Healing of NSAID-Associated Gastric Ulcers in Patients Continuing NSAIDs

Results

Patients and Disposition

The study was conducted from February 2001 to April 2003. In all, 440 patients were randomized at 75 study sites as follows: Bulgaria, 89 patients from nine sites; Indonesia, 51 patients from two sites; Romania, 45 patients from seven sites; the Ukraine, eight patients from three sites, and the US, 247 from 54 sites. Patient disposition in the study is shown in Figure 1. Of the 440 patients randomized, 30 were not included in the primary efficacy analysis because of no study drug use, the lack of a documented baseline GU, or a GCP violation at a single site identified after the site was audited. Of 410 patients included in the primary efficacy analyses, 88 (21%) were in Bulgaria, 51 (12%) were in Indonesia, 45 (11%) were in Romania, 8 (2%) were in the Ukraine and 218 (53%) were in the United States.

Figure 1.  (click image to zoom)

Patient disposition. GCP, good clinical practice; NSAID, non-steroidal anti-inflammatory drug; GU, gastric ulcer. * Some patients had more than one type of protocol deviation.      

Baseline demographics and characteristics for patients included in the efficacy analysis are summarized in Table 1 . The study population included more women than men, and most patients were white. The proportion of patients with positive H. pylori status, as determined by histology, was similar among the three groups and included 13.8% (30 of 218) of patients in the United States and 40.1% (77 of 192) of patients in the non-US countries. The most common chronic condition for which patients were taking NSAIDs was osteoarthritis (51% of the patients). Across the three treatment groups, most patients (88%) used non-selective NSAIDs; the most commonly used non-selective NSAIDs were aspirin, diclofenac, ibuprofen, and naproxen. Of these patients, approximately 14% (51/362) used only low-dose aspirin (80 to 325 mg per day). Baseline OGD findings showed that the mean maximum GU size was approximately 8.2 mm, and 129 patients (31%) had GUs > /=10 mm ( Table 2 ). Also, four patients (< 1%) had baseline GUs of maximum size < 5 mm. The GU healing results for these four patients were included in the mITT analysis for completeness. Excluding the healing results for these patients would not have changed the results of the analysis. Only 34 patients included in the efficacy population had concurrent baseline DUs ( Table 2 ).

Overall, for patients in the efficacy analysis, compliance with study medication was 97% (396 of 410 patients) and was similar among the three treatment groups. NSAID compliance was also generally similar among the treatment groups with an overall compliance rate of 88% (361 of 410) of the patients.Efficacy

Table 3 reports the GU healing rates at 4 and 8 weeks. Although the observed GU healing rates at week 8 were numerically higher with the esomeprazole treatments than with ranitidine, these results were not statistically significant. In contrast, at week 4, the observed GU healing rates were significantly higher for patients treated with esomeprazole 40 and 20 mg than for patients treated with ranitidine ( Table 3 ). The observed GU healing rates in the esomeprazole groups compared with the ranitidine group are shown for subgroups evaluated according to age group (Figure 2), baseline H. pylori status determined by histology (Figure 3), and non-selective vs. selective baseline NSAID used (Figure 4).

Figure 2.  (click image to zoom)

Gastric ulcer (GU) healing rates by age. E40, esomeprazole 40 mg once daily; E20, esomeprazole 20 mg once daily; R150, ranitidine 150 mg twice daily (mITT population).      

Figure 3.  (click image to zoom)

Gastric ulcer (GU) healing rates by baseline Helicobacter pylori status determined by histology. E40, esomeprazole 40 mg once daily; E20, esomeprazole 20 mg once daily; R150, ranitidine 150 mg twice daily. †Baseline H. pylori status was missing for one patient in the esomeprazole 40-mg group (mITT population).      

Figure 4.  (click image to zoom)

Gastric ulcer (GU) healing rates by baseline non-steroidal anti-inflammatory drug (NSAID) type. The non-selective NSAID group includes patients who were taking a cyclooxygenase (COX) 2-selective NSAID if they were also taking a non-selective NSAID (including low-dose aspirin). E40, esomeprazole 40 mg once daily; E20, esomeprazole 20 mg once daily; R150, ranitidine 150 mg twice daily. †One patient in the ranitidine 150-mg group was not taking an NSAID before or during the study (mITT population).      

