Continuation With Statin Therapy and the Risk of Primary Cancer: A Population-Based Study CM

Abstract

Introduction. Studies have suggested that statins may inhibit tumor cell growth and possibly revent carcinogenesis. The objective of this study was to investigate the association between persistent statin use and the risk of primary cancer in adults.
Methods. This retrospective study was conducted by using the computerized data sets of a large health maintenance organization (HMO) in Israel. The study population was 202,648 enrollees aged 21 or older who purchased at least 1 pack of statin medication from 1998 to 2006. The follow-up period was from the date of first statin dispensation (index date) to the date of first cancer diagnosis, death, leaving the HMO, or September 1, 2007, whichever occurred first. Persistence was measured by calculating the mean proportion of follow-up days covered (PDC) with statins by dividing the quantity of statin dispensed by the total follow-up time.
Results. During the study period, 8,662 incident cancers were reported. In a multivariable model, the highest cancer risk was calculated among nonpersistent statin users. A strong negative association between persistence with statin therapy and cancer risk was calculated for hematopoietic malignancies, where atients covered with statins in 86% or more of the follow-up time had a 31% (95% confidence interval, 0.55-0.88) lower risk than patients in the lowest ersistence level (≤12%).
Conclusion. Our study demonstrated that persistent use of statins is associated with a lower overall cancer risk and particularly the risk of incident hematopoietic malignancies. In light of widespread statin consumption and increases in cancer incidence, the association between statins and cancer incidence may be relevant for cancer prevention.

Introduction

Cancer is the second most common cause of death in the United States, exceeded only by heart diseases.^[1] Annual deaths from cancer are projected to continue rising and are estimated to be 17 million worldwide in 2030.^[2] Cancer is the leading cause of death in Israel (approximately 25% of all-cause mortality) and is a major cause of morbidity in the population.^[3]

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) effectively reduce cholesterol levels and decrease the incidence of cardiovascular and cerebrovascular events.^[4] Large randomized controlled trials (RCTs) that examined the safety and effectiveness of statins in reventing cardiovascular diseases indicated that statins were not associated with increased cancer risk.^[5] However, these RCTs were limited to short-term follow-up, the duration of which was insufficient to adequately evaluate carcinogenesis risk.^[6]

After statins were introduced into clinical practice, they were shown to have effects other than lipid lowering, referred to as pleiotropic effects.^[7] More than 15 years ago, cholesterol decrement was first shown to inhibit tumor cell growth, metastasis of tumor cells, and induction of apoptosis.^[7] Inhibition of HMG-CoA reductase by statin in effect prevents the synthesis of mevalonic acid, a precursor of nonsteroidal isoprenoids, lipid attachment molecules for small G roteins, such as Ras, Rho, and Rac. Thus, statins may inhibit the synthesis of isoprenoids and thereby suppress the activation of small G proteins.^[7]

Statins have been associated with a significantly lower risk of breast,^[8] colorectal,^[9] and lymph cancers^[10-12] in several observational studies.^[10,13] Most previous observational studies have been limited by a small number of cases, short follow-up period, unverified self-reports on use and consistency of statins therapy, and no assessment of statins efficacy.

Our previous study^[14] demonstrated a strong negative association between ersistent use of statins and all-cause mortality reduction among patients with and without a history of coronary heart disease (CHD). The observed reduced mortality in statin users cannot be explained by lower incidence of CHD death alone. The objective of this study was to investigate the association between ersistent use of statins and the risk of overall and site-specific cancer in adults, to assess dose-response relationship, and to examine the effects of varying types of statins. We focused on breast and genitourinary, colorectal, lung and bronchus, prostate, leukemia, hematopoietic, and lymphoma malignancies.

METHODS

We conducted this study among members of Maccabi Healthcare Services (MHS), established in 1941. MHS has become Israel’s second-largest health maintenance organization, with a membership of 2 million countrywide. All data for this analysis were obtained from MHS automated databases.

The cohort of statin users has been described previously.^[14,15] Briefly, the study was conducted with a follow-up spanning the period between the date of first dispensed statin to the date of cancer diagnosis, death, leaving MHS, or September 1, 2007, whichever occurred first. New users of statins were identified among all MHS enrollees aged 21 or older on January 1, 1998, who had at least 1 dispensed prescription of statin medications from January 1, 1998, to September 1, 2006; the date of first dispensation was classified as the index date. We included only patients who had no record of purchasing statin medication before the index date to allow for evaluation of new users. A total of 227,131 new users of statin medications were eligible for analysis. We excluded all patients who were diagnosed with cancer before the index date (n = 12,499). To avoid incidence-prevalence bias, we excluded cases diagnosed with cancer within 1 year from index date, and we excluded all patients with a minimal exposure period of statins under 1 year, the period required for statin medication to have any effect on the development of cancer (n = 11,984). After applying the inclusion and exclusion criteria, 202,648 (89%) patients were eligible for analysis.

