Predictors for outcome of failure of balloon dilatation in patients with achalasia

Background: Pneumatic balloon dilatation (PD) is a regular treatment modality for achalasia. The reported success rates of PD vary. Recurrent symptoms often require repeated PD or surgery. Objective: To identify predicting factors for symptom recurrence requiring repeated treatment. Methods: Between 1974 and 2006, 336 patients were treated with PD and included in this longitudinal cohort study. The median follow-up was 129 months (range 1-378). Recurrence of achalasia was defined as symptom recurrence in combination with increased lower oesophageal sphincter (LOS) pressure on manometry, requiring repeated treatment. Patient characteristics, results of timed barium oesophagram and manometry as well as baseline PD characteristics were evaluated as predictors of disease recurrence with Kaplan-Meier curves and Cox regression analysis. Results: 111 patients had symptom recurrence requiring repeated treatment. Symptoms recurred after a mean follow-up of 51 months (range 1-348). High recurrence percentages were found in patients younger than 21 years in whom the 5 and 10-year risks of recurrence were 64% and 72%, respectively. These risks were respectively 28% and 36% in patients with classic achalasia, respectively 48% and 60% in patients without complete obliteration of the balloon's waist during PD and respectively 25% and 33% in patients with a LOS pressure greater than 10 mm Hg at 3 months post-dilatation. These four predictors remained statistically significant in a multivariable Cox analysis. Conclusion: Although PD is an effective primary treatment in patients with primary achalasia, patients are at risk of recurrent disease, with this risk increasing during long-term follow-up. Young age at presentation, classic achalasia, high LOS pressure 3 months after PD and incomplete obliteration of the balloon's waist during PD are the most important predicting factors for the need for repeated treatment during follow-up. Patients who meet one or more of these characteristics may be considered earlier for alternative treatment, such as surgery

Preferences for colorectal cancer screening strategies: a discrete choice experiment

Background:Guidelines underline the role of individual preferences in the selection of a screening test, as insufficient evidence is available to recommend one screening test over another. We conducted a study to determine the preferences of individuals and to predict uptake for colorectal cancer (CRC) screening programmes using various screening tests. Methods:A discrete choice experiment (DCE) questionnaire was distributed among naive subjects, yet to be screened, and previously screened subjects, aged 50-75 years. Subjects were asked to choose between scenarios on the basis of faecal occult blood test (FOBT), flexible sigmoidoscopy (FS), total colonoscopy (TC) with various test-specific screening intervals and mortality reductions, and no screening (opt-out). Results:In total, 489 out of 1498 (33%) screening-naïve subjects (52% male; mean age±s.d. 61±7 years) and 545 out of 769 (71%) previously screened subjects (52% male; mean age±s.d. 61±6 years) returned the questionnaire. The type of screening test, screening interval, and risk reduction of CRC-related mortality influenced subjects' preferences (all P<0.05). Screening-naive and previously screened subjects equally preferred 5-yearly FS and 10-yearly TC (P=0.24; P=0.11), but favoured both strategies to annual FOBT screening (all P-values <0.001) if, based on the literature, realistic risk reduction of CRC-related mortality was applied. Screening-naive and previously screened subjects were willing to undergo a 10-yearly TC instead of a 5-yearly FS to obtain an additional risk reduction of CRC-related mortality of 45% (P<0.001). Conclusion:These data provide insight into the extent by which interval and risk reduction of CRC-related mortality affect preferences for CRC screening tests. Assuming realistic test characteristics, subjects in the target population preferred endoscopic screening over FOBT screening, partly, due to the more favourable risk reduction of CRC-related mortality by endoscopy screening. Increasing the knowledge of potential screenees regarding risk reduction by different screening strategies is, therefore, warranted to prevent unrealistic expectations and to optimise informed choice.British Journal of Cancer advance online publication, 2 March 2010; doi:10.1038/sj.bjc.6605566 www.bjcancer.com

Nurse-led follow-up of patients after oesophageal or gastric cardia cancer surgery: a randomised trial

Between January 2004 and February 2006, 109 patients after intentionally curative surgery for oesophageal or gastric cardia cancer were randomised to standard follow-up of surgeons at the outpatient clinic (standard follow-up; n=55) or by regular home visits of a specialist nurse (nurse-led follow-up; n=54). Longitudinal data on generic (EuroQuol-5D, European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30) and disease-specific quality of life (EORTC QLQ-OES18), patient satisfaction and costs were collected at baseline and at 6 weeks and 4, 7 and 13 months afterwards. We found largely similar quality-of-life scores in the two follow-up groups over time. At 4 and 7 months, slightly more improvement on the EQ-VAS was noted in the nurse-led compared with the standard follow-up group (P=0.13 and 0.12, respectively). Small differences were also found in patient satisfaction between the two groups (P=0.14), with spouses being more satisfied with nurse-led follow-up (P=0.03). No differences were found in most medical outcomes. However, body weight of patients of the standard follow-up group deteriorated slightly (P=0.04), whereas body weight of patients of the nurse-led follow-up group remained stable. Medical costs were lower in the nurse-led follow-up group (€2600 vs €3800), however, due to the large variation between patients, this was not statistically significant (P=0.11). A cost effectiveness acceptability curve showed that the probability of being cost effective for costs per one point gain in general quality-of-life exceeded 90 and 75% after 4 and 13 months of follow-up, respectively. Nurse-led follow-up at home does not adversely affect quality of life or satisfaction of patients compared with standard follow-up by clinicians at the outpatient clinic. This type of care is very likely to be more cost effective than physician-led follow-up

