Adherence to childhood cancer treatment: a prospective cohort study from Northern Vietnam.

OBJECTIVES: Global incidence and attention to childhood cancer is increasing and treatment abandonment is a major cause of treatment failure in low- and middle-income countries. The purpose of this study was to gain an understanding of factors contributing to non-adherence to treatment. DESIGN: A prospective cohort study with 2 year follow-up of incidence, family-reported motives and risk factors. SETTING: The largest tertiary paediatric oncology centre in Northern Vietnam. PARTICIPANTS: All children offered curative cancer treatment, from January 2008 to December 2009. PRIMARY AND SECONDARY OUTCOME MEASURES: Family decision to start treatment was analysed with multivariable logistic regression, and family decision to continue treatment was analysed with a multivariable Cox model. This assessment of non-adherence is thereby methodologically consistent with the accepted definitions and recommended practices for evaluation of treatment abandonment. RESULTS: Among 731 consecutively admitted patients, 677 were eligible for treatment and were followed for a maximum 2 years. Almost half the parents chose to decline curative care (45.5%), either before (35.2%) or during (10.3%) the course of treatment. Most parents reported perceived poor prognosis as the main reason for non-adherence, followed by financial constraints and traditional medicine preference. The odds of starting treatment increased throughout the study-period (OR 1.04 per month (1.01 to 1.07), p=0.002), and were independently associated with prognosis (OR 0.51 (0.41 to 0.64), p=<0.0001) and travel distance to hospital (OR 0.998 per km (0.996 to 0.999), p=0.004). The results also suggest that adherence to initiated treatment was significantly higher among boys than girls (HR 1.69 (1.05 to 2.73), p=0.03). CONCLUSIONS: Non-adherence influenced the prognosis of childhood cancer, and was associated with cultural and local perceptions of cancer and the economic power of the affected families. Prevention of abandonment is a prerequisite for successful cancer care, and a crucial early step in quality improvements to care for all children with cancer.

Elevated visual dependency in young adults after chemotherapy in childhood.

Chemotherapy in childhood can result in long-term neurophysiological side-effects, which could extend to visual processing, specifically the degree to which a person relies on vision to determine vertical and horizontal (visual dependency). We investigated whether adults treated with chemotherapy in childhood experience elevated visual dependency compared to controls and whether any difference is associated with the age at which subjects were treated. Visual dependency was measured in 23 subjects (mean age 25.3 years) treated in childhood with chemotherapy (CTS) for malignant, solid, non-CNS tumors. We also stratified CTS into two groups: those treated before 12 years of age and those treated from 12 years of age and older. Results were compared to 25 healthy, age-matched controls. The subjective visual horizontal (SVH) and vertical (SVV) orientations was recorded by having subjects position an illuminated rod to their perceived horizontal and vertical with and without a surrounding frame tilted clockwise and counter-clockwise 20° from vertical. There was no significant difference in rod accuracy between any CTS groups and controls without a frame. However, when assessing visual dependency using a frame, CTS in general (p = 0.006) and especially CTS treated before 12 years of age (p = 0.001) tilted the rod significantly further in the direction of the frame compared to controls. Our findings suggest that chemotherapy treatment before 12 years of age is associated with elevated visual dependency compared to controls, implying a visual bias during spatial activities. Clinicians should be aware of symptoms such as visual vertigo in adults treated with chemotherapy in childhood.

Decreased postural control in adult survivors of childhood cancer treated with chemotherapy.