Data on cancer occurrence during the study follow-up period were obtained from the Israel National Cancer Register (ICR). Established in 1960, the ICR collects information on diagnosed cancer cases from all medical institutions in the country with a completeness of above 93.5% for solid tumors and approximately 90% for nonsolid tumors.^[3] We classified all cancer cases according to the 3rd edition of the International Classification of Diseases for Oncology (ICD-O). All cases are based on histological reports, hospital discharge forms, oncology reports, and death certificates. Approximately 92% of registered cases had a valid histology or cytology report. The study population and the ICR were cross-linked by the members’ unique identifying number, given to all newborns or immigrants to Israel; name; sex; and date of birth.

Following previous categorization of statin therapy,^[16] we categorized initial statin therapy into 3 efficacy levels that were created on the basis of expected amounts of low-density lipoprotein cholesterol (LDL-C) reduction from baseline: low efficacy (daily dose of simvastatin, 10 mg or less; pravastatin, 10 mg; fluvastatin, 40 mg or less; lovastatin, 20 mg or less; or cerivastatin, 0.2 mg), moderate efficacy (daily dose of simvastatin, 20 mg; pravastatin, 20 mg or 40 mg; fluvastatin, 80 mg; lovastatin, 40 mg; atorvastatin, 10 mg; rosuvastatin, 10 mg or less; or cerivastatin, 0.3 or 0.4 mg), or high efficacy (daily dose of simvastatin, 40 mg or 80 mg; pravastatin, 80 mg; lovastatin, 80 mg; atorvastatin, 20 mg or more; rosuvastatin, 20 mg or more; or cerivastatin, 0.8 mg).

Continuation with statin therapy was individually assessed by calculating the mean proportion of follow-up days covered (PDC) with statins by dividing the quantity of statin packs dispensed by the total follow-up days. PDC was categorized into quintiles (≤12%, 13%–39%, 40%–66, 67%–85%, and ≥86%).

Demographic variables at index date included baseline values of age, sex, marital status, place of residency, years of stay in Israel (for new immigrants) and religiosity (categorized into ultra-orthodox Jewish, other Jewish, and non-Jewish). These categories were determined on the basis of self-reported data obtained by MHS for marketing purposes. Socioeconomic level was categorized into quartiles and determined according to the poverty index of the member’s census enumeration area (small areas defined by the Israeli Bureau of Statistics for the 1995 national census data collection). The poverty index, ranging from 0 (lowest) to 20 (highest), is based on several parameters including household income, educational qualifications, crowding, material conditions, and car ownership.^[17] History of other comorbid conditions at index date, such as diabetes mellitus, cardiovascular disease, hypertension, or obesity, was identified on the basis of outpatient diagnoses. Information on health service use, such as data on hospitalizations in general hospitals or visits to outpatient clinics during the year before the index date, was collected from ersonal medical files.

Chi-square test for categorical variables and Kruskal-Wallis test for continuous variables were performed to determine significant differences in baseline characteristics among quintiles of PDC. To address the effect of statin type, we conducted sensitivity analyses of simvastatin users (n = 159,197). Cox’s proportional hazards^[18] model with years of follow-up as the time scale was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) and to identify variables significantly associated with cancer incidence. The full multivariable model included the following baseline values: age at baseline (in 1-year intervals), sex, marital status, socioeconomic level by quartile, resence of chronic comorbidity, use of health services, and efficacy of the initial statins therapy. To estimate the effects of smoking status we performed subanalysis for participants with smoking status in the models. Assumptions of roportional hazards were performed, and the ratio of hazards was the same across time. Data were analyzed with SPSS version 15 (SPSS Inc, Chicago, Illinois). The study was approved by the Assuta Health Systems Institutional Review Board.

RESULTS

During the follow-up period (952,202 person years [PY], a mean of 4.70 PY per atient), 9,256 patients (4.6%) died and 2,787 (1.4%) left MHS. The mean age of the total population was 57.3 years (Table 1 ). In general, patients in the highest PDC quintile were more likely to be older, men, or new immigrants, to belong to a higher socioeconomic level, and to have chronic diseases. Of the initial statin medications purchased by the 202,648 study participants, 159,197 (78.6%) were simvastatin.

