Reproducibility and Prognostic Value of WHO1973 and WHO2004 Grading Systems in TaT1 Urothelial Carcinoma of the Urinary Bladder

Background

European treatment guidelines of TaT1 urinary bladder urothelial carcinomas depend highly on stage and WHO1973-grade but grading reproducibility is wanting. The newer WHO2004 grading system is still debated and both systems are currently used.

Aims

To compare reproducibility and prognostic value (of stage progression) of the WHO1973 and WHO2004.

Methods

One hundred and ninety-three primary urothelial carcinomas were reviewed. Follow-up data were retrieved from the patient records. Kappa statistics and Harrell''s C-index were used.

Results

Median follow-up was 75 months (range 1–127). 17 patients (9%) progressed, 82% of these within and 18% after 60 months. The distribution of WHO73-grades 1, 2 and 3 was 23%, 51% and 26%, interobserver agreement for each individual grade was 66% (kappa = 0.68), while for grades 1&2 versus 3 89% (kappa = 0.68). Intraobserver reproducibility was 68–63% for WHO73 and 88–89% for WHO73 as 1&2 vs.3. Progression free survival rates at 5 years were 95% (grade 1), 98% (grade 2) and 82% (grade 3) and 96% and 82% for grades 1&2 versus 3 (Hazard Ratio, HR, 5.4, p = 0.003). Using WHO2004, 62% were low grade and 38% high grade, inter-observer agreement 87% (kappa = 0.70), intraobserver reproducibility 93%, and progression free 5-year survival rates 97% and 85% (HR 6.6, p = 0.004). Positive and negative predictive values for stage progression within 5 years for the WHO73 (1&2 vs. 3) were 18% and 96%, and 15% and 97% for the WHO04. Using Harrell''s C-index, none of the grading systems was prognostically superior.

Conclusion

None of the grading systems is prognostically stronger than the others. Most importantly, inter-observer reproducibility and sensitivities for stage progression of both systems are low and need improvement for optimal treatment.     

Evaluation of Mitotic Activity Index in Breast Cancer Using Whole Slide Digital Images

Introduction

Mitotic Activity Index (MAI) is an important independent prognostic factor and an integral part of the breast cancer grading system. Thus, correct estimation of this prognostically relevant feature is essential for guiding treatment decision and assessing patient prognosis.The aim of this study was to validate the use of high resolution Whole Slide Images (WSI) in estimating MAI in breast cancer specimens.

Methods

MAI was evaluated in 100 consecutive breast cancer specimens by three observers on two occasions, microscopically and on WSI with a wash out period of 4 months. MAI was also translated to mitotic scores as in grading. Inter- and intra-observer agreement between microscopic and digital MAI counts and scores was measured.

Results

Almost perfect inter-observer agreements were obtained from counting MAI using a conventional microscope (intra-class correlation coefficient (ICCC) 0.879) as well as on WSI (ICCC 0.924). K coefficients reflected good inter-observer agreements among observers'' microscopic mitotic scores (average kappa 0.642). Comparable results were also observed among digital mitotic scores (average kappa 0.635). There was strong to perfect intra-observer agreements between MAI counts and mitotic scores for the two diagnostic modalities (ICCC 0.716–0.863, kappa 0.506–0.617). There were no significant differences in mitotic scores using both diagnostic modalities.

Conclusion

Scoring mitoses using WSI in breast cancer seems to be just as reliable and reproducible as when using a microscope. Further development of software and image quality will definitely encourage the use of WSI in routine pathology practice.     

Development and Validation of the Pre-Hospital Stroke Symptoms Coping Test

Background and Purpose

Measures of specific knowledge of coping with pre-hospital stroke symptoms can help educate high-risk patients and family caregivers. This study aimed to develop and validate the Pre-hospital Stroke Symptoms Coping Test (PSSCT).

Materials and Methods

Reliability and validity were analyzed using multiple data sources. The Delphi expert consultation method was applied to assess the test’s surface validity and content validity index. The final edition of the 19-item PSSCT contained 3 sections assessing coping with typical symptoms and symptoms associated with vomiting and twitching. Its psychometric properties were investigated in a community sample of 300 high-risk patients and family members.

