mcg/hr) was pulled from the market. The cited reason was a potential seal breach on one edge of the patch, which could result in fentanyl leaking from the patch. This recall included about 440,000 patches.
On April 5, 2004, Janssen expanded its recall of Duragesic to include 2.2 million patches (Control Numbers 0327192, 0327193, 0327294, 0327295, and 0330362). Again, the reason cited was the potential for a breach of the seal, which would result in fentanyl leakage. Janssen sent a “Dear Healthcare Professional” letter to inform of the expanded recall.
A leak of fentanyl from a Duragesic patch could cause patients to receive either too much or too little of the drug. If the fentanyl seeps out of the patch before its application to the skin, patients may receive too little medication to adequately treat their pain. In this situation, patients used to a specific does may experience withdrawal effects including sweating, sleeplessness, and abdominal discomfort.
Conversely, fentanyl leaks that occur while the patch is on the skin expose patients to a potentially life-threatening overdose of fentanyl. Duragesic is designed to deliver only a controlled amount of fentanyl into the patient’s skin. Patients wearing a defective patch that leaks fentanyl directly onto the skin will receive too much of the medication. If this occurs, patients could experience minor complications such as sedation, drowsiness, and nausea. Fentanyl overdose may result in more serious complications, including fatal hypoventilation (respiratory depression) or cardiac arrest.
When Jansen placed Duragesic on the market in 1991, reports of toxicity due to fentanyl overdosing were fairly common. In fact, one study in California of 112 deaths associated with fentanyl concluded that the general availability of the drug may be responsible for the high incidence of overdoses.
Furthermore, in a recent Duragesic lawsuit filed against Johnson & Johnson, Janssen, and ALZA, the plaintiffs alleged that “despite knowing of this defect, the defendants (Johnson & Johnson, Janssen, ALZA) took inadequate steps to advise physicians, hospitals, nursing Homes and other health care professionals of the defect and the significant damages to users of the Duragesic patches.”
Heat-Induced Overdose
ALZA and Janssen’s knowledge of the overdosing potential caused by external heat dates back to 1986, when ALZA did lab testing on a nitroglycerin-delivering patch using the same co-polymer membrane used in Duragesic patches. ALZA subsequently did lab testing on Duragesic in 1988-that showed that a five degree Centigrade increase in temperature doubled Duragesic’s release rate. Dr. Curtis Wright, the FDA Medical Review Officer, was quite concerned in 1989 and again in 1990 that ALZA had not responded to his request for more information on the effects of external heat. After Duragesic hit the market in April of 1991, ALZA and Janssen learned of six reports from healthcare providers that external heat appeared to increase blood fentanyl levels in patients in the hospital setting and at home.
However, the first time Janssen or ALZA made an effort to warn of the effects of external heat came in a January 17, 1994 “Dear Doctor” letter with an attached proposed labeling revision. The labeling contained a new heat warning, which was buried at page 10 of the attachment, but no mention was made in the letter itself to alert physicians that external heat applied to the patch was potentially life-threatening.
GOVERNMENT REGULATION
In 2004, the FDA influenced Janssen and ALZA to issue two Class I Recalls of Duragesic, “due to improper sealing of one of their edges,” which could result in a life-threatening overdose of fentanyl. Yet, this was not the first time the FDA encountered problems with the companies’ handling of Duragesic. In fact, prior to the recalls in 2004, the FDA has required Duragesic labeling revisions 13 times.
And, as recently as July 2005, the FDA issued a Public Health Advisory concerning the use of Duragesic Patches in response to reports of deaths in patients using the patch.
Beginning in 1994, the FDA sent ALZA a “warning letter” identifying certain violations and deviations from Good Manufacturing Practices (GMP) regulations under the Food and Drug Act. This prompted the company to issue a letter to all health care professionals warning of Duragesic misuse.