The objective of cancer treatment is to secure survival. However, as chemotherapeutic agents can affect the central and peripheral nervous systems, patients must undergo a process of central compensation. We explored the effectiveness of this compensation process by measuring postural behaviour in adult survivors of childhood cancer treated with chemotherapy (CTS). We recruited sixteen adults treated with chemotherapy in childhood for malignant solid (non-CNS) tumours and 25 healthy age-matched controls. Subjects performed posturography with eyes open and closed during quiet and perturbed standing. Repeated balance perturbations through calf vibrations were used to study postural adaptation. Subjects were stratified into two groups (treatment before or from 12 years of age) to determine age at treatment effects. Both quiet (p = 0.040) and perturbed standing (p ≤ 0.009) were significantly poorer in CTS compared to controls, particularly with eyes open and among those treated younger. Moreover, CTS had reduced levels of adaptation compared to controls, both with eyes closed and open. Hence, adults treated with chemotherapy for childhood cancer may suffer late effects of poorer postural control manifested as reduced contribution of vision and as reduced adaptation skills. These findings advocate development of chemotherapeutic agents that cause fewer long-term side effects when used for treating children.

Oculomotor Deficits after Chemotherapy in Childhood.

Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects' self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological complications following chemotherapy.

Autoimmune diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS).

OBJECTIVES: The pattern of autoimmune diseases in childhood cancer survivors has not been investigated previously. We estimated the risk for an autoimmune disease after childhood cancer in a large, population-based setting with outcome measures from comprehensive, nationwide health registries. METHODS: From the national cancer registries of Denmark, Iceland and Sweden, we identified 20 361 1-year survivors of cancer diagnosed before the age of 20 between the start of cancer registration in the 1940s and 1950s through 2008; 125 794 comparison subjects, matched by age, gender and country, were selected from national population registers. Study subjects were linked to the national hospital registers. Standardised hospitalisation rate ratios (SHRRs) and absolute excess risks (AERs) were calculated. RESULTS: Childhood cancer survivors had a significantly increased SHRR of 1.4 (95% CI 1.3 to 1.5) of all autoimmune diseases combined, corresponding to an AER of 67 per 100 000 person-years. The SHRRs were significantly increased for autoimmune haemolytic anaemia (16.3), Addison's disease (13.9), polyarteritis nodosa (5.8), chronic rheumatic heart disease (4.5), localised scleroderma (3.6), idiopathic thrombocytopenic purpura (3.4), Hashimoto's thyroiditis (3.1), pernicious anaemia (2.7), sarcoidosis (2.2), Sjögren's syndrome (2.0) and insulin-dependent diabetes mellitus (1.6). The SHRRs for any autoimmune disease were significantly increased after leukaemia (SHRR 1.6), Hodgkin's lymphoma (1.6), renal tumours (1.6) and central nervous system neoplasms (1.4). CONCLUSIONS: Childhood cancer survivors are at increased risk for certain types of autoimmune diseases. These findings underscore the need for prolonged follow-up of these survivors.

Increased health care utilization by survivors of childhood lymphoblastic leukemia is confined to those treated with cranial or total body irradiation: a case cohort study.

BACKGROUND: Previous studies have indicated that survivors of childhood acute lymphoblastic leukemia (ALL) have an increased morbidity measured in terms of health care utilization. However, earlier studies have several potentially important limitations. To overcome some of these, we investigated hospital contact rates, and predictors thereof, among 5-year survivors of ALL in a population-based setting, and compared them to a control cohort regarding outcome measures from a comprehensive nation-wide health register. METHODS: All individuals diagnosed with ALL before the age of 18 in Southern Sweden during 1970-1999 and alive January 2007 (n=213; male=107) were identified through the Swedish Cancer Register. Each subject was matched to fifty controls, identified in the Swedish Population Register. All study subjects were linked to the National Hospital Register and detailed information was obtained on all hospital contacts (hospital admissions and outpatients visits) starting five years after cancer diagnosis, and the corresponding date for the controls, until 2009. RESULTS: The median follow-up among the 5-year survivors of ALL was 16 years (range 5-33), accruing a total of 3,527 person-years. Of the 213 5-year survivors, 105 (49.3%) had at least one hospital contact compared to 3,634 (34.1%) of the controls (p<0.001). Survivors had more hospital contacts (3 [1-6] vs. 2 [1-4] contacts, p<0.001) and more total days in hospital (6 [2-18] vs. 3 [1-7] days, p<0.001) than the controls during the study period. Logistic regression analysis showed that survivors treated with cranial irradiation and/or total body irradiation (45% and 7%, respectively) had an increased risk of at least one hospital contact (OR 2.3, 95%CI; 1.5-3.6 and OR 11.0, 95%CI; 3.2-50.7, respectively), while there was no significant difference between the non-irradiated survivors and controls. CONCLUSIONS: We show that irradiated survivors of childhood ALL have an increased morbidity measured in terms of hospital contacts, in comparison to non-irradiated survivors and controls, while non-irradiated survivors have not. These findings are encouraging regarding the future morbidity of children currently treated for ALL, as radiotherapy is necessary only for a minority of these.