A total of 8,662 incident cancer cases were reported during the follow-up eriod ( Table 2 ). The incidence density rate of overall cancer was 9.10 per 1,000 PY (9.66 per 1,000 PY among men and 8.54 per 1,000 PY among women). Only 0.1% of cancers occurred within the first year of follow-up, whereas a total of 78.7% of cancers occurred after 3 years of follow-up. The most frequent types of diagnosed tumors in women were breast cancer (1,368 cases) and in men, prostate cancer (1,311 cases). Colorectal cancer was the most frequent type of malignancy among both sexes (1,247 cases). Among nonsolid cancers, the most frequent lymphomas were non-Hodgkin lymphoma (approximately 90%), and most leukemia cases were lymphocytic leukemia (40%) and myeloid leukemia (26.5%).

Figure.

Enlarge

Proportional Effects of Persistence With Statin Therapy on Reduction of Risk for Overall Cancer Per 10% of Followup Days Covered With Statins. Squares indicate adjusted hazard ratios for all covariates listed in Table 2. Horizontal lines indicate 95% confidence intervals. The 3 statin efficacy levels were created on the basis of expected amounts of low-density lipoprotein reduction from baseline. [A tabular description of this figure is also available.]

After adjusting for potential confounders and statin efficacy, an inverse association between persistence with statin therapy and cancer risk was observed for all-site and site-specific cancers ( Table 2 ). In a multivariable model, the highest cancer risk was calculated among nonpersistent statin users (lowest PDC quintile). However, we found no indication for a dose-response association between persistence with statin therapy and colorectal, breast, prostate, and lung cancers. Similar results were obtained when analyses were limited to atients with 3 or more years of follow-up and 5 or more years of follow-up and in subanalysis including only participants with known smoking status (data not shown). The sensitivity analysis included all study participants with smoking status (n = 63,863) with a total of 2,999 incident cancer cases. Of the 63,863 atients, 51,057 (79.9%) were never smokers, 4,166 (6.5%) were past smokers, and 8,640 (13.5%) were current smokers.

In the multivariable model, increased PDC quintile was associated with a significant risk reduction of all-site cancers with P = .001 for linear trend with an HR of 0.80 (0.76–0.86) for 5th PDC quintile compared with nonpersistent statin users (data not shown). The fully adjusted HR for hematopoietic cancers was 0.69 (95% CI, 0.55–0.88) for the highest PDC quintile; for lymphoma the HR was 0.69 (95% CI, 0.51–0.94, P = .002 for linear trend), and for leukemia the HR was 0.58 (95% CI, 0.37–0.91) ( Table 2 ).

When PDC with statins was analyzed as a continuous variable, an increase of 10% in PDC level was associated with an adjusted HR of 0.98 (95% CI, 0.97–0.99; = .02). In stratified analyses, substantially lower risk of cancer was calculated for patients aged 50 or older and for patients treated with high-efficacy statins (Figure).

Adjusted HR for all-site cancers and hematopoietic malignancies were stratified by sex ( Table 3 ). Although the negative association between continuation with statin therapy and leukemia risk between the sexes was similar, significant differences were observed between men and women in relation to the risk of lymphoma. In men, increased PDC with statins was associated with lower risk of lymphoma, reaching approximately 40% lower incidence among adherent patients.

DISCUSSION

The results of our cohort study indicate that patients with longer continuation of statin therapy had a lower risk of cancer compared with nonpersistent users. Our results are similar to those of several smaller studies, including a nested case-control study^[19]that demonstrated a lower cancer risk among statin users compared with bile acid–binding resin users and a cohort study of 12,251 statin users and 334,754 nonusers.^[20]

In a site-specific analysis, we found that persistent use of statins was associated with a significant decrement in the long-term risk of leukemia and lymphoma (mostly non-Hodgkin lymphoma). Early meta-analysis^[21] of 14 studies (6 RCTs, 7 case-control studies, and 1 cohort study) published between 1996 and 2006 indicated an insignificant inverse association between statin use and the risk of hematologic malignancies. However, a more recent study from the Cancer revention Study II Nutrition Cohort^[22] found that compared with nonusers, atients who used statins for more than 5 years had a significant 25% reduction for non-Hodgkin lymphoma. Also, an inverse association was reported among statin users for lymphoma in EPILYMPH,^[12] a multicenter case-control study. Moreover, in vivo and in vitro reports have provided evidence that statins inhibit the growth and promote the self-destruction of leukemia cells.^[23,24]

When our analyses were stratified by sex, the significant negative association between continuation with statins and lymphoma risk was limited to men only. The reduction of hematopoietic cancer risk by sex also has been reported in other studies of prescription medications,^[12,25] but few studies have addressed statins. An inverse relationship between risk of non-Hodgkin lymphoma and statins was reported in a study that compared 601 histologically confirmed incident cases of non-Hodgkin lymphoma and 717 population-based controls among Connecticut women.^[26] However, the association was limited only to women with short to moderate therapy periods. The potentially differential sex-specific effect of statins on non-Hodgkin lymphoma risks warrants further research.