In the late 1990s, the Department of Health and Human Services warned Janssen that its promotional materials to expand the use of Duragesic were in direct violation of the Federal Food, Drug, and Cosmetic Act and contained misrepresentations as to the safety and efficacy of the product. The agency determined that the promotional pieces were “false or misleading because they contain misrepresentations of safety information, broaden Duragesic’s indication, contain unsubstantiated claims, and lack fair balance.”
Following Janssen’s “voluntary” recall of Duragesic in 2004, the FDA issued a “Safety Alert” warning that the recall was “due to a potential leak in the product seal,” which could result in skin exposure to fentanyl. The warning adds that “skin exposure to any leaked medication from a DURAGESIC patch may cause nausea, sedation, drowsiness, or potentially life-threatening complications.” Govt Regulation 6. Janssen also wrote a letter to “Healthcare Professional[s]” informing them of the expanded recall in April 2004.
Furthermore, on September 2, 2004 the FDA issued Janssen another “warning letter.” This letter states that the latest Duragesic promotional pieces make “false or misleading claims about the abuse potential and other risks of the drug, including unsubstantiated effectiveness claims for Duragesic.” The letter states, “By suggesting that Duragesic has a lower potential for abuse compared to other opioid products, the file card could encourage the unsafe use of the drug, potentially resulting in serious or life-threatening hypoventilation.”
The Duragesic product label was again updated in June 2005 to add new safety information in several areas of labeling, and Janssen issued another “Dear Healthcare Professional” letter about these changes. Under a section entitled “Hypoventilation (Respiratory Depression),” the letter warns that “Serious or life-threatening hypoventilation may occur at any time during the use of DURAGESIC® especially during the initial 24-72 hours following initiation of therapy and following increases in dose.” Janssen also warns of a “potential for temperature-dependant increases in fentanyl released from the system resulting in possible overdose and death.” Therefore, the letter instructs all patients to avoid exposing Duragesic to “direct external heat sources, such as heating pads or electric blankets, heat lamps, saunas, hot tubs, and heated water beds, etc., while wearing the system.”
Finally, on July 15, 2005 the FDA issued a “Public Health Advisory” concerning the use of Duragesic Patches in response to reports of deaths in patients using the patch. The FDA stated it is conducting an investigation into the deaths related to fentanyl overdose in patients using Duragesic. According to the FDA, “Some patients and health care providers may not be fully aware of the dangers of this very strong narcotic painkiller. Therefore, FDA is issuing this public health advisory to alert patients and their caregivers and health care professionals by highlighting the following important safety information.”
MEDICAL LITERATURE
Fentanyl Overdose
Since Duragesic hit the marketplace in 1991, studies have shown continued high numbers of overdoses involving transdermal delivery of fentanyl. The most serious side effect is respiratory depression, which can be fatal. One study, published in 1991, examined 112 fentanyl-related deaths in the Eastern United States, mostly in California. Fentanyl deaths appeared to occur rapidly, “probably the result of acute respiratory depression.” While acknowledging the extreme potency of fentanyl, the author suggests that “the incidence of fentanyl-related deaths is probably determined by the general availability of the drug, rather than the relative potency of the analogs.”
In a study published in 2000, the Los Angeles County Department of the Coroner analyzed 25 cases involving fentanyl-related deaths. The author notes that the Los Angeles County Coroner’s Office evaluates nearly one case each month involving fentanyl patch-related death. Another study that same year identified 61 cases of transdermal drug overdoses in a Regional Poison Information System over a five-year period.
Head-Induced Overdose
Heat is expected to increase skin permeability, metabolism and elimination of fentanyl. If drug release from the system is much faster than permeation through the skin, the skin controls the transdermal absorption rate into the patient’s systemic circulation, rather than Duragesic’s special rate control membrane.
Several case reports have described the development of life-threatening overdose caused by a heating pad or rise in body temperature. Frolich et al. reported a narcotic overdose in a patient that was using a warming blanket to relieve pain following surgery. Medical Literature 17, see M.A. Frolich et al., Opioid Overdose in a Patient Using a Fentanyl Patch During Treatment with a Warming Blanket, 93 ANESTH. ANALG. 647-48 (2001) (unable to obtain hard copy). The increase in absorption may account for other heat-related toxicity associated with transdermal fentanyl. G. Newshan, Heat-Related Toxicity with the Fentanyl Transdermal Patch, 16 J. PAIN SYMPTOM MGMT. 277-78 (1998) (unable to obtain hard copy).