Adult life after childhood cancer in Scandinavia: diabetes mellitus following treatment for cancer in childhood.

AIM: An increased risk for diabetes mellitus (DM) adds significantly to the burden of late complications in childhood cancer survivors. Complications of DM may be prevented by using appropriate screening. It is, therefore, important to better characterise the reported increased risk for DM in a large population-based setting. MATERIALS AND METHODS: From the national cancer registries of the five Nordic countries, a cohort of 32,903 1-year survivors of cancer diagnosed before the age of 20 between start of cancer registration in the 1940s and 1950s through 2008 was identified; 212,393 comparison subjects of the same age, gender and country were selected from national population registers. Study subjects were linked to the national hospital registers. Absolute excess risks (AERs) and standardised hospitalisation rate ratios (SHRRs) were calculated. RESULTS: DM was diagnosed in 496 childhood cancer survivors, yielding an overall SHRR of 1.6 (95% confidence interval (CI), 1.5-1.8) and an AER of 43 per 100,000 person-years, increasing from approximately 20 extra cases of DM in ages 0-19 to more than 100 extra cases per 100,000 person-years in ages > or =50. The relative risks for DM were significantly increased after Wilms' tumour (SHRR, 2.9), leukaemia (2.0), CNS neoplasms (1.8), germ-cell neoplasms (1.7), malignant bone tumours (1.7) and Hodgkin's lymphoma (1.6). The risk for DM type 2 was slightly higher than that for type 1. CONCLUSION: Childhood cancer survivors are at increased risk for DM, with absolute risks increasing throughout life. These findings underscore the need for preventive interventions and prolonged follow-up of childhood cancer survivors.

Prolactin insufficiency but normal thyroid hormone levels after cranial radiotherapy in long-term survivors of childhood leukaemia.

BACKGROUND: Acute lymphoblastic leukaemia (ALL) patients treated with cranial radiotherapy (CRT) have an increased risk of GH deficiency (GHD). Little is known about insufficiencies of prolactin (PRL) and TSH, but also lactation failure has been reported in this population. OBJECTIVE: To study the long-term outcome of CRT on PRL and thyroid hormone levels in GHD ALL patients and the prevalence of lactation failure. DESIGN: Case-control study. PATIENTS: We examined 40 GHD and 4 GH insufficient ALL patients, in median 20 years (range: 8-27) after ALL diagnosis and 44 matched population controls. MEASUREMENTS: PRL secretion (area under the curve; AUC) after GHRH-arginine test in all patients and matched controls, and PRL and TSH AUC after a TRH-test in 13 patients and 13 controls. And basal PRL and thyroid hormone levels after 5 years with GH therapy and 8 years without GH therapy. RESULTS: Compared with controls, ALL patients had significantly lower basal and AUC PRL after GHRH-Arginine (P = 0·03, P = 0·02), and AUC PRL after TRH (P = 0·001). After 5 and 8 years, PRL levels decreased further (P = 0·01, P = 0·03), but thyroid hormones remained normal at baseline and at follow-up. PRL insufficiency was significantly associated with increased levels of BMI and insulin. Six out of seven pregnant ALL women reported lactation failure. CONCLUSIONS: Long-term ALL survivors treated with CRT have GHD and PRL insufficiency, and a high prevalence of lactation failure, but thyroid hormones remained normal. PRL insufficiency was associated with cardiovascular risk.

Severe difficulties with word recognition in noise after platinum chemotherapy in childhood, and improvements with open-fitting hearing-aids.