Our study had several methodologic strengths, including its historical rospective design, a large and unselected study population, systematic data collection, and a long follow-up period. The threat of methodologic biases was further reduced by an individual evaluation of statin persistence based on dispensing information, which is the most feasible method of estimating medication use in large populations.^[27] The use of the ICR cancer reports also reduced the threat of outcome misclassification bias. To minimize the potential effect of indication bias, only new users of statins who had at least 1 dispensed prescription of statins during the study period were eligible for analysis. Finally, the exposure start date is equal to the day of study initiation to avoid immortal time bias.^[28]

However, some potential limitations should be discussed. Statin users are frequently under continuous surveillance of various specialists, and more screening tests could have led to surveillance bias. However, such bias is usually associated with earlier cancer detection and higher observed cancer risk and thus cannot explain the negative association between PDC with statins and cancer risk observed in our cohort. A healthy user bias is another potential bias. Persistent users may be more likely to have more aspects of a healthy lifestyle such as diet, exercise, and avoidance of risky behaviors.^[29] To avoid this bias, our study models were adjusted for visits to primary physicians during the year before the index date. Moreover, our study indicated that ersistent use of statins is associated with reduced risk of hematopoietic neoplasms, for which screening tests are not available as they are for breast, colorectal, and prostate cancers.

Data on some variables that can be associated with statins and cancer, such as physical activity, diet, and family history of cancer, were missing in our analysis. However, none of these is an established risk factor for hematologic neoplasms. Smoking, a well-established risk factor for several types of cancer, is an additional confounder for which data were incomplete. Statins are more likely to be prescribed for cigarette smokers because of their higher risk of atherosclerotic cardiovascular disease. However, results from subanalyses for atients with valid smoking status were similar to overall analysis. The results of sensitivity analyses by follow-up duration suggest that the threat of methodologic biases such as misclassification of exposure were unlikely.

Our study showed that overall cancer risk decreased with increasing level of statin efficacy, but we found no significant differences between lipophilic and hydrophilic statins. Several studies^[9,30] have also failed to demonstrate differences in cancer risk between statin types except for 2 cohort studies of lipophilic statin users, who had a reduced risk of breast cancer^[8] and rostate cancer^[31] incidence compared with nonusers.

In light of widespread statin consumption and the indications for long-term or lifelong use, the association between statin use and lower cancer risk may contribute to improved public health. For example, the incidence of leukemia in Israel is 32 per 100,000 for Jewish men aged 60 to 69 years.^[3] Using the calculated HR of 0.56 to calculate the absolute reduction in risk, we determined that statin therapy could prevent 14 cases per 100,000 Jewish men in this age group. The observed effect might be greater with the introduction of more efficacious statins in recent years. Additional controlled clinical trials are needed to investigate the potential anticancer benefit of statins, particularly in nonsolid tumors.

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Update on Aspirin and Cancer Prevention

Jack Cuzick, PhD

We were very interested in the role of aspirin in preventing cancer. We did a consensus statement^[1] about 2 years ago in which we said the data looked very promising, but what was needed was longer follow-up of the ongoing trials. Much of that has now taken place, and some new results have come out, so the results look even more promising.

What is particularly clear is that the effect of aspirin on prevention is a long-term effect and that not very much happens in the 5 years after you start taking aspirin. The preventive effects are really quite long-term; that is very important in terms of how it should be used, if you are going to need to start 5 years before there is going to be any benefit.

There have been 2 recent papers. One was on patients with Lynch syndrome, which puts them at high risk for colorectal and a few other cancers. That was a trial of both starch and aspirin, and the initial results^[2] when they were published a few years ago were actually negative for both of these. There was no effect at all, and now with additional follow-up,^[3] we have seen what was seen in many other studies or was emerging in many other studies: that the effects take a long time to kick in, so now there is a substantial reduction in cancer, particularly colorectal cancer, but some additional cancers as well.

This was a high-dose trial, so again, it doesn't actually address directly the question of whether low-dose aspirin is appropriate. The dose that was tested was 600 mg/day (2 standard aspirin tablets per day), so there were many questions about how best to use aspirin both in the general population and in patients at high risk. The dose is one question.

There was another recent paper from Professor Rothwell and colleagues^[4] looking at a whole range of cancers in the randomized trials, and again, the same feature showed up -- that the effect is quite long-term. Not very much happened in the first 5 years of treatment, but after that, preventive effects emerge for a number of cancers. The most striking were, again, colorectal cancer, esophageal cancer, and to some extent stomach cancer. So it looks like all of the gastrointestinal cancers might be quite substantially affected, with maybe as much as a one-third reduction with long-term aspirin use.