One study, in 2003, examined the effect of heat on transdermal fentanyl absorption. The authors concluded that increases in skin temperature may result in increased systemic absorption of fentanyl. Therefore, warming blankets and heating pads should not be either used in conjunction with, or placed over Duragesic patches.
However, as of 2003, the Duragesic label warned that serum fentanyl concentrations may “theoretically” increase by one third in patients with a body temperature of 40 degrees Celsius because of accelerated drug release and increased skin permeability. The current label warns of a “potential for temperature-dependent increases in fentanyl release from the system.”
Mathew A. Passen
http://www.articlesbase.com/personal-injury-articles/duragesic-product-liability-personal-injury-lawsuits-723732.html
Personal Injury Law Firms experienced in negligence, malpractice and other types of personal injury actions have taken note of recent product liability actions involving the drug, Duragesic.
Duragesic® is the trade name for a pain-medication patch containing fentanyl, a potent opioid analgesic. Duragesic is a transdermal system-the medicine, fentanyl, is absorbed through the patient’s skin and into the bloodstream, providing pain relief for up to three days (72 hours) from a single patch application.
Duragesic is prescribed in five dosage strengths: 12, 25, 50, 75 and 100 mcg of fentanyl per hour. The 50, 75, and 100 ug/h doses are only prescribed for patients who are already on and tolerant to opioid therapy, and require continuous opioid administration. Moreover, the Duragesic label warns that 12 mcg/hour as an initiating dose has not been systematically evaluated; therefore, Duragesic should be used only in patients who are opioid-tolerant.
Fentanyl was found to be a good choice for transdermal application because of its physicochemical properties and high analgesic potency. However, Fentanyl is not without its serious adverse effects. Pharmacologically, fentanyl acts on the central nervous system causing analgesia, sedation, severe respiratory depression, muscle rigidity, seizures, coma, and hypotension. Adverse reactions include mood changes, euphoria, dysphoria, drowsiness, constricted pupils, nausea, and vomiting. The most serious side effect of fentanyl overdose is hypoventilation (respiratory depression), which can be fatal.
Development of Duragesic
Currently, only eleven transdermally administered drugs are on the market; seven of which were developed by ALZA. In 1981, ALZA responded to a plea from a White House-created committee of scientists and physicians to develop more potent analgesics with alternative delivery systems for critically ill and dying patients who were suffering from intractable pain. ALZA began work on a project to develop a fentanyl transdermal patch in late 1982.
In early 1983, ALZA representatives met with agents from the DEA to discuss the handling of fentanyl. Among other issues, the DEA expressed concern that the dosage be kept to an absolute minimum, because of the potential for overdose and abuse.
In 1991, ten years after ALZA proposed the development of a transdermal fentanyl patch, Duragesic was made available for sale in the United States. Originally, Duragesic was approved to treat acute, postoperative and moderate-to-severe pain. However, due to the slow onset of drug levels from the transdermal delivery and three day maintenance of drug levels with Duragesic, the system was more suited for treatment of chronic pain conditions, in particular, cancer patients. By 1998, the World Health Organization (WHO) recommended transdermal fentanyl for treatment of cancer pain in stable patients.
Since receiving FDA approval in 1990, ALZA and Janssen aggressively sought the expansion of Duragesic use beyond cancer patients. For example, transdermal fentanyl has been used to treat rheumatologic pain and severe back pain.
The FDA has also approved an expansion of Duragesic to treat pediatric patients.
