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Mohammad H. Qadri, MD, Ridah A. Al-Harfi, B.Sc, Mohammad A. Al-Gamdi, MHA, CDD Program, Diarrhea Control Center, Dammam, Saudi Arabia

هدف الدراسة: الغرض الرئيسي من هذه الدراسة تقييم الرضاعة من الثدي للأطفال أقل من 24 شهر وتحديد الأسباب التي تؤدي لفشل الرضاعة من الثدي للأمهات التي لا ترضعن أطفالهن.

طريقة الدراسة:أجريت هذه الدراسة على 1185 طفلا تحت سن 24 شهر مستخدمين مؤشرات الرضاعة الطبيعية والموصى بها من قبل منظمة الصحة العالمية لتقييم ممارسات الرضاعة الطبيعية عمليا خلال فترة 24 ساعة.

نتائج الدراسة:كان معدل الرضاعة الطبيعية (من الثدي فقط) 33.0 %، 11.5% للرضاعة الطبيعية السائدة للأطفال تحت سن 4 شهور. وكان المعدل الزمني المتمم للتغذية 31.7% فقط. كل هذه القيم تختلف عن المعدلات الموصى بها ، والسبب المفاد من الأمهات من ناحية فشل الرضاعة هو عدم كفاية لبن الثدي، إعلانات الألبان، التعلم من أمهات أخرى أدى إلى تتابع تكرار هذه الحالات.

الاستنتاجات:هذه الدراسة توضح الحد المتدني للرضاعة من الثدي للأطفال تحت سن 4 شهور كما توضح سبل تغيير سلوك الأمهات نحو الرضاعة الطبيعية من الثدي.ومن الممكن تحقيق ذلك بتظافر جهود موجهة للمجتمع  وخاصة لأمهات المستقبل وتقديم الدعم التوعوي لهن بعد الولادة لتلافي الفشل في استمرار الرضاعة الطبيعية من الثدي.

الكلمات المرجعية:الرضاعة الطبيعية القاصرة على الثدي، التغذية المتممة، فشل الرضاعة من  الثدي، التدعيم. 

Objectives: The main objective of this study was to determine the breastfeeding status for children under 24 months and assess the causes of breastfeeding failure among those mothers who do not breastfeed their babies.

Methodology: This study was conducted on a sampled population of 1185 children under 24 months of age, using breastfeeding indicators recommended by World Health Organization, for assessing breastfeeding practices within a recall period of 24 hours, in the Dammam area of Saudi Arabia.

Results: The exclusive breastfeeding rate and predominantly breastfeeding rates were 33% and 11.5%, respectively, under 4 months of age among these children. The timely complementary feeding rate was 31.7% only. All the values were far behind those recommended. The reasons given in order of their frequencies by the mothers for failure to breastfeed were insufficient milk, advice and example of other mothers and formula milk advertisement.

Conclusion: This study recognizes the low level of exclusive breastfeeding among children under 4 months of age and lays emphasis on changing the behavior of mothers towards exclusive breastfeeding. This can be achieved by special integrated community-based  approaches  among  potential  mothers  by supporting them after

Correspondence to:

Dr. Mohammad H. Qadri, CDD Program, Diarrhea Control Center, P.O. Box 3745, Dammam 31481, Saudi Arabia

delivery  and   proper   follow-up, to  prevent  failure  of  milk formation and discontinuation of breastfeeding.

Key Words: Exclusive breastfeeding, complementary feeding, breastmilk failure.


                Human milk is the natural, most appropriate of all available types of milk for an infant, and is uniquely adapted to its needs during the first 4 months of life. In many studies, breastfed children have been reported to be healthy and thriving, inspite of the variations in the individual breastmilk.1,2 This is important because an inadequate intake may result in compromised levels of activity before growth is affected.3 Even in infants who are small for their age a growth rate greater than that of NCHS 50th percentile has been observed.4 Detrimental effects of the early use of complementary feeding on the rate of growth and increased risk of mortality from diarrhoeal diseases is very well documented.5-7 However, fast urbanization and rapid socioeconomic changes in Saudi Arabia are putting breastfeeding in danger of decline. This study on the status of breastfeeding was conducted in the Dammam area of Saudi Arabia, in an attempt  to  determine  breastfeeding practices for children under 24 months of age, with the emphasis on exclusive breastfeeding of infants under 4 months of age and assess the causes of the failure of mothers to breastfeed their babies.


The population for this cross-sectional study consisted of children less than 24 months of age, who accompanied their mothers to five primary health care centers ( PHCC) in the Dammam area of Saudi Arabia. For the selection of these health centers a simple random sampling method was adopted and all the children in this age group were included in the study. A pre-designed and pre-tested questionnaire was used  to collect  information on age, sex, nationality, education of mothers and feeding practice of the preceding 24 hours. This 24-hour recall period has been used widely and found  appropriate. The  following  recommended WHO indicators for assessment were used in the study:8

Breastfeeding: The child who receives breast milk (direct from the breast or expressed).

Exclusive breastfeeding: The infant has received only breast milk from its mother or a wet nurse, or expressed breast milk, but no other liquids or solids with the exception of drops  or  syrups   consisting  of vitamins, mineral supplements or medicines.

Predominant brestfeeding: The  infant’s  predominant source of nourishment has been breast milk. However, the infant may also have received water and water based drinks (sweetened and flavored water, tea, infusions, etc), fruit juices, oral rehydration salts (ORS) solutions, drops and syrup forms of vitamins, minerals and medicines, and ritual fluids (limited quantities). With the exception of fruit juices and sugared water, no food-based fluid is allowed under this definition.

Complementary feeding: The child who has received both breast milk and solid (or semi solid) food.

Bottle-feeding: The child  has received  liquids/semi liquid food from a bottle with a nipple or a teat.


A total of 1185 children under 24 months of age were covered in the study. Out of these, 52.4% were boys and 47.6% were girls. The percentage of Saudi children was 87. The ag

e group distribution of these children was

done keeping the recommended indicators in view (Table 1). These measuring indicators are 4 periods of equal duration (4 months/120 days), which take into consideration age-based recommendations. Table 2 shows results of the study group compared with  the recommended levels. There  were   33.8%    children   who were

Table 1: Distribution of children under 24 months in the study

Age group in months


Boys (%)

Girls (%)

< 4


120 (49.23)

132 (50.7)

4 – 5


36 (48.0)

39 (52.7)

6 – 9


112 (54.63)

93 (45.37)

10 – 11


55 (52.38)

50 (47.62)

12 – 15


135 (54.0)

115 (46.0)

16 – 19


80 (53.33)

70 46.67)

20 – 23


75 (53.57)

65 (46.43)



621 (52.41)

564 (47.59)

Table 2: Comparison between observed and recommended levels of breastfeeding (BF)



Age *

Recommended levels

Observed levels (%)



< 4




Breastfeeding timely

< 4




Feeding rate


All infants after 6 months



Breastfeeding rate at 1 year


Preferably breastfed


Breastfeeding rate at 2 years


Preferably breastfed


Bottle feeding rate

< 24



* in months

Table 3: Distribution of indicators with other countries

Exclusive breastfeeding rate < 4months

Predominant breastfeeding rate <4months

Breastfeeding rate 12-15 months

Study group












Sri Lanka




Recommended WHO



Preferably breastfed

Table 4: Reasons given by the mothers for failure to breastfeed



Insufficient breasmilk


Learning from other mothers


Advertised baby foods




Lactation failure


Working outside home


Use of medicine


Refusal after illness


Breast infection


Advised by the doctors


exclusively breastfed up to  4  months  of  age. Predominantly breastfed children were only 11.54%. The timely complementary feeding rate was only  31.71%. However, continued breastfeeding rates at the ages of 1 year and 2 years were 42% and 32.14%, respectively. As we compare the observed levels with the recommended levels, we find that the children in the study group are far behind the recommended  levels. However,  the  comparison with other countries is shown in Table 3.

                                Table 4 shows the causes of breastfeeding failure in order of their frequency as learnt from the mothers. The majority of mothers attributed the failure to the insufficiency of milk; the next group stopped on the advice of other mothers and some as a result of advertised milk formula.


