Subjects, Materials, and Methods

In this part of the study the materials and methods were presented under the following headings:

Subjects:

Forty children with acute lymphoblastic leukemia, their ages ranged from 6: 12 years. These children were selected from the National Cancer Institute. These children randomly subdivided into two equal groups (twenty patients for each);  

Group (A) = (Exercise Program Group):

This group was composed of 20 children with acute lymphoblastic leukemia and represented the group who received the exercise program for 12 weeks in addition to perform the traditional medical intervention.

Group (B) = (Control Group):

This group was composed of 20 children with acute lymphoblastic leukemia and represented the control group who did not receive any form of physical therapy intervention but this group was instructed and encouraged to remain active during their cancer treatment approach.

Criteria of Patient Selection:

The patients had the following criteria:

a- Inclusive Criteria:

·        The age of the patients ranged from 6: 12 years.

·        All patients had the same medical care and have no evidence impairment of cardiac, pulmonary, renal, and hepatic function.

·        All patients received a good explanation of treatment and measurement devices.

·        Each child was evaluated by his/her oncologist before and every 2 weeks during training period.

·        The examination included a thorough physical evaluation and complete hematological and biochemical blood analysis.

b- Exclusive Criteria:

Children were excluded from the study for any of the following cases:

·        Children who underwent bone marrow transplantation because in this subpopulation of children with ALL treatment complication, side effects, and tumor recurrence are frequent which would compromise training adherence   .

·        Children with a history of antecedent neurological developmental of genetic disorder and those currently receiving physical therapy intervention will be excluded.

·        Severe anemia (hemoglobin <8 g.dl-1).

·        Neutrophil counts lower than 0.5x10µL-1.

·        Platelet count lower than 50 x 10µL-1.

·        Or anthracyclin–induce cardiac toxicity.

Equipment and Tools:

The main equipment and tools used in this study were classified into two types:

1-Measurement Tools:

   The measurement tools were:

1. a-Oxygen pro (zan-germany) cardio pulmonary exercise testing unit with the following parts: Fig (4)

·        Computer unit fed with software required for the control of the treadmill load, and manipulation and analyze the measured parameter as well, in addition to thermal printer to out the variables measured in the study. Fig (5).

·        Gas analyzer with flow (triple valve) sensor.

·        Treadmill, Fig (7).

·        A rubber mouthpiece (which is connected to the flow sensor and a face mask.

·        Weight and Height scales: it was used to measure weight and height of each subject involved.

Fig (5): A Computer Unit with a Thermal Printer.

Fig (7): A Motor-Driven Treadmill.

1. b-Hand-Held Dynamometry: was used to assess the muscle strength of both upper and lower body.

The muscle test has been done through using Hand-held Dynamometry (manufactured by instrument company 3700 sagamore parkway north lafaytte, in 47904 U.S.A). Hand-Held Dynamometrysystem is a hand-held device used objectively quantifying muscle strength. It is small enough to held in one hand easily read.

          The device has six function buttons and LCD screen that control the menus and allow the selection of options and as following: Fig. (8)

·        On/Off switch: that used to activate the device when switch to the '' on ''position.

·        Reset button: the reset button is located on the top of the device; it is placed for easy access the thumb regardless of right or left operation. The reset button clears the display of all data and sets the zero point for the measurements.

·        Range button: the range button toggles between high and low measurement rang. An H or L is displayed on the main measurements screen to indicate the device range setting. Changing the range cause the device to automatically reset and clear all time and force values.

·        Scroll/LB/KG: the lb/Kg button has dual functionality depending on which screen is accessed. In the main measurement screen, the lb/Kg button toggles the force measurement scale between pounds and kilograms. An indicator on the main measurement screen shows which scale is selected. When a menu or data display screen is active, this button becomes a scroll button. The scroll button was used to select option by advancing a cursor from on option to the next. The scroll button was also used step through data.

                                           

Fig.(8 ): The hand-Held Dynamometry Used in this Study Showed the Function Buttons and Main Measurement Screen.

1- On/off switch.                         2- Reset button.

            3- Range button.                          4- Scroll LB/KG button.

5- Enter/Store button.                    6- Menu button.    

7- LCD screen.

·        Enter/store button: the enter/store button has dual functionality depending on which screen is accessed. In the main measurement screen, the button was used as store button. Pressing the store button stores the current test data in the device memory. Only the peak force and peak time were stored in memory. When the menu screen are accessed, the button is used as an enter button the enter button is used to activate setting and menu option. It was also used to clear some error and warning messages.

