Logistic regression in medical decision making and epidemiology

In his recent textbook "Primer of Biostatistics", S, A, Glantz refers to the nowadays growing pressure on clinicians for more effective use of medical resources. He asserts that clinicians should be able to make better informed judgements about claims of medical efficacy. They can participate then more intelligently in the debate on how to allocate medical resources. These better informed judgements are the objective of "medical decision making", where the choices to be made in diagnostic and therapeutic strategies are studied Medical decision making is to be based for a great part on statistical reasoning. A statistical approach which has proven to be valuable in this field is a technique known as logistic regression analysis. The assessment of the performance of this logistic model is the subject of this thesis. Applications in medical decision making are considered, mainly with respect to medical diagnosis. Logistic regression analysis may be viewed as a sophisticated diagnostic aid. Multiple test outcomes and patient characteristics are incorporated into a logistic model for the probability that a patient belongs to a certain disease class. Performance of the logistic model in etiologic-epidemiological studies is another area of study. In this context logistic regression is used for the detection of risk factors, ad jus ted for confounding in order to obtain unbiased assessments. This thesis includes ten chapters, consisting of papers which have either been published or which were recently submitted for publication by the author, many of them in cooperation with various colleagues. The chapters have been grouped into three parts. Part 1 (chapter 1) presents a review of developments in logistic regression from 1970 up to 1986. It outlines statistical aspects of the model such as estimation. hypothesis testing and model selection. Part 2 (chapters 2 - 7) deals with logistic discriminant analysis in medical diagnosis. An extensive evaluation of a logistic model for the diagnosis of Crohn's disease by agglutination reactions is presented in chapter 2. Actually, this chapter results from our evolving insights since the first application of logistic discriminant analysis for the diagnosis of Crohn's disease (chapter 3). Comparison of logistic discrimination with some other discriminant analysis methods is studied in chapter 4 through application to real data from clinical practice, and in chapters 5 and 6 through the use of simulated data. This comparative evaluation was performed on datasets consisting of mixtures of continuous and discrete data. The underlying distribution in the first simulation study (chapter 5) is a fourdimensional normal from which discrete variables were obtained by discretizing the continuous variables. The simulation study in chapter 6 is based on a location model. Within each outcome combination of the discrete variables a multivariate normal distribution is assumed. The next chapter concerns the evaluation oflogistic discriminant analysis for modelling QSAR's, quantitative structure- activity relationships (chapter 7). It is used there as a technique for detecting which chemical compounds will be useful for the development of new drugs. The third and final part of this thesis (chapters 8- 10) is concerned with the application and evaluation of the logistic model in etiologic-epidemiological studies, particularly in case-control studies. In chapter 8 the first epidemiologic application of the logistic model in TheN etherlands, which uses estimates of the model parameters based on conditional likelihood, is presented. Risk factors for stroke are investigated in a case-control study conducted some years ago in Tilburg. In chapter 9 the (multiplicative) logistic model is compared with an (additive) linear model for case-control studies with one continuous exposure factor and without consideration of confounding variables. Some aspects concerning variables selection in epidemiologic studies, also relevant for logistic regression, are discussed in chapter 10. The thesis is concluded with a summary. 1

Detection of liver metastases from colorectal carcinoma: Is there a place for routine computed tomography arteriography?

Background. A prospective evaluation of the liver by preoperative ultrasonography, conventional computed tomography (CT), and continuous CT angiography (CCTA) was performed in 60 patients with primary or secondary colorectal carcinoma. Methods. The standards of reference were palpation of the liver and intraoperative ultrasonography. The imaging techniques were assessed independently of each other. Results. In 37 patients 105 liver metastases were identified; 23 patients had no metastases. CCTA had a high sensitivity of 94% (99 lesions identified) in contrast to ultrasonography (48%) and conventional CT (52%). The superiority of CCTA was also manifest in lesions less than 1 cm in diameter. However, the high sensitivity was accompanied by a high false-positive rate, particularly because of variations in the perfusion of normal liver parenchyma. Overall, CCTA had the highest accuracy (74%) compared with ultrasonography and CT (both 57%). The data indicate that preoperative ultrasonography and conventional CT have low sensitivity in the detection of liver metastases. Conclusions. Although CCTA seems to be superior to other preoperative imaging techniques, the too low specificity will hamper its routine application in patients with hepatic metastases from colorectal carcinoma

Chronic motor neuropathies: response to interferon-beta1a after failure of conventional therapies

OBJECTIVES: The effect of interferon-beta1a (INF-beta1a; Rebif) was studied in patients with chronic motor neuropathies not improving after conventional treatments such as immunoglobulins, steroids, cyclophosphamide or plasma exchange. METHODS: A prospective open study was performed with a duration of 6-12 months. Three patients with a multifocal motor neuropathy and one patient with a pure motor form of chronic inflammatory demyelinating polyneuropathy were enrolled. Three patients had anti-GM1 antibodies. Treatment consisted of subcutaneous injections of IBF-beta1a (6 MIU), three times a week. Primary outcome was assessed at the level of disability using the nine hole peg test, the 10 metres walking test, and the modified Rankin scale. Secondary outcome was measured at the impairment level using a slightly modified MRC sumscore. RESULTS: All patients showed a significant improvement on the modified MRC sumscore. The time required to walk 10 metres and to fulfil the nine hole peg test was also significantly reduced in the first 3 months in most patients. However, the translation of these results to functional improvement on the modified Rankin was only seen in two patients. There were no severe adverse events. Motor conduction blocks were partially restored in one patient only. Anti-GM1 antibody titres did not change. CONCLUSION: These findings indicate that severely affected patients with chronic motor neuropathies not responding to conventional therapies may improve when treated with INF-beta1a. From this study it is suggested that INF-beta1a should be administered in patients with chronic motor neuropathies for a period of up to 3 months before deciding to cease treatment. A controlled trial is necessary to confirm these findings

