Inter-rater agreement and reliability of the COSMIN (COnsensus-based Standards for the selection of health status Measurement Instruments) Checklist

Background  

The COSMIN checklist is a tool for evaluating the methodological quality of studies on measurement properties of health-related patient-reported outcomes. The aim of this study is to determine the inter-rater agreement and reliability of each item score of the COSMIN checklist (n = 114).     

Retrospective attenuation correction of PET data for radiotherapy planning using a free breathing CT.

PURPOSE: To evaluate the image quality of retrospectively attenuation corrected Positron Emission Tomography (PET) scans used for gross tumor volume (GTV) delineation in lung cancer patients. MATERIALS AND METHODS: Data of 13 lymph node positive lung cancer patients were acquired on separate CT and PET scanners under free breathing conditions (for radiotherapy planning). First we determined a protocol for CT/PET registration. Second, we compared the image quality of attenuation-corrected PET images using positron transmission images and CT images, in terms of signal-to-noise ratio (SNR) and lesion-to-background ratio (contrast). RESULTS: The largest differences between manual and automatic CT/PET registration were found in the anterior-posterior direction with a mean of 1.8 mm (SD 1.0 mm). Differences in rotations were always smaller than 1.0 degrees . The attenuation-corrected images using CT showed a larger SNR (mean 30%, SD 17%) and larger contrast (mean 14.0%, SD 8.5%) compared to attenuation-corrected images using positron transmission. For lymph nodes, the mean contrast was 16% (SD 6.4%) larger. CONCLUSIONS: This study demonstrated that attenuation correction based on CT provides a better image quality for GTV delineation than when using positron transmission for attenuation correction. Retrospective attenuation correction of PET scans based on registered CT is a good alternative for a dedicated PET/CT scanner if a free-breathing CT is available, e.g., for radiotherapy planning, and allows the use of CT with diagnostic quality for attenuation correction.     

Mathematical modelling of infection and disease due to Neisseria meningitidis and Neisseria lactamica

BACKGROUND: Invasive meningococcal disease, due to Neisseria meningitidis, is an important cause of morbidity and mortality in young children and adolescents. Nasopharyngeal carriage of meningococci (MC), is most prevalent in young adults whereas carriage of Neisseria lactamica (LC), a related non-pathogenic organism, is most prevalent in young children. The objective of this study was to use modelling techniques to test hypotheses on the processes that govern the incidence of meningococcal disease (MD). METHODS: Deterministic compartmental models were fitted to age structured data sets of MC, LC and MD. RESULTS: The model most consistent with the available data sets is one where LC inhibits MC, an inhibition that lasts for a mean of 4.7 years. The hypothesis that LC also acts as a natural immunogen against MD was consistent with this model. The second peak of MD observed among adolescents could be due to the peak in the acquisition of MC in this age group. CONCLUSIONS: The role of LC as a natural immunogen against asymptomatic and symptomatic meningococcal infection was consistent with available field data. If the introduction of novel meningococcal vaccines into a population changes the prevalence of MC or LC, this could have a substantial impact on the effectiveness of immunization programmes. This paper demonstrates the potential utility of modelling to estimate these effects.     

Short-term carcinogenicity testing of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ) in E{micro}-pim-1 transgenic mice

The usefulness of transgenic Eµ-pim-1 mice over-expressingthe pim-1 oncogene in lymphoid tissues, as sensitive test organismswas studied in a short-term carcinogenicity study. The micewere fed standard diet Altromin 1314 supplemented either with0.03% 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP)for 7 months or with 0.03% 2-amino-3-methylimidazo[4, 5-f] quinoline(IQ) for 6 months. PhIP and IQ are heterocyclic amines formedduring cooking of meat and fish and are mutagenic to bacteriaand cultured mammalian cells. PhIP is a potent mouse lymphomagen,while IQ is a liver carcinogen and also causes lung tumors andtumors of the forestomach in mice. We found that transgenicEµ-pim-1 mice are highly susceptible to PhIP induced lymphomagenesisbut do not respond to the IQ treatment. PhIP feeding of Eµ-pim-1mice not only increased the total number of T-cell lymphomasbut also decreased the latency time compared to either transgenicor wild-type controls. The effect was most pronounced in thetreated female Eµ-pim-1 mice, which showed a higher incidenceof PhIP induced T-cell lymphomas than transgenic males and astrongly reduced latency period after PhIP treatment comparedto non-transgenic mice. Our results suggest that the transgenicEµ-pim-1 mouse may be a useful model for short-term carcinogenicityscreening of potential genotoxic carcinogens having the lymphoidsystem as target tissue. The carcinogen IQ which does not havethe lymphoid system as a target was not recognized in this model.     

