Where children play most: physical activity levels of school children across four settings and policy implications.

OBJECTIVE: This study examined physical activity levels among 2,296 Queensland school children in the school, club sport, active transport and free time settings. Childhood physical activity contributes to musculoskeletal strength, psychosocial benefits and cardiovascular health. METHODS: Data were collected from parents by computer-assisted telephone interview on an annual preventive health monitoring survey conducted by the Queensland Government. RESULTS: Parents reported that children achieved the largest proportions of their physical activity in school (33%) or their free time (42%). Moderate participation levels were reported for active transport and organised sport and these activities contributed lower proportions to total physical activity (10% and 15%, respectively). After adjusting for age and sex, living in a family with higher levels of activity and with a parent that knows physical activity guidelines was associated with higher activity levels. Implications for public health: Increasing physical activity in settings where less active children are already participating, specifically in school settings and during free time, may have more immediate benefits than encouraging children to be active in new settings. Many children achieve seven or more hours of physical activity weekly but do not meet the physical activity guideline criterion of 60 minutes of physical activity daily; consequently, quantifying physical activity solely against the guidelines may underestimate children's physical activity.

The clinical relevance of compound heterozygosity for the C282Y and H63D substitutions in hemochromatosis.

BACKGROUND & AIMS: Two major mutations are defined within the hemochromatosis gene, HFE. Although the effects of the C282Y substitution have been well characterized, the clinical significance of the C282Y/H63D state remains unclear. This study assessed the phenotypic expression in C282Y/H63D subjects as compared with C282Y homozygotes. METHODS: Data were obtained from 91 C282Y/H63D probands, 158 C282Y/H63D subjects identified through family screening, and 483 C282Y homozygotes. Subjects underwent clinical evaluation, genotyping, biochemical assessment, and liver biopsy examination where clinically indicated. RESULTS: C282Y/H63D probands had significantly less clinical and biochemical expression than C282Y homozygotes. Biochemical expression was higher in C282Y/H63D probands than in C282Y/H63D subjects identified through family screening (P < .001). Of the C282Y/H63D subjects with serum ferritin levels greater than 1000 mug/L, all had known comorbid factors that could have contributed to the increased ferritin level. Of the 51 C282Y/H63D subjects who underwent liver biopsy examination, significantly increased iron stores were present in 9 subjects and hepatic fibrosis was present in 13. Twelve of the 13 had evidence of hepatic steatosis, excess alcohol consumption, or diabetes. The mobilizable iron level was significantly higher in C282Y homozygous males than in compound heterozygous males (P < .001). Genetic screening of C282Y/H63D first-degree relatives detected 5 C282Y homozygotes. CONCLUSIONS: C282Y/H63D subjects referred for assessment had a high prevalence of increased iron indices but did not develop progressive clinical disease without comorbid factors such as steatosis, diabetes, or excess alcohol consumption. When fibrosis was seen, 1 or more comorbid factors almost always were present. Thus, phlebotomy therapy is warranted and cascade screening of relatives should be performed because expressing C282Y homozygotes may be detected.

Circadian blood pressure variation after acute stroke.

We aimed to characterise the patterns of circadian blood pressure (BP) variation after acute stroke and determine whether any relationship exists between these patterns and stroke outcome. BP was recorded manually every 4 h for 48 h following acute stroke. Patients were classified according to the percentage fall in mean systolic BP (SBP) at night compared to during the day as: dippers (fall > or = 10-<20%); extreme dippers (> or = 20%); non-dippers (> or = 0-<10%); and reverse dippers (<0%, that is, a rise in mean nocturnal SBP compared to mean daytime SBP). One hundred and seventy-three stroke patients were included in the study (83 men, 90 women; mean age 74.3 years). Four patients (2.3%) were extreme dippers, 25 (14.5%) dippers, 80 (46.2%) non-dippers and 64 (36.9%) reverse dippers. There was a non-significant trend in the proportion of patients who were dead or dependent at 3 months in the extreme dipper (p=0.59) and reverse dipper (p=0.35) groups. Non-dipping and reverse-dipping were relatively common patterns of circadian BP variation seen in acute stroke patients. These patterns were not clearly associated with outcome.

Expression profiling correlates with treatment response in women with advanced serous epithelial ovarian cancer.

