Resting and exercise haemodynamic characteristics of patients with advanced heart failure and preserved ejection fraction.

AIMS: This study aimed to describe haemodynamic features of patients with advanced heart failure with preserved ejection fraction (HFpEF) as defined by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). METHODS AND RESULTS: We used pooled data from two dedicated HFpEF studies with invasive exercise haemodynamic protocols, the REDUCE LAP-HF (Reduce Elevated Left Atrial Pressure in Patients with Heart Failure) trial and the REDUCE LAP-HF I trial, and categorized patients according to advanced heart failure (AdHF) criteria. The well-characterized HFpEF patients were considered advanced if they had persistent New York Heart Association classification of III-IV and heart failure (HF) hospitalization < 12 months and a 6 min walk test distance < 300 m. Twenty-four (22%) out of 108 patients met the AdHF criteria. On evaluation, clinical characteristics and resting haemodynamics were not different in the two groups. Patients with AdHF had lower work capacity compared with non-advanced patients (35 ± 16 vs. 45 ± 18 W, P = 0.021). Workload-corrected pulmonary capillary wedge pressure normalized to body weight (PCWL) was higher in AdHF patients compared with non-advanced (112 ± 55 vs. 86 ± 49 mmHg/W/kg, P = 0.04). Further, AdHF patients had a smaller increase in cardiac index during exercise (1.1 ± 0.7 vs. 1.6 ± 0.9 L/min/m2 , P = 0.028). CONCLUSIONS: A significantly higher PCWL and lower cardiac index reserve during exercise were observed in AdHF patients compared with non-advanced. These differences were not apparent at rest. Therapies targeting the haemodynamic compromise associated with advanced HFpEF are needed.

Physical activity is associated with lower insulin and C-peptide during glucose challenge in children and adolescents with family background of diabetes.

AIMS: Children and adolescents with a family history of diabetes are at increased risk of overweight, but little is known about the potentially beneficial effects of physical activity on these children. The objective of this study was to investigate the association between moderate to vigorous physical activity (MVPA) and metabolic and inflammatory risks in children and adolescents with a family background of Type 1 diabetes or gestational diabetes. METHODS: Valid MVPA measurements, made with accelerometers, were available from 234 participants (median age, 10.2 years) who had a first-degree relative with either Type 1 or gestational diabetes. Anthropometric and metabolic measurements were made and cytokines measured, and were correlated with MVPA measurements, with stepwise adjustment for confounding factors, in a cross-sectional analysis. RESULTS: MVPA was negatively associated with insulin and C-peptide during challenge with an oral glucose tolerance test. MVPA was also significantly positively associated with the insulin sensitivity index, whereas no consistently significant associations were found between MVPA and BMI, blood pressure or cytokine levels. DISCUSSION: Our findings indicate that physical activity may have beneficial effects on insulin and C-peptide metabolism in children and adolescents with a family background of diabetes, but show no evidence of a protective association with other health-related outcomes.

Gait deviations in transverse plane after SCFE in dependence on the femoral offset.

Residual deformity of the femoral head after slipped capital femoral epiphysis (SCFE) may be accompanied by a loss of femoral offset and lead to femoro-acetabular impingement (FAI), especially during hip flexion. It is hypothesized that during phases of the gait cycle, when the hip is flexed, the offset-loss is compensated by an increased external rotation. The gait pattern of 36 patients suffering from SCFE, who were treated by pinning-in-situ, were compared to a control group of 40 healthy adults by an instrumented 3D-gait analysis. Total patient group was subdivided into 3 subgroups in dependence on the offset (offset groups (OG)) quantified by the angle α according to Nötzli: OG1: α-angle <55°, OG2: α-angle between 55 and 75°, OG3: α-angle >75°. Comparisons were made at 3 instants: initial foot contact (0% gait cycle (GC)), 40-60% GC and 90-100% GC. Patients showed an increased external hip rotation during all 3 periods of the GC with a tendency of increasing external rotation in association with offset-loss. Only during hip extension (40-60% GC) there was a weak correlation between angle α and hip rotation (r=-0.375, p=0.024). In conclusion, the offset-loss does not lead to a functional relevant impingement during walking which needs compensation strategies like increasing external rotation during periods of hip flexion.

Risk Stratification in Women with Gestational Diabetes According to and Beyond Current WHO Criteria.

