Anna Lindgren

Test-Retest Variability in Glaucomatous Visual Fields

We measured test-retest variations in computerized visual fields from glaucomatous eyes. Fifty-one patients were tested four times within a four-week period; the severity of disease varied from incipient to advanced. We determined the dependence of threshold variability on defect depth and test point location. In areas of the visual field initially found to have moderate loss of sensitivity, variation in follow-up measurements ranged from normal sensitivity to absolute defect, with little dependence on distance from fixation. Conversely, large changes were considerably more unusual in locations initially showing normal or near-normal sensitivities, and variability was lowest in the most central portion of the field. Our findings suggest that differentiation between true progression and random variation will be facilitated if these factors are taken into account, as well as if comparisons are based on more than two tests. The complex nature of interest variation in glaucoma makes it natural to approach this problem with the help of computer-assisted analyses.

On‐demand vs. prophylactic treatment for severe haemophilia in Norway and Sweden: differences in treatment characteristics and outcome

Summary.  Using an 11‐year panel of 156 Norwegian and Swedish patients with severe haemophilia, and including retrospective case‐book data from birth, we compared the differences in the haemophilia‐related resource use between on‐demand and prophylactic treatment. Patients treated on‐demand had more surgery (arthrodeses, prostheses implantations and synovectomies) and more days lost from work. Median annual factor‐concentrate consumption among adults (18+) was 211 000 IU [interquartile range (IQR) 154 000–268 000] or 3 024 IU kg−1 year−1 for patients on prophylactic treatment and 55 000 IU (IQR 28 000–91 000) for on‐demand patients (780 IU kg−1 year−1). This was partly explained by the fact that the median dose per kg body weight was twice as great 28, (IQR 24–32) for prophylaxis compared with 14 (IQR 12–16) for on‐demand. Prescribed dose per kg body weight was found to be an important factor explaining the variation in total annual factor‐concentrate consumption per patient for both types of treatment. Other variables included in the panel‐data regression analysis were the number of weeks on secondary prophylaxis for on‐demand patients and age, body weight and type of haemophilia for children (0–17 years) on prophylaxis. Differences were consistently substantial and will affect both costs and benefits of the two treatment strategies.

Normal vaginal delivery is to be recommended for haemophilia carrier gravidae

Ljung R, Lindgren A‐C, Petrini P, Tengborn L. Normal vaginal delivery is to be recommended for haemophilia carrier gravidae. Acta Pædiatr 1994;83:609–11. Stockholm. ISSN 0803–5253

Traffic-related air pollution associated with prevalence of asthma and COPD/chronic bronchitis. A cross-sectional study in Southern Sweden

BackgroundThere is growing evidence that air pollution from traffic has adverse long-term effects on chronic respiratory disease in children, but there are few studies and more inconclusive results in adults. We examined associations between residential traffic and asthma and COPD in adults in southern Sweden. A postal questionnaire in 2000 (n = 9319, 18–77 years) provided disease status, and self-reported exposure to traffic. A Geographical Information System (GIS) was used to link geocoded residential addresses to a Swedish road database and an emission database for NOx.ResultsLiving within 100 m of a road with >10 cars/minute (compared with having no heavy road within this distance) was associated with prevalence of asthma diagnosis (OR = 1.40, 95% CI = 1.04–1.89), and COPD diagnosis (OR = 1.64, 95%CI = 1.11–2.4), as well as asthma and chronic bronchitis symptoms. Self-reported traffic exposure was associated with asthma diagnosis and COPD diagnosis, and with asthma symptoms. Annual average NOx was associated with COPD diagnosis and symptoms of asthma and chronic bronchitis.ConclusionLiving close to traffic was associated with prevalence of asthma diagnosis, COPD diagnosis, and symptoms of asthma and bronchitis. This indicates that traffic-related air pollution has both long-term and short-term effects on chronic respiratory disease in adults, even in a region with overall low levels of air pollution.

Association of a lack of psychosocial resources and the risk of giving birth to small for gestational age infants: a stress hypothesis

Objective To test the stress hypothesis that women who give birth to small for gestational age infants lack important psychosocial coping resources, such as a sufficient social network, social support and control in daily life.

Diastolic blood pressure and area of residence: multilevel versus ecological analysis of social inequity

STUDY OBJECTIVES To study geographical differences in diastolic blood pressure and the influence of the social environment (census percentage of people with low educational achievement) on individual diastolic blood pressure level, after controlling for individual age and educational achievement. To compare the results of multilevel and ecological analyses. DESIGN Cross sectional analysis performed by multilevel linear regression modelling, with women at the first level and urban areas at the second level, and by single level ecological regression using areas as the unit of analysis. SETTING Malmö, Sweden (population 250 000). PARTICIPANTS 15 569 women aged 45 to 73, residing in 17 urban areas, who took part in the Malmö Diet and Cancer Study (1991–1996). MAIN RESULTS In the “fixed effects” multilevel analysis, low educational achievement at both individual (β=1.093, SE=0.167) and area levels (β=2.966, SE=1.250) were independently associated with blood pressure, although in the “random effects” multilevel analysis almost none of the total variability in blood pressure across persons was attributable to areas (intraclass correlation=0.3%). The ecological analysis also found an association between the area educational variable and mean diastolic blood pressure (β=4.058, SE=1.345). CONCLUSIONS The small intraclass correlation found indicated very marginal geographical differences and almost no influence of the urban area on individual blood pressure. However, these slight differences were enough to detect an effect of the social environment on blood pressure. The ecological study overestimated the associations found in the “fixed” effects multilevel analysis, and neither distinguished individual from area levels nor provided information on the intraclass correlation. Ecological analyses are inadequate to evaluate geographical differences in health.