Results

The PSSCT was readily accepted by participants. It demonstrated adequate surface validity and content validity, and good internal consistency (KR₂₀ = 0.822) and test-retest reliability (0.769), with difficulty (P) and degree of differentiation (D) ranges of 0.28–0.83 and 0.15–0.66, respectively. It was also able to distinguish between individuals who had/had not experienced a stroke. Experienced individuals scored significantly higher overall and on coping with typical symptoms and twitching (P<0.01).

Conclusions

The PSSCT can practically and directly assess critical knowledge regarding coping with pre-hospital stroke symptoms and has good reliability and validity.     

A Meta-Analysis of Parental Smoking and the Risk of Childhood Brain Tumors

Objective

Previous studies regarding the association between parental smoking and the risk of childhood brain tumors (CBT) have reported inconsistent results. We performed a meta-analysis to summarize evidence on this association and to quantify the potential dose-response relationship.

Methods

A systematic literature search was conducted in the Medline and Embase databases. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Dose–response meta-analysis was also performed for studies that reported categorical risk estimates for a series of smoking exposure levels.

Results

A total of 17 studies fulfilled the inclusion criteria. In the meta-analyses, the summary RRs (95% CIs) of CBT for maternal smoking during pregnancy, paternal smoking during pregnancy, maternal smoking before pregnancy, and paternal smoking before pregnancy were 0.96 (0.86–1.07), 1.09 (0.97–1.22), 0.93 (0.85–1.00), and 1.09 (1.00–1.20), respectively. Dose-response meta-analysis also showed no significant association between parental smoking and the risk of CBT.

Conclusions

Findings from our meta-analysis indicate that parental smoking may not be associated with a risk of CBT.     

Unilateral Condylar Hyperplasia: A 3-Dimensional Quantification of Asymmetry

Purpose

Objective quantifications of facial asymmetry in patients with Unilateral Condylar Hyperplasia (UCH) have not yet been described in literature. The aim of this study was to objectively quantify soft-tissue asymmetry in patients with UCH and to compare the findings with a control group using a new method.

Material and Methods

Thirty 3D photographs of patients diagnosed with UCH were compared with 30 3D photographs of healthy controls. As UCH presents particularly in the mandible, a new method was used to isolate the lower part of the face to evaluate asymmetry of this part separately. The new method was validated by two observers using 3D photographs of five patients and five controls.

Results

A significant difference (0.79 mm) between patients and controls whole face asymmetry was found. Intra- and inter-observer differences of 0.011 mm (−0.034–0.011) and 0.017 mm (−0.007–0.042) respectively were found. These differences are irrelevant in clinical practice.

Conclusion

After objective quantification, a significant difference was identified in soft-tissue asymmetry between patients with UCH and controls. The method used to isolate mandibular asymmetry was found to be valid and a suitable tool to evaluate facial asymmetry.     

Exercise-based cardiac rehabilitation in patients with chronic heart failure: a Dutch practice guideline

Rationale

To improve the quality of exercise-based cardiac rehabilitation (CR) in patients with chronic heart failure (CHF) a practice guideline from the Dutch Royal Society for Physiotherapy (KNGF) has been developed.

Guideline development

A systematic literature search was performed to formulate conclusions on the efficacy of exercise-based intervention during all CR phases in patients with CHF. Evidence was graded (1–4) according the Dutch evidence-based guideline development criteria.

Clinical and research recommendations

Recommendations for exercise-based CR were formulated covering the following topics: mobilisation and treatment of pulmonary symptoms (if necessary) during the clinical phase, aerobic exercise, strength training (inspiratory muscle training and peripheral muscle training) and relaxation therapy during the outpatient CR phase, and adoption and monitoring training after outpatient CR.

Applicability and implementation issues

This guideline provides the physiotherapist with an evidence-based instrument to assist in clinical decision-making regarding patients with CHF. The implementation of the guideline in clinical practice needs further evaluation.