·        Menu button: the menu button was used to enter the main menu the main menu was used to select the device option and access the submenus.

·          The LCD screen on the front section of device used to display force and time.

   The main measurement screen showed all of the current measurement information. This screen was shown whenever a measurement was in progress. This screen was also the default start- up display.

¨     Peak force: the peak measurement force was displayed in large numbers on the upper left of the main measurement screen. This value was the peak pounds or kilograms applied during a test. Force values were displayed tenths of pound or kilogram.

¨     Peak time: the peak time value is displayed in the second on the button left of the screen under the peak force. This number is the time during the test when the peak force occurred. Time value was displayed to hundredths of second.

¨     Instaneous force: the instaneous force value was displayed on the upper right on the main measurement screen this value was the force applied to the device at any time.

¨     Running time: the running time value was displayed on the lower right of the main measurement screen .this value showed the total time that force has been applied after a test had ended; this showed the total length of the test in seconds.

¨     Range indicator (H or L): the range shows if the device is set in the high or low measurement setting. If in Kg's the high range would 0Kg-1361Kg, and the low rang would 0Kg-22.6Kg. If in lbs, the high rang would 0lbs-300lbs, and the low range would 0lbs-50lbs. the range indicator was the upper most indicators in the center of the main measurement screen.

¨     Scale 3 indicator (lb or KG): the scale indicator shows if the device is set in pound or kilograms. The scale indicator was the second indicator in the center of the main measurement screen.

¨     Low battery indicator: the low battery is present when a law battery condition exists. The low battery indicator was third indicator in the center of the main measurement screen.

¨     Time unit label: the time unit label indicate is the –S- on the button center of the main measurement screen. This label indicated that the time measurements were in seconds, this label did not change.

1. c- Iowa Fatigue Scale

It was used to measure the degree of fatigue in this children and QoL. It is a self report questionnaire developed by Department of Family Medicine, University of Iowa College of Medicine to measure the degree of fatigue and its progression. It is consisted of many questions about the quality of life and its affection by fatigue. The 11 item scale contains four subscales: cognitive, fatigue, energy and productivity. Patients with a higher fatigue score are much more likely to have lower health status, greater depression and more somatic symptoms, (Appendix I) (Hartz et al., 2003).     

Therapeutic Tools:

·        Strength training include exercise engaging the major muscle groups (bench press , shoulder press , leg extension , leg press , leg curl , abdominal crunch , low back extension ,arm curl ,elbow extension ).

·        Stretching exercise of the muscles involved in the previous exercise was stretched.

·        Aerobic exercise consisted of pedaling a cycle ergometer, running and walking on treadmill.

Procedures of the Study:

A verbal explanation about the important of the study procedure, main aim and conceptual approach was explained to every patient.

The procedure of this study was divided into two main procedures:

Measurement Procedures:

·        Before starting the study a consent form was taken from each parent of participant as an agreement to be included in the present study. Also before initiating the treatment program the following task was performed :

·        The children's hemoglobin level and plat let count was obtained from the medical record to observe changes in physical stability.

·        Each subject was examined medically in order to exclude any abnormal medical problem which previously mentioned.

·        Measurement was taken pre-test assessment and post test assessment and 12 week later after the intervention program as follow ;

(1)Procedures of Cardiopulmonary Exercise Test:

Prior to the study each subject was instructed:

·        Not to eat at least 2 hours before exercise testing.

·        Not to do unusual physical activities for at least 48 hours before testing.

·        To dress appropriately for exercise especially with regard to footwear.

·        Exercise testing was performed according to the recommendation and guidance of the American heart association ( AHA) (Fletcher et al .,2001)

On the testing day:

The cardiopulmonary exercise testing was electronically calibrated by click upon the icon of calibration at the computer monitor. Before starting Gas-calibration, the following steps were checked in advance:

·        Zan testing unit had been ON for a minimum warm up time of 20 min.

·        Gas bottle was opened

·        Gas-suction tube removed from flow sensor and connected to calibration nipple (Cal) on front panel of Zan Testing Unit (it is recommended that Gas-calibration must be carried out before every measurement).

·        Calibration was started with (Enter); the flow of Calibration-Gas was clearly audible. As Calibration was ok, the results wer saved with (Enter) (the recommended composition for calibration gas is: 5%Co2, 15.9%O2). At the end, Gas bottle was closed and Gas-Suction tube was removed to flow sensor.