The majority of epithelial ovarian carcinomas are of serous subtype, with most women presenting at an advanced stage. Approximately 70% respond to initial chemotherapy but eventually relapse. We aimed to find markers of treatment response that might be suitable for routine use, using the gene expression profile of tumor tissue. Thirty one women with histologically-confirmed late-stage serous ovarian cancer were classified into 3 groups based on response to treatment (nonresponders, responders with relapse less than 12 months and responders with no relapse within 12 months). Gene expression profiles of these specimens were analyzed with respect to treatment response and survival (minimum 36 months follow-up). Patients' clinical features did not correlate with prognosis, or with specific gene expression patterns of their tumors. However women who did not respond to treatment could be distinguished from those who responded with no relapse within 12 months based on 34 gene transcripts (p < 0.02). Poor prognosis was associated with high expression of inhibitor of differentiation-2 (ID2) (p = 0.001). High expression of decorin (DCN) and ID2 together was strongly associated with reduced survival (p = 0.003), with an estimated 7-fold increased risk of dying (95% CI 1.9-29.6; 14 months survival) compared with low expression (44 months). Immunohistochemical analysis revealed both nuclear and cytoplasmic distribution of ID2 in ovarian tumors. High percentage of nuclear staining was associated with poor survival, although not statistically significantly. In conclusion, elevated expression of ID2 and DCN was significantly associated with poor prognosis in a homogeneous group of ovarian cancer patients for whom survival could not be predicted from clinical factors.

Screening for hemochromatosis in asymptomatic subjects with or without a family history.

BACKGROUND: Hemochromatosis in white subjects is mostly due to homozygosity for the common C282Y substitution in HFE. Although clinical symptoms are preventable by early detection of the genetic predisposition and prophylactic treatment, population screening is not currently advocated because of the discrepancy between the common mutation prevalence and apparently lower frequency of clinical disease. This study compared screening for hemochromatosis in subjects with or without a family history. METHODS: We assessed disease expression by clinical evaluation and liver biopsy in 672 essentially asymptomatic C282Y homozygous subjects identified by either family screening or health checks. We also observed a subgroup of untreated homozygotes with normal serum ferritin levels for up to 24 years. RESULTS: Prevalence of hepatic iron overload and fibrosis were comparable between the 2 groups. Disease-related conditions were more common in male subjects identified by health checks, but they were older. Hepatic iron overload (grades 2-4) was present in 56% and 34.5% of male and female subjects, respectively; hepatic fibrosis (stages 2-4) in 18.4% and 5.4%; and cirrhosis in 5.6% and 1.9%. Hepatic fibrosis and cirrhosis correlated significantly with the hepatic iron concentration, and except in cases of cirrhosis, there was a 7.5-fold reduction in the mean fibrosis score after phlebotomy. All subjects with cirrhosis were asymptomatic. CONCLUSIONS: Screening for hemochromatosis in apparently healthy subjects homozygous for the C282Y mutation with or without a family history reveals comparable levels of hepatic iron overload and disease. Significant hepatic fibrosis is frequently found in asymptomatic subjects with hemochromatosis and, except when cirrhosis is present, is reversed by iron removal.

Steatosis is a cofactor in liver injury in hemochromatosis.

BACKGROUND & AIMS: Obesity-related steatosis is an increasingly common histologic finding and often coexists with other chronic liver diseases. Although obesity and steatosis are recognized risk factors for more advanced fibrosis in chronic hepatitis C and alcoholic liver disease, it has not been determined whether these factors influence the progression of other diseases in which steatosis is not a feature of the primary liver insult. METHODS: We studied 214 patients with hemochromatosis who were homozygous for the C282Y substitution in HFE and had undergone liver biopsy prior to phlebotomy. RESULTS: Steatosis was present in 41.1% of these patients, and 14.5% had moderate or severe steatosis. Median serum alanine aminotransferase (ALT) and ferritin levels were higher (P < .001), and median transferrin saturation (P = .01) and hepatic iron concentration (HIC) were lower (P = .003) in subjects with steatosis compared with subjects without steatosis. Bivariate analysis revealed a significant association between steatosis and fibrosis (P = .001). Following multiple logistic regression, steatosis was independently associated with fibrosis (odds ratio [OR] 4.3, 95% confidence interval [CI]: 2.1-8.8; P < .001) along with male sex (OR, 5.1; 95% CI: 2.0-12.5; P < .001), excess alcohol consumption (males > or = 50 g/day, females > or = 40 g/day) (OR, 3.9; 95% CI: 1.8-8.5; P = .001), and hepatic iron content (OR, 1.4; 95% CI: 1.2-1.6; P < .001). Both higher BMI (OR, 3.3; 95% CI: 1.8-6.3; P < .001) and alcohol consumption (males > or = 30 g/day, females > or = 10 g/day) (OR, 3.4; 95% CI: 1.2-10.0; P = .023) were independently associated with the presence of steatosis. CONCLUSIONS: These findings indicate that obesity-related steatosis may have a role as a cofactor in liver injury in hemochromatosis. This has important clinical implications and suggests that obesity should be actively addressed in the management of patients with hemochromatosis, as well as other liver diseases.