Though the changes in child mortality are difficult to measure and cannot be easily attributed to a specific  intervention, the estimated  benefits  and the protective effects of  breastfeeding against infant mortality and in terms of child survival have been well documented.9,10 The infant should be exclusively breastfed for at least 4 months of life and if possible for 6 months, as recommended by WHO and UNICEF. Human milk meets all the nutritional requirements of infants for the first 6 months of life, and is associated with a lower incidence of diarrhea than partial or artificial feeding.11-13 In our study (Table 2), the breastfeeding indicators, particularly exclusive breastfeeding under 4 months of age, which was only 33% were far below the recommended levels but comparable to the results from other countries as reported by WHO (Table 3).14 The declining trend of exclusive breastfeeding from 90% to 50% at the age of 3 months has also been reported in Saudi Arabia.15 The low level of exclusive breastfeeding is a matter of concern, because this indicates that these infants are being exposed to increased nutritional and other risks with the introduction of complementary foods. Even in societies where breastfeeding is the norm, mothers often introduce complementary feeding or drinks at an early age.

                                The exact age at which complementary feeding should be introduced varies from child to child. However the preference for 4-6 months is that all infants of less than 4 months should be fed exclusively on breastmilk. Retarded growth on breastmilk means  that   the child is receiving  complementary feeds. Solids/semi solid  foods  should not be  introduced to infants before the age of 4 months.16 After 6  months all infants should receive other foods in addition to the breastmilk, since this does not provide the adequate amounts of nutrients needed by an infant of that age. However, it has been shown that the children who remain breastfed are less likely to develop deficiency signs.17-19 One of the commonest reasons given by the mothers in our study, for not breastfeeding their babies and introducing complementary foods early, was that the milk was insufficient for the baby. This  assessment  by mothers regarding the insufficiency of milk and the poor quality of milk has also been reported by WHO and many independent studies.20-24 It is well-known  that  almost  all mothers can produce enough milk for one or even two babies, provided the baby suckles effectively and breastfeeds as often as he or she wants. Even when the mother thinks her milk is insufficient, her baby gets all the milk he or she needs. In societies where the mother’s diet is often poor, most are able to produce breastmilk in amounts adequate for the proper growth of their babies.14,25

                                All the causes shown in table 4 are simple and modifiable and do indicate that if informed about the benefits and  process of breastfeeding, these mothers are likely to start breastfeeding. Basically, breastfeeding requires a behavioral change, involving a change in attitude towards breastfeeding. A mother who wishes to breastfeed her baby, with professional and family support is likely to succeed as mothers of earlier generations had done even with little breast preparation. Doctors who are in frequent contact with mothers during perinatal period, the most  sensitive  and  receptive period, are in a good position to encourage breastfeeding, give support  and  solve problems. Lactation problems which generally arise in the immediate postnatal period, particularly among new mothers, lead to breastfeeding failure if not resolved in time. It has been shown that a coherent approach to breastfeeding by health workers has a major  impact   on  the  initiation and sustaining of breastfeeding.26

                                Other aspects of breastfeeding which have  been examined  include ethnicity, income, education, personal and social determinants. It has been emphasized that urbanization, education and standard of living directly influence breastfeeding practice and as these factors increase breastfeeding declines.27,28 Moreover, with the influence of aggressive marketing of infant formulas directly to parents via television and the media, breastfeeding is no longer fashionable.29 In Saudi Arabian society, the tremendous socioeconomic change, and urbanization have contributed to the downward trend. Special practical approaches applicable to our society should be developed and  adopted to make exclusive breastfeeding successful. This could be done by building mothers’ confidence on their ability to provide enough breastmilk, by removing her doubts on how breastfeeding works, emphasizing its advantages and giving proper follow-up support.30,31 Although maternity services, training in lactation management and rooming in, in certain  places  have  increased the initiation of breastfeeding, what is needed is support for the continuation of breastfeeding at home particularly in the rural areas, where a substantial proportion of deliveries generally occur. We have to develop integrated community-based approaches such as voluntary mother counseling through home visits and self-help groups, assist and foster the role of medical personnel during perinatal period.

                                In  conclusion, we  believe that the practice of exclusive breastfeeding is very low and its improvement can further reduce infant morbidity and mortality and that breastfeeding up to 2 years of age should be encouraged. In order to achieve the recommended goals for breastfeeding, certain things must be done:

1.        Assist expectant mothers in pre- and postnatal periods to initiate breastfeeding.

2.        Increase community-based educational programs  for mothers and families to dispel the myths and misconceptions about breastfeeding.

3.        Popularize breastfeeding in the media  to counter aggressive advertisement of infant formulas.

4.        Ensure post delivery support with the proper follow-up to provide information and solve lactation problems.

5.        Prepare future  doctors  to meet  this challenge of helping mothers to breastfeed their babies successfully in order to improve their children’s health.


We are highly grateful and appreciative of the assistance given by the doctors in the primary health care centers in the Dammam area.



1.   Kohler L, Meeuwisse G, Mortensson W. Food intake and growth of infant between six and twenty six weeks  of age on bareastmilk, cows milk, formula or soy formula. Acta Paediatr Scand 1984;73:40-8.

2.Butte NF, Garza C, Smith EO, Nichols BL. Human milk and growth in exclusive breastfed infants. J Paedtr 1984;104:187-95.

3.   Underwood BA, Hofvander Y. Appropriate timing for complementary feeding of the breastfed infant. Acta Paediatr Scand 1982;294(Suppl):1-32.

4.   Rowland MGM. The “why and when” of introducing food to infants. Growth in young breastfed infants and some nutritional implications. Am J Clin Nutr 1985;41:459-63.

5.    Seward JF, Serdule MK. Infant feeding and infant growth. Pediatrics 1984;74(Suppl):728-62.

6.     Victora CG, Vaughan JP, Lomberdi C, Fuchs SMC, Gingate LP, Smith PG, et al. Evidence for protection by breastfeeding against infant death from infectious diseases in Brazil. Lancet 1987;2:319-22.

7.    Feachem RG, Kobeinky MA. “Intervention for the control of diarrhoeal diseases among children: promotion of breastfeeding”. Bull WHO 1984;62(2):271-91.

8.   World Health Organization, indicators for assessing breastfeeding practices, June 91. WHO/CDD/SER/91.

9. American Academyof Paediatrics, committee on nutrition, on the feeding of supplementary food in infants. Pediatr 1980;65:1178-81.

10.  Akre J. Infant feeding: physiological basis. Bull WHO 67 (suppl); 1-108.

11. Habicht JP, Da Vanzo J, Butz WP. Does breastfeeding really save lives or are potential benefits due to biases. Am J Epidemiol 1986;123:279-90.

12. Qadri MH, Al-Gamdi MA, Musharaf A, Haq MI. A study on diarrhoeal disease in children under 5 years of age. Annals of Saudi Medicine 1992;12(5):459-62.

13. Al-Sekait MA. A study of factors affecting incidence of diarrhoeal disease in chidren under 5 years in Saudi Arabia. Saudi Medical Journal 1988;9(5):491-7.

14. World Health Organization, Interim Report 1994. Division of diarrhoeal and acute respiratory disease control. WHO/CDR/95.1.

15. Al-Sekait MA. A study of the factors influencing breastfeeding pattern in Saudi Arabia. Saudi Medical Journal 1988;9(6):596-601.

16. American Public Health Association Policy Statement. Infant feeding in United States. Am J Public Health 1981;71:207-10.

17. Scrimshaw NS, Waterlow JC, Schurch B. Energy and protein requirements. Eur J Clin Nutr 1996;50(Suppl):1-4.

18. Dewey K, Brown K, Allen L. Presentation on recent recomemndations for infant and young feeding based on recent studies on growth of exclusive breastfed infants and revised estimates of energy/protein requirements. March 1996, at USAID, Washington DC.