The pregnancy outcomes in women with gestational diabetes mellitus (GDM) and 'overt diabetes in pregnancy' were compared and the need for further subclassification was investigated with respect to postpartum outcome risk. Data from 944 women who had been uniformly diagnosed as having GDM in Munich, Germany, between 1998 and 2010, were re-classified into GDM and 'overt diabetes in pregnancy'. Pregnancy related outcomes in the offspring were derived from Bavarian birth registry data. Classification and regression trees were used to identify further GDM sub-phenotypes. In total, 88 women (9.3%) were re-classified as having 'overt diabetes in pregnancy'. Compared to women with GDM, women with 'overt diabetes in pregnancy' used insulin more frequently, and were at increased risk for large for gestational age infants [odds ratio 2.50 (95% confidence interval 1.02, 6.13)], preterm delivery [odds ratio 3.28 (1.02, 10.50)], and low APGAR-score at 5 min [odds ratio 12.70 (1.58, 102.2)]. In the 856 women with GDM, classification and regression tree analyses provided further risk stratification in that a combination of fasting glucose>5.3 mmol/l and 1-h glucose>11.1 mmol/l at GDM diagnosis predicted insulin requirement [OR 5.57 (3.75, 8.27) compared to the rest], and maternal body mass index (BMI)≥35 kg/m(2) predicted large for gestational age status. The new differentiation between GDM and 'overt diabetes in pregnancy' is a first step towards refining classification relevant to fetal and maternal postpartum risk. A combination of glucose levels and maternal BMI at diagnosis of GDM may provide further improvement.

Systematic review, network meta-analysis and exploratory cost-effectiveness model of randomized trials of minimally invasive techniques versus surgery for varicose veins.

BACKGROUND: A Health Technology Assessment was conducted to evaluate the relative clinical effectiveness and cost-effectiveness of minimally invasive techniques (foam sclerotherapy (FS), endovenous laser ablation (EVLA) and radiofrequency ablation (RFA)) for managing varicose veins, in comparison with traditional surgery. METHODS: A systematic review of randomized clinical trials (RCTs) was undertaken to assess the effectiveness of minimally invasive techniques compared with other treatments, principally surgical stripping, in terms of recurrence of varicose veins, Venous Clinical Severity Score (VCSS), pain and quality of life. Network meta-analysis and exploratory cost-effectiveness modelling were performed. RESULTS: The literature search conducted in July 2011 identified 1453 unique citations: 31 RCTs (51 papers) satisfied the criteria for effectiveness review. Differences between treatments were negligible in terms of clinical outcomes, so the treatment with the lowest cost appears to be most cost-effective. Total FS costs were estimated to be lowest, and FS was marginally more effective than surgery. However, relative effectiveness was sensitive to the model time horizon. Threshold analysis indicated that EVLA and RFA might be considered cost-effective if their costs were similar to those for surgery. These findings are subject to various uncertainties, including the risk of bias present in the evidence base and variation in reported costs. CONCLUSION: This assessment of currently available evidence suggests there is little to choose between surgery and the minimally invasive techniques in terms of efficacy or safety, so the relative cost of the treatments becomes one of the deciding factors. High-quality RCT evidence is needed to verify and further inform these findings.

Clinical effectiveness and cost-effectiveness of minimally invasive techniques to manage varicose veins: a systematic review and economic evaluation.