Conclusion

This guideline outlines best practice standards for physiotherapists concerning exercise-based CR in CHF patients. Research is needed on strategies to improve monitoring and follow-up of the maintenance of a physical active lifestyle after supervised CR.     

Coffee Consumption and Risk of Breast Cancer: An Up-To-Date Meta-Analysis

Objectives

This updated meta-analysis was conducted to assess the association between coffee consumption and breast cancer risk.

Methods

We conducted a systematic search updated July 2012 to identify observational studies providing quantitative estimates for breast cancer risk in relation to coffee consumption. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least square trend estimation was used to assess dose–response relationships.

Results

A total of 26 studies (16 cohort and 10 case–control studies) on coffee intake with 49497 breast cancer cases were included in the meta-analysis. The pooled RR showed a borderline significant influence of highest coffee consumption (RR = 0.96; 95% CI 0.93–1.00), low-to moderate coffee consumption (RR = 0.99; 95% CI 0.95–1.04), or an increment of 2 cups/day of coffee consumption (RR = 0.98; 95% CI 0.97–1.00) on the risk of breast cancer. In stratified analysis, a significant inverse association was observed in ER-negative subgroup. However, no significant association was noted in the others.

Conclusions

Our findings suggest that increased coffee intake is not associated with a significantly reduced risk of breast cancer, but we observe an inverse association in ER-negative subgroup analysis. More large studies are needed to determine subgroups to obtain more valuable data on coffee drinking and breast cancer risk.     

Evaluation of Construct and Criterion Validity for the ‘Liverpool Osteoarthritis in Dogs’ (LOAD) Clinical Metrology Instrument and Comparison to Two Other Instruments

Objective

To test the ‘Liverpool Osteoarthritis in Dogs’ (LOAD) questionnaire for construct and criterion validity, and to similarly test the Helsinki Chronic Pain Index (HCPI) and the Canine Brief Pain Inventory (CBPI).

Design

Prospective Study.

Animals

222 dogs with osteoarthritis.

Procedure

Osteoarthritis was diagnosed in a cohort of dogs on the basis of clinical history and orthopedic examination. Force-platform analysis was performed and a “symmetry index” for peak vertical force (PVF) was calculated. Owners completed LOAD, CBPI and HCPI instruments. As a test of construct validity, inter-instrument correlations were calculated. As a test of criterion validity, the correlations between instrument scores and PVF symmetry scores were calculated. Additionally, internal consistency of all instruments was calculated and compared to those previously reported. Factor analysis is reported for the first time for LOAD, and is compared to that previously reported for CBPI and HCPI.

Results

Significant moderate correlations were found between all instruments, implying construct validity for all instruments. Significant weak correlations were found between LOAD scores and PVF symmetry index, and between CBPI scores and PVF symmetry index.

Conclusion and Clinical Relevance

LOAD is an owner-completed clinical metrology instrument that can be recommended for the measurement of canine osteoarthritis. It is convenient to use, validated and, as demonstrated here for the first time, has a correlation with force-platform data.     

Potential Risk Factors of Persistent Low Back Pain Developing from Mild Low Back Pain in Urban Japanese Workers

Study Design

Two-year, prospective cohort data from the Japan epidemiological research of occupation-related back pain study in urban settings were used for this analysis.

Objective

To examine the association between aggravated low back pain and psychosocial factors among Japanese workers with mild low back pain.

Summary of Background Data

Although psychosocial factors are strongly indicated as yellow flags of low back pain (LBP) leading to disability, the association between aggravated LBP and psychosocial factors has not been well assessed in Japanese workers.

Methods

At baseline, 5,310 participants responded to a self-administered questionnaire including questions about individual characteristics, ergonomic work demands, and work-related psychosocial factors (response rate: 86.5%), with 3,811 respondents completing the 1-year follow-up questionnaire. The target outcome was aggravation of mild LBP into persistent LBP during the follow-up period. Incidence was calculated for the participants with mild LBP during the past year at baseline. Logistic regression was used to explore risk factors associated with persistent LBP.