19. Sommer A, West KP. Vitamin A deficiency: health, survival and vision. New York: Oxford UniversityPress, 1996.

20. Winikoff B, Castle MA, Laukaran VH. Feeding infants in four societies, causes and consequences of mother choices. USA:Green Wood Press; 1988.

21. Maritines JC, Ashworth A, Krikwood B. Breastfeeding among the urban poor in southern Brazil: reasons for termination in the first 6 monhs of life. Bull WHO 1989;67(2):151-61.

22. Hiller VC. Studies on perceived breastmilk insufficiency, a prospectice study in a group of Swedish women. Acta Paed Scan 1991;80:627.

23. Forman MR, Lewando-Hundt G, Gaurdard GL, Chang D. Factors influencing milk insufficiency and its long term health effects: the Bedouin infant feeding study. Intern J of Epidemiology 1991;21(1):53-8.

24. Segura-Millan S, Dewey KG, Perz ER. Factors associated with perceived insufficiency of milk in a low income population in Mexico. J Nutr 1994;124:202-12.

25. Prentice AM, Goldberg GR, Prentice A. Body mass index and lactation performance. Eur J Clin Nutr 1994;48(Suppl 3):78-89.

26. Adair LS, Popkin BM, Ginlkey DK. The duration of breastfeeding and how is it affected by biological, sociodemographics. Health Sector and food industry, factors, Demography 1993;30(1):63-80.

27. Yeung DL, Pennell MD, Leung M, Hall J. Breastfeeding: prevalence and influence factors. Can J Public Health 1981;72:323-30.

28. McCann MF, Liskin LS, Piotrow PT. Breastfeeding, fertility and family planning. Pop Rep J 1981;9:525-75.

29. Ryan AS, Lewandowski G, Krieger FN. The decline in breastfeeding 1984-1989. Paediatrics 1991;8:873-74.

30. World Health Organization, Breastfeeding counseling, A training course. Division of Doarrhoeal Disease and Acute Respiratory Disease Control, Document WHO/CDR.93, 3-6

31. UNICEF. Breastfeeding counseling. Nutrition section, Document UNICEF Nut /93.1-4.




Abdulrazzak Alhamad, MD,* Eiad A. Al-Faris,MRCGP†

Departments of *Psychiatry and †Family and Community Medicine, Collegeof Medicine, King Saud University, Riyadh, Saudi Arabia

هدف الدراسة: الهدف من هذه الدراسة هو تقنين الترجمة العربية لاستبانة الصحة العامة-28 في عيادات الرعاية الصحية الأولية بالمملكة العربية السعودية.

طريقة الدراسة:تم اختيار ستين مريضا سعوديا بطريقة عشوائية منظمة حيث طلب منهم تعبئة نموذج استبانة الصحة العامة –28 ثم تم فحصهم من قبل استشاري الطب النفسي باستخدام الترجمة العربية لبيان المقابلة السريرية.

نتائج الدراسة:لقد وجد أن الحد الأفضل للاستبانة عند أعلى قيمتين لحساسية الاستبانة ودقته هي 4/5 ووجد أن معايير التقنين عند هذا الحد هي الحساسية (72%)، الدقة ( 74%) مقدار التشخيص الإيجابي (72%) ، مقدار التشخيص السلبي ( 74%) ونسبة خطأ التشخيص (27%). وقد وجد معامل الارتباط (+ 0.61) ومعامل ارتباط سبيرمان ( + 0.57) ووجد أن المساحة تحت منحنى روك ( 69%). إن نتائج هذه الدراسة في الحد الأفضل مشابهة لغيرها من الدراسات في الرعاية الصحية الأولية. وبالرغم من أن معايير التقنين منخفضة نسبيا، إلا أنها في حدود الذي وجدته الدراسات الأخرى سواء في الولايات المتحدة أو بريطانيا أو الدول الأخرى النامية. وهذا يؤكد الاقتراح بضرورة إيجاد استبيان للصحة العامة خاص بالبيئة العربية يقوم على النسخة المترجمة لاستبيان الصحة العامة مع إضافة أسئلة تختص بالبيئة للمساعدة في تشخيص المرض النفسي.

الخلاصة:إن النسخة العربية لاستبيان الصحة العامة-28 تعتبر مقننة على البيئة السعودية في عيادات الرعاية الصحية الأولية ويمكن أن تساعد أطباء الرعاية الأولية كثيرا على زيادة اكتشاف الإضرابات النفسية وكذلك في الأبحاث المسحية لها.

الكلمات المرجعية:استبيان، الصحة العامة، الرعاية الأولية، المملكة العربية السعودية.

Objective:The objective of this study was to validate an Arabic version of the General Health Questionnaire (GHQ-28) in a primary care setting in Saudi Arabia.

Methodology: A total of 60 Saudi patients selected by means of systematic random sampling  were  asked  to fill out the GHQ-28 Arabic version. The psychiatrist interviewed all patients using the Arabic version of the Clinical Interview Schedule (CIS).

Results:The best cut-off level  for the GHQ-28 indicating best trade-off between sensitivity and specificity was 4/5, where the validity values were, sensitivity; 72%, specificity; 74%, positive predictive value; 72%, negative predictive value; 74% and misclassification rate; 27%. The correlation coefficient was r = +0.61 and the Spearman’s Rank-difference correlation was rs = +0.57. The area under the ROC Curve was 69%. The cut-off point 4/5 in this study is the same as recommended by others in primary  care settings. Although  the validity parameters are relatively low,

Correspondence to:

Dr. Abdulrazzak Alhamad, Assistant Professor and Consultant Psychiatrist, Head, Division of Psychiatry, College of Medicine, King Saud University, P.O. Box 7805, Riyadh 11472, Saudi Arabia

they are within the range  found by other studies in  USA, UKand developing   countries. This supports the suggestion to develop an  Arabic  Screening  Questionnaire based on the translated GHQ with the addition of culturally specific items.

Conclusion:The GHQ-28 Arabic Version is a valid instrument that may be of great help to primary care doctors in improving detection of psychiatric morbidity and in epidemiological research.

Key Words:General Health Questionnaire, Primary Care, Saudi Arabia


The General Health Questionnaire (GHQ) in its full 60-items, or abbreviated 30 and 28 items version is by  far the most popular screening instrument.1 It is a self-reporting questionnaire developed by Goldberg (1970), to detect functional psychiatric disorders in the community and primary care settings.2,3 It has been extensively tested in various cultures and linguistic groups in primary care and other settings generally showing good validity results.4-9 Tarnopolsky et al suggested that the GHQ should be standardized on the population where it is to be applied, because validity coefficients obtained in one setting do not necessarily hold in another.4 Psychiatric disorders are shown to form a major part of morbidity in Saudi primary health care, and the vast majority of cases  are missed.10,11 Therefore, validation of a screening instrument such as the GHQ in the patients’ language takes a little time, and is  important  in  epidemiological research to improve detection  and  recognition of psychiatric morbidity.3,4 A medline and a Saudi literature search showed no study that validated the GHQ in primary health care in Saudi Arabia.

The objective of the present study was to validate an Arabic version of the GHQ-28 (see appendix) in primary care setting in Saudi Arabiaagainst the  Psychiatrist’s assessment by  means of the  Clinical  Interview Schedule (CIS).


Subjects:The study was carried out in the primary care center attached to King Abdulaziz University Hospital. It is situated in the center of Riyadhand serves mostly a Saudi population of different social classes. The study population included patients of both sexes above 14 years of age attending the primary care clinics for any reason.

A total of 60 Saudi patients selected by means of systematic random sampling were asked to fill out the GHQ-28 Arabic version while waiting  to  be seen by their doctor. Patients who were found to be illiterate or experienced difficulty in filling out the questionnaire were helped by a trained nurse.

All patients were interviewed by the first author, a consultant psychiatrist with eleven years post-qualification experience, using the Arabic version of the CIS. Each patient was given a score on the psychiatric severity  rating (0-4) as follows: 0=no  psychiatric disturbance, 1=mild subclinical psychiatric  disturbance, 2=clinically significant (mild) psychiatric  disturbance, 3=clinically  significant (moderate)  psychiatric disturbance, 4=clinically significant (marked) psychiatric disturbance.

