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KNOWLEDGE AND PRACTICE ON CALCIUM SUPPLEMENT AMONG PRIMARY CARE PATIENTS ATTENDING OUTPATIENT CLINIC AT PUSAT PERUBATAN PRIMER UKM PRIMARY INVESTIGATOR : DR AIDA BT JAFFAR K13591 FAMILY MEDICINE DEPARTMENT CO INVESTIGATOR : DR FATHIMA BEGUM BT SYED MOHIDEEN P49543 FAMILY MEDICINE DEPARTMENT Page TABLE OF CONTENT CHAPTER I 1 INTRODUCTION 1.1 Introduction 3 1.2 Research Justification 4 1.3 Literature Review 4 1.4 Research Questions 7 1.5 Research Objective 7 1.6 Conclusion 8 CHAPTER II METHODOLOGY 2.1 Introduction 9 2.2 Background of the Study 9 2.3 Study Design 9 2.4 Target Population 9 2.5 Sampling Frame 10 2.6 Sampling Unit 10 2.7 Sampling Method 10 Inclusion and Exclusion Criteria 10 2.7.1 1 2.8 Sample Size 11 2.9 Study Tools 11 2.10 Study Protocol 12 2.11 Data Analysis 13 2.12 Research Ethics 13 2.13 Research Variables 13 2.13.1 Dependent Variables 13 2.13.2 Independent Variables 13 2.14 Variables Definition 14 2.14.1 Dependent Variables 14 2.14.2 Independent Variables 14 2.15 Conclusion 15 APPENDICES A Patient Infomation Sheet 16 B Consent Form 20 C Questionnaire 22 D Working Activity Schedule 29 E Budget 30 2 CHAPTER I INTRODUCTION 1.1 INTRODUCTION Calcium is an important mineral in the body for structure and physiological function. It is abundantly found in the body structure whereby 99% of calcium is found in the bone and teeth whereas another 1% of body calcium is required for muscle and vascular contraction, vasodilatation, blood clotting, nerve transmission, intracellular signaling and also for hormonal secretion (1). Knowing its function in the blood, serum calcium is tightly regulated by the brain and kidney, thus does not fluctuate with changes in the dietary intake of calcium. The bone, on the other hand is used as a reservoir for and as source of calcium to maintain the constant concentration of calcium in the blood, muscle and intracellular fluids (1). Calcium can be found naturally in dairy foods like milk. Studies show that milk is a good source calcium and magnesium (2). Previously, it was thought that those patients taking calcium as supplementation to replace for low dietary calcium intake may have magnesium deficiency. Magnesium deficiency can lead to increase in parathyroid hormone that assists in reabsorption of magnesium in distal convoluted tubule. But parathyroid hormone promotes calcium release from the bone, thus resulting in osteoporosis with time (2). Magnesium although are able to be replaced by supplementation, studies shows that magnesium supplementation for longer than 2 weeks however does not cause significant changes in bone resorption as it still can occur causing osteoporosis at long run (3)(4)(5). However, Green et al (2) in their study on acute effect of high calcium milk showed that high calcium skimmed milk with or without additional magnesium has no additional impact on serum parathyroid hormone or bone resorption that can cause osteoporosis. But as dietary calcium like milk calcium is absorbed more slowly thus it is better than taking elemental calcium. Yet for those not tolerating milk calcium, elemental calcium can still be considered as it important to maintain adequate intake of calcium everyday for bone health. 3 Vitamin D on the other hand, is a fat-soluble vitamin that is naturally present in very few foods and also produced endogenously when the skin is exposed under the sun (6). Vitamin D helps in calcium absorption in the gut and assists calcium to play its physiological role. For instance, Vitamin D plays an important role in bone growth and remodeling, thus preventing osteoporosis (6). 1.2 RESEARCH JUSTIFICATION According to Malaysian Osteoporosis guideline 2012, calcium supplementation may be required when the dietary calcium is inadequate. Nevertheless, the practice of calcium supplementation has its own risk and benefit. Regan et al (7) in their study on ‘Why US Adults Use Dietary Supplements?’ shows that calcium is the second most preferred supplement used after multivitamin. The user’s reported that their motivation for calcium use is bone health (74%) but sadly 75% of their supplement decisions are being made without the recommendation of a health professional. Therefore, this study aimed to assess our primary care patient’s knowledge and practice on calcium supplement and the associated sociodemographic factors 1.3 LITERATURE REVIEW Bone continuously remodels. This physiological process is closely related to human age and nutritional intake. There is constant resorption and deposition of calcium into the bone whereby bone formation exceed resorption in periods of growth in children and adolescents. Whereas in early and middle adulthood, both process are relatively equal. However, in aging adults particularly in postmenopausal women, bone breakdown exceeds formation, resulting in bone loss and increasing the risk of osteoporosis and fracture(1). Based on a study, Dietary calcium intake in postmenopausal Malaysian women by Chee et al 2002 (8), shows that calcium intake is low among Malaysian women. The mean calcium intake from the dietary records was 447.4 ± 168 mg/day and from the FFQ it was 498.7 ± 211 mg/day. This is far behind than what is 4 recommended by the National Coordinating Committee on Food and Nutrition 2005, Ministry of Health Malaysia. Based on National Coordinating Committee on Food and Nutrition 2005, women aged more than 50 years old, should take at least 1000mg of calcium per day (9). However, the recommendation refers to total intake per day for both dietary and supplementation knowing the fact that our population generally takes low calcium in their diet as shown by Chee et al (8). Nevertheless, Chee et al (8) study shows that most of the calcium source was from diet as recommended, for instance, vegetables and bean sources (32%), dairy products (26%), eggs, meat and seafood (16%) and cereals (12%)(8). Clinical Guidance on the Management of Osteoporosis 2012, suggest calcium supplementation may be given when dietary intake is insufficient (10).This is because calcium deficiency leads to reduction in bone mass due to the increase resorption of calcium from bone for physiological function of the body. Therefore, contributes to the development of osteoporosis among elderly in particular (11). As a consequence, fracture to even trivial injury becomes common, especially among women and this is associated with high disability and poor quality of life, increase in healthcare cost and increase in mortality (12). Similar to our guideline, Australian guideline also recommends diet with sufficient calcium intake (13). However, supplements can be given for people at risk of calcium deficiency yet are not meeting the recommended dietary intakes to prevent fractures. Supplements are usually combined with Vitamin D as this promotes calcium absorption. Clinical Guidance on the Management of Osteoporosis 2012, also recommends vitamin D supplements even among children and expectedly among adults who are deficient of vitamin D (10)(14). As for the requirement, those adult who are 50 year old or more, National Coordinating Committee on Food and Nutrition 2005, Ministry of Health Malaysia recommends 400 IU of vitamin D per day (9). And expectedly, elderly who are lack of outdoor activities, immobile, institutionalized and diet lack of vitamin D will benefit from 800 IU per day (14). In addition, Vitamin D supplementation has also shown improvements in muscle strength, balance and risk of falling, and also improves in survival (15) (16). As for the calcium supplements, there are many types available. Commonly, there are calcium carbonate, lactate, citrate and gluconate. Among these, calcium 5 carbonate has the highest elemental calcium that is about 40%, followed by citrate 21% and lactate 13% (10). In our clinical setting, calcium carbonate and lactate are commonly used. Calcium carbonate is absorbed most efficiently with food as its absorption is dependent on gastric acid for absorption (17). Nevertheless, percentage of calcium absorbed depends on total elemental calcium in a calcium supplement (1) and calcium carbonate has