OBJECTIVE: To investigate word recognition in noise in subjects treated in childhood with chemotherapy, study benefits of open-fitting hearing-aids for word recognition, and investigate whether self-reported hearing-handicap corresponded to subjects' word recognition ability. DESIGN: Subjects diagnosed with cancer and treated with platinum-based chemotherapy in childhood underwent audiometric evaluations. STUDY SAMPLE: Fifteen subjects (eight females and seven males) fulfilled the criteria set for the study, and four of those received customized open-fitting hearing-aids. RESULTS: Subjects with cisplatin-induced ototoxicity had severe difficulties recognizing words in noise, and scored as low as 54% below reference scores standardized for age and degree of hearing loss. Hearing-impaired subjects' self-reported hearing-handicap correlated significantly with word recognition in a quiet environment but not in noise. Word recognition in noise improved markedly (up to 46%) with hearing-aids, and the self-reported hearing-handicap and disability score were reduced by more than 50%. CONCLUSIONS: This study demonstrates the importance of testing word recognition in noise in subjects treated with platinum-based chemotherapy in childhood, and to use specific custom-made questionnaires to evaluate the experienced hearing-handicap. Open-fitting hearing-aids are a good alternative for subjects suffering from poor word recognition in noise.

Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy.

OBJECTIVE: Bone mineral density (BMD) in survivors of acute lymphoblastic leukaemia (ALL) seems to vary with time, type of treatments and GH status. We aimed to evaluate BMD in ALL patients with GH deficiency (GHD), with and without GH therapy. DESIGN: Case-control study. METHODS: We examined 44 (21 women) GHD patients (median 25 years) treated with cranial radiotherapy (18-24 Gy) and chemotherapy and matched population controls for BMD with dual-energy X-ray absorptiometry. For 5 and 8 years, two subgroups with (0.5 mg/day) (n=16) and without GH therapy (n=13) and matched controls were followed respectively. RESULTS: At baseline, no significant differences in BMD or Z-scores at femoral neck and L2-L4 were recorded (all P>0.3). After another 8 years with GHD, the Z-scores at femoral neck had significantly decreased compared with baseline (0.0 to -0.5; P<0.03) and became lower at the femoral neck (P=0.05), and at L2-L4 (P<0.03), compared with controls. After 5 years of GH therapy, only female ALL patients had a significantly lower femoral neck Z-scores (P=0.03). The female ALL patients reached an IGF1 level of -0.7 s.d. and male patients reached the level of +0.05 s.d. CONCLUSIONS: On average, 25 years after diagnosis, GH-deficient ALL patients experienced a significant decrease in Z-scores at femoral neck, and if Z-scores continue to decrease, there could be a premature risk for osteoporosis. GH therapy was not shown to have a clear beneficial effect on BMD. Whether higher GH doses, particularly in women, will improve Z-scores needs further investigation.

Estrogen receptor α single nucleotide polymorphism modifies the risk of azoospermia in childhood cancer survivors.

OBJECTIVE: Cancer treatment in childhood leads to permanent azoospermia in a significant number of boys and those who are diagnosed with cancer before puberty do not have the option of pretreatment cryopreservation of spermatozoa. However, there is an interindividual variation in the sensitivity to gonadotoxic effects of cancer therapy, which probably is due to genetic factors. Identification of genetic markers for the risk of azoospermia in childhood cancer survivors may help in identifying boys to whom testicular cryopreservation should be offered. METHODS: Fifty-one single nucleotide polymorphisms (SNPs) being markers of 12 different haplotype blocks in the androgen receptor, estrogen receptor (ER) α and ER ß genes were examined in 127 adult childhood cancer survivors. RESULTS: In ERα, markers of one specific haplotype block (rs2207396, rs9340958, rs9340978) were associated with an increased risk of azoospermia. Compared with those with the GG genotype, patients being heterozygous for the A allele in rs2207396 had a significantly increased risk of azoospermia [odds ratio (OR): 3.8; 95% confidence interval: 1.5-9.5; P=0.008], this OR being even higher in the subgroup treated with alkylating drugs (OR: 8.8; 95% confidence interval: 2.1-36; P=0.004). In this subgroup, 48% of the patients carried the A allele of rs2207396, this proportion being 70% among the azoospermic patients. CONCLUSION: Use of genetic markers of high risk of posttreatment azoospermia may, in the future, prove an important clinical tool in selection of boys to whom preservation of testicular tissue before cancer therapy should be offered.