Results

Of 1,675 participants who had mild LBP during the preceding year, 43 (2.6%) developed persistent LBP during the follow-up year. Multivariate analyses adjusted for individual factors and an ergonomic factor found statistically significant or almost significant associations of the following psychosocial factors with persistent LBP: interpersonal stress at work [adjusted odds ratio (OR): 1.96 and 95% confidence interval (95%CI): 1.00–3.82], job satisfaction (OR: 2.34, 95%CI: 1.21–4.54), depression (OR: 1.92, 95%CI: 1.00–3.69), somatic symptoms (OR: 2.78, 95%CI: 1.44–5.40), support from supervisors (OR: 2.01, 95%CI: 1.05–3.85), previous sick-leave due to LBP (OR: 1.94, 95%CI: 0.98–3.86) and family history of LBP with disability (OR: 1.98, 95%CI: 1.04–3.78).

Conclusions

Psychosocial factors are important risk factors for persistent LBP in urban Japanese workers. It may be necessary to take psychosocial factors into account, along with physical work demands, to reduce LBP related disability.     

The Smartphone Addiction Scale: Development and Validation of a Short Version for Adolescents

Objective

This study was designed to investigate the revised and short version of the smartphone addiction scale and the proof of its validity in adolescents. In addition, it suggested cutting off the values by gender in order to determine smartphone addiction and elaborate the characteristics of smartphone usage in adolescents.

Method

A set of questionnaires were provided to a total of 540 selected participants from April to May of 2013. The participants consisted of 343 boys and 197 girls, and their average age was 14.5 years old. The content validity was performed on a selection of shortened items, while an internal-consistency test was conducted for the verification of its reliability. The concurrent validity was confirmed using SAS, SAPS and KS-scale. Receiver operating characteristics analysis was conducted to suggest cut-off.

Results

The 10 final questions were selected using content validity. The internal consistency and concurrent validity of SAS were verified with a Cronbach''s alpha of 0.911. The SAS-SV was significantly correlated with the SAS, SAPS and KS-scale. The SAS-SV scores of gender (p<.001) and self-evaluation of smartphone addiction (p<.001) showed significant difference. The ROC analysis results showed an area under a curve (AUC) value of 0.963(0.888–1.000), a cut-off value of 31, sensitivity value of 0.867 and specificity value of 0.893 in boys while an AUC value of 0.947(0.887–1.000), a cut-off value of 33, sensitivity value of 0.875, and a specificity value of 0.886 in girls.

Conclusions

The SAS-SV showed good reliability and validity for the assessment of smartphone addiction. The smartphone addiction scale short version, which was developed and validated in this study, could be used efficiently for the evaluation of smartphone addiction in community and research areas.     

A Novel Region-Growing Based Semi-Automatic Segmentation Protocol for Three-Dimensional Condylar Reconstruction Using Cone Beam Computed Tomography (CBCT)

Objective

To present and validate a semi-automatic segmentation protocol to enable an accurate 3D reconstruction of the mandibular condyles using cone beam computed tomography (CBCT).

Materials and Methods

Approval from the regional medical ethics review board was obtained for this study. Bilateral mandibular condyles in ten CBCT datasets of patients were segmented using the currently proposed semi-automatic segmentation protocol. This segmentation protocol combined 3D region-growing and local thresholding algorithms. The segmentation of a total of twenty condyles was performed by two observers. The Dice-coefficient and distance map calculations were used to evaluate the accuracy and reproducibility of the segmented and 3D rendered condyles.

Results

The mean inter-observer Dice-coefficient was 0.98 (range [0.95–0.99]). An average 90^th percentile distance of 0.32 mm was found, indicating an excellent inter-observer similarity of the segmented and 3D rendered condyles. No systematic errors were observed in the currently proposed segmentation protocol.

Conclusion

The novel semi-automated segmentation protocol is an accurate and reproducible tool to segment and render condyles in 3D. The implementation of this protocol in the clinical practice allows the CBCT to be used as an imaging modality for the quantitative analysis of condylar morphology.     