On the combination of omics data for prediction of binary outcomes

Enrichment of predictive models with new biomolecular markers is an important task in high-dimensional omic applications. Increasingly, clinical studies include several sets of such omics markers available for each patient, measuring different levels of biological variation. As a result, one of the main challenges in predictive research is the integration of different sources of omic biomarkers for the prediction of health traits. We review several approaches for the combination of omic markers in the context of binary outcome prediction, all based on double cross-validation and regularized regression models. We evaluate their performance in terms of calibration and discrimination and we compare their performance with respect to single-omic source predictions. We illustrate the methods through the analysis of two real datasets. On the one hand, we consider the combination of two fractions of proteomic mass spectrometry for the calibration of a diagnostic rule for the detection of early-stage breast cancer. On the other hand, we consider transcriptomics and metabolomics as predictors of obesity using data from the Dietary, Lifestyle, and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) study, a population-based cohort, from Finland

Predictive Value of Updating Framingham Risk Scores with Novel Risk Markers in the U.S. General Population

Background: According to population-based cohort studies CT coronary calcium score (CTCS), carotid intima-media thickness (cIMT), high-sensitivity C- reactive protein (CRP), and ankle-brachial index (ABI) are promising novel risk markers for improving cardiovascular risk assessment. Their impact in the U.S. general population is however uncertain. Our aim was to estimate the predictive value of four novel cardiovascular risk markers for the U.S. general population. Methods and Findings: Risk profiles, CRP and ABI data of 3,736 asymptomatic subjects aged 40 or older from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 exam were used along with predicted CTCS and cIMT values. For each subject, we calculated 10-year cardiovascular risks with and without each risk marker. Event rates adjusted for competing risks were obtained by microsimulation. We assessed the impact of updated 10-year risk scores by reclassification and C-statistics. In the study population (mean age 56±11 years, 48% male), 70% (80%) were at low (<10%), 19% (14%) at intermediate (≥10–<20%), and 11% (6%) at high (≥20%) 10-year CVD (CHD) risk. Net reclassification improvement was highest after updating 10-year CVD risk with CTCS: 0.10 (95%CI 0.02–0.19). The C-statistic for 10-year CVD risk increased from 0.82 by 0.02 (95%CI 0.01–0.03) with CTCS. Reclassification occurred most often in those at intermediate risk: with CTCS, 36% (38%) moved to low and 22% (30%) to high CVD (CHD) risk. Improvements with other novel risk markers were limited. Conclusions: Only CTCS appeared to have significant incremental predictive value in the U.S. general population, especially in those at intermediate risk. In future research, cost-effectiveness analyses should be considered for evaluating novel cardiovascular risk assessment strategies

Survival of patients with nonseminomatous germ cell cancer: a review of the IGCC classification by Cox regression and recursive partitioning

The International Germ Cell Consensus (IGCC) classification identifies good, intermediate and poor prognosis groups among patients with metastatic nonseminomatous germ cell tumours (NSGCT). It uses the risk factors primary site, presence of nonpulmonary visceral metastases and tumour markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH). The IGCC classification is easy to use and remember, but lacks flexibility. We aimed to examine the extent of any loss in discrimination within the IGCC classification in comparison with alternative modelling by formal weighing of the risk factors. We analysed survival of 3048 NSGCT patients with Cox regression and recursive partitioning for alternative classifications. Good, intermediate and poor prognosis groups were based on predicted 5-year survival. Classifications were further refined by subgrouping within the poor prognosis group. Performance was measured primarily by a bootstrap corrected c-statistic to indicate discriminative ability for future patients. The weights of the risk factors in the alternative classifications differed slightly from the implicit weights in the IGCC classification. Discriminative ability, however, did not increase clearly (IGCC classification, c=0.732; Cox classification, c=0.730; Recursive partitioning classification, c=0.709). Three subgroups could be identified within the poor prognosis groups, resulting in classifications with five prognostic groups and slightly better discriminative ability (c = 0.740). In conclusion, the IGCC classification in three prognostic groups is largely supported by Cox regression and recursive partitioning. Cox regression was the most promising tool to define a more refined classification

A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care

Age, gender and disability predict future disability in older people: the Rotterdam Study

<p>Abstract</p> <p>Background</p> <p>To develop a prediction model that predicts disability in community-dwelling older people. Insight in the predictors of disability is needed to target preventive strategies for people at increased risk.</p> <p>Methods</p> <p>Data were obtained from the Rotterdam Study, including subjects of 55 years and over. Subjects who had complete data for sociodemographic factors, life style variables, health conditions, disability status at baseline and complete data for disability at follow-up were included in the analysis. Disability was expressed as a Disability Index (DI) measured with the Health Assessment Questionnaire.</p> <p>We used a multivariable polytomous logistic regression to derive a basic prediction model and an extended prediction model. Finally we developed readily applicable score charts for the calculation of outcome probabilities.</p> <p>Results</p> <p>Of the 5027 subjects included, 49% had no disability, 18% had mild disability, 16% had severe disability and 18% had deceased at follow-up after six years. The strongest predictors were age and prior disability. The contribution of other predictors was relatively small. The discriminative ability of the basic model was high; the extended model did not enhance predictive ability.</p> <p>Conclusion</p> <p>As prior disability status predicts future disability status, interventive strategies should be aimed at preventing disability in the first place.</p