BACKGROUND: Varicose veins are enlarged, visibly lumpy knotted veins, usually in the legs. Uncomplicated varicose veins can cause major discomfort and some complications. They are part of chronic venous disease (CVD), which is reported to have a substantial negative impact on health-related quality of life (HRQoL). Traditional treatments for varicose veins involve surgical stripping and ligation and liquid sclerotherapy (LS), but can be invasive and painful. New minimally invasive treatments offer an alternative. These treatments typically involve use of laser, radiofrequency or foam sclerosant. They are increasingly widely used and offer potential benefits such as reduced complications, faster recovery, fewer physical limitations and improved quality of life. OBJECTIVE: The aim of this report is to evaluate the clinical effectiveness, safety and cost-effectiveness of the minimally invasive techniques of foam sclerotherapy (FS), endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) in comparison with other techniques, including traditional surgical techniques, LS and conservative management, in the management of varicose veins. DATA SOURCES: A systematic search was made of 11 bibliographic databases of published and unpublished literature from their inception to July 2011: MEDLINE; EMBASE; Cumulative Index to Nursing and Allied Health Literature; The Cochrane Library; Biological Abstracts; Science Citation Index (SCI); Social Sciences Citation Index; Conference Proceedings Citation Index-Science; UK Clinical Research Network; Current Controlled Trials; and ClinicalTrials.gov. REVIEW METHODS: A systematic review of randomised controlled trials (RCTs) to assess the clinical effectiveness of minimally invasive techniques compared with other treatments, principally surgical stripping, in terms of recurrence of varicose veins, retreatment and clinical symptoms, as measured by the Venous Clinical Severity Score (VCSS), pain and quality of life. Network meta-analysis and exploratory cost-effectiveness modelling were performed. RESULTS: The literature search identified 1453 unique citations, of which 34 RCTs (54 papers) satisfied the criteria for the clinical effectiveness review. The minimally invasive techniques reported clinical outcomes similar to surgery. Rates of recurrence were slightly lower for EVLA, RFA and FS, especially for longer follow-up periods; VCSS score was lower for EVLA and FS than for stripping, but slightly higher for RFA; short-term pain was less for FS and RFA but higher for EVLA; higher quality-of-life scores were reported for all evaluated interventions than for stripping. Differences between treatments were therefore negligible in terms of clinical outcomes, so the treatment with the lowest cost appears to be most cost-effective. Our central estimate is that total FS costs were lowest and FS is marginally more effective than stripping. However, this result was sensitive to the model time horizon. Threshold analysis indicated that EVLA and RFA might be considered cost-effective if their costs are equivalent to stripping. These findings are subject to uncertainty on account of the risk of bias present in the evidence base and the variation in costs. LIMITATIONS: The relative clinical effectiveness and cost-effectiveness of the techniques are principally based on rates of post-operative technical recurrence rather than symptomatic recurrence, as this was the reported outcome in all trials. The true proportion of treated individuals who are likely to present with symptoms of recurrence requiring retreatment is therefore not certain. A figure reflecting the likely proportion of treated individuals who would experience symptomatic recurrence requiring retreatment (with its associated costs), therefore, had to be calculated by the authors based on a small number of studies. The findings of this report also need to be verified by data from future trials with longer follow-up and using more standardised outcome measures. CONCLUSIONS: This assessment of the currently available evidence suggests there is little to choose between the minimally invasive techniques in terms of efficacy or cost, and each offers a viable, clinically effective alternative to stripping. FS might offer the most cost-effective alternative to stripping, within certain time parameters. High-quality RCT evidence is needed. Future trials should aim to measure and report outcomes in a standardised manner, which would permit more efficient pooling of their results. STUDY REGISTRATION: PROSPERO number CRD42011001355. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A model of the cost-effectiveness of intensity-modulated radiotherapy in comparison with three-dimensional conformal radiotherapy for the treatment of localised prostate cancer.

AIMS: To determine the cost-effectiveness of intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3DCRT) for men with localised prostate cancer from a UK National Health Service perspective. MATERIALS AND METHODS: A discrete event simulation model was developed to simulate the progress of patients through advancing disease states until death from prostate cancer or other causes. Clinical effectiveness data for IMRT and 3DCRT were derived from a systematic review. Four scenarios were modelled based on different clinical studies. A probabilistic sensitivity analysis was undertaken and the incremental cost per quality adjusted life years (ICER) calculated. RESULTS: In scenarios where estimated survival was greater for IMRT than 3DCRT, IMRT was clearly cost-effective (ICER <£20 000). For scenarios where only a difference in late gastrointestinal toxicity was assumed, the ICER was highly sensitive to uncertain model parameters, including the magnitude of the difference, the duration of gastrointestinal toxicity and the cost difference between treatments. For the most likely scenario, a 15% difference in late gastrointestinal toxicity, the ICER was £35 000, with a 20% probability that it is cost-effective at a maximum threshold of £20 000 and a 48% probability at a threshold of £30 000. CONCLUSION: If IMRT can be used to prolong survival, it is very cost-effective. Otherwise cost-effectiveness is uncertain.

Human enterovirus infections in children at increased risk for type 1 diabetes: the Babydiet study.