The experience of pain from the shoulder-neck area related to the total body pain, self-experienced health and mental distress

The present paper presents the relationship between the total body-pain (TBP) score, defined as the total number of areas shaded on a pain drawing, and the pain from one area, the Shoulder-Neck (SN), among subjects in or out of full-time gainful work respectively. Furthermore, relationships between pain-score, self-experienced health (SEH) and level of mental distress, measured with the General Health Questionnaire (GHQ) were investigated. The analyses is based on a general population sample of 8,116 men and women, 45-60 years of age, completing a questionnaire in the Malmö Shoulder Neck Study. The TBP-score was higher with increasing pain from the SN area, being out of full-time work and among women. Independently of working status, the SEH decreased with increasing pain in the SN area, which was enhanced, by increasing TBP-score. The proportion of women out of full-time gainful work was twice as high as for men. Women showed the same SEH levels with regard to their pain status, independently of their working status while men working full-time scored higher than women did. Oppositely, men out of full-time work had the lowest SEH in relation to their pain status. The GHQ scores of mental distress varied essentially in the same way as the SEH did. The results emphasize the need for an assessment of the number of pain locations and which one that first gave symptoms when studying possible causal relationships between low force musculoskeletal load and development of localized pain. If such data are not collected in epidemiological studies on causes for musculoskeletal pain it will at best lead to unnoticed effect modifications. At worst a potential confounding situation may occur. The relationship between the self-experienced health, mental distress and chronic pain identifies chronic pain as a major public-health problem and suggests a multidisciplinary approach in the treatment and rehabilitation already before work capacity is lost.

Traffic exposure associated with allergic asthma and allergic rhinitis in adults. A cross-sectional study in southern Sweden

BackgroundThere is conflicting evidence that traffic-related air pollution is a risk factor for allergic conditions. Few studies have investigated this in adults. In adults, a high proportion of asthma, rhinitis and eczema is triggered by non-allergic factors. We investigated traffic as a risk factor for allergic versus non-allergic asthma and rhinitis, and eczema, in adults.A questionnaire from 2000 (n = 9319, 18–77 years) provided individual data about disease outcome and self-reported traffic exposure. Additional exposure assessments were obtained using Geographical Informations Systems (GIS). Residential addresses were linked to the national Swedish Road Database and to a pollutant database with modelled annual means of NOx (Nitrogen Oxids).ResultsLiving within 100 m from a road with a traffic intensity of >10 cars/min (24 hour mean) was associated with prevalence of current asthma reported to be triggered by allergic factors (OR = 1.83, 95% CI = 1.23–2.72) and with allergic rhinitis (OR = 1.30, 95%CI = (1.05–1.61). No relation was seen with asthma or rhinitis triggered by other factors. Living within 100 m of a road with >10 cars/min was also associated with hand-eczema during the last 12 months (OR = 1.63, 95% CI = 1.19–2.23), but not with allergic eczema or diagnosed hand-eczema. Consistent results were seen using self-reported traffic, but the associations with NOx were less consistent.ConclusionExposure to traffic was associated with a higher prevalence of allergic asthma and allergic rhinitis, but not with asthma or rhinitis triggered by non-allergic factors. This difference was suggested by the overall pattern, but only clear using GIS-measured traffic intensity as a proxy for traffic exposure. An association was also found with hand-eczema during the last 12 months. We suggest that asthma and rhinitis should not be treated as homogenous groups when estimating effects from traffic in adults.

Elevated level of wnt5a protein in localized prostate cancer tissue is associated with better outcome.

Background Wnt5a is a non-canonical secreted glycoprotein of the Wnt family that plays an important role in cancer development and progression. Previous studies report that Wnt5a is upregulated in prostate cancer and suggested that Wnt5a affects migration and invasion of prostate tumor cell. This study aimed to evaluate the prognostic value of Wnt5a protein expression in prostate cancer tissue and its potential to predict outcome after radical prostatectomy in patients with localized prostate cancer. Methodology and Results Immunohistochemical analysis of a tissue microarray containing prostate specimens of 503 patients with localized prostate cancer showed significantly higher Wnt5a protein expression in cancer compared to benign cores from the same patients (p<0.0001). Patients with high expression of Wnt5a protein had significantly better outcome in terms of time to biochemical recurrence compared to patients with low expression levels (p = 0.001, 95%CI 1.361–3.570, Hazards ratio 2.204). A combination of high Wnt5a expression with low levels of Ki-67 or androgen receptor expression had even better outcome compared to all other groups. Furthermore, we found that Wnt5a expression significantly correlated with VEGF and with Ki-67 and androgen receptor expression, although not highly significant. In vitro, we demonstrated that recombinant Wnt5a decreased invasion of 22Rv1 and DU145 cells and that siRNA knockdown of endogenous Wnt5a protein led to increased invasion of 22Rv1 and LNCaP cells. Conclusion We demonstrate that preserved overexpression of Wnt5a protein in patients with localized prostate cancer predicts a favorable outcome after surgery. This finding together with our in vitro data demonstrating the ability of Wnt5a to impair the invasive properties of prostate cancer cells, suggests a tumor suppressing effect of Wnt5a in localized prostate cancer. These results indicate that Wnt5a can be used as a predictive marker and that it also is a plausible therapeutic target for treatment of localized prostate cancer.

Quantile regression with censored data using generalized L 1 minimization

We propose a way to estimate a parametric quantile function when the dependent variable, e.g. the survival time, is censored. We discuss one way to do this, transforming the problem of finding the p-quantile for the true, uncensored, survival times into a problem of finding the q-quantile for the observed, censored, times. The q-value involves the distribution of the censoring times, which is unknown. The estimation of the quantile function is done using the asymmetric L1 technique with weights involving local Kaplan-Meier estimates of the distribution of the censoring limit.