Young age at diagnosis is a risk factor for negative late socio-economic effects after acute lymphoblastic leukemia in childhood.

BACKGROUND: The increasing number of survivors after childhood cancer requires characterization of the late complications of these diseases and their treatment. We examined a large number of possible socio-economic late effects following treatment for acute lymphoblastic leukemia (ALL) in order to identify factors leading to a poor outcome. PROCEDURE: All individuals who had been diagnosed with ALL and who were alive in January 2007 (n = 213; men = 107) were identified from a database of all patients with cancer before the age of 18 in Southern Sweden from 1970 to 1999. For each subject, 50 matched controls were identified from the Swedish Population Register. Information on marital status, children, education, employment, income, and support from the community was obtained from Statistics Sweden. RESULTS: At the ages of 25 and 30, survivors of ALL had attained a lower level of education than controls. At the age of 30, they were less often employed (70% vs. 82%, P = 0.019), less often married (19% vs. 32%, P = 0.019), and had children to a lesser extent (31% vs. 47%, P = 0.011) than controls. We identified young age at diagnosis as a risk factor for adverse outcome in the majority of the socio-economic variables studied, apart from the known risk of cranial irradiation treatment. Furthermore, female survivors had a greater risk of achieving a lower level of education than both male survivors and controls. CONCLUSIONS: Young age at diagnosis, as well as treatment with cranial irradiation, is a risk factor for socio-economic late effects after treatment for ALL in childhood.

Sperm DNA integrity in men treated for childhood cancer.

PURPOSE: It is not known whether childhood cancer and its treatment are associated with sperm DNA damage, which subsequently affects fertility and might be transmitted to the offspring. The aim of this study is to assess DNA fragmentation index (DFI) as an indicator of sperm DNA integrity in childhood cancer survivors (CCS), with treatment regimen taken into account. EXPERIMENTAL DESIGN: In 99 CCS and 193 age-matched healthy controls, DFI was assessed by using sperm chromatin structure assay. RESULTS: In the whole group of CCS, DFI was increased compared with the controls, with borderline statistical significance [mean difference, 1.8%; 95% confidence interval (95% CI), -0.0088%-3.7%]. Those treated with radiotherapy only (mean difference, 6.0%; 95% CI, 1.6-10%) or surgery only (mean difference, 2.9%; 95% CI, 0.083-5.8%) had statistically significantly higher DFI than the controls. The odds ratio (OR) for having DFI >20%, which is associated with reduced fertility, was significantly increased in CCS compared with the control group (OR, 2.2; 95% CI, 1.1-4.4). For the radiotherapy-only group, the OR was even higher (OR, 4.9; 95% CI, 1.3-18). DFI was not associated with dose of scattered testicular irradiation or type of chemotherapy given. CONCLUSIONS: DFI was increased in CCS, with those treated with chemotherapy being the only exception. This sperm DNA impairment may be associated with the disease per se rather than due to the treatment, and may have negative consequences in terms of fertility and risk of transmission to the offspring.

Hypogonadism risk in men treated for childhood cancer.

