Resampling Evaluation of Signal Detection and Classification : With Special Reference to Breast Cancer, Computer-Aided Detection and the Free-Response Approach

The first part of this thesis is concerned with trend modelling of breast cancer mortality rates. By using an age-period-cohort model, the relative contributions of period and cohort effects are evaluated once the unquestionable existence of the age effect is controlled for. The result of such a modelling gives indications in the search for explanatory factors. While this type of modelling is usually performed with 5-year period intervals, the use of 1-year period data, as in Paper I, may be more appropriate. The main theme of the thesis is the evaluation of the ability to detect signals in x-ray images of breasts. Early detection is the most important tool to achieve a reduction in breast cancer mortality rates, and computer-aided detection systems can be an aid for the radiologist in the diagnosing process. The evaluation of computer-aided detection systems includes the estimation of distributions. One way of obtaining estimates of distributions when no assumptions are at hand is kernel density estimation, or the adaptive version thereof that smoothes to a greater extent in the tails of the distribution, thereby reducing spurious effects caused by outliers. The technique is described in the context of econometrics in Paper II and then applied together with the bootstrap in the breast cancer research area in Papers III-V. Here, estimates of the sampling distributions of different parameters are used in a new model for free-response receiver operating characteristic (FROC) curve analysis. Compared to earlier work in the field, this model benefits from the advantage of not assuming independence of detections in the images, and in particular, from the incorporation of the sampling distribution of the system's operating point. Confidence intervals obtained from the proposed model with different approaches with respect to the estimation of the distributions and the confidence interval extraction methods are compared in terms of coverage and length of the intervals by simulations of lifelike data

Resampling Evaluation of Signal Detection and Classification : With Special Reference to Breast Cancer, Computer-Aided Detection and the Free-Response Approach

The first part of this thesis is concerned with trend modelling of breast cancer mortality rates. By using an age-period-cohort model, the relative contributions of period and cohort effects are evaluated once the unquestionable existence of the age effect is controlled for. The result of such a modelling gives indications in the search for explanatory factors. While this type of modelling is usually performed with 5-year period intervals, the use of 1-year period data, as in Paper I, may be more appropriate. The main theme of the thesis is the evaluation of the ability to detect signals in x-ray images of breasts. Early detection is the most important tool to achieve a reduction in breast cancer mortality rates, and computer-aided detection systems can be an aid for the radiologist in the diagnosing process. The evaluation of computer-aided detection systems includes the estimation of distributions. One way of obtaining estimates of distributions when no assumptions are at hand is kernel density estimation, or the adaptive version thereof that smoothes to a greater extent in the tails of the distribution, thereby reducing spurious effects caused by outliers. The technique is described in the context of econometrics in Paper II and then applied together with the bootstrap in the breast cancer research area in Papers III-V. Here, estimates of the sampling distributions of different parameters are used in a new model for free-response receiver operating characteristic (FROC) curve analysis. Compared to earlier work in the field, this model benefits from the advantage of not assuming independence of detections in the images, and in particular, from the incorporation of the sampling distribution of the system's operating point. Confidence intervals obtained from the proposed model with different approaches with respect to the estimation of the distributions and the confidence interval extraction methods are compared in terms of coverage and length of the intervals by simulations of lifelike data

Resampling Evaluation of Signal Detection and Classification : With Special Reference to Breast Cancer, Computer-Aided Detection and the Free-Response Approach

The first part of this thesis is concerned with trend modelling of breast cancer mortality rates. By using an age-period-cohort model, the relative contributions of period and cohort effects are evaluated once the unquestionable existence of the age effect is controlled for. The result of such a modelling gives indications in the search for explanatory factors. While this type of modelling is usually performed with 5-year period intervals, the use of 1-year period data, as in Paper I, may be more appropriate. The main theme of the thesis is the evaluation of the ability to detect signals in x-ray images of breasts. Early detection is the most important tool to achieve a reduction in breast cancer mortality rates, and computer-aided detection systems can be an aid for the radiologist in the diagnosing process. The evaluation of computer-aided detection systems includes the estimation of distributions. One way of obtaining estimates of distributions when no assumptions are at hand is kernel density estimation, or the adaptive version thereof that smoothes to a greater extent in the tails of the distribution, thereby reducing spurious effects caused by outliers. The technique is described in the context of econometrics in Paper II and then applied together with the bootstrap in the breast cancer research area in Papers III-V. Here, estimates of the sampling distributions of different parameters are used in a new model for free-response receiver operating characteristic (FROC) curve analysis. Compared to earlier work in the field, this model benefits from the advantage of not assuming independence of detections in the images, and in particular, from the incorporation of the sampling distribution of the system's operating point. Confidence intervals obtained from the proposed model with different approaches with respect to the estimation of the distributions and the confidence interval extraction methods are compared in terms of coverage and length of the intervals by simulations of lifelike data