Janssen’s most recent advertising campaign to expand the use of Duragesic was thwarted by the FDA. In the late 1990s, the company sent a document called Top Ten List to doctors urging physicians to switch their patients to Duragesic patches rather than use more traditional type pain relievers. Among the reasons listed is the phrase “It’s not just for end stage cancer any more!” However, in 2000, the Department of Health and Human Services wrote a letter to Janssen informing the company that its promotional pieces concerning the “Broadening of indication” for Duragesic were misleading and contained misrepresentations. The government agency responded, “The suggestion that Duragesic can be used for any type of pain management promotes Duragesic for a much broader use that is recommended by the PI, and thus, is misleading.”
Currently, Duragesic is the most widely prescribed transdermal medication. From 2002 to 2003, the total number of fentanyl patch prescriptions within the United States rose from 4.5 million to 5.4 million-a twenty percent increase. And the resulting sales figures for Duragesic have been enormous: total annual sales in the United States have reached one and a half billion ($1,500,000,000.00) dollars annually.
And in 2005, Duragesic sales generated two point one billion ($2,100,000,000.00) dollars worldwide.
Duragesic Defects:
Package Leak-Subsequent Recalls
The design/manufacturing defect most applicable to our case is an improper sealing of one edge of the Duragesic patch, resulting in millions of patches being recalled. During 2004, ALZA (through Janssen) initiated two large Class I recalls of Duragesic for this exact reason. The first was February 17, 2004 at which time Duragesic Control No. 0327192 (75 mcg/hr) was pulled from the market. The cited reason was a potential seal breach on one edge of the patch, which could result in fentanyl leaking from the patch. This recall included about 440,000 patches.
On April 5, 2004, Janssen expanded its recall of Duragesic to include 2.2 million patches (Control Numbers 0327192, 0327193, 0327294, 0327295, and 0330362). Again, the reason cited was the potential for a breach of the seal, which would result in fentanyl leakage. Janssen sent a “Dear Healthcare Professional” letter to inform of the expanded recall.
A leak of fentanyl from a Duragesic patch could cause patients to receive either too much or too little of the drug. If the fentanyl seeps out of the patch before its application to the skin, patients may receive too little medication to adequately treat their pain. In this situation, patients used to a specific does may experience withdrawal effects including sweating, sleeplessness, and abdominal discomfort.
Conversely, fentanyl leaks that occur while the patch is on the skin expose patients to a potentially life-threatening overdose of fentanyl. Duragesic is designed to deliver only a controlled amount of fentanyl into the patient’s skin. Patients wearing a defective patch that leaks fentanyl directly onto the skin will receive too much of the medication. If this occurs, patients could experience minor complications such as sedation, drowsiness, and nausea. Fentanyl overdose may result in more serious complications, including fatal hypoventilation (respiratory depression) or cardiac arrest.
When Jansen placed Duragesic on the market in 1991, reports of toxicity due to fentanyl overdosing were fairly common. In fact, one study in California of 112 deaths associated with fentanyl concluded that the general availability of the drug may be responsible for the high incidence of overdoses.
Furthermore, in a recent Duragesic lawsuit filed against Johnson & Johnson, Janssen, and ALZA, the plaintiffs alleged that “despite knowing of this defect, the defendants (Johnson & Johnson, Janssen, ALZA) took inadequate steps to advise physicians, hospitals, nursing Homes and other health care professionals of the defect and the significant damages to users of the Duragesic patches.”
Heat-Induced Overdose
ALZA and Janssen’s knowledge of the overdosing potential caused by external heat dates back to 1986, when ALZA did lab testing on a nitroglycerin-delivering patch using the same co-polymer membrane used in Duragesic patches. ALZA subsequently did lab testing on Duragesic in 1988-that showed that a five degree Centigrade increase in temperature doubled Duragesic’s release rate. Dr. Curtis Wright, the FDA Medical Review Officer, was quite concerned in 1989 and again in 1990 that ALZA had not responded to his request for more information on the effects of external heat. After Duragesic hit the market in April of 1991, ALZA and Janssen learned of six reports from healthcare providers that external heat appeared to increase blood fentanyl levels in patients in the hospital setting and at home.