The observed GU healing rates were reanalysed including the 15 patients (five in each treatment group) that were excluded from the mITT population because of GCP violations. The results of this reanalysis provided healing rates that were almost identical to those seen in Table 3 . Therefore, removing these patients from the mITT analysis did not affect the findings of this study.

As a secondary analysis of GU healing, the estimated GU healing rates through the final visit (based on Kaplan-Meier estimation) were 92.1% (95% CI, 87.4%-96.8%), 94.6% (95% CI, 90.7%-98.5%) and 89.2% (95% CI, 83.7%-94.7%) in the esomeprazole 40-mg, esomeprazole 20-mg and ranitidine groups, respectively. Estimated GU healing rates through week 4 (based on Kaplan-Meier estimation) were 71.6% (95% CI, 63.9%-79.4%), 75.2% (95%CI, 67.8%-82.5%), and 58.4% (95% CI, 49.9%-66.8%) for the esomeprazole 40-mg, esomeprazole 20-mg, and ranitidine groups, respectively. Comparisons of the time-to-event curves showed that the time to first healing of GUs was significantly different for esomeprazole 40 mg and esomeprazole 20 mg compared with ranitidine, (P = 0.047 and P = 0.002, respectively).

For the 34 patients in the efficacy analysis who had concurrent DUs at baseline, the DU healing rates at week 8 were 90% (nine of 10 patients) with esomeprazole 40 mg, 68.8% (11 of 16 patients) with esomeprazole 20 mg, and 87.5% (seven of eight patients) with ranitidine.Safety

The safety population included 432 patients: 140 patients in the esomeprazole 40-mg group, 145 patients in the esomeprazole 20-mg group, and 147 patients in the ranitidine 150-mg group. The overall percentage of patients with AEs in this study was 56% (79/140) with esomeprazole 40 mg, 58% (84/145) with esomeprazole 20 mg and 58% (85/147) with ranitidine 150 mg. The number of patients with AEs considered by the site investigator to be related to study drug was also similar among the three treatment groups: 12 (9%) for esomeprazole 40 mg, 13 (9%) for esomeprazole 20 mg and 10 (7%) for ranitidine 150 mg. The most commonly reported AEs for esomeprazole 40 mg, esomeprazole 20 mg and ranitidine 150 mg were gastrointestinal and included gastritis [22 (16%), 25 (17%) and 25 (17%) patients, respectively], flatulence [18 (13%), 27 (19%) and 20 (14%), patients respectively], new onset or worsening of existing dyspepsia [14 (10%), 19 (13%) and 18 (12%) patients, respectively], and new onset or worsening of existing nausea [17 (12%), 11 (8%) and 17 (12%) patients, respectively].

Fourteen of the 440 randomized patients had 16 serious AEs (four patients in the esomeprazole 40-mg group, six in the esomeprazole 20-mg group and four in the ranitidine group), but none was the same and none was considered related to treatment. There was one death that occurred due to an unknown cause on the third day of treatment with esomeprazole 20 mg; the investigator did not consider the death to be related to study medication. Of 440 patients, 17 (3.9%) discontinued the study due to AEs; the number in each treatment group was similar. There were no clinically relevant trends in the results of laboratory tests, physical examinations or vital signs.  Printer- Friendly Email This

Aliment Pharmacol Ther.  2007;26(8):1101-1111.  ©2007 Blackwell Publishing
This is a part of article Healing of NSAID-Associated Gastric Ulcers in Patients Continuing NSAIDs Taken from “Nexium Generic Esomeprazole” Information Blog

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Healing from within - Healing Allergies

Grass Allergies

"We are responsible for everything in our lives, including how the chemistry of our body or does not work." Wayne Dyer's words struck me like lightning, as I listened to his book registered, you can see when you believe.

Grass Allergies

Over the years I have suffered tremendously with bouts of allergies and asthma, it was only then that could eliminate a confirmation of my allergy problems. He had asthma under control, because it was in the middleWest, where I was born and raised. This step removed from contact with livestock and grain of hair from dust and other pollens in the area, I had extreme allergic reactions.

