A joint latent variable model approach to item reduction and validation.

Many applications of biomedical science involve unobservable constructs, from measurement of health states to severity of complex diseases. The primary aim of measurement is to identify relevant pieces of observable information that thoroughly describe the construct of interest. Validation of the construct is often performed separately. Noting the increasing popularity of latent variable methods in biomedical research, we propose a Multiple Indicator Multiple Cause (MIMIC) latent variable model that combines item reduction and validation. Our joint latent variable model accounts for the bias that occurs in the traditional 2-stage process. The methods are motivated by an example from the Physical Activity and Lymphedema clinical trial in which the objectives were to describe lymphedema severity through self-reported Likert scale symptoms and to determine the relationship between symptom severity and a "gold standard" diagnostic measure of lymphedema. The MIMIC model identified 1 symptom as a potential candidate for removal. We present this paper as an illustration of the advantages of joint latent variable models and as an example of the applicability of these models for biomedical research.

A high response rate to liposomal doxorubicin is seen among women with BRCA mutations treated for recurrent epithelial ovarian cancer.

OBJECTIVE: Ten percent of ovarian cancer is attributed to hereditary syndromes, most commonly to mutations in the BRCA1 or BRCA2 genes. These cancers are characterized by a prolonged sensitivity to platinum agents in spite of presentation at advanced stages. We hypothesized that women with BRCA-associated ovarian cancer would also show a high response rate to pegylated liposomal doxorubicin (Doxil). METHODS: A retrospective cohort study was conducted to compare the response rate, progression-free, and overall survival among women with BRCA-associated or sporadic ovarian cancer who were treated with Doxil. RESULTS: A response to Doxil was seen in 13 of 23 patients with BRCA mutations (56.5%; 3 by RECIST criteria and 10 by CA125 levels) compared with only 8 of 41 women with non-hereditary cancers (19.5%; 2 by RECIST criteria and 6 by CA125 levels; p=0.004). This was associated with an improved progression-free and overall survival as measured from the time of Doxil administration. Notably, platinum sensitivity did not directly correlate with a response to Doxil. CONCLUSIONS: Women with BRCA-associated ovarian tumors demonstrate a greater sensitivity to cytotoxic therapy with Doxil than has previously been reported in unselected cases.

Predictors of suicide relative to other deaths in patients with suicide attempts and suicide ideation: a 30-year prospective study.

BACKGROUND: Although there is a large literature that prospectively examines predictors of suicide, low base rates of suicide and imprecision of measurement hinder definitive conclusions from being drawn. METHOD: This study examined predictors of suicide relative to other types of death in a sample of 297 patients who had been hospitalized for suicide ideation or a suicide attempt between 1970 and 1975 and who were confirmed dead in 2005. Many predictors were measured using well-validated assessment instruments. RESULTS: Fifty-five patients had died by suicide. Univariate predictors of an increased risk for eventual suicide included younger age, completion of at least a high school degree, a diagnosis of a psychotic disorder, taking active precautions against discovery during the attempt, and a non-zero score on the suicide item of the Beck Depression Inventory, whereas African American ethnicity was associated with a decreased risk of eventual suicide. Variables that remained significant in a multivariate analysis included younger age, African American ethnicity, and taking active precautions against discovery during the attempt. Risk factors did not vary as a function of whether eventual suicide occurred less than or more than five years after the initial evaluation or by attempter v. ideator status. LIMITATIONS: Despite the attempt to maximize statistical power by following a high-risk sample for 30 years, the number of deaths by suicide was still relatively low. CONCLUSIONS: Taking active precautions against discovery of a suicide attempt has the potential to be an important predictor of eventual suicide and should be assessed by clinicians. Future prospective studies should assess predictors at multiple time points to gain a richer clinical picture of the circumstances surrounding deaths by suicide.

Core symptoms that discriminate premenstrual syndrome.

OBJECTIVE: To identify core symptoms that discriminate premenstrual syndrome (PMS) in prospective daily diary ratings and determine the association of these symptoms with functional impairment. METHODS: The study analyzed prospective daily symptom ratings and functional impairment data provided by 1081 women who requested PMS treatment at an academic medical center. The data were obtained before any treatment procedures. A random-split sample design provided separate developmental and validation datasets. Logistic regression was used to identify a reduced set of symptoms that best discriminated PMS. The results were validated in a separate dataset. Optimal cutoff points in the symptom scores were identified for clinical use. RESULTS: Statistical modeling identified 6 symptoms that discriminated PMS and not PMS as well as 17 symptoms in daily diary ratings. The identified core symptoms included anxiety/tension, mood swings, aches, appetite/food cravings, cramps, and decreased interest in activities. The area under the curve (AUC) was 0.84 in both models. The sums of the premenstrual symptom scores also discriminated PMS and not PMS and correctly classified 84%-86% of the cases. CONCLUSIONS: Six symptoms rated in daily diaries discriminate between PMS and not PMS among women seeking treatment and are significantly associated with functional impairment. The findings suggest that the burden of daily diaries to confirm PMS can be reduced to a smaller number of symptoms that distinguish the patients who meet this requirement. Results also support the concept that a clinical diagnosis of PMS can be developed around a core symptom group.