AIMS/HYPOTHESIS: The aim of this study was to examine human enteroviruses (HEVs) and other intestinal viruses derived from children who participated in the Babydiet intervention study and to analyse the findings according to the appearance of islet autoantibodies, dietary intervention, maternal type 1 diabetes and clinical symptoms. METHODS: In the Babydiet study the influence of first gluten exposure (6 or 12 months) on the development of islet autoimmunity was investigated in 150 children with increased genetic and familial risk for type 1 diabetes. Blood and stool samples were collected at 3 monthly intervals until the age of 3 years and yearly thereafter. Infections and clinical symptoms were recorded daily for the first year. In the present study, 339 stool samples collected from 104 children during the first year of life were analysed for HEVs and a certain proportion of the samples were analysed for other intestinal viruses. RESULTS: HEV was detected in 32 (9.4%) samples from 24 (23.1%) children. Altogether 13 serotypes were identified, with HEV-A species being the most common. Children with gastrointestinal symptoms had norovirus (3/11) and sapovirus (1/11) infections in addition to HEV (1/11). Of the 104 children, 22 developed islet autoantibodies. HEV infections were detected in 18% (4/22) and 24% (20/82) of islet-autoantibody-positive and -negative children, respectively (p = 0.5). The prevalence of HEV was similar in the gluten-exposed groups and in children from mothers with type 1 diabetes or from affected fathers and/or siblings (p = 1.0 and 0.6, respectively). CONCLUSIONS/INTERPRETATION: No correlation was found between the presence of HEV in the first year of life and the development of islet autoantibodies. There was no association between HEV infections and dietary intervention, maternal diabetes or clinical symptoms.

Intensity-modulated radiotherapy for the treatment of prostate cancer: a systematic review and economic evaluation.

BACKGROUND: Prostate cancer (PC) is the most common cancer in men in the UK. Radiotherapy (RT) is a recognised treatment for PC and high-dose conformal radiotherapy (CRT) is the recommended standard of care for localised or locally advanced tumours. Intensity-modulated radiotherapy (IMRT) allows better dose distributions in RT. OBJECTIVE: This report evaluates the clinical effectiveness and cost-effectiveness of IMRT for the radical treatment of PC. DATA SOURCES: The following databases were searched: MEDLINE (1950-present), EMBASE (1980-present), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982-present), BIOSIS (1985-present), the Cochrane Database of Systematic Reviews (1991-present), the Cochrane Controlled Trials Register (1991-present), the Science Citation Index (1900-present) and the NHS Centre for Reviews and Dissemination databases (Database of Abstracts of Reviews of Effects, NHS Economic Evaluation Database, Health Technology Assessment) (1991-present). MEDLINE In-Process & Other Non-Indexed Citations was searched to identify any studies not yet indexed on MEDLINE. Current research was identified through searching the UK Clinical Research Network, National Research Register archive, the Current Controlled Trials register and the Medical Research Council Clinical Trials Register. In addition, abstracts of the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and European Society for Therapeutic Radiology and Oncology conferences were browsed. REVIEW METHODS: A systematic literature review of the clinical effectiveness and cost-effectiveness of IMRT in PC was conducted. Comparators were three-dimensional conformal radiotherapy (3DCRT) or radical prostatectomy. Outcomes sought were overall survival, biochemical [prostate-specific antigen (PSA)] relapse-free survival, toxicity and health-related quality of life (HRQoL). Fifteen electronic bibliographic databases were searched in January 2009 and updated in May 2009, and the reference lists of relevant articles were checked. Studies only published in languages other than English were excluded. An economic model was developed to examine the cost-effectiveness of IMRT in comparison to 3DCRT. Four scenarios were modelled based on the studies which reported both PSA survival and late gastrointestinal (GI) toxicity. In two scenarios equal PSA survival was assumed for IMRT and 3DCRT, the other two having greater PSA survival for the IMRT cohort. As there was very limited data on clinical outcomes, the model estimates progression to clinical failure and PC death from the surrogate outcome of PSA failure. RESULTS: No randomised controlled trials (RCTs) of IMRT versus 3DCRT in PC were available, but 13 non-randomised studies comparing IMRT with 3DCRT were found, of which five were available only as abstracts. One abstract reported overall survival. Biochemical relapse-free survival was not affected by treatment group, except where there was a dose difference between groups, in which case higher dose IMRT was favoured over lower dose 3DCRT. Most studies reported an advantage for IMRT in GI toxicity, attributed to increased conformality of treatment compared with 3DCRT, particularly with regard to volume of rectum treated. There was some indication that genitourinary toxicity was worse for patients treated with dose escalated IMRT, although most studies did not find a significant treatment effect. HRQoL improved for both treatment groups following radiotherapy, with any group difference resolved by 6 months after treatment. No comparative studies of IMRT versus prostatectomy were identified. No comparative studies of IMRT in PC patients with bone metastasis were identified. LIMITATIONS: The strength of the conclusions of this review are limited by the lack of RCTs, and any comparative studies for some patient groups. CONCLUSIONS: The comparative data of IMRT versus 3DCRT seem to support the theory that higher doses, up to 81 Gy, can improve biochemical survival for patients with localised PC, concurring with data on CRT. The data also suggest that toxicity can be reduced by increasing conformality of treatment, particularly with regard to GI toxicity, which can be more easily achieved with IMRT than 3DCRT. Whether differences in GI toxicity between IMRT and 3DCRT are sufficient for IMRT to be cost-effective is uncertain, depending on the difference in incidence of GI toxicity, its duration and the cost difference between IMRT and 3DCRT.

