Incidence rates of progressive childhood encephalopathy in Oslo,Norway: a population based study

Background  

Progressive encephalopathy (PE) in children is a heterogeneous group of diseases mainly composed of metabolic diseases, but it consists also of neurodegenerative disorders where neither metabolic nor other causes are found. We wanted to estimate the incidence rate and aetiology of PE, as well as the age of onset of the disease.     

More forearm fractures among urban than rural women: The NOREPOS study based on the Tromsø study and the HUNT study

Higher rates of hip fracture and all fractures combined have been observed in urban compared with rural areas, but whether there are urban‐rural differences in distal forearm fracture rates is less studied. The aim of this longitudinal study was to compare the incidence of forearm fracture in postmenopausal women in urban and rural areas in Norway and to investigate risk factors that could explain potential fracture differences. The study included data from 11,209 women aged 65 years or more who participated in two large health studies, the Tromsø Health Study in 1994–1995 and the Nord‐Trøndelag Health Study in 1995–1997. Forearm bone mineral density (BMD) was measured by single‐energy X‐ray absorptiometry in a subsample of women (n = 7333) at baseline. All women were followed with respect to hospital‐verified forearm fractures (median follow‐up 6.3 years). A total of 9249 and 1960 women lived in areas classified as rural and urban, respectively. Urban women had an increased forearm fracture risk [relative risk (RR) = 1.29, 95% confidence interval (CI) 1.09–1.52] compared with women in rural areas. Rural women had higher body mass index (BMI) than urban women, and the RR was moderately reduced to 1.21 (95% CI 1.02–1.43) after BMI adjustments. Rural women had the highest BMD. In the subgroup with measured BMD, adjustments for BMD changed the urban versus rural RR from 1.21 (95% CI 0.96–1.52) to 1.05 (95% CI 0.83–1.32), suggesting that BMD is an important explanatory factor. In conclusion, higher rates of forearm fractures was found in urban compared with rural women. © 2011 American Society for Bone and Mineral Research.     

Prognostic significance of risk group stratification in elderly patients with acute myeloid leukaemia

Prognostic factors were studied in a series of 211 acute myeloid leukaemia (AML) patients over 60 years of age, treated at a single centre. The patients were allocated into three risk groups based on cytogenetics, occurrence of antecedent haematological disorder and leucocyte count. Only 3% had low-risk features, 39% had intermediate- and 58% had adverse-risk features. Complete remission (CR) was achieved in 43% of all patients. In multivariate analyses, the number of cycles needed to achieve CR and the risk group were significantly associated with the duration of CR. Median survival time for the entire cohort of patients was only 107 d. Advanced age, low induction treatment intensity, treatment during earlier years and adverse-risk group were associated with shorter overall survival times. Risk group classification may help selection of elderly patients with a good chance of benefiting from intensive treatment to actually receive such treatment, while sparing others with a low probability of survival benefit from toxic treatment. Low intensity induction treatment reduces the chance of obtaining complete remission, produces inferior survival times and should consequently be avoided when the aim is to obtain complete remission. In elderly AML patients, introducing age and re-evaluation of intermediate and good prognosis patients regarding response to induction treatment may improve the risk group classification.     

Correlation Between Trough Plasma Dabigatran Concentrations and Estimates of Glomerular Filtration Rate Based on Creatinine and Cystatin C

Aims

Dabigatran is largely cleared by renal excretion. Renal function is thus a major determinant of trough dabigatran concentrations, which correlate with the risk of thromboembolic and haemorrhagic outcomes. Current dabigatran dosing guidelines use the Cockcroft–Gault (CG) equation to gauge renal function, instead of contemporary equations including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations employing creatinine (CKD-EPI_Cr), cystatin C (CKD-EPI_Cys) and both renal biomarkers (CKD-EPI_CrCys).