the highest elemental calcium that is about 40% (10). As recommended, for maximum absorption, the amount of calcium taken should not be more than 500mg to 600mg per dose. But for those patients needing more than 600mg of calcium supplement per day, the dose can be taken as divided doses (10). However, some of this absorbed calcium will be eliminated in sweat, urine and feces and this amount is affected by the type of dietary intake (1). For instance, taking coffee and tea can modestly increase calcium excretion and reduce absorption (18). Nevertheless, there is another study showing that moderate intake of caffeine that is one cup of coffee or 2 cups of tea per day in young women has no negative effects on bone (19). Use of calcium supplement has a conflicting report, whereby some data suggest that excessive use of calcium supplementation is associated with cardiovascular event (myocardial infarction and stroke) (20)(21)(22)(23)(24). In addition, from a meta-analysis, calcium supplement taken without vitamin D increases the risk of MI (21). However, the risk of cardiovascular events observed in these studies involves high doses of calcium supplements (1000-2000mg). Lower doses are considered to be safe (10). Similarly, in a systemic review; calcium supplements do not significantly increase the risk of nephrolithiasis or renal colic if taken in recommended doses (25). In addition, based on NHANES 2005-2006 study shows that high intake of calcium beyond the recommended dietary allowances provide no benefit for lumbar and hip bone mineral density in older adult (50-70y.o) (26). Another issue is that, there are some patients who rather be on calcium supplementation than taking dairy foods which are known to have high calcium level but can cause high serum cholesterol. From a systemic review which shows that the effects of dairy foods on Coronary Heart Disease, it is proven that calcium rich food are not associated with a higher risk of Coronary Artery Disease (27). Recently U.S PSTF, published an article on 7th May 2013, suggesting against daily supplementation with 400 iu or less vitamin D3 and 1000mg or less of calcium 6 for the primary prevention of fractures in noninstitutionalized post-menopausal women (D recommendation) (25). This is because the current evidence is insufficient to assess the balance of the benefits and harms of combined vitamin D and calcium supplementation for the primary prevention of fractures. 1.4 RESEARCH QUESTIONS 1) What is the knowledge of primary care patient’s calcium supplement? 2) How is the practice on calcium supplement among our primary care patients? 3) Does sociodemographic factor influence the level of knowledge and practice on calcium supplement? 1.5 RESEARCH OBJECTIVE 1.5.1 General Objective To study on knowledge and practice of calcium supplement among primary care patients attending outpatient clinic in Pusat Perubatan Primer, UKM. 1.5.2 Specific 1) To describe the knowledge on calcium supplement among primary care patient 2) To describe the practice on calcium supplement among primary care patient. 3) To describe the association between knowledge and practice on calcium supplement 4) To describe the association between knowledge, practice on calcium supplement and sociodemographic factor among patients attending outpatient clinic in Pusat Perubatan Primer, UKM. 7 1.6 CONCLUSION It is important to know primary care patients‘ understanding and practice on calcium supplement as calcium supplement has its own risk and benefit. 8 CHAPTER II RESEARCH METHODOLOGY 2.1 INTRODUCTION Cross sectional study will be conducted among primary care patients attending outpatient clinic at Pusat Perubatan Primer, Universiti Kebangsaan Malaysia. 2.2 STUDY BACKGROUND The study will be conducted in Outpatient Clinic, Pusat Perubatan Primer, Universiti Kebangsaan Malaysia. There are 2 groups of patient attending this clinic. Those walk in cases for acute problems and the other groups are on appointment basis, attending for chronic diseases mainly diabetes, hypertension with or without complications. There are also patient attending for asthma and chronic airway disease. This clinic located at Bandar Tasik Selatan, Cheras. 