Changes of hemostatic variables during hormone replacement therapy

Hormone replacement therapy (HRT) is accompanied by many changes in the hemostatic system. Because several individual hemostatic variables have been suspected to be reasonable indicators of the hemostatic balance and because this balance is thought to play an important role in the pathogenesis of several diseases, careful examination of the changes in this system induced by HRT could be helpful, first to improve HRT and second to improve our understanding of mechanisms of cardiovascular disease. The effects of (several forms of) HRT on individual hemostatic variables are discussed in this article. The pattern that emerges is that HRT stimulates coagulation, inhibits anticoagulation, and stimulates fibrinolysis (partly by inhibition of fibrinolysis). There are, however, few data that give clear insight into the effects of HRT on hemostatic variables. Controlled randomized clinical studies are needed to evaluate further the effects of HRT on the hemostatic system, to understand the interplay between inflammation and coagulation (both pathways being affected by HRT), and to understand how HRT-associated changes are affected by differences in genetic background.     

Changing patterns of keratin expression could be associated with functional maturation of the developing human bladder

PURPOSE: We investigate the keratin phenotype of human transitional epithelium at various gestational ages and whether keratin composition of transitional epithelium is related to bladder function and morphology. MATERIALS AND METHODS: Consecutive sections from formalin fixed paraffin embedded blocks of autopsy bladder tissue from 21 male and 5 female fetuses, gestational age 12 to 40 weeks and 7 infants 2 days to 19 months old were cut and stained with antibodies recognizing basal cell keratins 5, 14 and 17, intermediate squamous cell keratin 13 and columnar cell keratins 7, 8, 18 and 20. RESULTS: With gestational age there were distinct changes in expression of keratins recognizing columnar cells, consisting of focal loss of keratin 7 in transitional epithelium, restriction of keratin 20 expression to umbrella cells and expression of keratin 18 throughout the full thickness of transitional epithelium. Basal cell keratin 5 was found above the basal cell layer while keratins 14 and 17 were not found. Squamous cell keratin 13 was found throughout the full thickness of the urothelium. CONCLUSIONS: The changes with gestational age in expression of some keratins may be related to the development of the reservoir function of the bladder. The impermeability of transitional epithelium, particularly during early fetal development, is possibly a function of umbrella and intermediate transitional cells.     

Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death

In 328 type 2 diabetic patients followed for 9.0 years (mean), we investigated whether endothelial dysfunction and chronic inflammation (estimated from plasma markers) can explain the association between (micro)albuminuria and mortality. Of the patients, 113 died. Mortality was increased in patients with baseline microalbuminuria or macroalbuminuria (odds ratios as compared with normoalbuminuria, 1.78 [P < 0.05] and 2.86 [P < 0.01]) and in patients with soluble vascular cell adhesion molecule 1 in the third tertile and C-reactive protein in the second and third tertiles (odds ratios as compared with the first tertile, 2.05 [ P < 0.01], and 1.80 [P < 0.05] and 2.92 [ P < 0.01]). These associations were mutually independent. The mean yearly change in urinary albumin excretion was 9.4%; in von Willebrand factor, 8.1%; in tissue-type plasminogen activator, 2.8%; in soluble vascular cell adhesion molecule 1, 5.2%; in soluble E-selectin, -2.3%; in C-reactive protein, 3.8%; and in fibrinogen, 2.3%. The longitudinal development of urinary albumin excretion was significantly and independently determined by baseline levels of and the longitudinal development of BMI, systolic blood pressure, serum creatinine, glycated hemoglobin and plasma von Willebrand factor (baseline only), soluble E-selectin (baseline only), tissue-type plasminogen activator, C-reactive protein, and fibrinogen. The longitudinal developments of markers of endothelial function and inflammation were interrelated. In type 2 diabetes, increased urinary albumin excretion, endothelial dysfunction, and chronic inflammation are interrelated processes that develop in parallel, progress with time, and are strongly and independently associated with risk of death.     