However, the first time Janssen or ALZA made an effort to warn of the effects of external heat came in a January 17, 1994 “Dear Doctor” letter with an attached proposed labeling revision. The labeling contained a new heat warning, which was buried at page 10 of the attachment, but no mention was made in the letter itself to alert physicians that external heat applied to the patch was potentially life-threatening.
GOVERNMENT REGULATION
In 2004, the FDA influenced Janssen and ALZA to issue two Class I Recalls of Duragesic, “due to improper sealing of one of their edges,” which could result in a life-threatening overdose of fentanyl. Yet, this was not the first time the FDA encountered problems with the companies’ handling of Duragesic. In fact, prior to the recalls in 2004, the FDA has required Duragesic labeling revisions 13 times.
And, as recently as July 2005, the FDA issued a Public Health Advisory concerning the use of Duragesic Patches in response to reports of deaths in patients using the patch.
Beginning in 1994, the FDA sent ALZA a “warning letter” identifying certain violations and deviations from Good Manufacturing Practices (GMP) regulations under the Food and Drug Act. This prompted the company to issue a letter to all health care professionals warning of Duragesic misuse.
In the late 1990s, the Department of Health and Human Services warned Janssen that its promotional materials to expand the use of Duragesic were in direct violation of the Federal Food, Drug, and Cosmetic Act and contained misrepresentations as to the safety and efficacy of the product. The agency determined that the promotional pieces were “false or misleading because they contain misrepresentations of safety information, broaden Duragesic’s indication, contain unsubstantiated claims, and lack fair balance.”
Following Janssen’s “voluntary” recall of Duragesic in 2004, the FDA issued a “Safety Alert” warning that the recall was “due to a potential leak in the product seal,” which could result in skin exposure to fentanyl. The warning adds that “skin exposure to any leaked medication from a DURAGESIC patch may cause nausea, sedation, drowsiness, or potentially life-threatening complications.” Govt Regulation 6. Janssen also wrote a letter to “Healthcare Professional[s]” informing them of the expanded recall in April 2004.
Furthermore, on September 2, 2004 the FDA issued Janssen another “warning letter.” This letter states that the latest Duragesic promotional pieces make “false or misleading claims about the abuse potential and other risks of the drug, including unsubstantiated effectiveness claims for Duragesic.” The letter states, “By suggesting that Duragesic has a lower potential for abuse compared to other opioid products, the file card could encourage the unsafe use of the drug, potentially resulting in serious or life-threatening hypoventilation.”
The Duragesic product label was again updated in June 2005 to add new safety information in several areas of labeling, and Janssen issued another “Dear Healthcare Professional” letter about these changes. Under a section entitled “Hypoventilation (Respiratory Depression),” the letter warns that “Serious or life-threatening hypoventilation may occur at any time during the use of DURAGESIC® especially during the initial 24-72 hours following initiation of therapy and following increases in dose.” Janssen also warns of a “potential for temperature-dependant increases in fentanyl released from the system resulting in possible overdose and death.” Therefore, the letter instructs all patients to avoid exposing Duragesic to “direct external heat sources, such as heating pads or electric blankets, heat lamps, saunas, hot tubs, and heated water beds, etc., while wearing the system.”
Finally, on July 15, 2005 the FDA issued a “Public Health Advisory” concerning the use of Duragesic Patches in response to reports of deaths in patients using the patch. The FDA stated it is conducting an investigation into the deaths related to fentanyl overdose in patients using Duragesic. According to the FDA, “Some patients and health care providers may not be fully aware of the dangers of this very strong narcotic painkiller. Therefore, FDA is issuing this public health advisory to alert patients and their caregivers and health care professionals by highlighting the following important safety information.”