2.3 STUDY DESIGN Cross-sectional study 2.4 TARGET POPULATION All patients attending outpatient clinic (age more than 20), Pusat Perubatan Primer, Universiti Kebangsaan Malaysia. 9 2.5 SAMPLING FRAME All patients attending outpatient clinic (age more than 20), Pusat Perubatan Primer, Universiti Kebangsaan Malaysia who meet the inclusion and exclusion criteria. 2.6 SAMPLING UNIT Patients attending outpatient clinic (age more than 20), Pusat Perubatan Primer, Universiti Kebangsaan Malaysia who meet the inclusion and exclusion criteria from 1st April 2013 to 31st June 2013. 2.7 SAMPLING METHOD Systematic sampling 2.7.1 Inclusion and exclusion criteria i. Inclusion criteria for this study: a. Adult, age more than 20. b. Malaysian c. Consented participant ii. Exclusion criteria for this study: a. Unable to read, write or understand Malay or English language (questionnaire only available in Malay or English version). b. Patient with underlying malignancy and hyperparathyroid c. Patient with medical problem requiring calcium as supplement 10 2.8 SAMPLE SIZE The sample size calculation for this study design was done using the formula as below (Kish L. 1965): Sample size, n = (Z1-α)²P(1-P) D² n = sample size Z = Z statistic for confidence interval, Z1-α = 1.96 (standard value for normal distribution data at significant value or alpha (α) at 0.05) P = prevalence or expected prevalence is 0.5* D = degree of significant *After many literature review done, there is no similar study elsewhere, thus expected prevalence used in this study will be 50% or 0.5. Sample size, n = (1.96)² 0.5 (1- 0.52) 0.05² = 365 Considering 10% drop out in view of possible incomplete questionnaire or unmet inclusion and exclusion criteria. Therefore the sample size needed for this study is 402 respondents. 2.9 STUDY TOOL A questionnaire will be developed for this study on knowledge and practice of calcium supplement among primary care patients in 2 main languages that is in Bahasa Melayu and English. This questionnaire is based on literature reviews regarding calcium supplement and is divided into 3 parts: Part A: Assess on sociodemographic data has 6 items. Part B: Assess on knowledge of calcium supplement has 12 items 11 Part C: Assess on practice on calcium supplement has 12 items At total there are 30 questions. This questionnaire will be discussed by the expert panel involving 1 Orthopedic specialist, 2 Family Medicine Specialist, and a pharmacist. Later, the questionnaire will be translated backward and forward before the pilot test. 2.10 STUDY PROTOCOL Approval from Ethics Excluded from study if disagree Patients attending outpatient clinic are chosen by systematic sampling Subjects briefed on the study, consent taken and given questionnaire. Both groups of patients, taking and not taking calcium supplements will be included in the study Data Collection Data analysis and report writing 12 2.11 DATA ANALYSIS Data will be analyze using SPSS software version 22.0. The analysis will use descriptive statistics for all study variables and all items in the questionnaire. Chisquare will be used to test for significant association between categorical variables of socio-demographic factors, practice and knowledge on calcium supplement. Parametric test will be used for normal distribution data while non-parametric test will be used for non-normally distributed data. The results are considered to be significant if p < 0.05. 2.12 RESEARCH ETHICS This research will be conducted on a voluntary basis where the selected respondents will voluntarily agree to take part in this study. All respondents will be briefed regarding the manner and purpose of this research. All respondents who agree to take part in this study will have to give their written consent to participate in this research. Permission to carry out this study will be acquired through a written consent from Research Ethics Committee in Universiti Kebangsaan Malaysia. 