Methods

A linear regression model including the dabigatran etexilate maintenance dose rate, relevant interacting drugs and genetic polymorphisms (including CES1), was used to analyse the relationship between the values from each renal function equation and trough steady-state plasma dabigatran concentrations.

Results

The median dose-corrected trough steady-state plasma dabigatran concentration in 52 patients (38–94 years) taking dabigatran etexilate was 60 µg/L (range 9–279). The dose-corrected trough concentration in a patient on phenytoin and phenobarbitone was >3 standard deviations below the cohort mean. The CG, CKD-EPI_Cr, CKD-EPI_Cys and CKD-EPI_CrCys equations explained (R², 95 % CI) 32 % (9–55), 37 % (12–60), 41 % (16–64) and 47 % (20–69) of the variability in dabigatran concentrations between patients, respectively. One-way analysis of variance (ANOVA) comparing the R² values for each equation was not statistically significant (p = 0.74).

Discussion

Estimates of renal function using the four equations accounted for 32–47 % of the variability in dabigatran concentrations between patients. We are the first to provide evidence that co-administration of phenytoin/phenobarbitone with dabigatran etexilate is associated with significantly reduced dabigatran exposure.

Electronic supplementary material

The online version of this article (doi:10.1007/s40268-014-0045-9) contains supplementary material, which is available to authorized users.     

Exploratory Efficacy of Calcium-Vitamin D Milk Fortification and Periodontal Therapy on Maternal Oral Health and Metabolic and Inflammatory Profile

In this 2 × 2 factorial, outcome-assessor blinded, feasibility randomised trial we explored the effect of a non-pharmaceutical multi-component intervention on periodontal health and metabolic and inflammatory profiles among pregnant women with periodontitis receiving prenatal care in a Brazilian public health centre. 69 pregnant women (gestational age ≤20 weeks, T0) were randomly allocated into four groups: (1) fortified sachet (vitamin D and calcium) and powdered milk plus periodontal therapy during pregnancy (early PT) (n = 17); (2) placebo sachet and powdered milk plus early PT (n = 15); (3) fortified sachet and powdered milk plus late PT (after delivery) (n = 19); (4) placebo sachet and powdered milk plus late PT (n = 18). Third trimester (T1) and 6–8 weeks postpartum (T2) exploratory outcomes included periodontal health (% sites with bleeding on probing (BOP)), glucose, insulin, C-Reactive Protein, serum calcium and vitamin D. The mean BOP was significantly reduced in the early PT groups, while BOP worsened in the late PT groups. No significant effect of fortification on BOP was observed. Changes in glucose levels and variation on birthweight did not differ among groups This feasibility trial provides preliminary evidence for estimating the minimum clinically important differences for selected maternal outcomes. A large-scale trial to evaluate the interventions’ clinical benefits and cost-effectiveness is warranted.     

Biomarkers of endothelial activation and thrombosis in tunnel construction workers exposed to airborne contaminants

Objectives

The aims were to study biomarkers of systemic inflammation, platelet/endothelial activation and thrombosis in tunnel construction workers (TCW).

Methods

Biomarkers and blood fatty acids were measured in blood of 90 TCW and 50 referents before (baseline) and towards the end (follow-up) of a 12 days work period. They had been absent from work for 9 days at baseline. Air samples were collected by personal sampling.

Results

Personal thoracic air samples showed geometric mean (GM) particulate matter and α-quartz concentrations of 604 and 74 µg/m³, respectively. The arithmetic mean (AM) concentration of elemental carbon was 51 µg/m³. The GM (and 95% confidence interval) concentration of the pro-inflammatory cytokine TNF-α decreased from 2.2 (2.0–2.4) at baseline to 2.0 pg/mL (1.8–2.2) (p?=?0.02) at follow-up among the TCW. Also the platelet activation biomarkers P-selectin and CD40L decreased significantly [25.4 (24.1–26.6) to 24.4 (22.9–26.0)] ng/mL, p?=?0.04 and 125 (114–137) to 105 (96–115) pg/mL, p?<?0.001, respectively. ICAM-1 concentrations increased from 249 (238–260) to 254 (243–266) ng/mL (p?=?0.02). No significant alterations were observed among the referents when assessed by paired sample t test. Unbeneficial alterations in blood fatty acid composition were observed between baseline and follow-up, mainly among referents.