MEDICAL LITERATURE
Fentanyl Overdose
Since Duragesic hit the marketplace in 1991, studies have shown continued high numbers of overdoses involving transdermal delivery of fentanyl. The most serious side effect is respiratory depression, which can be fatal. One study, published in 1991, examined 112 fentanyl-related deaths in the Eastern United States, mostly in California. Fentanyl deaths appeared to occur rapidly, “probably the result of acute respiratory depression.” While acknowledging the extreme potency of fentanyl, the author suggests that “the incidence of fentanyl-related deaths is probably determined by the general availability of the drug, rather than the relative potency of the analogs.”
In a study published in 2000, the Los Angeles County Department of the Coroner analyzed 25 cases involving fentanyl-related deaths. The author notes that the Los Angeles County Coroner’s Office evaluates nearly one case each month involving fentanyl patch-related death. Another study that same year identified 61 cases of transdermal drug overdoses in a Regional Poison Information System over a five-year period.
Head-Induced Overdose
Heat is expected to increase skin permeability, metabolism and elimination of fentanyl. If drug release from the system is much faster than permeation through the skin, the skin controls the transdermal absorption rate into the patient’s systemic circulation, rather than Duragesic’s special rate control membrane.
Several case reports have described the development of life-threatening overdose caused by a heating pad or rise in body temperature. Frolich et al. reported a narcotic overdose in a patient that was using a warming blanket to relieve pain following surgery. Medical Literature 17, see M.A. Frolich et al., Opioid Overdose in a Patient Using a Fentanyl Patch During Treatment with a Warming Blanket, 93 ANESTH. ANALG. 647-48 (2001) (unable to obtain hard copy). The increase in absorption may account for other heat-related toxicity associated with transdermal fentanyl. G. Newshan, Heat-Related Toxicity with the Fentanyl Transdermal Patch, 16 J. PAIN SYMPTOM MGMT. 277-78 (1998) (unable to obtain hard copy).
One study, in 2003, examined the effect of heat on transdermal fentanyl absorption. The authors concluded that increases in skin temperature may result in increased systemic absorption of fentanyl. Therefore, warming blankets and heating pads should not be either used in conjunction with, or placed over Duragesic patches.
However, as of 2003, the Duragesic label warned that serum fentanyl concentrations may “theoretically” increase by one third in patients with a body temperature of 40 degrees Celsius because of accelerated drug release and increased skin permeability. The current label warns of a “potential for temperature-dependent increases in fentanyl release from the system.”
Mathew A. Passen
http://www.articlesbase.com/personal-injury-articles/duragesic-product-liability-personal-injury-lawsuits-723732.html
For many people the patio area provides a very valuable area to enjoy a wide range of social and outdoor activities for relaxing and entertaining with family and friends. Oversized patio layouts and poorly executed construction methods are not only an inefficient use of space but are also unnecessarily expensive and are also surprisingly commonplace. Sprawling patio layouts share more in common the characteristics of the shopping mall car park and lack any sense of being an integral part of the garden space. But with some consideration of the user requirements and site characteristics and careful execution it is very possible to create a pleasing perfect patio which is not only viusually appealing, but also integrated and practical.
Scope
A good starting point will be to undertake a site assessment and analysis of the client needs and user requirements. The adage ‘don’t fire a canon to kill a fly’, comes to mind, therefore from the outset it is important to determine the scope, i.e., how will the area(s) be used, by whom, how many users and when do these needs arise. Scope can also influence patio layout/profile and indeed levels, and these aspects are important factors to be considered in developing a creative but distinctive patio layout.
Position
Some of the previous questions might be obvious, but how many times have we seen patios which are too small or worse are poorly positioned for the event? Too sunny or more likely too shaded and cold when being used? Put simply if the main activity and time of day is around ‘lunch events’ then it would be obvious that the patio position should reflect this need. It is important to note site characteristics, all level might be fine for many people but some might be challenged by variable levels. The latter can also be exploited in the design and layout. Site orientation including the direction of sun travel should be noted as well as the positions of the sunny but also the shaded areas and the relevant times. Again this will be important for planning the various patio areas for breakfast, lunch and evening/dinner activities. Frequently space availability (or lack of) and site orientation do frequently impinge on patio positioning options. Typically patios are used more in evenings and are therefore positioned away from the house so as to catch the evening sun. In order cases, some very fortunate users may have separate patios and thus optimum positioning options for sun and/or shade.