Cardiovascular and antacid treatment and mortality in oxygen-dependent pulmonary fibrosis : A population-based longitudinal study

BACKGROUND AND OBJECTIVE: Severe idiopathic pulmonary fibrosis is associated with an increased risk of cardiovascular disease and gastro-oesophageal reflux, which may influence prognosis. We evaluated associations between cardiovascular and antacid medications, and mortality, in oxygen-dependent pulmonary fibrosis (PF) of unknown cause.METHODS: Prospective population-based study of adults starting long-term oxygen therapy (LTOT) for PF in Sweden 2005-2009. PF of unknown cause was defined by excluding patients with known or probable secondary PF. Time-dependent associations between medications and all-cause mortality were analysed using extended Cox regression, adjusting for potential confounders including age, sex, vital capacity, blood gases, body mass index, performance status, comorbidity and concurrent medications.RESULTS: Of 462 included patients, 329 (71%) died under observation. No patient was lost to follow-up. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) were associated with reduced adjusted mortality (HR 0.63; 0.47-0.85) and antiplatelet drugs with increased mortality (HR 1.49; 1.11-2.00), largely driven by higher mortality in women. There were no associations with mortality for antacid treatments, β-blockers, diuretics or statins.CONCLUSION: In oxygen-dependent PF, treatment with ACEI/ARB was associated with improved survival, antiplatelet drugs with decreased survival, whereas there was no association between antacid, β-blocker, diuretic or statin treatment and survival

The identification of complex interactions in epidemiology and toxicology : a simulation study of Boosted Regression Trees

Background: There is a need to evaluate complex interaction effects on human health, such as those induced by mixtures of environmental contaminants. The usual approach is to formulate an additive statistical model and check for departures using product terms between the variables of interest. In this paper, we present an approach to search for interaction effects among several variables using boosted regression trees. Methods: We simulate a continuous outcome from real data on 27 environmental contaminants, some of which are correlated, and test the method's ability to uncover the simulated interactions. The simulated outcome contains one four-way interaction, one non-linear effect and one interaction between a continuous variable and a binary variable. Four scenarios reflecting different strengths of association are simulated. We illustrate the method using real data. Results: The method succeeded in identifying the true interactions in all scenarios except where the association was weakest. Some spurious interactions were also found, however. The method was also capable to identify interactions in the real data set. Conclusions: We conclude that boosted regression trees can be used to uncover complex interaction effects in epidemiological studies

Surgery for chronic otitis media causes greater taste disturbance than surgery for otosclerosis

Objectives: Patients with otosclerosis more often complain about postoperative taste disturbance than patients with chronic otitis media, which seems paradoxical. We aim to investigate if and potentially why this seems to be the case, since the chorda tympani nerve (CTN) is thought to be severely traumatized less frequently during surgery in the former than in the latter. Study Design: Prospective cohort study. Setting: Department of Otorhinolaryngology at Hospital of Vastmanland, Vasteras, Sweden. Patients: Sixty-five adults undergoing primary middle ear surgery were included. Thirty-seven were operated on for chronic suppurative otitis media with or without cholesteatoma (CSOM) and 28 for otosclerosis. Interventions: Middle ear surgery due to otosclerosis or CSOM. Subjective and objective taste measurements and quality of life (QoL) questionnaire. Main Outcome Measures: Taste was assessed using electrogustometry (EGM) and the filter paper disc (FPD) method before and up to 1 year after surgery. Questionnaires on taste disturbance, including a visual analogue scale (VAS), and QoL were completed before and up to 1 year after surgery. Results: Subjective taste disturbance anytime during the 1-year follow-up were reported by 62 and 46%, respectively. The difference in EGM 1 week after surgery compared with preoperative EGM was significantly greater among CSOM patients than otosclerosis. One year postoperatively, the difference is non-significant. Conclusion: Surgery for CSOM causes greater initial and more long-lasting taste disturbances as compared with surgery for otosclerosis. One-year postoperative taste normalizes for both CSOM and otosclerosis patients according to VAS and EGM measurements. No real change in QoL was seen 1-year postoperatively. Level of evidence: Level 2 evidence is prospective observational research with an experimental design