2.13 STUDY VARIABLES 2.13.1 Dependent variable Knowledge and practice on calcium supplement 2.13.2 Independent variables Socio-demographic factors i. Gender ii. Age iii. Ethnicity iv. Level of education 13 v. Employment status vi. Household income 2.14 VARIABLES DEFINITION 2.14.1 Dependent variable Practice will be measured in percentage and knowledge on calcium supplement will be categorized into three groups based on the marks from likert scale 2.14.2 Independents variables i. Gender Gender is categorised into male and female. ii. Age Age of the case respondent is defined as the age of patient based on the date of birth stated in MyKad. iii. Ethnicity Ethnicity is categorised into Malay, Chinese, Indian or Others. ‘Others’ denotes all other ethnics not belonging to the three major races. iv. Level of education Refer to the latest formal education level of patients and will be classified into none, primary, secondary and tertiary. 14 vii. Employment status Employment status will be defined as working and not working. viii. Household income Household income is defined as the total income for all the members of a household in Malaysian Ringgit for typical month. 2.15 CONCLUSION In conclusion, a cross sectional study will be conducted in Out Patient Clinic, Pusat Perubatan Primer, Universiti Kebangsaan Malaysia. A total sample size of 402 respondents attending this clinic will have to answer the research questions of this study. Finally, the data collected will be analysed using the SPSS version 22.0 software to generate the descriptive and analytical statistics. 15 APPENDIX A PATIENT INFORMATION SHEET Research Title Knowledge and practice on calcium supplement among primary care patients attending outpatient clinic at Pusat Perubatan Primer, UKM Introduction Calcium supplement is taken as an addition to our nutritional intake by some patients. However, there are some patients who find that it is not necessary. Use of calcium supplement is still controversial by some patients, thus this study is done to see patients knowledge and practice on calcium supplement What would this involve? Patients are asked to sign the consent form before participating in the study. Patients need to answer a questionnaire on the knowledge and practice on calcium supplement. The benefits This study will identify the reason patient request for calcium supplement. The risks No risks involved in this study as it doesn’t involve any procedure. Confidentiality The results of the data obtained will be reported in a collected manner with no reference to a specific individual. Hence, the data from each individual will remain confidential. Do I have to take part? The participation into this study is voluntary. If you prefer not to take part, you do not have to give reason and your decision will not affect the intervention. The right to withdraw Any respondents has the right to withdraw their consent at any time should they feel uncomfortable at any stage of the research. No penalties will be given to those who withdrawn. Payment and compensation You do not have to pay for participating in this study. Similarly, no payment is available to you for participating in this study. 16 If I have any questions, whom can I ask at any time point of study? Dr. Fathima Begum bt Syed Mohideen (019-2782611) Jabatan Perubatan Keluarga, Fakulti Perubatan, Pusat Perubatan Universiti Kebangsaan Malaysia, Jalan Yaakob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur. 17 LAMPIRAN A MAKLUMAT UNTUK PESAKIT Tajuk penyelidikan Kajian mengenai pengetahuan dan amalan penggunaan kalsium sebagai supplemen oleh pesakit yang menghadiri klinik pesakit luar di Pusat Perubatan Primer, UKM Pengenalan Supplemen kalsium dianggap sebagai nutrisi tambahan oleh sesetengah pesakit. Walau bagaimana pun, sesetengah pesakit merasakan tidak perlu untuk mengambil kalsium tambahan ini atas sebab yang mereka ketahui sendiri. Penggunaan kalsium sebagai nutrisi tambahan masih kontroversi bagi sesetengah pihak. Oleh yang demikian, kajian ini bertujuan untuk mengetahui pendapat para pesakit yang menghadiri klinik pesakit