The impact of neighbourhood walkability on the effectiveness of a structured education programme to increase objectively measured walking.

Background: Incorporating physical activity into daily activities is key for the effectiveness of lifestyle education interventions aimed at improving health outcomes; however, consideration of the environmental context in which individuals live is not always made. Walkability is a characteristic of the physical environment, and may be a potential facilitator to changing physical activity levels. Methods: Using data collected during the Walking Away from Diabetes randomized controlled trial, we examined the association between the walkability of the home neighbourhood and physical activity of participants. We also determined whether home neighbourhood walkability of participants was associated with the intervention effect of the education programme. Results: Data from 706 participants were available for analysis. Neighbourhood walkability was not significantly associated with any of the physical activity measures at baseline, or at 12, 24 or 36 months following the intervention (P > 0.05 for all). There was no association between walkability and change in purposeful steps/day from baseline to 36 months in the usual care or intervention arm; 25.77 (-99.04, 150.58) and 42.97 (-327.63, 413.45), respectively. Conclusion: Neighbourhood walkability appeared to have no association with objectively measured physical activity in this population. Furthermore, the walkability of participant's neighbourhood did not influence the effectiveness of a lifestyle programme.

Cancer of Unknown Primary: a Cancer Registry Study of Factors Affecting Access to Diagnosis.

AIM: A potential impact of the centralisation of cancer services in the UK is difficulty in gaining access for members of the population living far from them. This could lead to delayed presentation of cancer with more advanced disease and clinical deterioration at diagnosis. A patient may be recorded in the cancer registry as having cancer of unknown primary (CUP) if the clinical state at presentation precludes investigation. Other patients may be so recorded if investigation identifies sites of metastatic tumour but the primary is not found. We hypothesised that the first group would include more patients who experienced difficulties in gaining access to health services through residing in deprived areas or through poorer geographical access to healthcare facilities. MATERIALS AND METHODS: We compared the diagnosis of CUP with a comparator tumour, carcinoma of the rectum, where diagnosis is facilitated by an alarm symptom and where variations in access are lower. Records from the Northern and Yorkshire Cancer Registry from 1994 to 2002 with ICD 10 C77-C80 (CUP, including categories where investigations may have been incomplete or no primary cancer was found) and C20 (malignant neoplasm of rectum) were combined with travel time to services (primary care, secondary and tertiary services) and the Index of Multiple Deprivation. Logistic regression modelled predictors of CUP were compared with C20 and, within CUP, the odds of a histological basis of diagnosis. RESULTS: The registry classified 7428 patients as C80, 8849 as C77-C79, and 10 804 as C20. Compared with C20, the number of cases of C80 showed a statistically significant increasing trend with increasing travel time to primary care. Risk also increased strongly with age and deprivation. The results for C77-C79 were similar to those for C80, except that the travel time to primary care showed no effect. Considering all CUP alone, histological diagnosis significantly declined with travel time to the nearest hospital. There was no association with gender and the likelihood of histological diagnosis, but a marked decline with age, a downward trend with deprivation, and an increase when the nearest hospital was a cancer centre. CONCLUSIONS: These findings facilitate the understanding of factors associated with the group of patients that includes those with the least effective access to cancer services.

The influence of geographical access to health care and material deprivation on colorectal cancer survival: evidence from France and England.

This article investigates the influence of distance to health care and material deprivation on cancer survival for patients diagnosed with a colorectal cancer between 1997 and 2004 in France and England. This population-based study included all cases of colorectal cancer diagnosed between 1997 and 2004 in 3 cancer registries in France and 1 cancer registry in England (N=40,613). After adjustment for material deprivation, travel times in England were no longer significantly associated with survival. In France patients living between 20 and 90min from the nearest cancer unit tended to have a poorer survival, although this was not statistically significant. In England, the better prognosis observed for remote patients can be explained by associations with material deprivation; distance to health services alone did not affect survival whilst material deprivation level had a major influence, with lower survival for patients living in deprived areas. Increases in travel times to health services in France were associated with poorer survival rates. The pattern of this influence seems to follow an inverse U distribution, i.e. maximal for average travel times.

Management of colorectal cancer explains differences in 1-year relative survival between France and England for patients diagnosed 1997-2004.