Mastectomy by inverted drip incision and immediate reconstruction: data from 510 cases

BACKGROUND: Immediate reconstruction of the breast can be performed in selected cases after mastectomy for breast cancer or after prophylactic mastectomy in patients with a high risk of developing breast cancer. Despite the frequency with which these procedures are performed, data from large series of subpectoral implantation of silicone prostheses in combination with a skin-saving approach are lacking. METHODS: In this retrospective study, data on complications and late surgical interventions in 356 patients who underwent 510 mastectomies with an inverted drip incision and immediate reconstruction (MIDIIR) were analyzed to determine potential prognostic factors of early complications. RESULTS: In 82% of the MIDIIRs, the postoperative course was uneventful. In 18%, the complications were infection (32 cases), necrosis of the skin flap (29 cases), bleeding (31 cases), and protrusion of the prosthesis (20 cases), resulting in surgery in 9, 12, 15, and 20 cases, respectively. At the end of the follow-up period, 30 (6%) prostheses were definitively removed. Age, size of the prostheses, radiotherapy, previous lumpectomy, and indication for mastectomy were not significant factors for the prognosis of early complications. CONCLUSIONS: With the right technique and indications, MIDIIR is a very safe procedure and should be one of the surgical treatments that can be offered in the overall management of patients with, or at high risk for, breast cancer

A new applicator design for endocavitary brachytherapy of cancer in the nasopharynx

Introduction: In attempting to improve local tumor control by higher doses of radiation, there has been a resurgence of interest in the implementation of brachytherapy in the management of primary and recurrent cancers of the nasopharynx. Brachytherapy with its steep dose fall-off is of particular interest because of the proximity of critical dose limiting structures. Recent developments in brachytherapy, such as the introduction of pulsed-dose-rate and high-dose-rate computerized afterloaders, have encouraged further evolution of brachytherapy techniques. Materials and methods: We have designed an inexpensive, re-usable and flexible silicone applicator, tailored to the shape of the soft tissues of the nasopharynx, which can be used with either low-dose-rate brachytherapy or high (pulsed)- dose-rate remote controlled afterloaders. Results and conclusions: This Rotterdam nasopharynx applicator proved to be easy to introduce, patient friendly and can remain in situ for the duration of the treatment (2-6 days). The design, technique of application and the first consecutive 5 years of clinical experience in using this applicator are presented

Indices from flow-volume curves in relation to cephalometric, ENT- and sleep-O2 saturation variables in snorers with and without obstructive sleep-apnoea

In a group of 37 heavy snorers with obstructive sleep apnoea (OSA, Group 1) and a group of 23 heavy snorers without OSA (Group 2) cephalometric indices, ENT indices related to upper airway collapsibility, and nocturnal O2 desaturation indices were related to variables from maximal expiratory and inspiratory flow-volume (MEFV and MIFV) curves. The cephalometric indices used were the length and diameter of the soft palate (spl and spd), the shortest distance between the mandibular plane and the hyoid bone (mph) and the posterior airway space (pas). Collapsibility of the upper airways was observed at the level of the tongue base and soft palate by fibroscopy during a Muller manoeuvre (mtb and msp) and ranked on a five point scale. Sleep indices measured were the mean number of oxygen desaturations of more than 3% per hour preceded by an apnoea or hypopnoea of more than 10 s (desaturation index), maximal sleep oxygen desaturation, baseline arterial oxygen saturation (Sa,O2) and, in the OSA group, percentage of sleep time with Sa,O2 < 90%. The variables obtained from the flow-volume curves were the forced vital capacity (FVC), forced expiratory and inspiratory volume in 1 s (FEV1 and FIV1), peak expiratory and peak inspiratory flows (PEF and PIF), and maximal flow after expiring 50% of the FVC (MEF50). The mean of the flow-volume variables, influenced by upper airway aperture (PEF, FIV1) was significantly greater than predicted.(ABSTRACT TRUNCATED AT 250 WORDS

A randomized phase II study comparing two schedules of the 21-day regimen of gemcitabine and carboplatin in advanced non-small cell lung cancer

Purpose: Carboplatin area under the curve (AUC) 5 ml/min on day 1 with gemcitabine 1,250 mg/m2on day 1 and day 8 is a widely used regimen in advanced non-small cell lung cancer. Grade 3-4 thrombocytopenia and neutropenia are frequent. The aim of this study is to investigate whether toxicity of gemcitabine/carboplatin could be reduced by administering carboplatin on day 8 instead of

Reliability and responsiveness of a graduated tuning fork in immune mediated polyneuropathies. The Inflammatory Neuropathy Cause and Treatment (INCAT) Group

The interobserver and intraobserver reliability of the Rydel-Seiffer (RS) graduated tuning fork was evaluated in 113 patients with a clinically stable immune mediated polyneuropathy (83 patients who had had Guillain-Barre syndrome (GBS) in the past, 22 with a chronic inflammatory demyelinating polyneuropathy (CIDP), and eight with a polyneuropathy associated with a gammopathy of undetermined significance). Additionally, the responsiveness of this instrument was serially investigated in 20 patients with recently diagnosed GBS or CIDP and changing clinical conditions. The measures were done in triplicate at eight different locations in the limbs and the values were compared with the recently published vibration threshold reference values. Good interobserver and intraobserver agreements (quadratic weighted kappa=0.67-0.98) and high responsiveness values (standardised response mean scores>0.8) were demonstrated for the RS tuning fork. These results provide, in addition to literature findings, further evidence for incorporation of this easily applicable instrument in routine neurological examination