Instruments:For the  present  study the instruments CIS and GHQ-28 were translated into Arabic by two Arab psychiatrists. The reliability of the Arabic versions was checked with a translation into English by another psychiatrist who had no knowledge of the instrument and  they were found  to  be in close agreement. The underlying assumption is that   the psychiatrist’s assessment using the CIS is the gold standard against which the  GHQ-28  is  compared. The CIS is divided  into  four  sections containing ratings based on symptoms reported by the patient (arranged in ten groups), twelve items that represent the interviewer’s view of the manifest abnormalities and an ICD clinical diagnosis. The scoring of the GHQ-28 depends on the response category the patient chooses for each of the 28-items and  the scoring developed by Goldberg (1970) was used to count responses in codes 3 and 4 only. The GHQ-28 version was chosen for the study because it was short and was found to be more valid than both the GHQ-12 and the GHQ-30.12

Validation parameters:The validity of the GHQ-28 was estimated by the following: evaluating the sensitivity and specificity at best trade-off point; estimating the positive predictive value, the negative predictive value and the misclassification rate; determining the simple correlation coefficient (r) and the Spearman’s Rank-Difference Correlation values; finding the confidence intervals between observed data values of GHQ-28 and its predicted data values in a scattergram; and using the Receiver (relative) operating characteristic (ROC) analysis. The ROC curve is  a graphic representation of the relationship between sensitivity and specificity for a diagnostic instrument. It is constructed by plotting the sensitivity (true positive rate) against the false positive rate (1-specificity) for all possible GHQ-28 cut-off points. The resulting plot, which takes the shape of a curve, is known as a ROC curve (figure 1).13


A total of sixty patients, 30 males and 30 females were included in the study. The age range was 14-70 and the mean age was 28.1+ 10.77. The mean age for males was 29.17 + 10.99 and for females was 27.1 + 10.63.

Figure 1:ROC curve of the GHQ-28

Table 1 shows different cut-off levels of the GHQ-28 (2/3) through (20/21) and their comparable sensitivity, specificity, positive predictive values and negative predictive values. Patients who  scored above  these threshold levels were considered as probable cases while those who scored below them were considered probable normals. The overall best cut-off level indicating the best diagnostic ability of the GHQ-28 was found to be 4/5, where the misclassification rate was 27%, the sensitivity was 72%, the specificity was 74%, the percentage  of  cases missed was 14%, the positive predictive value was 72% and the negative predictive value was 74%. The validity values for males and females respectively were sensitivity 64% and 80%, specificity 81% and 66.9% and misclassification rate was 26.7% for both sexes.

The ROC curve of the GHQ-28 (Figure 1), showed that it was a valid test and the area   under the curve measured graphically was 69%. When the GHQ-28 scores were plotted against the CIS overall severity rating scores, the correlation coefficient was r=+0.61 and  the p-value approached zero; the Spearman’s Rank-difference correlation was rs=+0.57 and

Table 1:GHQ-28 threshold scores and their validity parameters

Threshold score

Sensitivity %

Specificity %

+ve predictive value %

-ve predictive value %
































































































the p-value approached zero which is highly significant (figure 2). The scattergram of data and regression line were also found to be highly significant and the confidence limit was 99.0% (figure 3).


This study has shown that the GHQ-28 is a valid and useful screening instrument of psychiatric morbidity in a primary care setting in Saudi patients. The best cut-off point was found to be 4/5 which is comparable to what was recommended by Goldberg for general practice settings.3 This cut-off point represented the best trade-off between sensitivity (72%) and specificity (74%). Although, the validity of the GHQ-28 in our study was not high, it was still in the range  reported  in  many other studies.4,9,14,15Even though, Goldberg9 had higher sensitivity and specificity values, other studies conducted in British and United States  communities  had  lower values for sensitivity and specificity comparable to our rsults.15-17 Table 2 shows data comparing different validation studies  of  the 

Figure 2:GHQ-28 and CIS scores


Table 2: GHQ-28 different validation studies


Cut-off point

Sensitivity %

Specificity %

Correlation coefficient (r)

Misclassification rate

Goldberg (1972)






Goldberg & Hillier (1979)






Tarnopolsky et al (1979)






Present study






Figure 3:Scattergram of data & regression line & confidence intervals

GHQ-28 in the primary care setting. The  relatively  lower value of sensitivity for males and specificity for females is consistent with other studies.18,19 On the other hand, since previous studies have not shown strong associations between sex and GHQ validity,2 our results might show that a higher cut-off level may be used for females. This may be explained by the tendency of Saudi females to somatise.13,20 Women in general tend to report more symptoms5 and score high on the GHQ, thus attaining  false-positive  rates,  and  reducing the specificity.

The validity of the GHQ-28 was also shown to be very good by the ROC curve, which had been used previously in the validation of the GHQ-28.5,13,18

The use of longer GHQ versions may increase validity,2,3 but shorter ones such as the GHQ-28 are still valid and take much less time. Primary care physicians miss about 50% of psychiatric cases10,16,21 and the use of the GHQ-28 may  be  useful to improve detection rate. Goldberg suggests that when a patient is found to have a high score, the most natural response by the clinician is to look at the questionnaire again with the patient and ask additional probing questions suggested by particular symptoms.3,16 It is also important to note that GHQ-28 has been found to have an important role in alerting primary care doctors not  to miss  new episodes of psychiatric morbidity in patients with chronic physical diseases.16

Hence, GHQ-28 is useful in epidemiology.3,4,16,18 The present validation study is also important for researchers who intend to estimate the prevalence of psychiatric disorders in primary care in  the Saudi communities and plan services to improve recognition and diagnosis of psychiatric morbidity in primary care.

The fairly low  validity in our study conforms with other validity studies in developing countries and may strongly support the suggestion by other researches22,23 to develop and  validate  a new Arabic screening questionnaire that builds on the translated GHQ with the addition of specific items relevant to the Saudi culture for the identification of psychiatric morbidity.


1.   Mayou R, Hawton K. Psychiatric disorders in the General Hospital. British J Psych 1986;149:172-90.

2.   Goldberg D. Manual of the General Health Questionnaire. Windsor( UK): National Foundation for Educational Research; 1978.

3.   Goldberg D. Use of the General Health Questionnaire in Clinical Work. BMJ 1986;293:1188-9.

4.   Tarnopolsky A, Hand DJ, Mclean EK. Validity and uses of a screening questionnaire (GHQ) in the community. British J Psych 1979;134:508-15.

5.   Bridges KW, Goldberg DP. The validation of the GHQ-28 and the use of the MMSE in neurological inpatients. British J Psych 1986;148:548-53.

6.   Mari JJ, Williams P. Minor psychiatric disorder in primary care in Brazil: A pilot study. Psychological Medicine 1984;14:223-72.

7.   Cheng TA. A pilot study of mental disorders in Taiwan. Psychological Medicine 1985;15:195-204.

8.   Sato T, Takeichi M. Lifetime prevalence of specific disorders in a general medicine clinic. General Hospital Psychiatry 1993;15:224-33.

9.   Goldberg DP, Blackwell B. Psychiatric illness in general practice: a detailed study using a new method of case identification. BMJ 1970;2:439-43.

10.Al-Faris EA, Alhamad A, Al-Shammari S. Hidden and conspicuous psychiatric morbidity in Saudi primary health care (A pilot study). The Arab J of  Psychiatry 1995;6:162-75.

11.Al-Faris E, Al-Subaie A, Khoja T, Al-Ansary L, Abdul-Raheem F, Al-Hamdan N, et al. Training primary health care physicians in Saudi Arabia to recognise psychiatric illness. Acta Psychiatr Scand 1997;96:439-44.

12.Banks MH. Validation of the General Health Questionnaire in a young community sample. Psychological Medicine 1983;13:349-53.

13.Ly Kouras, Adrachta D, Kalfakis N, Oulis P, Voulgani A, Christodoulu GN, et al. GHQ-28 as an aid to detect mental disorders in neurological inpatients. Acta Psychiatr Scand 1996;93:212-6.