There also was emerging evidence for a few other cancers, notably breast cancer, ovarian cancer, lung cancer, and prostate cancer. The evidence is less clear and less striking, but overall the deaths from cancer in these studies were reduced by 20%, so there is something going on above and beyond just what was seen in the colon cancer study.

There are many possible mechanisms. It could be as simple as the fact that aspirin reduces inflammation, and inflammation is associated with more rapid cell turnover. The more times a cell divides, the greater the chance for an error that could lead to a mutation leading to cancer. It could be as simple as that. There are many more complicated explanations as well. There is plenty of room for research, both at the mechanistic level in terms of trying to understand what is going on, and more applied research, in trying to figure out what is the best way that we can live with low-dose aspirin for cancer prevention. The data from the Rothwell paper suggest that the low dose may be as effective as the higher dose, but we probably need more evidence to be quite certain about that.

The other major issue is at what age to start and stop taking aspirin, and that is very much a balance between the benefits in terms of cancer and heart disease and the risks in terms of gastrointestinal bleeding. There is emerging evidence that bleeding effects are only serious in individuals over the age of 70 years and that typically in younger people, they aren't so serious and they tend to disappear after stopping treatment, without any serious problems. That needs to be looked at more, but it does suggest that one should maybe be thinking about starting aspirin around age 50-55 years, and maybe taking it for 5-10 years and then trying to finish taking it before you get to age 65-70 years, when the side effects are potentially more serious. That is very much an area for research. We don't really have clear answers, but those are suggestions.

The other major area for research is trying to identify subpopulations at increased risk for gastric bleeding and trying to find ways to either avoid aspirin in that group or address the issues. One of the things that is striking and quite simple is that there is substantial evidence that the bleeding and the ulcers caused by aspirin are a particular problem in people who have Helicobacter pylori infection, so maybe a simple thing like testing and eradicating that organism before you start aspirin therapy might go a long way toward reducing those side effects

Heart Screens for Kids Not Ready for Prime Time

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By Amy Norton

NEW YORK (Reuters Health) Mar 12 - Routine electrocardiography in children could detect some cases of potentially fatal heart problems, but with many false-positives along the way, a new meta-analysis study suggests.

Children and teenagers are at very low risk of potentially fatal heart disorders. But whenever a young person dies suddenly of cardiac arrest, it's a shock -- and often widely publicized, especially deaths among young athletes.

"There's been this debate about whether ECG screening would be practical and effective in preventing these tragic deaths," said Dr. Laurel Leslie of Tufts Medical Center in Boston, the senior researcher on the new study.

Some countries, including Italy and Israel, already have mandatory EKG screening for young athletes. The U.S. is not one of them

There have also been questions about whether EKG screening could be a good idea in kids being prescribed stimulants for attention-deficit hyperactivity disorder -- though that is not currently recommended.

One of the prime arguments against such screening is that heart disorders that are detectable by EKG are so rare in kids that the risk of false-positives outweighs the potential benefits.

For the new study, published March 5th in Pediatrics, Dr. Leslie and her colleagues analyzed the potential effectiveness of routinely screening symptom-free kids for three heart disorders: hypertrophic cardiomyopathy, long QT syndrome and Wolff-Parkinson-White syndrome.

The three conditions, while rare, are the most common EKG-detectable causes of sudden cardiac death in kids, said Dr. Angie Mae Rodday of Tufts, who also worked on the study.

Using data from 30 studies on the heart conditions, the researchers found that EKG screening would have a very low risk of false negatives. But it would carry a high risk of false positives. Even under the best scenario the researchers considered, 59% of kids with a positive EKG screen would, in fact, not have any of the three heart conditions.

"That's related to the fact that these are rare disorders," Dr. Rodday said.

Based on the studies the researchers reviewed, the three heart conditions together occur at a rate of 188 cases for every 100,000 kids.

Sudden death from heart problems is rarer still. In the U.S., estimates range from less than one to about six such deaths for every 100,000 children and teens.

This study is just one step in considering whether routine EKG screening is worthwhile, Dr. Rodday said.

There's also logistics -- like who would do all of that screening? Some pediatricians have EKG devices in their offices. "But some of these disorders are pretty hard to interpret," Dr. Leslie noted.

That means it may take a pediatric cardiologist to interpret the results. And there are only about 1,500 pediatric cardiologists nationwide.