BACKGROUND: Few international population-based studies have provided information on potential determinants of international disparities in cancer survival. This population-based study was undertaken to identify the principal differences in disease characteristics and management that accounted for previously observed poorer survival in English compared with French patients with colorectal cancer. METHODS: The study population comprised all cases of colorectal cancer diagnosed between 1997 and 2004 in the areas covered by three population-based cancer registries in France and one in England (N=40 613). To investigate the influence of clinical and treatment variables on survival, we applied multivariable excess hazard modelling based on generalised linear models with Poisson error. RESULTS: Poorer survival for English patients was primarily due to a larger proportion dying within the first year after diagnosis. After controlling for inter-country differences in the use of chemotherapy and surgical resection with curative intent, country of residence was no-longer associated with 1-year survival for advanced colon cancer patients (excess hazard ratio (EHR)=0.99 (0.92-1.01), P=0.095)). Longer term (2-5 years) excess hazards of death for colon and rectal cancer patients did not differ between France and England. CONCLUSION: This study suggests that difference in management close to diagnosis of colon and rectum cancer is related to differences in survival observed between France and England. All efforts (collection and standardisation of additional variables such as co-morbidity) to investigate the reasons for these disparities in management between these two countries, and more generally across Europe, should be encouraged.

Biogeochemical value of managed realignment, Humber estuary, UK.

We outline a plausible, albeit extreme, managed realignment scenario ('Extended Deep Green' scenario) for a large UK estuary to demonstrate the maximum possible biogeochemical effects and economic outcomes of estuarine management decisions. Our interdisciplinary approach aims to better inform the policy process, by combining biogeochemical and socioeconomic components of managed realignment schemes. Adding 7494 ha of new intertidal area to the UK Humber estuary through managed realignment leads to the annual accumulation of a 1.2 x 10(5) t of 'new' sediment and increases the current annual sink of organic C and N, and particle reactive P in the estuary by 150%, 83% and 50%, respectively. The increase in intertidal area should also increase denitrification. However, this positive outcome is offset by the negative effect of enhanced greenhouse gas emissions in new marshes in the low salinity region of the estuary. Short-term microbial reactions decrease the potential benefits of CO(2) sequestration through gross organic carbon burial by at least 50%. Net carbon storage is thus most effective where oxidation and denitrification reactions are reduced. In the Humber this translates to wet, saline marshes at the seaward end of estuaries. Cost-benefit analysis (CBA) was used to determine the economic efficiency of the Extended Deep Green managed realignment. When compared to a 'Hold-the-Line' future scenario, i.e. the present state/extent of sea defences in the estuary, the CBA shows that managed realignment is cost effective when viewed on >25 year timescales. This is because capital costs are incurred in the first years, whereas the benefits from habitat creation, carbon sequestration and reduced maintenance costs build up over time. Over 50- and 100-year timescales, the Extended Deep Green managed realignment scenario is superior in efficiency terms. The increased sediment accumulation is also likely to enhance storage of contaminant metals. In the case of Cu, a metal that currently causes significant water quality issues, Cu removal due to burial of suspended sediment in realigned areas translates to a value of approximately pounds sterling 1000 a(-1) (avoided clean up costs). Although this is not formally included in the CBA it illustrates another likely positive economic outcome of managed realignment. Although we focus on the Humber, the history of reclamation and its biogeochemistry is common to many estuaries in northern Europe.

Investigation of women with endometrial carcinoma using serum vascular endothelial growth factor (VEGF) measurement.

This study assessed whether serum VEGF measurement in women presenting with endometrial cancer could predict advanced stage disease. Preoperative sera from 37 women undergoing laparotomy for suspected endometrial cancer were assayed for VEGF, CA125 and platelet count. Significant positive correlation was shown between VEGF and platelet levels (P = 0.003, r = 0.477). However, no correlation was demonstrated between VEGF and stage overall, and no significant difference was shown between those with early (stage 1A/1B, n = 20) compared to those with advanced (stage >1B, n = 13) or disseminated (stage >2, n = 7) disease. Serum VEGF measurement was not beneficial in the preoperative assessment of stage in patients with endometrial carcinoma. Strong correlation with platelet levels suggests that this is one of the sources of VEGF measured.

Age-independent indices in second-trimester serum screening for Down's syndrome are useless.

Serum screening for fetal Down's syndrome in the second trimester is far more efficient in older mothers than in younger ones because the risk calculation is based on maternal age. In recent publications, several authors have tried to better the 'classical' test for Down's syndrome screening by creating an age-independent index. This procedure, however, requires the assumption that at least for one parameter the mean MOM or the variance is not constant in relation to maternal age, leading to a smaller overlap in younger women. This study, based on almost 3000 normal cases and 161 cases with Down's syndrome, could not demonstrate any relationship between maternal age and MOM distribution for alpha-fetoprotein, unconjugated oestriol, total human chorionic gonadotropin (hCG), and free beta hCG. We conclude that for a constant false-positive rate, the detection rate of the 'classical' test for Down's syndrome screening in younger women cannot be bettered by creating an age-independent index.

Xanthoderma: an unusual presentation of hypothyroidism.