14.Goldberg DP. The detection of psychiatric illness by questionnaire. London: Oxford UniversityPress; 1972.

15.  Goldberg D. Identifying psychiatric illness among general medical patients. BMJ 1985; 291:161-2.

16.Wright AF, Perini AF. Hidden psychiatric illness: use of the general health questionnaire in General Practice. Journal of the Royal Collegeof General Practitioners 1987;37:164-7.

17.  Cleary PD, Goldberg ID, Kessler IG, Nyez GR. Screening for mental disorder among primary care patients. Archives of general psychiatry 1982;39:837-40.

18.  Stanfeld SA, Marmot MG. Social class and minor psychiatric disorder in British civil servants: a validated screening survey using the GHQ. Psychological Medicine 1992;22:739-49.

19.Hobbs P, Ballinger  CB, Greenwood C, Martin B, McClure A. Factor analysis and validation of the General Health Questionnaire in men: A general practice survey. British J Psych 1984;144:270-5.

20.Racy J. Somatisation in Saudi women: a therapeutic challenge. British J Psych 1980; 137:212-6.

21.  Goldberg D, Steele JJ, Johnson A, Smith C. Ability of Primary Care Physicians to make accurate ratings of psychiatric symptoms. Archives of General Psychiatry 1982;39:829-33.

22. Fontanesi F, Gobetti C, Zumermann-Tansella CH, Tansella M. Validation of the Italian version of the GHQ in a general practice setting. Psychological Medicine 1985;15:411-15.

23. Cheng T, Williams P. The design and development of a screening questionnaire (CHQ) for use in community studies of mental disorders in Taiwan. Psychological Medicine 1986;16:415-22.




Khalid S. Al-Ghamdi,FFCM (KFU), Rumana Rehman, MBBS

Armed Forces Hospital, Jubail, Saudi Arabia

هدف الدراسة: تقييم توزيع اعتلال نسبة الدهون والسمن بين مرضى السكر المراجعين لعيادة الرعاية الصحية الأولية.

طريقة الدراسة:شملت الدراسة جميع مرضي السكر المسجلين في عيادة الرعاية الصحية الأولية في مستشفى القوات المسلحة بقاعدة الملك عبد العزيز البحرية بالجبيل، شرقي المملكة العربية السعودية، وعددهم 282 مريض سكر سجلوا وأجريت لهم المقابلة الشخصية بواسطة أطباء الرعاية الصحية الأولية. ثم سجلت أوزانهم وأطوالهم وكذلك تم تسجيل نسبة السكر والكوليسترول في الدم بعد صيام 12 ساعة.

نتائج الدراسة: أظهرت الدراسة وجود السكر من النوع الأول بين 10.3% من عينة الدراسة بينما شكلت الغالبية ( 89.7%) النوع الثاني. كان مؤشر كتلة الجسم طبيعيا في 22.7% من عينة الدراسة. بينما كان 40.8% من العينة زائدين في الوزن و 36.5% منهم بدينين ( ذوى سمنة). مؤشر كتلة الجسم كان أعلى في النساء من الرجال(بدلالة إحصائية أقل من 0.001). نسبة الكوليسترول في الدم كانت أعلى من الحد الطبيعي في 26% من عينة الدراسة، والبروتين الدهني القليل الكثافة في 27% من العينة والترايجلسرايدات في 11%. أما البروتين الدهني الكثير الكثافة فقد كان أقل من المستوى الطبيعي في 38% من عينة الدراسة. وشكل اعتلال الدهون المختلطة 5 % من مرضى السكر المشاركين بالدراسة.

الاستنتاجات:زيادة الدهون والسمن كانت عالية بين مرضى السكر. وهذا يتطلب عناية خاصة في مجال الوقاية والعلاج.

الكلمات المرجعية:مرض السكر، الدهون، زيادة الكوليسترول، مؤشر كتلة الجسم، السمن.    

Objective:Evaluate the pattern of dyslipidemia and obesity among diabetics, attending the Primary Care Clinic.

Subjects and Methods:All diabetics (282) registered in the Primary Care Clinic of the Armed Forces Hospital at King Abdulaziz Naval Base, Jubail, Eastern Saudi Arabia, were interviewed by primary care doctors.Weight and height were recorded; fasting blood glucose and cholesterol levels were measured after 12-hour fasting.

Results: The study revealed that among 89.7% type 2 and 10.3% type 1 diabetes mellitus, 22.7% had a normal Body Mass Index ( BMI) 40.8%  were overweight, and 36.5%, obese. Females had a significantly higher BMIthan males (P<0.001). Total cholesterol was more than normal in 26%, LDL in 27% and Triglycerides in 11% but HDLlower than normal in 38%. However, mixed hyperlipidemia was seen in 5% of the study population.

Conclusion: Obesity and dyslipidemia  were  high among   diabetic  patients and special attention is required in prevention and treatment.

Key Words:Diabetes mellitus, lipids, hypercholesterolemia, BMI, obesity.

Correspondence to:

Dr. Khalid S. Al-Ghamdi, P.O. Box 3473, Almadina Almunawara, Saudi Arabia



Diabetes mellitus is one of the secondary causes of hypercholestrolemia.1 Hypercholesterolemia in diabetics is an additional risk factor for coronary heart disease (CHD),2,3 therefore, mortality and morbidity due to CHD are higher among those patients.4It was documented that abnormal plasma lipid level is frequently seen in diabetics especially triglycerides.5

Hyperlipidemia has been investigated in the Kingdom among healthy adults6 and patients.7 However, hyperlipidemia among diabetics has only recently been studied.8,9

These and other factors have urged the authors to evaluate the pattern of dysplipidemia and obesity among diabetics attending the Primary Health Care (PHC) Center in the Military Hospital, Jubail, in the Eastern Province of Saudi Arabia.


A total  of 282  diabetic patients were registered at the diabetic clinic in the Primary Care Department at this Military Hospitalfrom 1994 (the date when the diabetic clinic first started) through 1996. Complete history, physical examination, and investigations were done on every patient registered in this clinic.

Two nurses were assigned to this clinic after some training. Weight was measured with a previously calibrated weighing machine and height measured by those nurses. Both were recorded to the nearest decimal point.

Among the different investigations done for those patients were the fasting serum lipids. Other  investigations,  such as fasting plasma glucose and HbA1c were not used in this particular study.

Fasting serum lipids were done on a sample of blood after fasting for 12 hours. The method used for determining the cholesterol and trigylcerides levels in the laboratory was the Enzmatic method (CHILL). The BMI(which is weight divided by the square of the height) was used to assess the  degree of  obesity. The BMI  was considered normal if it was below 25 kg/m2, 25-29.9 kg/m2 overweight and 30 kg/m2 or greater was obese.10 According to the national cholesterol education program,2 the total cholesterol was considered high if it was 6.2 m mol/L and low density lipoprotein ( LDL) 4.15 m mol/L. High density lipoprotein (HDL) was regarded low <0.9 m mol/L.

All statistics were done with a personal computer using Epi-Info program. Statistics used in this study were the Chi-Squared and Student “T” test.


There were 282 diabetic patients attending the diabetic clinic at the Primary Care Department. Two hundred and fifty three were type II diabetes mellitus (89.7%) and the rest were type I (10.3%). Their ages ranged from 19 years to 91 years of age with a mean (SD) of 46 years ± 12.98.

Table 1 shows  the  distribution  of  the different groups of BMIwith their sexes. There were 212 male patients (75.2%) and 70 females (24.8%). Sixty-four of the attending patients had a normal (<25 kg/m2) BMI, 115 patients (40.8%) were over weight and 103 patients (36.5%) obese. The females had a significantly higher BMIthan the males (p<0.001).

Table 2 shows that the total cholesterol level was high (6.2 m mol/L) in 73 patients (26%). There was no significant difference between the two types of diabetes (P=0.65). Low density lipoprotein was high (4.15 m mol/L) in 76 patients (27%). On the other hand, the HDLwas low (<0.9 m mol./L) in 108 patients (38%). The triglycerides were high (4.5 m mol/L) in 32 patients (11%). Mixed hyperlipidemia (high cholesterol and triglycerides) was  found  in  13  diabetic  patients (5%).