Respiratory outcomes after a 1-year treatment of obstructive sleep apnoea with bibloc versus monobloc oral appliances : a multicentre, randomized equivalence trial

Objective: The benefit of bibloc over monobloc appliances in treating obstructive sleep apnoea (OSA) has not been evaluated in randomized trials. We hypothesized that these types of appliances would be equally effective. Material and methods: In this multicentre, randomized equivalence trial, patients with OSA received one type of bibloc or one type of monobloc treatment. At baseline, a 1-night polygraphy study was done, and this was repeated after 1 year. The outcome was any change in the apnoea–hypopnoea index (AHI) and the limits of equivalence between the two devices were set at ±5 AHI units. Results: Of 302 patients, 146 were randomly assigned to bibloc and 156 to monobloc appliances. In 88 and 104 patients, respectively, there were significant reductions in the AHI (p < .001) with a mean change of −16.7 (95% CI −19.4 to −14.1) in the bibloc and −11.8 (−14.9 to −8.7) in the monobloc groups. The proportions of responders defined as having an AHI <10 were 68% and 65% for the bibloc and monobloc groups, respectively. Treatment-related adverse events were mild, transient and the dropouts were more frequent in the bibloc group. Conclusions: Both types of treatments positively and significantly reduced respiratory disturbances, but at the 1-year follow-up, they were not significantly different in treating OSA, with a numerically greater reduction of the AHI value with the bibloc appliance. However, the higher proportion of treatment-related adverse events and higher proportion of dropouts among bibloc users should be balanced against the advantage of a greater reduction in the AHI

Safety of benzodiazepines and opioids in very severe respiratory disease : national prospective study

Objective To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD). Design Population based longitudinal consecutive cohort study. Setting Centres prescribing long term oxygen therapy in Sweden. Patients 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register. Main outcome measures Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs. Results 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation. No patient was lost to follow-up. Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively. Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend. Opioids also had a dose response relation with mortality: lower dose opioids (<= 30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44). Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99). Associations were not modified by being naive to the drugs or by hypercapnia. Conclusions Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease

Minimal Clinically Important Differences and Feasibility of Dyspnea-12 and the Multidimensional Dyspnea Profile in Cardiorespiratory Disease

Context: Breathlessness is a cardinal symptom in cardiorespiratory disease and consists of multiple dimensions that can be measured using the instruments Dyspnea-12 (D12) and the Multidimensional Dyspnea Profile (MDP). Objectives: The objective of the study is to determine the minimal clinically important differences (MCIDs) of all D12 and MDP summary and subdomain scores as well as the instruments' feasibility in patients with cardiorespiratory disease. Methods: Prospective multicenter cohort study of outpatients with diagnosed cardiorespiratory disease and breathlessness in daily life. D12 and MDP were assessed at baseline, after 30-90 minutes and two weeks. MCIDs were calculated using anchor-based and distributional methods for summary and subdomain scores. Feasibility was assessed as rate of missing data, help required, self-reported difficulty, and completion time. Results: A total 182 outpatients (53.3% women) were included; main diagnoses were chronic obstructive pulmonary disease (COPD; 25%), asthma (21%), heart failure (19%), and idiopathic pulmonary fibrosis (19%). Anchor-based MCIDs were for D12 total score 2.83 (95% CI 1.99-3.66); D12 physical 1.81 (1.29-2.34); D12 affective 1.07 (0.64-1.49); MDP A1 unpleasantness 0.82 (0.56-1.08); MDP perception 4.63 (3.21-6.05), and MDP emotional score 2.37 (1.10-3.64). The estimates were consistent with small-to-moderate effect sizes using distributional analysis, and MCIDs were similar between COPD and non-COPD patients. The instruments were generally feasible and quick to use. Conclusion: D12 and MDP are responsive to change and feasible for use for assessing multidimensional breathlessness in outpatients with cardiorespiratory disease. MCIDs were determined for use as endpoints in clinical trials