A young woman presented with progressive yellowing of her skin over a period of six months. Liver function tests were requested by her general practitioner and the results prompted the Chemical Pathology Department to instigate further tests to reach the final diagnosis. Hypercarotenaemia had caused her yellow skin, and various other biochemical abnormalities pointed towards primary hypothyroidism as an underlying cause. Thyroxine replacement treatment successfully corrected all the biochemical abnormalities including hypercarotenaemia. As far as is known, yellow skin as a sole presenting feature of hypothyroidism is extremely rare.

Prenatal screening for trisomy 18 with free beta human chorionic gonadotrophin as a marker.

OBJECTIVE: To determine the relation between maternal serum alpha fetoprotein and free beta human chorionic gonadotrophin concentrations in pregnancies complicated by trisomy 18 and establish whether prenatal biochemical screening for this condition could be developed in a way similar to that proposed for trisomy 21. DESIGN: Serum alpha fetoprotein and free beta human chorionic gonadotrophin concentrations in women with singleton pregnancies affected by cytogenetically confirmed trisomy 18, uncomplicated by neural tube defect or ventral wall defect, were identified from prospective trisomy 21 screening programmes. Additionally, stored maternal serum from similar pregnancies was analysed retrospectively. Analyte concentrations from singleton unaffected pregnancies were identified from a prospective screening programme as controls. Statistical parameters of the affected and unaffected populations were compiled. SETTING: Biochemical screening laboratories in Britain and the United States. SUBJECTS: 52 women with singleton pregnancies complicated by trisomy 18; control population of 6661 women with unaffected singleton pregnancies. MAIN OUTCOME MEASURES: Median values of each analyte and their distribution in the affected and unaffected populations; detection rate of trisomy 18 and the false positive rate. RESULTS: Maternal serum alpha fetoprotein and free beta human chorionic gonadotrophin concentrations were significantly lower in pregnancies complicated by trisomy 18 (median values 0.71 and 0.37 respectively). By using a multivariate risk algorithm incorporating maternal age risk of trisomy 18 and the concentration of the two biochemical markers it was predicted that 50% of trisomy 18 cases (unaffected by neural tube defect or ventral wall defect) could be detected with a 1% false positive rate. CONCLUSION: Second trimester biochemical screening for trisomy 18 could be a valuable addition to trisomy 21 screening programmes.

Dual analyte immunoassay in neural tube defect and Down's syndrome screening: results of a multicentre clinical trial.

We report a multicentre clinical field trial of a novel dual analyte enzyme immunoassay method for the simultaneous measurement of alpha-fetoprotein (AFP) and free beta-human choriogonadotropin (hCG) in the same microtitre well. The assay was shown to have good technical performance in the hands of all trial centres, with between assay coefficients of variation better than 10% for both analyte across the whole of the assay ranges. The method compared well with single analyte measuring procedures and produced acceptable performance as judged by external quality assurance criteria. Recovery of added analyte and analyte dilution curves also showed acceptable performance. In clinical evaluation of a large set of neural tube defect cases, good clinical discrimination from unaffected cases was observed using AFP. With over 150 Down's syndrome cases, the combination of AFP and free beta hCG confirmed the high detection rates achievable using this marker combination, with detection rates in excess of 70% in early gestation. We conclude that the combination of clinically superior markers coupled with technologically innovative assay design will lead to more efficient Down's screening programmes.

Biparietal diameter and crown-rump length in fetuses with Down's syndrome: implications for antenatal serum screening for Down's syndrome.

OBJECTIVES: 1. To compare the ultrasound biparietal diameter and crown-rump length of fetuses with and without Down's syndrome in the first half of pregnancy; 2. To investigate the effect of estimation of gestational age using either measure on the detection rate of serum screening for Down's syndrome. DESIGN: Matched case-control study. Cases were singleton Down's syndrome pregnancies with a biparietal diameter or a crown-rump length recorded. Five controls were matched to each case on: medical centre; the date of the ultrasound scan examination (within two years); gestational age measured as the number of days since the first day of the last menstrual period; and the ultrasound measure used (ie the biparietal diameter (the measure of choice), or the crown-rump length otherwise). If a woman had a serum screening test for Down's syndrome, the biparietal diameter or crown-rump length measurement had to be taken prior to the screening test so that the result of the test could not influence whether a scan was performed. SETTING: Ten antenatal screening centres in seven countries in Europe and North America. SUBJECTS: Two hundred and one women with singleton Down's syndrome pregnancies and 1005 women with unaffected singleton pregnancies. RESULTS: The median biparietal diameter of fetuses with Down's syndrome was identical to that among the controls (median difference 0.0 mm, 95% confidence intervals (CI) -0.5 to 0.5 mm). The estimates of gestational age based on biparietal diameter yielded a median gestational age less than that based on the women's last menstrual period: three days less for cases and two days less for controls; small but statistically significant differences probably reflected a minor systematic difference in the conversion of a biparietal diameter to a gestational age estimate. The median crown-rump length of fetuses with Down's syndrome was also identical to that among controls (median difference 0.0 mm, 95% CI-1.5 to 2.0 mm). There was no significant difference between the median gestational age estimate based on crown-rump length and that based on the women's last menstrual period. CONCLUSION: In antenatal screening for Down's syndrome the routine use of an ultrasound biparietal diameter or crown-rump length measurement to estimate gestational age will not adversely affect the detection rate. To avoid differences in gestational age estimates using the last menstrual period and the biparietal diameter influencing screening performance, separate medians should be derived for each serum marker using the two methods of estimating gestational age. The appropriate set of medians can then be used to calculate the multiple of the median value for each woman screened depending on the method used to estimate her gestational age.