CONTEXT: Pediatric cancer treatment may imply an increased risk of hypogonadism, leading to metabolic disorders and osteoporosis. Such complications are potentially preventable. OBJECTIVE: The aim of this study was to assess diagnosis- and treatment-dependent risk of hypogonadism in male childhood cancer survivors (CCS). DESIGN: Male CCS who were treated during the period 1970-2002 and who in 2004 were 18-45 yr of age were eligible. SETTING: The study was conducted in a university hospital clinic. PATIENTS: A consecutive group of CCS treated at Lund University Hospital was selected for the study, of whom 151 (38%) agreed to participate. Furthermore, 141 healthy fertile men served as controls. INTERVENTIONS: We measured serum levels of free and total testosterone, SHBG, and LH. MAIN OUTCOME MEASURES: Odds ratios (OR) for biochemical hypogonadism, defined as total testosterone less than 10 nmol/liter and/or LH above 10 IU/liter, were calculated and related to type of cancer, treatment received, as well as testicular volume. RESULTS: Hypogonadism was more commonly detected in CCS than in controls (OR, 6.7; 95% CI, 2.7, 17). The increased presence of hypogonadism was noted in the following treatment groups: brain surgery, chemotherapy (with and without radiotherapy), and testicular irradiation. Low total testicular volume (

Adult survivors of childhood acute lymphoblastic leukaemia with GH deficiency have normal self-rated quality of life but impaired neuropsychological performance 20 years after cranial irradiation.

OBJECTIVE: Cranial radiotherapy (CRT) was, until recently, important for achieving long-term survival in acute lymphoblastic leukaemia (ALL). Because survival rates have improved markedly, the long-term complications, such as GH deficiency (GHD) and neuropsychological impairment, have become increasingly important. DESIGN AND PATIENTS: The level of self-reported quality of life and neuropsychological functioning was investigated in 44 adults (21 women) with a median age of 25 years who had been treated for childhood onset (CO) ALL with CRT (median 24 Gy). Comparison was made with matched population controls. A subset of patients with GHD was evaluated for neuropsychological functioning after 1 year of GH treatment. RESULTS: Compared to controls, the patients had significantly lower performance in neuropsychological tests. Early age at treatment had a significant negative impact on neuropsychological performance in adulthood. No relationship was found between dose of CRT, time since treatment of ALL or gender and neuropsychological performance. Compared to controls, the patients did not show a poor quality of life or a lowered availability of social interactions or social networks; however, significantly more patients were living alone or with their parents. After GH testing, the patients were all considered GH deficient or insufficient, but no relationship was observed between stimulated peak GH secretion and neuropsychological performance. Treatment with GH for 1 year in a subgroup of the patients did not improve their neuropsychological performance. CONCLUSIONS: This study showed that adults treated with CRT for CO ALL had GHD and significantly impaired neuropsychological performance, although self-reported quality of life was not affected. The effect of GH treatment in this patient group has to be further elucidated.

Growth hormone deficiency predicts cardiovascular risk in young adults treated for acute lymphoblastic leukemia in childhood.

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, and until recently prophylactic cranial radiotherapy (CRT) was important for achieving long-term survival. Hypothalamic-pituitary hormone insufficiency is a well-recognized consequence of CRT for childhood cancer. Another problem is increased cardiovascular risk, which has been shown in long-term survivors of other childhood cancers. In the only previously reported study on cardiovascular risk after childhood ALL, obesity and dyslipidemia were recorded in a small subgroup treated with CRT, compared with patients treated with chemotherapy. The mechanisms behind the increase in cardiovascular risk in survivors of childhood cancer are not clarified. The aim of the present study was to elucidate mechanisms of increased cardiovascular risk in former childhood ALL patients. A group of 44 ALL survivors (23 males, median age 25 yr, range 19-32 yr at the time of study) treated with CRT (median 24 Gy, 18-30 Gy) at a median age of 5 yr (1-18 yr) and chemotherapy were investigated for prevalence of GH deficiency and cardiovascular risk factors. Comparison was made with controls randomly selected from the general population and individually matched for sex, age, smoking habits, and residence. All patients and controls underwent a GHRH-arginine test, and patients with a peak GH 3.9 microg/liter or greater were further investigated with an additional insulin tolerance test. Significantly higher plasma levels of insulin (P = 0.002), blood glucose (P = 0.01), and serum levels of low-density lipoprotein cholesterol, apolipoprotein (Apo) B, triglycerides, fibrinogen, and leptin (all P