Size
An area to sit, read and eat will have different space needs. Small sites do limit options, access routes can also influence size. Too small and the area will appear cramp, unappealing and probably unusable. Too large and perhaps ‘car park look’ comes to mind. Getting the balance right will be influenced by a number of factors scope, space availability etc. As a general guide, we would recommend that the minimum airspace/footprint should be 3.0 metre/10 feet, but with space availability permitting a better layout would be in the range 4.5m-5.0m/15-16 feet. This area allows for adults to sit comfortably at tables or later stretch the legs without fear of running out of space. In smaller sites, which may necessitate the use of compact but round tables, typically minimum diameters would be 3.0m/10feet, but these are small spaces for 4-6 adults.
Therefore for groups comprising 4-6 adults, the practical size requirements for the main patio area would be approx 4.5m x 5.0m or 15ft x 16ft. Clearly reading areas or informal /alfresco areas will require much less space. Access routes should be a minimum of 1.2m-1.5m /4-5 feet wide. There is little point building pedestrian routes/pathways 3.0m/10feet wide? Better to reduce the paved space and space gained utilise for additional planting/lawn/features?
Transition
One frequently (very popular with designers/architects) comes across the expression ‘seamless transition’. What does this expression mean? Essentially this refers to the physical extension of the interior area to the exterior space, in which one leads from the former to the latter. In otherwords the garden or ‘outdoor room’ appears as an integral part of the house. To exit the interior and enter the exterior space ideally on same level, continuity of colour and textures, no steps and an open aspect or view to the garden area. The traditional Frenchstyle patio doors opening out to a patio area with panoramic garden views comes to mind! Incorporating planted beds within the patio areas and also against the house walls not only contributes to achieving a seamless transition but also a much more attractive patio area that is more integrated within garden but probably a more cost effective utilisation of available space. What should be avoided at all costs, is where the patio area is simply a buffer zone stretching the width of the site and a simple division between House and garden.
Construction
There is an increasing but vast range of patio materials from which to choose. The unique characteristics and appeal of natural paving stone is very popular, with sandstone, granite, and limestone being the most popular. Colour, size and orientation should also be carefully considered within the overall preferred garden style. For example, warm earthy sandstone tones might appeal or be more compatible with traditional Victorian/Mixed Border style Herbaceous gardens, but the light or neutral tones of granite paving might be stunning in more contemporary or minimalist gardens. The paving patterns can also influence the overall look, small complex patterns might be ideal for ‘townhouse gardens’ but appear fussy in larger sites. Large rectangular slabs can be laid to emphasise the width or turned around to stretch the length. The slab size must also conform to design style, a traditional layout for a larger area might involve a random joint incorporating 4 or more sizes of paving slab. A contemporary layout might be one size laid in a staggered or ‘soldier course’.
Texture
Where possible try and introduce texture, ideally in various forms of the primary material. For example, if you are planning on constructing a patio with sandstone, do consider using sandstone risers for steps but also sandstone setts for lawn edging and sandstone chippings for borders and trims. Not only will this provide interesting textural contrasts but a more co-ordinated effect. Whereas some might prefer the visual contrast of mixing apples with oranges, I would much prefer a more coherent appearance of one material and use layout to reflect functionality but also visual contrast.
Obstacles
In many cases there is no scope to reposition/remove unsightly utilities such as rainwater downpipes, gulleys, manholes, inspection chambers etc. But the presence of many of these unsightly necessities can be disguised or concealed by design. Recess frames are excellent to conceal covers but provide easy access to waste water, and integrated planted beds can be positioned to conceal pipework etc.
Finally the perfect patio is an integrated space that requires careful and creative planning but must also be well constructed if maximum enjoyment is to be realised.
Owen Chubb
http://www.articlesbase.com/landscaping-articles/planning-perfect-patios-677738.html