Conclusions

TCW had slightly reduced systemic inflammation and platelet activation although highly exposed to particulate matter, α-quarz and diesel exhaust, which might be due to increased physical activity during the exposure period. The slightly increased ICAM-1 may indicate monocyte recruitment to the lungs. The diet was substantially altered towards a less beneficial fatty acid profile.

     

Cost differences between digital tomosynthesis and standard digital mammography in a breast cancer screening programme: results from the To-Be trial in Norway

Background

Several studies in Europe and the US have shown promising results favouring digital breast tomosynthesis compared to standard digital mammography (DM). However, the costs of implementing the technology in screening programmes are not yet known.

Methods

A randomised controlled trial comparing the results from digital breast tomosynthesis including synthetic mammograms (DBT) vs. DM was performed in Bergen during 2016 and 2017 as a part of BreastScreen Norway. The trial included 29,453 women and allowed for a detailed comparison of procedure use and screening, recall and treatment costs estimated at the individual level.

Results

The increased cost of equipment, examination and reading time with DBT vs. DM was €8.5 per screened woman (95% CI 8.4−8.6). Costs of DBT remained significantly higher after adding recall assessment costs, €6.2 (95% CI 4.6−7.9). Substantial reductions in either examination and reading times, price of DBT equipment or price of IT storage and connectivity did not change the conclusion. Adding treatment costs resulted in too wide confidence intervals to draw definitive conclusions (additional costs of tomosynthesis €9.8, 95% CI –56 to 74). Performing biopsy at recall, radiation therapy and chemotherapy was significantly more frequent among women screened with DBT.

Conclusion

The results showed lower incremental costs of DBT vs. DM, compared to what is found in previous cost analyses of DBT and DM. However, the incremental costs were still higher for DBT compared with DM after including recall costs. Further studies with long-term treatment data are needed to understand the complete costs of implementing DBT in screening.

     

Bioequivalence determination of topical ketoprofen using a dermatopharmacokinetic approach and excised skin penetration

Ketoprofen is a photolabile drug. The aim of the present study was to compare the bioavailability of ketoprofen in a photo-stabilised formulation with a gel without photoprotection using a new dermatopharmacokinetic tape-stripping model and an established ex vivo penetration method using human skin. Analyses of the stratum corneum showed that during the first 45 min about 12 microg/cm2 ketoprofen was absorbed into the skin from the formulations. The area under the ketoprofen content-time curve (AUC0-6 h) for the ratio photo-stabilised gel/transparent gel was 73% with a 90% confidence interval (CI) 65-83. The rate of penetration of ketoprofen through isolated skin was approximately 0.2 microg/cm2 h for both formulations. AUC0-36 h for the ratio was 84% with 90% CI 64-105. Thus, the two methods did not disagree in terms of relative efficacy of the two gels. However, the difference obtained in vivo was statistically significant, whereas no significant data arise from the ex vivo study. Comparing the amount of ketoprofen in the skin after 45 min with the amount penetrated through the excised skin during 36 h, suggests a change in the thermodynamic activity of ketoprofen during the exposure. A supersaturated formulation may well have been formed initially due to evaporation of ethanol.     

Psychometric properties of the Brief Pain Inventory among patients with osteoarthritis undergoing total hip replacement surgery

Background  

Pain is a cardinal symptom of osteoarthritis (OA) of the hip and important for deciding when to operate. This study assessed the internal consistency reliability, validity and responsiveness of the Brief Pain Inventory (BPI) among patients with OA undergoing total hip replacement (THR).