In table 3,  it  is  shown  that diabetic males 

Table 1:The body mass index among the genders


Male (212)

No. (%)

Female (70)

No. (%)

Total (%)

< 25

55 (25.94)

9 (12.86)

64 (22.70)


93 (43.87)

22 (31.43)

115 (40.80)


64 (30.19)

39 (55.71)

103 (36.50)


212 (100)

70 (100)

Chi squared = 15.36  p-value=<0.001

Table 2:Distribution of diabetic patients having dyslipidemia

Type of lipids



No (%)

No. (%)

Total cholesterol

209 (74)

73 (26)

Low density lipid

206 (73)

76 (27)

High density lipid

174 (62)

108 (38)


250 (89)

32 (11)

Cholesterol + triglycerides

269 (95)

13  (5)

Table 3:Distribution of the mean value of lipids among the genders

Type of lipids

Males (212)

Females (70)


Mean* (SD)

Mean* (SD)


5.496 (1.11)

5.709 (1.08)


Low density lipid

3.566 (1.19)

3.685 (1.05)


High density lipid

1.104 (0.44)

1.266 (0.45)

< 0.001


2.675 (3.43)

2.256 (2.50)


*all values were measured in m mol/L


had a lower level of total cholesterol and LDLthan females. However, this difference was not statistically significant (p=0.245 and 0.444, respectively). Whereas the females had slightly higher levels of HDLthan males the difference was significant p<0.001. However, the triglycerides levels were slightly lower among diabetic  females than  males but  the  difference did not attain statistical significance.


Conflicting views have been reported  in several   studies2-5  about obesity  as   an independent  risk  factor  for  CHD. However, the  studies agree  on   the    association between obesity and hypercholesterolemia.

  In this study, female diabetics had higher BMIthan  males (p<0.001), which is consistent with the previous finding by Khandekar in 1994 in the Kingdom of Saudi Arabia.8 High intake of calories and fats may be  attributed  to the vast improvement in the economy of the country. This has influenced the change in dietary habits of the people.

It was alarming to see that 55.7% of the female diabetics were found to be obese compared to 30.2% of the males (i.e., BMI? 30 kg/m2). This may be partially explained by the fact that most females in Saudi Arabialead a sedentary life style indoors with little exercise.

Most males, however, have a more active lifestyle. Most of the males in this study were in the military and performed a variety of activities and exercise.

Atherosclerosis accounts for a considerable percentage of all diabetic mortality, the majority  of  which  is  the consequence of coronary artery disease. Hyperlipidemia is an important cause for atherosclerosis. This study  shows  the  distribution  of  the different types of dyslipidemia among our diabetic patients.


One quarter of the study population had hypercholesterolemia. Al-Nuaim9 reported 14% hypercholesterolemia among his diabetics in 1995. This figure is increasing with time, so the problem requires serious intervention in the form of health education, dietary instructions, and physical exercises.


It was reported that hypertriglyceridemia is associated with low HDLamong diabetics.2,4 Low density lipid is considered as an independent risk factor for CHD with levels 4.15 mmol/L. Twenty seven percent of the study population had this risk. None of the above mentioned references reported their mean level of LDL.


The serum level of HDLwas found to be low in 38% of the study population. This is the highest among the different types of dyslipidemia. A high level of HDLis considered a negative risk factor for CHD. Therefore, it is important to study this high proportion of diabetics in greater detail. Hypertriglyceridemia was seen in 11% of this study population and this is similar to the figure (15%) reported by Al-Nuaim.9 Reports from elsewhere by Stern et al11 showed a higher percentage (23%). The different race, socioeconomic state, and dietary habit may explain this.


In an early study by Bacchus in 198212 the cholesterol levels among healthy subjects, in this country, were reported as 4.27 m mol/L among males and 4.23 m mol/L among females. In 1991, Inam7 reported a level of 5.25 m mol/L among males and 5.49 m mol/L among females. However, in 1985 the cholesterol level among diabetics in this country was reported  as 5.2 m mol/L among  non-insulin   dependent diabetes mellitus (NIDDM).13 In this study,  the  mean cholesterol level among all the diabetic males was found to be 5.49 m mol/L and  5.71 m mol/L  among  diabetic females. These  figures  are very close to the levels reported by Khandekar8 (i.e., 5.52 m mol/L for males and 5.97 m mol/L for females). Khandekar used the same method to determine cholesterol and triglycerides  levels  in a Saudi diabetic population.


The higher level of HDLamong females than males is another evidence of the positive effect of estrogen, as  previously documented.14


The study revealed that obesity and dyslipidemia were high among diabetic patients and required special attention. This can be done through health education at the primary care level and the diabetic clinics. More health education on diet is required particularly for females with the help of the primary care physicians and the media.


1. Blake GH, Triplett LC. Management of hypercholesterolemia. American Family Physician 1995;51(5):1157-66.

2. Summary of the second report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high   blood cholesterol in adults (adult treatment panel II). JAMA 1993;269(23):3015-23.

3.Haffner SM, Stern MP, Hazuda HP. Role of obesity and fat distribution in non-insulin dependent diabetes mellitus in Mexican American and non-Hispanic whites. Diab Care 1986;9:153-61.

4.  Betteridge DJ. Diabetic dyslipidemia. Am J Med 1994; 96(6A):25S-31S.

5. Guerci B, Ziegler O. Hyperlipidemia during diabetes mellitus. Recent developments. Presse Med 1994; 23(2):82-8.

6. Mitwalli AH, AlMaatouq MA, AlWakeel J, Alam AA. Hypercholesterolemia in health adult males. A public survey in central Saudi Arabia. Ann Saudi Med 1994;14(6):499-502.

7. Inam S, Cumberbatch M, Judzewitsch R. Importance of cholesterol screening in Saudi Arabia. Saudi Medical Journal 1991;12(3):215-20.

8. Khandekar S, Noeman SA, Muralidhar K, Gadallah M, Al-Sawaf KS. Central adiposity and atherogenic lipids in Saudi diabetics. Ann Saudi Med 1994;14(4):329-32.

9. Al-Nuaim A, Famuyiwa O, Greer W. Hyperlipidemia among Saudi diabetic patients – pattern and clinical characteristics. Ann Saudi Med 1995;15(3):240-3.

10. Foster DW. Eating disorders: obesity, anorexia nervosa, and bulemia nervosa. In: Maxcy-Rosenau, editor. Public Health and Preventive Medicine. 12th ed. California: Appleton & Lange; 1986:1335-59.

11. Stern MP, Patterson JK, Haffner SM, Hazuda HP, Mitchell BD. Lack of awareness and treatment of hyperlipidemia in type II diabetes in a community survey. JAMA 1989;262(2): 360-4.

12. Baccus RA, Kilshaw BM, Madkour MM. Establishment of male Saudi Arabian reference ranges from biochemical analysis. Saudi Med J 1982;3:249-58.

13.  Kinggston M, Skooge WC. Diabetes in Saudi Arabia. Saudi Med J 1986;7:130-42.

14.Gambrell RD. Update on hormone replacement therapy. Am Family Physician 1992;46:87S-96S.




Ezzeldin M. Ibrahim,FRCPI,* Fatma A. Al-Mulhim,†KFUF, Fahd A. Al-Muhanna, KFUF,* Ali Al-Amri, ABIM*

Departments of *Internal Medicine and †Radiology, Collegeof Medicineand Medical Sciences, King Faisal University, Saudi Arabia

الهدف من الدراسة: تهدفهذه الدراسةإلى تقييم كفاءة العامل المنشط لكرات الدم البيضاء في علاج التهابات الفم المصاحبة للعلاج الكيماوي لمرضى السرطان.

طريقة الدراسة:أجريت هذه الدراسة على 49 مريضا وتم استثناء 9 منهم لتناقص عدد كريات الدم البيضاء لديهم. الغالبية من الأربعين مريضا المتبقين ( 71%) كانوا يعانون من تقرحات بالفم من الدرجة الثالثة والرابعة.