Assessing the Assessment in Emergency Care Training

Objective

Each year over 1.5 million health care professionals attend emergency care courses. Despite high stakes for patients and extensive resources involved, little evidence exists on the quality of assessment. The aim of this study was to evaluate the validity and reliability of commonly used formats in assessing emergency care skills.

Methods

Residents were assessed at the end of a 2-week emergency course; a subgroup was videotaped. Psychometric analyses were conducted to assess the validity and inter-rater reliability of the assessment instrument, which included a checklist, a 9-item competency scale and a global performance scale.

Results

A group of 144 residents and 12 raters participated in the study; 22 residents were videotaped and re-assessed by 8 raters. The checklists showed limited validity and poor inter-rater reliability for the dimensions “correct” and “timely” (ICC = .30 and.39 resp.). The competency scale had good construct validity, consisting of a clinical and a communication subscale. The internal consistency of the (sub)scales was high (α = .93/.91/.86). The inter-rater reliability was moderate for the clinical competency subscale (.49) and the global performance scale (.50), but poor for the communication subscale (.27). A generalizability study showed that for a reliable assessment 5–13 raters are needed when using checklists, and four when using the clinical competency scale or the global performance scale.

Conclusions

This study shows poor validity and reliability for assessing emergency skills with checklists but good validity and moderate reliability with clinical competency or global performance scales. Involving more raters can improve the reliability substantially. Recommendations are made to improve this high stakes skill assessment.     

Definitions and standardization of a new grading scheme for eyelid contour abnormalities after trichiasis surgery

Background

Clear definitions of outcomes following trichiasis surgery are critical for planning program evaluations and for identifying ways to improve trichiasis surgery. Eyelid contour abnormality is an important adverse outcome of surgery; however, no standard method has been described to categorize eyelid contour abnormalities.

Methodology/Principal Findings

A classification system for eyelid contour abnormalities following surgery for trachomatous trichiasis was developed. To determine whether the grading was reproducible using the classification system, six-week postoperative photographs were reviewed by two senior graders to characterize severity of contour abnormalities. Sample photographs defining each contour abnormality category were compiled and used to train four new graders. All six graders independently graded a Standardization Set of 75 eyelids, which included a roughly equal distribution across the severity scale, and weighted kappa scores were calculated. Two hundred forty six-week postoperative photographs from an ongoing clinical trial were randomly selected for evaluating agreement across graders. Two months after initial grading, one grader regraded a subset of the 240 photographs to measure longer-term intra-observer agreement. The weighted kappa for agreement between the two senior graders was 0.80 (95% CI: 0.71–0.89). Among the Standardization Set, agreement between the senior graders and the 4 new graders showed weighted kappa scores ranging from 0.60–0.80. Among 240 eyes comprising the clinical trial dataset, agreement ranged from weighted kappa 0.70–0.71. Longer-term intra-observer agreement was weighted kappa 0.86 (95% CI: 0.80–0.92).

Conclusions/Significance

The standard eyelid contour grading system we developed reproducibly delineates differing levels of contour abnormality. This grading system could be useful both for helping to evaluate trichiasis surgery outcomes in clinical trials and for evaluating trichiasis surgery programs.     

Hyaluronan and N-ERC/Mesothelin as Key Biomarkers in a Specific Two-Step Model to Predict Pleural Malignant Mesothelioma

Purpose

Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis.

Patients and Methods

Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre.

Results

Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82–20.39), N-ERC/mesothelin (4.81, 3.19–7.93), CERC/mesothelin (3.58, 2.43–5.59) and syndecan-1 (1.34, 1.03–1.77). A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97–1.00) in the model generation dataset and 0.83 (0.74–0.91) in the validation dataset, respectively.

Conclusions

A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.     

Validity of U.S. Nutritional Surveillance: National Health and Nutrition Examination Survey Caloric Energy Intake Data, 1971–2010

Importance

Methodological limitations compromise the validity of U.S. nutritional surveillance data and the empirical foundation for formulating dietary guidelines and public health policies.