Suitability of live and fire-killed small-diameter ponderosa and lodgepole pine trees for manufacturing a new structural wood composite.

Finding alternative uses for raw material from small-diameter trees is a critical problem throughout the United States. In western states, a lack of markets for small-diameter ponderosa pine (Pinus ponderosa) and lodgepole pine (Pinus contorta) can contribute to problems associated with overstocking. To test the feasibility of producing structural composite lumber (SCL) beams from these two western species, we used a new technology called steam-pressed scrim lumber (SPSL) based on scrimming technology developed in Australia. Both standing green and fire-killed ponderosa and lodgepole pine logs were used in an initial test. Fire-killed logs of both species were found to be unsuitable for producing SPSL but green logs were suitable for producing SPSL. For SPSL from green material, ponderosa pine had significantly higher modulus of rupture and work-to-maximum load values than did SPSL from lodgepole pine. Modulus of elasticity was higher for lodgepole pine. The presence of blows was greater with lodgepole pine than with ponderosa. Blows had a negative effect on the mechanical properties of ponderosa pine but no significant effect on the mechanical properties of SPSL from lodgepole pine. An evaluation of non-destructive testing methods showed that X-ray could be used to determine low density areas in parent beams. The use of a sonic compression wave tester for NDE evaluation of modulus of rupture showed some promise with SPSL but requires further research.

Early infant diet in children at high risk for type 1 diabetes.

Infant diet affects health and development. The aim of our study was to investigate WHO infant feeding compliance in children who have a first degree family history of type 1 diabetes (T1D). One hundred and fifty children who were first degree relatives of patients with T1D were intensively followed from birth in the BABYDIET intervention study. Infant feeding, infections, and medication were recorded daily by participating families. Weight and length of children were obtained from paediatric records. Only 5% of the families followed the WHO recommendations for infant feeding that include full breastfeeding for at least 6 months (18.8% of children) and introduction of complementary foods under continued breastfeeding thereafter (22.2% of children). Maternal age in the first quartile (<29 years; p<0.0001), and maternal smoking (p<0.0001) were associated with an earlier introduction of solid food and reduced breastfeeding. Full breastfeeding > or =6 months was associated with reduced frequency of gastrointestinal infections (12 vs. 38%, p=0.02) and antibiotic treatment (24 vs. 48%, p=0.04). Our findings indicate that WHO infant feeding recommendations were poorly followed by families with a family history of T1D. Action to improve levels of infant feeding behaviour is essential, especially among young mothers with T1D.

Identification of historical specimens and wildlife seizures originating from highly degraded sources of kangaroos and other macropods.

Forensic investigations are an important area in the regulation of food mis-description, wildlife seizures and the international trade in wildlife and its products. An early, but important stage in dealing with many biological materials that are submitted for forensic scrutiny is species identification. We describe a method and new primers to amplify three small DNA fragments of the cytochrome b region of the mitochondrial DNA that are suitable for marsupial species identification from degraded sources, such as wildlife seizures. They were designed as consensus sequences from a comparison of 21 marsupial species. The primers also contained sequences intended specifically not to amplify human DNA, thereby reducing the likelihood of amplifying contaminants. Examples of the utility of these primers are given using a range of conditions that may be applied using such an approach, including (1) field-collected sub-fossil bones, (2) an example of museum mis-identification from a specimen collected in 1930 and (3) a skull collected from Bernier Island, in the harsh mid-west of Western Australia.

Use of classical and novel biomarkers as prognostic risk factors for localised prostate cancer: a systematic review.