·        The subjects were measured for height and weight, and then the computer unit was fed up the subjects' demographic parameters.

1.     Age           (date of birth)

2.     Sex           male or female

3.     Weight      in(Kg)

4.     Height       in (cm)

Exercise Test:

·        A clean and sterilized facemask was applied and fitted to the face of the participant and connected to the flow to the sensor. The expired air was obtained from a valve connected to a mouthpiece and then was analyzed for VO2 volume. Data was delivered to a computer and was integrated to calculate O2 consumption.(fig 9)

·        After a 3 min standing rest period, the participant was asked to walk for 5 min at 0% grad for warm up.

·        Maximum oxygen consumption (VO2max) determined for each participant by maximum exercise testing according to Bruce protocol.

·        Participants were verbally encouraged to continue the test until exhaustion.

·        A cool-down period of 5 min was allowed and then the test was terminated.

Fig (9): The Child was Asked to Run on Treadmill Until Exhaustion.

Bruce Protocol:

The starting speed of the Bruceprotocol is 1.7 mph and 10% grade, and progressing to increased treadmill speed and grades every 3 minutes until exhaustion as shown in (table 1)      (Hillegas and Sadowsky,2001)

Table (1): Bruce Treadmill Protocol

Stage	Time(min)	Speed(mph)	Grade	MET
I	3	1.7	10%	4-5
II	3	2.5	12%	6-7
III	3	3.4	14%	8-10
IV	3	4.2	16%	11-13
V	3	5.0	18%	14-16
VI	3	6.0	20%	17-19

Criteria for terminating exercise testing:

Absolute:

1-    Drop in systolic blood pressure (persist below baseline, despite an increasing in workload).

2-    Development of chest pain.

3-    Signs of poor perfusion (cyanosis or pallor).

4-    Subject's request to stop.

Relative: 

5-    Fatigue, shortness of breath, leg cramps or claudicating pain.

6-    General appearance.

7-    Hypertensive response (systolic pressure > 250 mm hg and /or diastolic blood pressure >115mmhg) (Fletcher et al., 2001).

Maximum oxygen consumption (VO2max) (ml/min/Kg) was obtained through breath-by breath gas exchange analysis. VO2max was considered to be attained if subject reported a feeling of fatigue and if one of the following criteria was reached:

a)     Failure of VO2 to increase despite of increased work rate.

b)    Respiratory exchange ratio( RER)> 1.1

c)     Maximal heart rate within 10 beats/min of age-predicted maximum (220-age).

 (2)Muscle Strength Assessment Procedures:

     a- Knee Extensor:

          The hand-held dynamometry was one instrument used to test knee extensor muscle performance. All subjects were tested by the same tester. Subjects were seated at the edge of a treatment table and positioned at about 90^ohips flexion and 80^oknee flexion; lower leg vertical to floor; foot not touching floor. The hand-held dynamometry was position two finger widths above the lateral malleolus on the anterior of tibia. Subjects' were asked to stabilize their pelvis by holding onto the edge of the treatment table. A make test was used , in which the tester matches the muscle force generated by the subject, as contrasted with a break test, in which the tester attempts to exceed the force generated by the subject.

Four warm-up contractions were performed, with subjects instructed to gradually increase their knee extension force over 3 seconds. Subjects were instructed to give approximately 50% effort in the first three warm-ups and a maximal contraction on the fourth worm-up. Four maxima trials were then performed, with the peak force of the fourth contraction recorded.

B-Elbow Flexor:

Subjects were seated at the edge of a treatment table. Subjects were asked to hold onto the edge of the treatment table by the other hand to stabilize the trunk. The examined elbow should be held against the patient's side to avoid shoulder movement and put the elbow in supination of the forearm with the elbow at a right angle. The hand-held dynamometry was positioned at the distal end of the forearm above the wrist (to avoid twisting the wrist). The subject was asked to flex his/her elbow while the pressure was in the direction of extension.    

A make test was used , in which the tester matches the muscle force generated by the subject, as contrasted with a break test, in which the tester attempts to exceed the force generated by the subject.

Four warm-up contractions were performed, with subjects instructed to gradually increase their elbow flexion force over 3 seconds. Subjects were instructed to give approximately 50% effort in the first three warm-ups and a maximal contraction on the fourth worm-up. Four maxima trials were then performed, with the peak force of the fourth contraction recorded. Fig (11)

Fig. (11): Procedure of Measuring Elbow Flexor Muscle Strength through Hand-Held Dynamometry.