Grass Allergies

I have often spoken to anyone who will listen how the mind heals the body and allows the body to be sick. This knowledge has been in my mind, reading and research. As I talked about my "beliefs / knowledge ', my struggle with allergies hung heavy in my head. In all my reading, nothing clickedSolution at that time in September 1989. I was 47 years. As I learned studying transactional analysis, Dr. Dyer, was also the premise. "We are responsible for everything in our lives" "OK, Wayne," I said, "I agree. And now, how can I be responsible for the chemicals in my body when my immune system is damaged? My Chemical of the immune system, "I remembered." I am responsible for these chemicals are doing their job. What should I do or not do, is thatresponsible for chemicals that are not doing their job, "I asked sincerely.

Grass Allergies

A few days after I started, really, a detective. I revisited as a child in the manger. With great pride and joy, my father, the story was able to silence a screaming baby said. By contrast, big and muscular as the work of farmers, stroked his back with three or four hard drives, pounding, "Hey," he announced proudly. "It felt like screaming Order," he said,"Because you're still crying stopped."

My father was physically abused as a child, and brought the legacy of his upbringing. He did not consider the fast "blow on the back like little unfair, we do not necessarily look like everyone else, when our education abused, some people would not be illegal. In the days of my father's childhood, and my, was this type of behavior with a child considered a strict discipline of a child apparentlyrequire corrective action. But surely, I started my abuse when I was a child in the cradle. When I returned to my childhood, went out without new memories. It 'been frustrating. I had not found new clues. "Chemicals. I am responsible for my chemicals. How can I be responsible for chemistry?" The answer is difficult, but I was determined. "Chemistry? What mechanism triggers the release of chemicals that?"

"You Gads! The brain. The brain sends messages to allSystems of the body. Part of the brain that controls the chemicals often called the "old brain" is: It 'the "fight or flight mechanism, which transmits immediately (no need for a conscious control) chemicals so that the system can" fight or flight. "
"So, what has to do with allergies?" I asked, "allergies, allergies, allergy attack, allergy attack -. I get somewhere I attacked from pollen - So what is the relationship between allergy and the attacks?Being an abused child? . The attack of allergy - allergy attack "Days and weeks passed, I'm hot idea again." Allergy attack, abuse, allergy attack, child maltreatment: there is a link. I know there is a link. What is the connection? "

When the human system is attacked by something, your immune system immediately sends chemicals to fight the invasion. "My system has been damaged as a child who is afraid," I complained. "What can I do now, I am responsible for chemicals in my body?" Iremember. "How do I create a system of work that has been damaged? If my brain controls the chemicals and my thoughts to check my brain, I can control by chemicals. Yet
How do I register? The link where is the connection? "

I started thinking about incidents of physical violence. I saw my father figure who was threatening to me - with a red face, raised his hand, cursing and screaming. Hit a shot, turn their heads held high. ATTACK! My father put me verbally andphysically. And 'the link! An allergy attack is verbal / physical - has been in my mind as the same thing.

To understand the physiological and psychological concept that must be the reality that the physical body and psyche are closely related to accept. It is not separate from others. To understand the genesis of allergy attacks with verbal and physical abuse in my psyche, we must recognize my experience as a child in the cradle. The five senses: hearing, sight, smell,Taste and touch are just a way to understand a child of their world and communication. Three of the five senses by technology so on, like my father to feed the crying baby, the father of the child to listen to the songs and at first instance by the fact that someone comes to comfort. The father said: "Always be [quiet]" with a loud voice, while the impact of a hard, fast tape (touch) The shock of the voice (hearing) and very difficult step (touch) is.responded with a restriction in wines (breathing) - breathing and smell are synonymous.

The shock of the voice and the physical impact of the explosion hit the child. If the child wakes up in the autonomic nervous system, breathing, the child breathes the smell of livestock and grain of the hair feeling that permeates the clothes of his father. In many cases, the mother responds to the crying child, but the child can not be distinguished in a position to react if the mother or father. SoThe child quickly realizes his father's footsteps, he must escape, but no luck. Your fight or flight mechanism is triggered, and how surge protection chemicals through his body, the extra oxygen your heart rate and increased respiration. While looking for oxygen, they cry at the same time, narrows, the two come into conflict. This leads to a swelling of the airways, which is manifested as asthma - bronchial passage limited.

However, the peopledeveloped immunity to the things that are for the environment. With few exceptions, the human immune system as a system that works chemically enough to protect the body. In an experiment, like me, the child's psyche is affected by three of the five senses. This suggests a strong influence. As in my case, my hair smells of cattle and grain are associated with fear and unable to breathe. And my asthma / allergies, a physical reaction to fear,And do not feel in combination with strong odors. I remember the experience asthma attacks when I was expecting a stressful situation with my father or if he attacked me verbally.