And then there's cost, Dr. Leslie said. "People point out that EKGs are inexpensive," she said, noting that the actual test runs about $10 to $25. But that's a lot when multiplied by millions of kids, and there's also the cost of interpreting those tests -- and then any follow-up that may be needed
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Sudden Cardiac Arrest: Identifying Kids at Risk

An Article from Medscape.com

Victoria L. Vetter, MD, MPH

Posted: 04/09/2012

I am Dr. Victoria Vetter, a pediatric cardiologist at the Children's Hospital in Philadelphia. I'm speaking to you today about a policy statement just published by the American Academy of Pediatrics on pediatric sudden cardiac arrest. This paper identifies the conditions that are associated with sudden cardiac arrest in children. This can include structural functional abnormalities, such as hypertrophic cardiomyopathy and dilated cardiomyopathy; coronary anomalies; electrical conditions, such as long QT syndrome; and acquired conditions, such as commotio cordis, when there is a blow to the chest.

The paper outlines the warning signs and symptoms associated with sudden cardiac arrest. This would include fainting or syncope with exercise, chest pain with exercise, shortness of breath not associated with asthma in response to exercise, a family history of sudden cardiac arrest in someone younger than 50 years of age, or having a member who might be affected with one of the conditions that can cause sudden cardiac arrest.

Unfortunately, many individuals do not know their family history, but this is very important. Pediatric providers should make every attempt to investigate this in all children they are seeing, particularly those who are active, as sudden cardiac arrest is most likely to occur during activity. Of course, this includes most of our children. Providers also should be asking questions that specifically relate to the symptoms that were previously mentioned. Since this is a genetic condition, a molecular or genetic evaluation of affected family members or children who experience sudden cardiac arrest can often identify the cause of the arrest and identify additional individuals.

While we do not have a registry that counts the number of children who experience a sudden cardiac arrest, we are hopeful that the information in this policy statement will encourage people to consider that option, and thus identify the children who are experiencing these conditions. Further, if a school has an automated external defibrillator (AED) and an emergency plan to activate when such an event occurs, the child is much more likely to survive. Currently, the survival rate is 10%. It can be as high as 64% in schools where an emergency response plan is in effect.

Also, we would hope that individuals involved in schools would use this as an opportunity to develop curricula that include cardiopulmonary resuscitation and AED use. Every child who graduates from high school could then become a community bystander who would be available to help resuscitate an individual should they experience a sudden cardiac arrest.

The ways in which children can be identified with this condition include the warning signs and symptoms mentioned above. Unfortunately, symptoms are present in less than 50% of individuals. Thus, there is much discussion in the country at this time about other ways in which we might identify these individuals, including a debate about whether an electrocardiogram, which can identify up to 70%-95% of these conditions, should be used and whether genetic testing should be used in a more proactive fashion.

The paper concludes with a number of recommendations about the ways in which pediatricians may effectively work toward decreasing the tragedy of sudden cardiac arrest in our children.

© 2012 Children's Hospital of Philadelphia and Medscape

MEETING WITH PHARMACY BOARD

To all Assist.Pharmacist of Malaysia,

Pharmacy Board had invited Association to attend a special meeting regarding the new Pharmacy Act and Registration of Assist.Pharmacist of Malaysia. They will also discuss on the Standard of Diploma in Pharmacy and the qualification.
Meeting will be held on 23rd March 2012,  9.00am at Pharmacy Services Division head quaters, Petaling Jaya

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PERUTUSAN TAHUN BARU 2012 - YDP PPFM