Objectives

Evaluate the validity of the National Health and Nutrition Examination Survey (NHANES) caloric intake data throughout its history, and examine trends in the validity of caloric intake estimates as the NHANES dietary measurement protocols evolved.

Design

Validity of data from 28,993 men and 34,369 women, aged 20 to 74 years from NHANES I (1971–1974) through NHANES 2009–2010 was assessed by: calculating physiologically credible energy intake values as the ratio of reported energy intake (rEI) to estimated basal metabolic rate (BMR), and subtracting estimated total energy expenditure (TEE) from NHANES rEI to create ‘disparity values’.

Main Outcome Measures

1) Physiologically credible values expressed as the ratio rEI/BMR and 2) disparity values (rEI–TEE).

Results

The historical rEI/BMR values for men and women were 1.31 and 1.19, (95% CI: 1.30–1.32 and 1.18–1.20), respectively. The historical disparity values for men and women were −281 and −365 kilocalorie-per-day, (95% CI: −299, −264 and −378, −351), respectively. These results are indicative of significant under-reporting. The greatest mean disparity values were −716 kcal/day and −856 kcal/day for obese (i.e., ≥30 kg/m2) men and women, respectively.

Conclusions

Across the 39-year history of the NHANES, EI data on the majority of respondents (67.3% of women and 58.7% of men) were not physiologically plausible. Improvements in measurement protocols after NHANES II led to small decreases in underreporting, artifactual increases in rEI, but only trivial increases in validity in subsequent surveys. The confluence of these results and other methodological limitations suggest that the ability to estimate population trends in caloric intake and generate empirically supported public policy relevant to diet-health relationships from U.S. nutritional surveillance is extremely limited.     

Verbal Autopsy: Reliability and Validity Estimates for Causes of Death in the Golestan Cohort Study in Iran

Background

Verbal autopsy (VA) is one method to obtain valid estimates of causes of death in the absence of valid medical records. We tested the reliability and validity of a VA questionnaire developed for a cohort study in Golestan Province in northeastern Iran.

Method

A modified version of the WHO adult verbal autopsy was used to assess the cause of death in the first 219 Golestan Cohort Study (GCS) subjects who died. The GCS cause of death was determined by two internists who independently reviewed all available medical records. Two other internists (“reviewers”) independently reviewed only the VA answers and classified the cause of death into one of nine general categories; they repeated this evaluation one month later. The reliability of the VA was measured by calculating intra-reviewer and inter-reviewer kappa statistics. The validity of the VA was measured using the GCS cause of death as the gold standard.

Results

VA showed both good validity (sensitivity, specificity, PPV, and NPV all above 0.81) and reliability (kappa>0.75) in determining the general cause of death independent of sex and place of residence. The overall multi-rater agreement across four reviews was 0.84 (95%CI: 0.78–0.89). The results for identifying specific cancer deaths were also promising, especially for upper GI cancers (kappa = 0.95). The multi-rater agreement in cancer subgroup was 0.93 (95%CI: 0.85–0.99).

Conclusions

VA seems to have good reliability and validity for determining the cause of death in a large-scale adult follow up study in a predominantly rural area of a middle-income country.     

Trend in Annual Risk of Tuberculous Infection in North India

Setting

Six selected districts in Northern India.

Objectives

To find out the trend in Annual risk of tuberculous infection (ARTI) in north India.

Study Design

Two rounds of community level surveys were conducted during 2000–2001 and 2009–10 respectively. Representative samples of children 1–9 years of age were tuberculin tested and maximum transverse diameter of induration was recorded in mm at about 72 hours. ARTI was computed from the estimated Prevalence of infection using mirror-image technique and anti-mode method.

Results

ARTI was found to decline from 1.9% (confidence interval: 1.7–2.1) at round I to 1.1% (confidence interval: 0.8–1.3) at round II at the rate of 8% per year during the intervening period.

Conclusion

A significant reduction in the risk of tuberculous infection among children was observed between two rounds of surveys carried out at an interval of about 9 years.