luar, tentang penggunaan kalsium ini. Apa yang akan dilakukan? Pesakit diminta untuk menandatangani borang keizinan sebelum mengambil bahagian dalam kajian ini. Pesakit perlu menjawab soal selidik berkaitan penggunaan dan pengetahuan mengenai kalsium sebagai nutrisi tambahan. Faedah penyelidikan Kajian ini akan mengenalpasti sebab penggunaan kalsium di kalangan pesakit luar. Risiko Kajian ini tidak melibatkan sebarang risiko dan tidak melibatkan sebarang prosedur. Kerahsiaan Keputusan yang diperolehi akan dimaklumkam secara keseluruhan dan tidak merujuk pada nama individu. Maka maklumat dan keputusan dari setiap pesakit adalah sulit. Perlukah saya mengambil bahagian? Penglibatan dalam penyelidikan ini adalah secara sukarela. Sekiranya anda tidak bersetuju, anda tidak perlu memberikan sebab dan ini tidak menjejaskan intervensi yang akan diberikan. Hak untuk menarik diri Pesakit boleh menarik diri dari penyelidikan ini pada bila-bila masa tanpa menjejaskan intervensi yang diberikan. Bayaran dan pampasan 18 Anda tidak akan dikenakan apa-apa bayaran dan anda juga tidak akan dibayar bagi penglibatan dalam penyelidikan ini. Jika saya ada sebarang pertanyaan, siapa boleh saya hubungi? Dr. Fathima Begum bt Syed Mohideen (019-2782611) Jabatan Perubatan Keluarga, Fakulti Perubatan, Pusat Perubatan Universiti Kebangsaan Malaysia, Jalan Yaakob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur. 19 APPENDIX B CONSENT FORM FOR PATIENT Research Title: Knowledge and practice on calcium supplement among primary care patients attending outpatient clinic at Pusat Perubatan Primer, UKM . I ____________________________________(name), NRIC: ___________________, have read the information of this study and have also been given the explanation by a doctor about the purpose of this document. I understand the aims of the study including its risks and benefits. I *agree/disagree to participate in the study as stated above. I *would like to know/don’t want to know the result of this study (*delete where necessary) Signature : _____________________ Date : _____________________ Witness Medical Officer Name : Name : IC no : IC no : Signature : Signature : Date: Date: 20 LAMPIRAN B BORANG KEIZINAN DARIPADA PESAKIT Tajuk kajian Kajian mengenai pengetahuan dan amalan penggunaan kalsium sebagai supplemen oleh pesakit yang menghadiri klinik pesakit luar di Pusat Perubatan Primer, UKM. Saya _____________________________(nama) no. KP: ______________________, telah membaca maklumat tentang kajian ini dan juga telah diberi penerangan oleh doktor tentang dokumen ini. Saya faham akan tujuan kajian ini termasuk berkaitan risiko dan manfaatnya . Saya *bersetuju/tidak bersetuju untuk mengambil bahagian dalam kajian yang telah dinyatakan di atas ini. Saya *ingin mengetahui/tidak ingin mengetahui keputusan penyelidikan ini (*potong mana yang tidak berkenaan) Tandatangan : _______________________ Tarikh : ________________ Saksi Pegawai Perubatan Nama : Nama : No KP : No KP : Tandatangan : Tandatangan : Tarikh : Tarikh : 21 LAMPIRAN C Part A 1) Age (in years) =______ 2) Gender Male Female 3) Ethnicity Malay Chinese Indian Others 4) Level of education None Primary Secondary 5) Employment status Working Not working 6) Household income =________________ 22 Tertiary Part B For questions in Part B and Part C please circle 1 if you strongly disagree and circle 5 if you strongly agree with the statement given. Strongly Disagree 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. . 11. 