نتائج الدراسة:أظهرت الدراسة أن العلاج أدى إلى تناقص علامات الإصابة الإجمالي     ±  معدل انحراف المتوسط من 3.3 ±0.11 عند بداية التجربة إلى 2.1 ±0.12 بعد يومين من العلاج وإلى 0.95 ±0.11 بعد 5 أيام وإلى 0.23 ±0.07 بعد 10 أيام، وكان التناقص ذو مغزى إحصائي. كما تناقص متوسط علامات الإصابة الوظائفية  ±معدل انحراف المتوسط من 3.03 ±0.13 عند بداية العلاج إلى 1.58 ±0.13 بعد يومين من العلاج وإلى 0.68 ±0.11 بعد 5 أيام ثم إلى 0.15 ±0.06 بعد 10 أيام وهذا التناقص كان ذو مغزى إحصائي. وأثبتت الدراسة أن هناك قصر في مدة تقرحات الفم حيث كان 12 مريض (30%) لا يعانون من أي إصابة أو نقط من الدرجة الأولى في الإصابة الإجمالية بعد يومين من العلاج وتزايدت هذه النسبة إلى 37% بعد خمسة أيام ونسبة 100% عند انتهاء العلاج كما أن 19 مريضا (48%) وجدوا لا يعانون من أي إصابة أو نقط من الدرجة الأولى من الإصابة الوظائفية بعد يومين من العلاج وتزايدت هذه النسبة إلى 78% بعد خمسة أيام ونسبة 100% عند انتهاء العلاج كما أثبتت الدراسة عدم وجود أي آثار سلبية من العلاج.

الاستنتاجات:كان لاستخدام العامل المنشط لكرات الدم البيضاء في صورة مضمضة للفم تأثير واضح وأكيد على حدة ومدة تقرحات الفم الناتجة عن العلاج الكيميائي. ولهذا ننصح بإجراء دراسة كبيرة مقارنة مع البلاسيبو لتأكيد هذه الفائدة وتحديد الجرعة المثالية.

الكلمات المرجعية:العلاج الكيميائي، تقرحات الفم، العامل المنشط للخلايا البيضاء.

Objective:The study was designed to assess prospectively the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of chemotherapy-induced oral mucositis in non-neutropenic cancer patients.

Material and Methods:In a prospective open study, adult cancer patients with chemotherapy-induced, neutropenia-independent oral mucositis were treated with GM-CSF (Schering Plough Corporation, Kenilworth, NJ) prepared  as  mouthwash solution (5 to 10 µgm /ml). GM-CSF was administered within 24 hours of occurrence of

oral mucositis at a frequency of 4 to 6 times daily. Systemic GM-CSF was not permissible. Oral mucositis was graded according to the modified Radiation Therapy Oncology Group criteria.

Correspondence to:

Prof. Ezzeldin M. Ibrahim,Professor of Medicine and Oncology, King Fahd Hospital of the University, P.O. Box 40004, Al-Khobar 31952, Saudi Arabia

Results:Forty-nine patients were recruited but nine were subsequently excluded as they experienced neutropenia during GM-CSF therapy. The remaining 40 patients were all evaluable. Most patients had either Grade 3 or 4 gross (71%) or functional (70%) mucositis. The mean ±SEM gross oral mucositis scores for all 40 patients combined decreased from 3.3 ± 0.11 at baseline to 2.1 ± 0.12 (p<0.0001) after 2 days, 0.95 ± 0.11 (p<0.0001) after 5 days and 0.23 ± 0.07 (p <0.0001) after 10 days of therapy. Likewise, the mean ± SEM functional oral mucositis scores decreased from 3.03 ± 0.13 at baseline to 1.58 ± 0.13 (p<0.0001) after 2 days, 0.68 ± 0.11 (p<0.0001) after 5 days, and 0.15 ± 0.06 (p<0.0001) after 10 days of therapy. The duration of  severe oral mucositis was also shortened as Grade 0 or 1 (gross mucositis grading score) was evident in 12 (30%), 29 (73%), and 40 (100%) patients by the 2nd, 5th and 10th  day  of therapy, respectively. Similarly, Grade 0 or 1 (functional mucositis grading score) reported in 19 (48%), 31 (78%), and 40 (100%) patients by the 2nd, 5th and 10th day of therapy, respectively. The use of GM-CSF mouthwash was not associated with any apparent ill effect.

Conclusion: GM-CSF mouthwash as used in this study has a significant recuperative efficacy on the severity, morbidity, and duration of chemotherapy-induced oral mucositis. A large randomized, placebo-controlled study is warranted to ascertain that benefit and determine the optimal dosage and schedule.

Key Words:Chemotherapy, mucositis, G-CSF, GM-CSF



Oral mucositis as a consequence of cytotoxic therapy is a major cause of morbidity and dose-limiting toxicity in cancer patients. It was reported in up to 90% of patients after somatotoxic chemotherapy.1 Moreover, the duration and severity of that complication is strikingly associated with high-dose chemoradiotherapy and hematopoietic stem-cell transplantation.2-4 The pain in mucositis is usually intensively excruciating and may lead to weight loss from odynodysphagia. Furthermore, the breakdown of the mucosal epithelium barrier exposes cancer patients to infection and subsequent septicemia particularly in association with chemotherapy-induced neutropenia.5,6 On the other hand, neutropenia and local secondary infection can also aggravate oral mucositis after chemotherapy. Moreover, severe sloughing of the oral  mucosa  may  lead to airway compromise and may necessitate parenteral nutrition.

                        The efficacy of recombinant human hematopoietic growth factors in improving the neutropenic state is well documented.7-11 Recently, a coincidental 75% decrease in oral mucositis associated with granulocyte colony-stimulating factor (G-CSF) and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy of genitourinary cancer was first reported by Gabrilove et al.12 The mucosal protection effects of G-CSF of granulocyte-macrophage colony-stimulating factor (GM-CSF) were also observed in other chemotherapy regimens.13-16 One report showed a lowered incidence of oral mucositis when GM-CSF was given after 5-FU/leucovorin chemotherapy of low myelotoxicity.17 In most of these reported studies, however, the effect of hematopoietic growth factors on oral mucositis was not the primary end point.


                        Systemic administration of G-CSF or GM-CSF is effective in both reducing the severity and shortening the duration of neutropenia after chemotherapy. There is still some uncertainty as to whether GM-CSF has a direct salutary effect on the oral mucosal healing process independent of the improvement of neutropenia. However, a recently published crossover study has demonstrated the prophylactic efficacy of GM-CSF in head and neck cancer patients receiving a somatotoxic chemotherapy combination.18 In this study, the reduction of the severity and duration of oral mucositis, that was the primary study goal, was independent of chemotherapy dose-intensity, myelotoxicity, or median leukocyte nadirs.

                        On the other hand, data that advocate the therapeutic efficacy of hematopoietic growth factors are very limited and only anecdotal.19 We theorized that GM-CSF could have an advantageous therapeutic effect on oral mucositis that may be shown best if the agent is used as mouthwash. Our preliminary data on a small number of patients supported that concept.20 Therefore, the present larger study was designed to assess the healing effect of GM-CSF mouthwash on oral mucositis independent of the confounding effect of neutropenia or its correction. The therapeutic strategy also eliminates the variability in somatotoxic potential of various chemotherapeutic agents.



Eligibility criteria:In a prospective, open label study, adult patients seen at King Fahd Hospital of the University, Al-Khobar, with chemotherapy induced oral mucositis without neutropenia (neutrophilic count 2.0 x 109/l) were eligible. Patients were enrolled between July 1996 and June 1997. Patients who developed neutropenia during GM-CSF mouthwash were  excluded  from  the main analysis. Patients could not have concurrent fungal or bacterial infection (as proven by culture), and no local radiotherapy to the oropharynx region within 3 months. Any agent that may ameliorate or worsen the mucositis was not permitted. Systemic GM-CSF was not routinely given, and rendered enrolled patients non-evaluable if required.