OBJECTIVES: To provide an evidence-based perspective on the prognostic value of novel markers in localised prostate cancer and to identify the best prognostic model including the three classical markers and investigate whether models incorporating novel markers are better. DATA SOURCES: Eight electronic bibliographic databases were searched during March-April 2007. The reference lists of relevant articles were checked and various health services research-related resources consulted via the internet. The search was restricted to publications from 1970 onwards in the English language. METHODS: Selected studies were assessed, data extracted using a standard template, and quality assessed using an adaptation of published criteria. Because of the heterogeneity regarding populations, outcomes and study type, meta-analyses were not undertaken and the results are presented in tabulated format with a narrative synthesis of the results. RESULTS: In total 30 papers met the inclusion criteria, of which 28 reported on prognostic novel markers and five on prognostic models. A total of 21 novel markers were identified from the 28 novel marker studies. There was considerable variability in the results reported, the quality of the studies was generally poor and there was a shortage of studies in some categories. The marker with the strongest evidence for its prognostic significance was prostate-specific antigen (PSA) velocity (or doubling time). There was a particularly strong association between PSA velocity and prostate cancer death in both clinical and pathological models. In the clinical model the hazard ratio for death from prostate cancer was 9.8 (95% CI 2.8-34.3, p < 0.001) in men with an annual PSA velocity of more than 2 ng/ml versus an annual PSA velocity of 2 ng/ml or less; similarly, the hazard ratio was 12.8 (95% CI 3.7-43.7, p < 0.001) in the pathological model. The quality of the prognostic model studies was adequate and overall better than the quality of the prognostic marker studies. Two issues were poorly dealt with in most or all of the prognostic model studies: inclusion of established markers and consideration of the possible biases from study attrition. Given the heterogeneity of the models, they cannot be considered comparable. Only two models did not include a novel marker, and one of these included several demographic and co-morbidity variables to predict all-cause mortality. Only two models reported a measure of model performance, the C-statistic, and for neither was it calculated in an external data set. It was not possible to assess whether the models that included novel markers performed better than those without. CONCLUSIONS: This review highlighted the poor quality and heterogeneity of studies, which render much of the results inconclusive. It also pinpointed the small proportion of models reported in the literature that are based on patient cohorts with a mean or median follow-up of at least 5 years, thus making long-term predictions unreliable. PSA velocity, however, stood out in terms of the strength of the evidence supporting its prognostic value and the relatively high hazard ratios. There is great interest in PSA velocity as a monitoring tool for active surveillance but there is as yet no consensus on how it should be used and, in particular, what threshold should indicate the need for radical treatment.

Exposure to environmental factors in drinking water: risk of islet autoimmunity and type 1 diabetes--the BABYDIAB study.

Type 1 diabetes (T1D) is characterized by autoimmunity against pancreatic islets, and autoantibodies may be present for years before diagnosis. Environmental factors during early life, including drinking water, may play a role in pathogenesis of T1D. The German BABYDIAB study is a prospective observational study that followed newborn offspring of mothers or fathers with T1D from birth to 17 years of age. The present study was a nested case-control analysis, where subjects with islet autoimmunity were defined as cases (n=95), those without as controls (n=139). Drinking water quality was obtained from the German Water Supply Authorities for the participating families for the first year of the child's life. There was no significant association between water acidity or drinking water quality (concentration of minerals and elements) and islet autoimmunity risk. Increased progression to diabetes in islet autoantibody-positive children was associated with exposure to water with lower pH values (less than cohort median, 7.62; odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.1-5.7; p=0.03) but was not significant after correction for multiple comparisons. Concentrations of nitrate, nitrite, iron, aluminum, and manganese were not associated with risk of T1D progression. This is the first prospective study with water quality measured before the onset of islet autoimmunity and T1D. Consistent with a previous cross-sectional case-control study, we found an association between drinking water pH and the rate of T1D development in at-risk children. The association is marginal and requires validation in other prospective cohorts.

[Effect of breastfeeding on the risk of becoming overweight in offspring of mothers with type 1 diabetes]. / Einfluss des Stillens auf das Risiko für Ubergewicht bei Kindern von Müttern mit Typ-1-Diabetes.