Salam sejahtera, salam 1 Malaysia dan salam muhibah kepada semua Penolong Pegawai Farmasi Malaysia.
Tahun 2011 sudahpun berlalu. Kita telah mengorak langkah ke tahun 2012 dan akan bermulalah episod baru dalam kehidupan kita khasnya kepada para Penolong Pegawai Farmasi Malaysia.
Rakan-rakan seperjuangan sekelian, ingin saya mengambil kesempatan untuk mengucapkan Selamat Tahun baru 2012 kepada anda semua semoga anda semua diberkati dengan kesihatan yang baik, bahagia bersama keluarga tersayang, kejayaan dalam karier dan komited dalam tugas harian demi pembangunan negara dan kesejahteraan pelanggan kita.
Saya selaku Yang DiPertua Persatuan Penolong Pegawai Farmasi, ingin menyeru semua Penolong Pegawai Farmasi agar terus cemerlang dan produktif dalam tugas seharian serta menunjukkan kualiti perkhidmatan yang tinggi dan penuh tanggungjawab kepada Jabatan, negara dan masyarakat. Saya juga menyeru kepada semua ahli-ahli agar turut aktif dalam Persatuan dan Kesatuan serta sama-sama berusaha menambah keahlian dalam Persatuan dan Kesatuan. Kejayaan aktiviti serta tuntutan Persatuan dan Kesatuan adalah di tangan anda.
Adalah sangat penting untuk memastikan bilangan ahli yang ramai dan majoriti. Sebarang tuntutan tidak akan di endahkan jika jumlah keahlian kita masih seperti tahun-tahun sebelumnya yang kurang dari 60%.
Seperti yang sedia maklum, skim SBPA akan dikuatkuasaka mulai 1 Jan 2012 walaupun tarikh akhir SBPA diletakkan pada 15 Jan 1011. Saya andaikan sudah pasti ramai yang menandatangani borang opsyen tersebut. Skim tersebut dilihatkan sebagai satu kaedah penjenamaan semula sistem penyampaian perkhidmatan awam yang lebih kualiti, efisien, memenuhi stake holder, Lean Services, tegas mengendalikan aspek disiplin anggota dan yang bermasalah supaya Virus dalam perkhidmatan awam tidak merebak kepada rakan-rakan yang bekerja dengan baik.
Semoga skim baru ini memberi satu motivasi ditempat kerja dan karier. Bagi mereka yang masih tidak berpuashati, haruslah membuat pendirian mengubah sikap dan terus maju ke hadapan (Move Forward).
Rakan-rakan seperjuangan yang di kasihi, baru-baru ini kita digemparkan dengan isu kes kehilangan ubat hampir RM1 juta ringgit di salah sebuah Hospital terkemuka di Malaysia dan didalangi oleh anggota Farmasi sendiri. Walaupun kita telah tahu mereka yang terlibat bukanlah di kalangan Pen.Pegawasi Farmasi, tetapi Persatuan ingin mengambil iktibar dan menyeru kepada semua PPF supaya teruskan sikap Profesionalisma, komitmen tinggi, amanah dan jujur dalam melaksanakan tugas seharian demi masyarakat, pelanggan, Jabatan dan negara tercinta.

Buangkan sikap terlalu berkira dalam tugas seharian, tingkatkan komitmen dan tanamkan kesabaran serta nilai-nilai positif dan juga semangat kerja berpasukan bersama-sama dengan Pegawai Farmasi. Kita harus mencari jalan seiring dengan Pegawai Farmasi demi kemajuan Perkhidmatan Farmasi dan aktiviti-aktiviti yang di rancangkan. Libatkan diri dalam semua aktiviti yang dijalankan dengan penuh ikhlas dan tonjolkan kebolehan anda sebagai PPF yang berkaliber dan efisien.
Akhir sekali, saya bagi pihak Persatuan Penolong Pegawai Farmasi Malaysia ingin mengucapkan syabas kepada semua Penolong Pegawai Farmasi di atas kejayaan sepanjang tahun 2011 baik ditempat kerja mahupun kejayaan dalam keluarga disayangi. Juga saya ingin mengucapkan tahniah kepada PPF yang dinaikkan pangkat Gred U32, U36, U38 dan U40.
SELAMAT MAJU JAYA DAN SELAMAT MENJALANKAN TUGAS 2012 !

GANESAN G.NARAYANAN
YANG DIPERTUA
PERSATUAN PENOLONG PEGAWAI FARMASI MALAYSIA
1 JANUARI 2012

OPSYEN UMUR 60 & FAEDAH PERSARAAN

Taklimat sbpa umum bp 6.12.2011

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HISTORY OF PHARMACY

History of pharmacy

Although people have been using medicinal substances to treat themselves for as far back as there have been people, the pharmacy profession has more recent origins. Nevertheless, its roots can be found over 4000 years ago.

Pharmacy’s roots

The pharmacy profession can be traced back at least as far as the Sumerian population, living in modern day Iraq. From around 4000 BC, they used medicinal plants such as liquorice, mustard, myrrh, and opium. There were separate people who worked to prepare medicines, as a separate role from diagnosis and treatment which was carried out by medics. These precursors to pharmacists also combined their role with that of a priest. The Sumerians wrote the earliest surviving prescriptions from at least 2700 B.C. – so nearly 5000 years ago.

The Ancient Egyptians had specific preparers of medicine, known as Pastophor. Pharmacy was viewed as a high status branch of medicine, and again, like the Sumerians, these pharmacists were also priests who worked and practised in the temples.

From surviving papyrus scrolls, notably the Ebers Papyrus which dates from 1500 BC, we know that the Egyptians made and used infusions, ointments, lozenges, suppositories, lotions, enemas, and pills. The Ebers Papyrus includes 875 prescriptions and 700 drugs.

Meanwhile, in China in about the same era (2000 BC), a man called Shen Nung wrote the first Pen T’sao or native herbal, which contained descriptions of 365 plant-based drugs.