Individual quality of life factors distinguishing low-burden and high-burden caregivers of dementia patients

Dementia patient (n = 72) and caregiver characteristics and individual quality of life (IQoL) factors distinguishing low- and high-burden caregivers were evaluated. Measures included patient cognitive, functional and behavioural status, and caregiver burden, well-being, social support appraisal and IQoL. The caregivers were divided by median split into low- and high-burden groups. In the high-burden group daughters were over-represented, psychological morbidity was higher, QoL was lower, the patients were more behaviourally disturbed, and there was a trend towards more negative appraisal of informal social support. Of the many QoL factors elicited from caregivers, only 'time for self' and 'finances' differed significantly between the groups. A need for more time away from the patient is a major QoL concern for highly burdened caregivers, and a perceived lack of adequate informal support and/or financial constraints are contributory factors.     

Comparative epidemiology of scrapie outbreaks in individual sheep flocks

Data recording the course of scrapie outbreaks in 4 sheep flocks (2 in Cheviot sheep and 2 in Suffolks) are compared. For each outbreak the data on scrapie incidence and sheep demography and pedigrees cover periods of years or decades. A key finding is that the incidence of clinical cases peaks in sheep 2-3 years old, despite very different forces-of-infection. This is consistent with age-specific susceptibility of sheep to scrapie, as has been reported for cattle to bovine spongiform encephalopathy and for humans to variant Creutzfeldt-Jakob disease. Scrapie incidence was higher in ewes than rams and at certain times of years, though these effects were not consistent between flocks. There was no evidence for high levels of vertical transmission.     

Irradiation of paranasal sinus tumors, a delineation and dose comparison study.

PURPOSE: To determine the influence of observer variation and treatment planner variation on the dose delivered to the target and normal structures when irradiating paranasal sinus carcinomas. PATIENTS AND METHODS: Nine patients with paranasal sinus tumors underwent debulking surgery and subsequent radiation therapy. Two observers from two different institutions delineated the clinical target volumes (CTVs) for the elective and the boost volumes. These volumes were expanded in three dimensions with a 5-mm margin. At both institutions, a three-dimensional conformal treatment plan of 46 Gy to the elective volumes, plus 20 Gy to the boost target volumes, was designed. The delineated volumes and treatment plans were compared. RESULTS: The mean volume ratio between institutions of the elective CTVs was 0.9 (standard error = 0.05). The differences were located mainly at the bottom of the nasal cavity and at the frontal border of the target areas. The differences in boost CTVs were large; the mean volume ratio was 2.6 (standard error = 0.58). After expansion of the CTV, the mean distance between the planning target volume (PTV) and the chiasm differed by 0.5 cm between the two institutions. Cases with smaller distances between the PTV and the chiasm had more underdosage to the PTV. This effect was less pronounced for institution A (1 vol.%/cm) than for institution B (10 vol.%/cm) treatment plans, which were less conformal. When the treatment plan was designed for the PTV of institution B, 23 volume % of the PTV of institution A received <95% of the prescribed dose. If the treatment plan was designed for the (on average larger) PTV of institution A, the underdosed volume of PTV at institution B was 17%. The relative underdosage to the "other" PTV was larger when the original treatment plan was more conformal. CONCLUSION: In the irradiation of paranasal sinus cancer, both the treatment planner and the observer have a significant influence on the dose to the target and organs at risk. Both effects are similar in magnitude. The observer effect increases with more conformal treatment plans. Minimizing the observer variation is important for adequate irradiation of paranasal sinus cancer.