BACKGROUND AND OBJECTIVE: Breastfeeding is considered to be a protective factor against obesity in healthy children. But previous studies about the effect of breastfeeding in the offspring of diabetic mothers have provided inconsistent results. It was the aim of this study to assess the effect of breastfeeding on the risk of becoming overweight at two years of age in children of these mothers. METHODS: In a prospective cohort study data on exclusive or partial breastfeeding habits, were obtained from questionnaires given to 816 mothers, aged between 17 and 43 years, with type 1 diabetes. Weight and height of their children was obtained from their pediatric records. Children with a BMI > or = 90th percentile were classified as being overweight. RESULTS: 77.9 % of all mothers started breastfeeding after the child's birth. Six months later 33.1 % were still breast-feeding. 14.5 % of all children were overweight at two years of age. After adjusting for smoking in pregnancy and the child's gender and birth weight, there was a risk reduction for overweight of 60 % (OR=0.405; 95%-CI: 0.211-0.779) for breastfeeding duration of 12 to 25 weeks. A similar positive association was found for predominant breastfeeding for a duration of at least four months (OR=0.500; 95%-CI: 0.282-0.887). Protective effects were already present when the duration of breastfeeding was four weeks or more. CONCLUSIONS: Mothers with type 1 diabetes breastfed less and for a shorter duration than those in the general population. Breastfeeding duration of at least four weeks was associated with a reduced risk for overweight at two years of age. Special needs regarding diabetes management have to be taken into account.

[Breastfeeding in women with gestational diabetes]. / Stillverhalten bei Frauen mit Gestationsdiabetes.

BACKGROUND AND OBJECTIVE: Children born to mothers with gestational diabetes are at an increased risk of developing obesity. Breastfeeding is acknowledged as beneficial for child development and it is suggested that breastfeeding protects against becoming obese. The aim of this study was to document breastfeeding habits of women with gestational diabetes and to identify factors that affect breastfeeding habits. METHODS: Breastfeeding habits (breastfeeding of any duration) were recorded of 257 mothers with gestational diabetes (mean age 31.4 +/- 4.8 years) who participated in a prospective post-partum study between 1989 and 1999 and compared to breastfeeding habits of 527 healthy mothers (mean age 30.3 +/- 4.2 years), all enrolled in the prospective BABYDIAB study between the years 1989 and 2000. Breastfeeding data were prospectively obtained by questionnaire and interview. RESULTS: Compared to children of healthy mothers, fewer children of mothers with gestational diabetes were breastfed (75% vs 86%; P<0.0001). Among breastfed children the duration of full or any breastfeeding was shorter in children of mothers with gestational diabetes (median for full breastfeeding 9 weeks. [mothers with gestational diabetes] vs. 17 weeks. [healthy mothers]; p<0.0001; median duration of any breastfeeding 16 weeks. vs. 26 weeks.; p<0.0001). After stratification for other risk factors the duration of breastfeeding significantly differed between mothers with gestational DM and those who were healthy (hazard ratio [HR] 1.4; p<0.05 for full breastfeeding; HR 1.5; p<0.0001 for any breastfeeding). Full and any breastfeeding was shorter in women with insulin-dependent gestational diabetes than in those with diet-controlled gestational diabetes (full breast-feeding 4 weeks. vs. 12 weeks.; p<0.01 and any breastfeeding 10 weeks. vs. 20 weeks,; p<0.0001). Fewer women with gestational diabetes and a body weight index (BMI) >30 kg/m2 breastfed (65% vs 80%; p=0.01) and for a shorter duration than women with a BMI <30 kg/m2 (any breastfeeding 12 weeks. vs. 17 weeks; p=0.02). The type of DM therapy independently correlated with reduced breastfeeding duration (HR 1.7; p=0<0.01). CONCLUSIONS: Mothers with gestational diabetes, especially mothers with insulin-dependent gestational diabetes, and obese mothers breastfed their children significantly less and for a shorter duration than healthy mothers. These findings could explain the higher risk of their children developing obesity later in life and should be considered when counselling women with gestational diabetes.

Variable pulsed light is less painful than light-emitting diodes for topical photodynamic therapy of actinic keratosis: a prospective randomized controlled trial.