Listening to my past feelings, watching my reaction, I accepted the fact that my immune system was damaged. The doctors also told me that my immune system was ineffective, but it took him to a fact of genetics, luck, something I had to accept. Accepted obediently reports my fate;Finally, the doctors know the human body and are healers, who know better. The next step, I began to observe my physical reactions when I started with allergic reactions. "What I say to myself, what I said to my brain?

My brain, chemicals, power to send my immune system. Why do not my chemical were there when I need them? "I watched and observed. One day I noticed a feeling of having very thin, so thin that I hardly notice his presence. The body felt so weak anddistance. I just recognized. Listening to "What is the origin of this feeling weak Listen carefully, observe, listen, yes, yes, this is:?. Shutdown, power off, do not move, do not think, feel, do not answer, you can not do anything, stop "." My heart was so quiet. It 'was very low. I took my wrist and had to be a difficult time to find. "How is it connected to my chemistry? How does the immune system chemicals that are not linked post? "I continued to watch and listen to my bodyResponse to odors.

Ye Gads! The thought crossed my mind. My fight or flight instruction has not been activated. Instead, I told my system to stop the fight-flight. WHAT? The fight or flight mechanism is of fundamental importance for the survival of the system. I told myself down. My thoughts then returned to the accident, when my father tried to chase me with the horse. I realized that this was the time I finished the combat system in flight for more than it has ever been arrested. "Do not move,not moving, not thinking, not feeling, not responding, you can not do anything, stop. "My heart stopped when the horse is frightened at a bus stop in front of me, his warm breath blowing in my face. From that moment, I do not remember feeling pain, when my father hit me. I was completely closed.

As the days passed, I continued to listen and watch my breathing. As I look, I realized it was passive, like a sneeze is a sneeze allergies. The thought was: "There is nothingYou can make the attacks pollen and you will see a lot of pain and feel sick and can barely function, but it only lasts a short time. Designed to withstand the pain - go -. It will pass. "As a child I could not flee or fight to survive emotionally verbal and physical attacks, I was passive and said:" The best approach is to do nothing. "This process of unconscious thought blocked the transmission of chemicals to protect the survival of my system of all evil. If chemicals have beensent, I could feel the pain before and after the terrible attack. I did not know what this pain cold, and then asked me to close.

Eureka, the last link! I had prepared my brain to be sent to the chemical base for fight or flight to protect the system. No wonder that the doctor gave me shots of adrenaline, it did not work as my natural chemicals. Adrenaline is the chemical most important sends the immune system to fight or flee. The next step was to monitor the messages that I have givenme when I sneeze. The trend has been steady, I was very passive, I could feel my senses off. All my muscles relaxed, no outward emotion. Nothing! I listened, watched and listened. After many years said to turn off your brain, learn how to fight was not easy. It 'was closed in a natural way. However, I felt, and every time I was feeling down, I have a way of taking revenge. I asked the race of chemicals in the blood throughout the body. Ipractice, practice. Gradually, I noticed a difference in the severity and duration of allergy attacks. Spring is here in 1990 (a difficult season, especially because I was allergic to pollens of trees and grass): no sneezing, watery eyes, cough it. Eureka! I did. I did it! This was and remains a physical and psychological victory with broad implications. I wanted to shout from the rooftops. I wanted to tell everyone - the metaphysical works of healing!

With each pollenI always anti-allergy season. For three years, it was necessary that I consciously made the effort, "recalls" to defend myself. I do not have total concentration. Also, if I have allergic reactions to products, I do not consider myself responsible for the generation of the immune system to defend itself. This is because the immune system protects the system against the elements, though I be the elimination of all allergiesReactions, I could set unrealistic demands and unrealistic form a psychological breakdown.

A word of warning to all, I think, have described this process as simple and easy: it was very difficult and requires concentration, commitment and dedication. During the initial phase of the recovery, not distraction led to a reduction in the concentration and reduce its effectiveness. It 'been daunting, at times, and I heard him say: "See you can not reallyChange the damage, are not as good as you think you are. "This was an example for all to deny things and sad that my father told me. It struck me, I was so words of others to control what I could or not able to accomplish today, and I was still under investigation .

Healing from within - Healing Allergies

Grass Allergies

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