Stalls and shops selling medicinal goods existed around 1900 B.C. in the town of Sippara on the Euphrates river. However, the earliest recorded shop dealing with sales of medicines in London was opened in 1345.

The history of pharmacy in Britain

The word 'pharmacist' was first used in a publication in England in 1834 according to the Oxford English Dictionary in a novel by Lytton called The Last Days of Pompeii.   However, it was certainly in use from the 18th century with the meaning of someone who prepared and dispensed medicines.  Nevertheless, at the beginning of the 19th century most people working in this area would have called themselves chemists and/or druggists. The terms pharmacist and pharmaceutical chemist (now usually shortened to chemist) came later in the 1800s.

The word “pharmacy” has a much longer history in England. Chaucer in The Knight’s Tale (written around 1386) uses the word to describe a medical preparation of plants “farmacies of herbs.”

The term apothecary, often used between the 1600s and 1800s, does not refer to the chemist and druggist, or pharmacist.  It was used for individuals living in London who had passed the examinations of the Worshipful Society of Apothecaries of London, founded in 1617, or to their often less well qualified counterparts in the provinces. The role of the apothecary developed out of the role of the spicer or pepperer – or grocers – someone whose trade included crude drugs and prepared medicines.  The Grocers had their own Guild – professional body in the City of London- from the 13the century. The Apothecaries split from them in 1617 to form their own Society.

Although the apothecary's practice included a strong dispensing element, it was more all encompassing than the handling of drugs and chemicals. Apothecaries were also examining and treating patients, but they did not charge for these services – only for the medicines supplied. 

Following a ruling in the Rose Case (1701-1703/4), apothecaries became legally ratified members of the medical profession, able to prescribe as well as dispense medicines.  

As apothecaries moved into a more advisory role, pharmacists (or chemists and druggists) could develop their own area of preparation and supply of medicines. However, this put them in competition with the apothecaries who were also still involved in the same area.  The apothecaries attempted to control the chemists and druggists' activities in 1748 with a proposed new law to control the supply of medicines. This didn't progress.

In the early 1800s, an Association was formed to put together a proposal to Parliament to set up a body that examined and regulated apothecaries, surgeon-apothecaries, midwives and dispensing chemists. The chemists and druggists took action, arguing that they were best placed to set their own standards, as they were more experienced in making up prescriptions and making medicines than the apothecaries, so they should not be put under their control. The chemists and druggists won their argument, and when the Apothecaries Act of 1815 was finally created, the apothecaries did not have control over making medicines.

Some key dates in pharmacy history

1820		The alkaloid quinine was first extracted from the bark of cinchona trees by two French chemists, Pierre Joseph Pelletier and Joseph Biename Caventou.
1874		Diamorphine or Heroin was first synthesised from morphine.
1883		First edition of The Extra Pharmacopoeia published, edited by William Martindale and Dr Wynn Westcott.
1899		Aspirin, was launched by the German company.
1910		Salvarsan, the first 'magic bullet' drug, effective against syphilis was discovered by Paul Ehrlich and Dr Sahachiro Hata.
1915		Medicine stamp duty was doubled as a wartime fundraiser.
1917		The Venereal Disease Act prohibited the advertising of medicines for VD and selling mixtures containing scheduled substances.  It introduced the concept of 'prescription only' medicines.
1922		The Dangerous Drugs Act regulated the import and sale of potential 'drugs of addiction', including the derivatives of opium, cocaine and cannabis so widely used in proprietary remedies.
1928		Penicillin discovered by Alexander Fleming.
1938		The Food and Drugs Act prohibited the adulteration and mislabeling of drugs.
1939		The Cancer Act restricted the advertisement of products claiming to treat cancer.
1940		Under the Finance (No. 2) Act purchase tax was imposed on a range of goods including most drugs and medicines.
1941		The Pharmacy and Medicines Act repealed the old medicine stamp duty. It forbade the general advertisement of products claiming to treat a number of specific illnesses including Bright's disease, cataract epilepsy and TB, or to be effective in procuring an abortion.  For the first time manufacturers were required to list the active ingredients of products on their packaging.
1948		The National Health Service made prescription medicine available to all. Until the introduction, in the 1950s, and subsequent hefty increasing of prescription charges, proprietary medicines were no longer seen as a cheap alternative to seeing the doctor.
1961		Ibuprofen was first synthesised by a team at the Boots Pure Drug Company in December.
1964		Introduction of Adverse Drug Reaction 'yellow card' scheme in reponse to the thalidomide tragedy of 1961.

- From Royal Pharmaceutical Society of Great Britain