Public awareness of warning symptoms, risk factors, and treatment of stroke in northwest India.

BACKGROUND AND PURPOSE: This study assessed public awareness of warning symptoms, risk factors, and treatment of stroke in Ludhiana, Punjab, North West India. METHODS: A hospital-based survey was conducted between February 2002 and September 2002 by the Stroke section of Christian Medical College. The study subjects were relatives of patients without history of stroke, attending the outpatient department of the hospital. Trained medical students, interns, and a nurse interviewed subjects using a structured, pretested, open-ended questionnaire. RESULTS: Nine hundred forty-two individuals were interviewed during the study period (56.4% men, mean age 40.1 years, age range 15 to 80 years). Forty-five percent of the subjects did not recognize the brain as the affected organ in stroke. In the multivariate analysis, higher education (P<0.001; odds ratio 2.6; 95%, CI 1.8 to 3.8) and upper socioeconomic status (P<0.005; odds ratio 1.6; CI, 1.1 to 2.2) correlated with a better knowledge of which organ was affected in stroke. Twenty-three percent of the participants did not know a single warning symptom of stroke. Twenty-one percent of the subjects could not identify even a single risk factor for stroke. Seven percent of the study population believed that oil massage would improve stroke victims. A small proportion of subjects believed in witchcraft, faith healing, homeopathic, and ayurvedic treatment (3%). CONCLUSIONS: This hospital-based survey reveals a better awareness of stroke warning signs and risk factors. However, knowledge regarding the organ involved, etiology, and treatment of stroke is lacking. Considerable education is needed to increase public awareness in modern concepts of stroke treatment.

Serum markers of hepatic fibrogenesis in cystic fibrosis liver disease.

BACKGROUND/AIMS: Hepatic fibrosis contributes to adverse outcome in cystic fibrosis (CF). Early detection of CF liver disease (CFLD) may identify patients at risk of significant complications. To evaluate the utility of serum markers to detect hepatic fibrosis in children with CFLD vs. CF patients without liver disease (CFnoLD) and controls. METHODS: Sera from 36 CFLD, 30 CFnoLD and 39 controls were assessed for tissue inhibitor of matrix metalloproteinase (MMP) (TIMP)-1, collagen (CL)-IV, MMP-2, hyaluronic acid (HA) and prolyl hydroxylase (PH) by enzyme immunoassay and were correlated with hepatic fibrosis score in CFLD. RESULTS: TIMP-1, PH and CL-IV were increased in CFLD vs. CFnoLD and controls. Fibrosis score was negatively correlated with TIMP-1 (r=-0.34, P=0.06) and PH (r=-0.48, P=0.008). Receiver-operating characteristics analysis showed CL-IV (AUC 0.785, P<0.0001) and TIMP-1 (AUC 0.765, P<0.0001) differentiated CFLD from CFnoLD and controls, while PH (AUC 0.814, P<0.0001) predicted early fibrogenesis. Diagnostic accuracy improved using logistic regression combining (i) CL-IV, TIMP-1, PH to identify CFLD (AUC 0.831, P<0.0001) and (ii) TIMP-1, PH to identify CFLD patients with no fibrosis (AUC 0.852, P<0.02). CONCLUSIONS: Elevated TIMP-1, CL-IV, PH may be indicators of hepatic fibrogenesis in CF. Increased TIMP-1, PH may be early markers of CFLD.