Free beta human choriogonadotropin in Down's syndrome screening: a multicentre study of its role compared with other biochemical markers.

To ascertain the value of maternal serum free beta-human choriogonadotropin subunit measurement in Down's syndrome screening and to compare its effectiveness when screening with a variety of biochemical markers, we have evaluated maternal serum free beta-human choriogonadotropin, total human choriogonadotropin, alpha-fetoprotein and unconjugated oestriol in a large multicentre study of over 2800 unaffected cases and 90 affected cases, the largest collection of Down's cases ever reported. Of all the markers identified to date, free beta-human choriogonadotropin is the marker of choice for use in Down's syndrome screening. When used in early gestation (14-16 weeks) in combination with alpha-fetoprotein and maternal age, it will allow the detection of 77% of Down's cases. A side-by-side comparison with the performance of total human choriogonadotropin shows the superior detection efficiency of free beta-human choriogonadotropin. Unconjugated oestriol adds nothing further to the detection rate compared with the use of alpha-fetoprotein and free beta-human choriogonadotropin alone, and its use results in a 1% increase in false positive rate. We conclude that unconjugated oestriol has no value in Down's screening. The superior detection rate obtained using free beta-human choriogonadotropin is a result of superior detection of Down's cases in women under 30 years old, where the free beta-human choriogonadotropin combination detects 100% more cases than does the total human choriogonadotropin combination.

Why the assay of serum cystine by protein precipitation and chromatography should be abandoned.

The higher bias of serum cystine estimations by a HPLC method compared with those by ion exchange techniques is shown to be largely due to differences in the sample preparation procedures of the two techniques. The ion exchange methods utilised sulphosalicylic acid serum protein precipitation and post-column ninhydrin derivatisation of cystine, whilst the high pressure liquid chromatography technique employed automated dialysis for removal of proteins and pre-column ortho-phthalaldehyde derivatisation of cystine after its conversion to cysteine and then to S-carboxymethylcysteine. Examination of these procedures showed that whilst the high pressure liquid chromatographic method accurately estimates total serum cystine and cysteine, many factors affect the precision and accuracy of serum cystine estimations using the ion exchange techniques. In particular, serum protein precipitation techniques that are currently employed for the preparation of samples for cystine analysis by ion exchange chromatography should be abandoned.

Acute and chronic pharmacokinetics of asymmetrical doses of slow release choline theophyllinate in asthma.

The day and night pharmacokinetics of assymetrical doses of slow release choline theophyllinate (Sabidal SR 270) were compared at day 1 and at day 4 of treatment when steady state had been achieved. Ten patients with chronic asthma were given oral choline theophyllinate 424 mg at 09.00 h and 848 mg at 21.00 h for 4 days. At regular intervals during day 1 and day 4 of treatment theophylline concentrations were measured in plasma and dried blood spots by fluorimmunoassay. Theophylline concentrations measured from dried blood spots were slightly lower than those in plasma, the difference remaining constant at all time points during day 1 and day 4 of treatment. On day 1 the mean peak plasma theophylline concentration was 5.4 +/- 1.0 (+/- s.e. mean) micrograms ml-1 4 h after the morning dose and 11.2 +/- 1.6 micrograms ml-1 4 h after the evening dose which were significantly (P less than 0.01) different. Similarly the areas under the plasma theophylline concentration-time curves at night were significantly (P less than 0.001) greater than those observed during the day. During day 4 mean peak plasma concentrations of theophylline after the morning and larger evening dose were 13.2 +/- 1.3 and 12.1 +/- 1.4 micrograms ml-1 respectively, which were not significantly different. No significant difference was observed between the areas under the plasma theophylline concentration-time curves during the day and at night. However the post-dose time to peak was significantly delayed at night (6 h) compared to the morning (2 h, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)