BACKGROUND: Photodynamic therapy (PDT) of actinic keratosis (AK) using methylaminolaevulinate (MAL) is an effective and safe treatment option, but the procedure is painful. OBJECTIVES: To evaluate the efficacy and pain associated with variable pulsed light (VPL), a prospective, randomized, controlled split-face study was performed. METHODS: Topical MAL-PDT was conducted in 25 patients with AK (n = 238) who were suitable for two-sided comparison. After incubation with MAL, irradiation was performed with a light-emitting diode (LED) (50 mW cm(-2); 37 J cm(-2)) vs. VPL (80 J cm(-2), double pulsed at 40 J cm(-2), pulse train of 15 impulses each with a duration of 5 ms, 610-950 nm filtered hand piece) followed by re-evaluation up to 3 months. RESULTS: The pain during and after therapy was significantly lower with VPL irradiation [t (d.f. = 24) = 4.42, P < 0.001]. The overall mean +/- SD infiltration and keratosis score at 3 months after treatment was 0.86 +/- 0.71 (LED system) vs. 1.05 +/- 0.74 (VPL device) (no statistically significant difference; P = 0.292). Patient satisfaction following both treatment modalities did not significantly differ at the 3-month follow up (P = 0.425). CONCLUSIONS: VPL used for MAL-PDT is an efficient alternative for the treatment of AK that results in complete remission and cosmesis equivalent to LED irradiation but causes significantly less pain.

[Smoking behavior during pregnancy of women with type 1 or gestational diabetes]. / Rauchverhalten während der Schwangerschaft bei Frauen mit Typ-1-Diabetes oder Gestationsdiabetes.

BACKGROUND AND OBJECTIVE: Smoking and diabetes mellitus (DM) are both risk factors for complications during pregnancy and disorders in the newborn. Smoking behavior during pregnancy was investigated in German families where either the pregnant woman or her spouse had diabetes. The relationship between maternal smoking during pregnancy, her metabolic state and the child's birth weight was analysed. PATIENTS AND METHODS: Data on smoking behavior during pregnancy of women and their spouses were obtained by questionnaire. 2 498 families were included: 1,439 women and 1,010 men with type 1 diabetes (T1D) and 1,059 women and 1,488 men without T1D, deliveries having taken place between 1989 and 2005 (no account was taken of the amount smoked or whether stopped during pregnancy). Also collected were data on 308 women with gestational diabetes (GDM), who delivered a baby between 1989 and 1997. RESULTS: Significantly more pregnant women with T1D and GDM smoked than pregnant women without diabetes (13.2% and 15.2% vs 8.7%, p=0.001). Children of smoking pregnant women with T1D had a significantly lower birth weight than those of non-smoking pregnant women with T1D (median 54th percentile vs 71st percentile, p<0.001), although smoking pregnant women had a higher HbA (1c) than non-smoking pregnant women with T1D (median 6.1% vs 5.7%, p<0.001). The number of women and men who smoked during pregnancy declined between 1989 and 2005 (women: 17.5% vs. 8.9%, p=0.02, men: 38.0% vs 24.7%, p<0.001). CONCLUSIONS: The lower birth weight of children of mothers who smoked demonstrates the detrimental consequences of smoking during pregnancy. Pregnant woman with diabetes are a high risk group that should be targeted with programmes that aim to stop smoking during pregnancy.

Breastfeeding habits in families with Type 1 diabetes.

AIMS: Breastfeeding is acknowledged to be beneficial for child development. Women with diabetes may be more likely not to breastfeed their children because of neonatal morbidity and instability in diabetes control. The aim of this study was to assess the effect of maternal Type 1 diabetes on breastfeeding habits. METHODS: Full breastfeeding and any breastfeeding were reported in the first year of life in 1560 children born in Germany between 1989 and 2004. Of those, 997 children had a mother with Type 1 diabetes, and the remaining 563 children had a father or sibling with Type 1 diabetes. RESULTS: Fewer children of mothers with Type 1 diabetes were breastfed than children of non-diabetic mothers (77 vs. 86%; P < 0.0001) and, amongst breastfed children, there was a shorter duration of full breastfeeding (12 vs. 17 weeks; P < 0.0001) and any breastfeeding (20 vs. 26 weeks, P < 0.0001) in children of mothers with Type 1 diabetes compared with children of non-diabetic mothers. Other factors associated with reduced frequency and duration of breastfeeding were pre-term delivery (P < 0.0001), young maternal age (P < 0.0001), and firstborn children (P < 0.0001). After stratification for each of these factors, breastfeeding remained significantly less frequent and of less duration in children of mothers with Type 1 diabetes as compared with children of non-diabetic mothers. CONCLUSIONS: Mothers with Type 1 diabetes breastfeed their children less than international recommendations. Counselling to increase frequency and duration of breastfeeding may be warranted in this population.