Treatment plan:GM-CSF(Schering Plough Corporation, Kenilworth, NJ) was prepared as a mouthwash solution with concentrations of 5 to 10µgm/ml. The  preparation was  administered within 24 hours of occurrence of oral mucositis. Patients were instructed to use the solution 4 to 6 times daily and to retain and gargle the  fluid for as long as possible. Therapy continued until complete resolution of the mucositis or if no benefit was achieved for 10 days. Informed written consent was obtained from each patient.

Evaluation methods:Patients were assessed daily and mucositis was graded according to modified Radiation Therapy Oncology Group criteria (Table 1).18 The duration of mucositis was also determined. Complete blood cell counts were performed every other day or more frequent if indicated.

Statistical analysis:Mucositis scores are expressed as the mean ± SEM. The ‘t’ test was used to compare the mean severity scores at entry for all patients combined against that at 2nd, 5th, and 10th day of therapy. As multiple comparisons were used (6 for each type of mucositis score), based on the Bonferroni method, a conservative p value less than 0.008 was considered significant.


Forty-nine patients entered onto the trial. All patients had received somatotoxic chemotherapeutic agents mainly 5-flurouracil, methotrexate, and anthracylines. Nonetheless, neutropenia developed in 9 patients 4 of whom  experienced  febrile  episodes that required institution of  systemic GM-CSF. All


Table 1:Oral mucositis grading scores

Type of

Grade (symptoms)







Gross (assessed by physician)



Patchy mucositis

(< ½mucosa)

Confluent fibrinous mucositis

( ½mucosa)

Hemorrhage and necrosis

Functional (assessed by patient)


Mild soreness, mild dysphagia, solid diet possible

Moderate soreness, moderate dysphagia, soft diet or liquid diet possible

Severe pain, severe dysphagia, liquids only

Requires parenteral or enteral support


9 patients were analyzed separately. The remaining 40 patients were evaluable and constituted the basis of this report. Table 2 depicts the clinical characteristics of those patients. There were 24 men and 16 women with a median age of 41 years (range, 18 to 75). Seventy-one percent and 70% of patients had either Grade 3 or 4 of the gross and functional mucositis grading scores, respectively.

                        Table 3 depicts the mean mucositis scores of all 40 patients combined at baseline and at the 2nd, 5th, and 10th day. The table shows that the mean mucositis scores, both gross and functional, decreased significantly as compared with estimates at entry.

                        The duration of severe oral mucositis was also shortened as Grade 0 or 1 (gross mucositis grading score) was evident in 12 (30%), 29 (73%), and 40 (100%) patients by the 2nd, 5th, and 10th day of therapy, respectively. Likewise, Grade 0 or 1 (functional mucositis grading score) reported in 19 (48%), 31 (78%), and 40 (100%) patients by the 2nd, 5th, and 10th day of therapy, respectively. The use of GM-CSF mouthwash was not associated with any apparent ill effect.

                        As for the 9 patients excluded from the analysis due to neutropenia, subjective and objective improvement was demonstrated within 3 to 4 days of therapy.


Reduction of chemotherapy-induced oral mucositis was first observed coincidentally with amelioration of neutropenia after chemotherapy  in clinical trials of G-CSF or GM-CSF  in cancer  patients.12 A decreased   incidence of oral mucositis was also observed in bone marrow transplant patients given G-CSF



Table 2:Patients’ characteristics



No. of patients (%)

Total no. of patients




24 (60)


16 (40)



12 (30)

Head and neck

9 (23)


7 (18)

Non-Hodgkin’s lymphoma

6 (15)


4 (10)

Hepatocellular carcinoma

1 (4)


1 (4)

Gross mucositis grading score at baseline


2 (5)


10 (25)


15 (38)


13 (33)

Functional mucositis grading score at baseline


2 (5)


10 (25)


20 (50)


8 (20)








Table 3:Mean mucositis grading scores for all  40 patients  combined at baseline and  compared to that at the 2nd, 5th and 10th day

Gross Oral Mucositis Grading Scores (mean ±SEM)

Baseline (3.30 ± 0.11)

2nd day (2.10 ± 0.12)

5th day (0.95 ± 0.11)

2nd Day (2.10 ± 0.12)


5th Day (0.95 ± 0.11)



10th Day (0.23 ± 0.07)




Functional Oral Mucositis Grading Scores (mean ±SEM)

Baseline (3.03 ± 0.13)

2nd day (1.58 ± 0.13)

5th day (0.68 ± 0.11)

2nd Day (1.58 ± 0.13)


5th Day (0.68 ± 0.11)



10th Day (0.15 ± 0.06)





or GM-CSF.13-17 The results from the first randomized, prospective controlled clinical study to evaluate the effect of GM-CSF versus no treatment indicated that GM-CSF was effective in the reduction of the severity  and  duration of    chemotherapy-induced oral mucositis.18

Preliminary data on a small number of patients supported the therapeutic efficacy of GM-CSF on oral mucositis.20 The present larger study confirmed the earlier conclusion as it showed a significant expeditious lowering of the severity, morbidity, and duration of oral mucositis independent of an effect of granulocyte stimulatory effect of GM-CSF. The mean mucositis grading scores, both gross and functional, decreased significantly as compared with estimates at base level. Moreover, the duration of severe oral mucositis was also shortened as Grade 0 or 1 (gross mucositis grading score) was apparent in 30%, 73% and 100% of patients by the 2nd, 5th and 10th day of therapy, respectively. Similarly, Grade 0 or 1 (functional mucositis grading score) reported in 48%, 78%, and 100% of patients by the 2nd, 5th, and 10th day of therapy, respectively.

                        The mechanism of reduction of chemotherapy-induced oral mucositis by G-CSF or GM-CSF is uncertain. One plausible reason may be that chemotherapy-induced neutropenia may predispose the patient to oral infections, which may initiate or aggravate the severity or prolong the duration of oral mucositis. Therefore, G-CSF or GM-CSF may be able to reduce chemotherapy-induced oral mucositis by shortening the duration of neutropenia after chemotherapy or by benefiting the oral neutrophil level recovery.21 Nevertheless, the benefit shown in our study and that of Chi et al18 was independent of systemic or local neutrophil recovery effect.

                        Another mechanism of the beneficial effect of  GM-CSF  on  chemotherapy-induced mucositis may be a direct stimulatory effect of GM-CSF on the growth or regeneration of the oral mucosa. GM-CSF may stimulate the oral mucosal cells to proliferate by enhancing interleukin-1 transcription and translation.22 The latter mechanism is connoted by the increase in oral mucositis and more myelotoxicity when chemotherapy and G-CSF were given concurrently.17,23 The elucidation for the increase in myelotoxicity when G-CSF and GM-CSF are given concurrently with chemotherapy is attributed


to the stimulation of bone marrow progenitor cells and the increased pool of precursors responsive to chemotherapy.17 In another study, concurrent administration of GM-CSF mouthwash with chemotherapy produced more oral mucositis as compared with placebo (42% vs 22%).24

                        In conclusion, therapeutic GM-CSF mouthwash can significantly reduce morbidity, severity, and duration of chemotherapy-induced oral mucositis. The effect is presumably related to its favorable acceleration of mucosal cells regeneration. The role of G-CSF or GM-CSF on chemotherapy-induced oral mucositis warrants a large, randomized, placebo-controlled clinical trial.


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4.     Berkowitz RJ, Strandjord SE,  Jones P, Hughes C, Barsetti J, Gordon EM, et al. Stomatologic complications of bone marrow transplantation in a pediatric population. Pediatr Dentistry 1987; 9: 105-10.

5.     Bergmann OJ. Oral infections and septicemia in immunocompromised patients with hematologic malignancies. J Clin Microbiol 1988; 26: 2105-9.

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8.     Antman KS, Griffin JD, Elias A, Socinski MA, Ryan L, Cannistra SA, et al. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on chemotherapy-induced myelosuppression. N Engl J Med 1988; 319: 593-8.

9.     Morstyn G, Campbell L, Souza LM, Alton NK, Keech J, Green M, et al.. Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy. Lancet 1988; 1: 667-72.

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