3-The QoL and Fatigue assessment procedure:

          Each child was instructed to complete answer the list of question with an assistant from his/her parents. The evaluation was carried out before and at the end of rehabilitation. (Appendix I)

Therapeutic Procedures:

All the children in the exercise group followed a 12 weeks training program consisting of three weekly session with a duration ranging from 90 min (in the first few weeks of the program ) to 120 min ( by the end of the program ) each session started and end with a low- intensity 15 min warm up and cool –down period consisting of walking on treadmill at very light work load and stretching exercise involving all major muscle groups the core portion of the training session is divided into strength and aerobic exercises.

·        Strength training included 11exercise engaging the major muscle group (bench press ,shoulder press ,leg extension ,leg press, leg curl ,abdominal crunch ,low back extension ,arm curl elbow extension ,seated raw , and lateral pull-down).for each exercise the children perform one set of 8-15 repetition (total of approximately 20-s duration )

·        Rest period of 1-2 min separate the exercises.

·        Stretching exercises of the muscles involved in the previous exercises were performed during the rest period between exercises

·        The load was gradually increased as the strength of each child improved.

·        Aerobic exercise consisted of pedaling a cycle ergo meter, running, walking and aerobic games involving large muscle group (i.e. jumping exercise, ballgames group games, etc).

·        The duration and intensity of the aerobic training was gradually increased during the 12 week period so that the subject start with at least 10 min of aerobic exercises at 50% of age predicted maximum heart rate (HR_Max), (calculated as 220 minus age minus rest heart rate) and progress to at least 30 min of contentious exercise at ≥ 7o% HR_max by the end of the 12 weeks program (San Juan et al., 2007).

Statistical Procedures:

- In this study, the obtained data were recorded on the evaluative sheet.

- These data were transferred into IBM card using IBM personal computer with statistical program.

The statistical procedures were focused to the following phases:-

1-Data Collection Phases: -

The data regarding to the patients’ age, sex, height, weight; collected before entry of the study. The data regarding to (IGA) had been collected before initiation of experiment (pre), and post-treatment.

The data collection was performed at the same sequences and procedures for all patients in the two groups of the study (exercise and control groups).

2-Data Analysis: -

          The collected data was analyzed statistically to obtain the following statistical tools:

(a)Descriptive Statistics:

·  In this study, the descriptive statistics in form of mean and standard deviation were calculated for all patients in both groups of the study to determine the homogeneity and central deviation. The mean is the sum of the observations on the number of the observations. The stander deviation is the squire root of the variance and it is expressed in the unit of the original measure. Variance is a measure of the variability around the mean within a data set.  

(b) Analytic Statistics:

The analysis and comparison of the data were made by these tools of statistics.

·        Paired T-test was used to compare the dependent variable

·        Cardiopulmonary endurance and physical fitness ,

● Muscle strength (elbow flexor and knee extensor),

·        Fatigue and Quality of life (QOL) , 

            In children receiving chemotherapy in ALL, within each group (i.e. pre-treatment and post-treatment to the individuals in both groups) to detect level of significant.

● Unpaired T-test was used to compare the dependent variable (

§  Cardiopulmonary endurance and physical fitness ,

§  Muscle strength (elbow flexor and knee extensor),

§  Fatigue and Quality of life (QOL) , 

     and independent (age, sex, height, weight of children) Variables between both groups to detect level of significant.

● Sign test was used to compare the data obtained, within each group (i.e. pre-treatment and post-treatment to the individuals in both study and control groups) to detect level of significant.

Sign test: - It is a non-parametric alternative to the one sample t-test; it is designed to test a hypothesis about the location of a population distribution. It is most often used to test the hypothesis about a population median, and often involves the use of matched pairs. It can be applied when the observations in a sample of data are ranks

·       Mann-Whitney test was used to compare the data obtained between the exercise and the control group.

     Mann-Whitney test: - It is a non-parametric alternative to the independent samples t-test. Like t-test Mann-Whitney tests the null-hypothesis that two independent samples come from the same population. Rather than being based on parameters of a normal distribution like mean and variance, the Mann-Whitney statistic are based on ranks. The Mann-Whitney statistic is obtained by counting the number of times an observation from the group with the smaller sample size precedes an observation from the larger group.

● Both descriptive and analytical statistics were used to examine, describes and analyses the collected data to detect if there was inter-group or intra-group difference before and after treatment.

● Each hypothesis was tested separately by the using the appropriate statistical tools. The data analysis and the level of significance were set at the level of 0.05....

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