12. The following are important part of bone health. a) Calcium b) Vitamin D c) Exercise Calcium requirement increases with increasing age Daily requirement of calcium is the same for both women and men of the same age. The following foods are good source of calcium. a) Milk b) Yogurt and cheese c) Green leafy vegetables d) Fish such as sardines, mackerel, tuna, anchovies e) Cod liver oil Calcium from food is better absorbed into body than calcium from supplements When dietary intake of calcium is inadequate, calcium supplement may be needed Calcium supplement should be taken at divided doses if daily requirement is more than 600mg Calcium supplement is not safe to be taken at high doses than recommended Calcium supplement has side effects like constipation Calcium supplements should not be taken together with; a) High iron foods (eg:liver) or iron tablets b) Alcohol The following foods are good source of Vitamin D. a) Milk b) Egg yolk c) Oily fish such as sardines, mackerel, tuna, salmon d) Cod liver oil e) Sunlight Vitamin D helps body to absorb calcium 23 Disagree Uncertain Agree Strongly Agree 1 1 1 1 2 2 2 2 3 3 3 3 4 4 4 4 5 5 5 5 1 2 3 4 5 1 1 1 1 2 2 2 2 3 3 3 3 4 4 4 4 5 5 5 5 1 1 2 2 3 3 4 4 5 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 1 2 2 3 3 4 4 5 5 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5 1 1 1 2 2 2 3 3 3 4 4 4 5 5 5 Part C If you decided to choose disagree or strongly disagree for question 1 in Part C, please do not proceed to next questions in Part C (that means you should not answer question 2 onwards). 1. 2. I take calcium supplement in the past 1 year I take calcium supplement because I cannot get enough calcium from daily diet 3. I am taking calcium supplement to prevent myself from fracture 4. I followed doctors suggestion to take calcium supplement 5. I will not follow suggestion from family or friends in taking calcium supplement 6. I take calcium supplement every day in past 1 year 7. I take calcium supplement according to the recommended dose 8. I do not take calcium that was given by doctors to my family or friends 9. I take calcium supplements with food 10. I often discuss with doctor regarding calcium supplement. 11. I understand well regarding doctor explanation on calcium supplement. 12. I take Vitamin D with calcium supplement Strongly Disagree 1 1 Thank you very much for your cooperation. 24 Disagree Uncertain Agree 2 2 3 3 4 4 Strongly Agree 5 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 1 2 2 3 3 4 4 5 5 1 2 3 4 5 1 1 2 2 3 3 4 4 5 5 1 2 3 4 5 1 2 3 4 5 APPENDIX D WORK ACTIVITY PLANNING (GANNT CHART) Dis 2013 Proposal submission Data collection April 2014 Jun 2014 August 2014 / / Data analysis / Thesis submission / 25 APPENDIX E BUDGET PERKARA UTAMA AMAUN ATAU KUANTITI JUMLAH (RM) Alat tulis (Pen) 440 X RM 1 440.00 Pen drive (4GB) 1 50.00 Percetakan jurnal 1 100.00 Token RM 5 X 440 2,200.00 Fotokopi: RM0.10 x 10 (440 set) 440.00 RM 100 x 4 400.00 i. Borang Maklumat Pesakit, Borang Keizinan Menyertai Kajian dan Borang Soal- Selidik Translators JUMLAH RM 3630 26 References 1) Institute of Medicine, Food and Nutrition Board. Dietary Reference Intake for Calcium and Vitamin D. Washington, DC; National Academic Press, 2010. 2) Green JH, Booth, Bunning R. 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JAMA 1994;271;280-3. 19) Massey LK, Whiting SJ. Caffein, urinary calcium, calcium metabolism and bone. J Nutr 1993;123:1611-4. 20) Bollan MJ et al. Effect of calcium supplementation and risk of cardiovascular event: meta analysis. BMJ 2010: 341:C3691 21) Bollan MJ et al. Calcium supplementation with or without Vit D and risk of cardiovascular event: reanalysis of women health initiative limited access dataset and meta-analysis BMJ 2011: 342:d2040 22) Lewis JR et al: Calcium supplementation and the risk of atherosclerotic vascular disease in older women; result of 5 year RCT. J Bone Miner Res 2011; 26(1):35-41 23) Li et al. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg). Heart (2012) ;98:920-925 24) Xiao et al. Dietary and supplemental calcium intake and cardiovascular mortality. JAMA Intern.Med.2013;173(8): 639-646 25) Candelas G et al. Calcium supplementation and kidney stone risk in osteoporosis: a systematic literature review. Clinical Exp Rheumatol2012 Nov-Dec;30(6):954-61 28 26) Anderson et al. calcium intake and femoral and lumbar bone density of elderly U.S men and women: NHANES 2005-2006 Analysis. 27) Robert A Gibson. The effects of dairy foods on CHD: A systemic review of prospective cohort studies. British journal of nutrition 2009: 102:1267 – 1275 28) U.S Preventive Task Force. Annals of Internal Medicine 2013:158;691-698 29 30