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Results for “Multivariate response regression”

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PubMed2003

C-reactive protein, antiinflammatory drugs, and quality of life in diabetes.

BACKGROUND: C-reactive protein (CRP) is an important biological marker of inflammation that has been linked to cardiovascular disease. The extent to which the inflammatory processes associated with elevated CRP concentrations impair physical functioning and quality of life, and whether this is modulated by hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) and aspirin, which have been shown to lower CRP concentrations, is unclear. OBJECTIVE: To determine whether an association exists between CRP concentrations and health-related quality of life among patients with diabetes, and to determine whether the association is affected by use of statins and nonsteroidal antiinflammatory drugs (NSAIDs). METHODS: A trained interviewer collected self-reported information regarding demographics, health-related quality of life (SF-12), and medication use, and a nurse collected a blood sample from 86 adult subjects with type 2 diabetes mellitus who were part of a larger population-based survey. The serum was analyzed for CRP using a highly sensitive assay. RESULTS: In simple bivariate analysis, there was a significant inverse relationship between CRP and the physical health component score of health-related quality of life (Spearman correlation coefficient [r] = -0.26; p = 0.025). For subjects on statins (r = -0.44; p = 0.02; n = 27), this relationship persisted, while for patients on NSAIDs or aspirin (r = -0.21; p = 0.17; n = 44), no relationship was observed. Similar findings were observed with self-rated health alone as an outcome variable. However, stepwise linear regression revealed no consistent relationship between CRP and health-related quality of life (i.e., standardized SF-12 physical component score) when demographic variables, disease duration, glucose control, serum creatinine, smoking, and medication use were controlled for. CONCLUSIONS: In multivariate regression modeling, the initial inverse relationship between CRP and health-related quality of life was lost, suggesting that other covariates are responsible for this association. While statins and NSAIDs may impact CRP or health-related quality of life independently, they do not appear to modulate a relationship between these factors.

Analysis of Variance↗

PubMed2001

Increased glucose-dependent insulinotropic polypeptide (GIP) secretion in acromegaly.

OBJECTIVE: Acromegaly is often associated with fasting and postprandial hyperinsulinemia, and the mechanisms involved are only partly understood. Hypersecretion of incretins such as glucose-dependent insulinotropic polypeptide (GIP) could play a role in determining hyperinsulinemia in acromegaly, but the available data are inconsistent. The aim of this study was to characterize the fasting and postprandial pattern of plasma GIP and insulin in a group of acromegalic patients. DESIGN AND METHODS: Eleven non-diabetic patients with newly diagnosed acromegaly and 11 sex- and age-matched healthy subjects were studied. Blood samples were taken at regular intervals in fasting conditions and for 3 h after a standard solid-liquid meal for growth hormone (GH), GIP and insulin measurements. RESULTS: Not only insulin, but also fasting and postprandial GIP levels were significantly higher in the patients with acromegaly than the healthy subjects (P<0.01). In the former group fasting GIP levels and the integrated GIP response to the meal correlated significantly with GH basal levels (r=0.83, P<0.01 and r=0.65, P<0.05, respectively). Moreover, multivariate linear regression analysis showed that the presence of acromegalic status was associated with higher fasting and postprandial GIP levels independently of sex, age, fasting and postprandial plasma glucose and insulin levels, and the occurrence of normal or impaired glucose tolerance. CONCLUSION: This study provides evidence that in patients with acromegaly fasting and postprandial GIP levels are abnormally high. GIP hypersecretion in turn might play a role in the pathogenesis of hyperinsulinemia that characterizes acromegaly.

Acromegaly↗

PubMed1999

Nursing facilities and managed care.

OBJECTIVE: To examine the extent to which Illinois nursing facilities have developed relationships with other healthcare providers, particularly managed care organizations (MCOs). STUDY DESIGN: A cross-sectional survey of nursing facilities designed to determine: 1) relationship objectives; 2) obstacles to developing relationships; 3) currently available services; 4) staffing for these services and; 5) nursing facility approaches to networking. The survey was sent to a census sample of 867 nursing facilities serving the elderly in Illinois. Descriptive and multivariate logistic regression analyses of relationships determined to be formal/risk-sharing were performed. STUDY POPULATION: The sample included 523 Illinois nursing facilities. A total response rate of 60% was achieved (523/867). RESULTS: Higher strategic goals, urban location, nonprofit ownership status, higher percentages of private pay and/or Medicare clients (vs Medicaid), and provision of home care and subacute services were all significant predictors of formal or risk-sharing relationships with MCOs. CONCLUSIONS: Facilities with more relationships and higher goals have more formal/risk-sharing relationships with MCOs. Facilities in urban areas have more relationships, likely due to the fact that rural facilities have fewer options and operate in different markets. In addition, nursing facilities rely on Medicare referrals from hospitals, and these Medicare patients, especially those in urban areas, are increasingly controlled by MCOs.

Aged↗

PubMed2004

Comparison of the hemolytic activity of isopropoxyethanol and phenoxyethanol.

OBJECTIVES: Administration of ethylene glycol monoalkyl ethers to rodents causes acute hemolytic anemia. Metabolic activation of these chemicals to alkoxyacetic acids is required to develop hemolytic effect. Current study was undertaken to compare the hemolytic activity of isopropoxyethanol (IPE) and phenoxyethanol (PhE) in male rats. The main goal of this study was to evaluate the role of alkyl and aryl group in hemolytic activity of ethylene glycol ethers. MATERIALS AND METHODS: Rats were treated subcutaneously with single doses of 0, 0.625, 1.25 and 2.5 mmol IPE/kg body weight or 0, 2.5, 5.0 and 10.0 mmol PhE/kg. At 0, 6, 24, 48, 144, 216, and 600 h after dosing, blood samples were collected from end tail of rats and various blood indices were measured. RESULTS: Administration of both chemicals resulted in a time- and dose-dependent swelling of erythrocytes as evidenced by an early increase in packed cell volumes and mean cell volume. Subsequently, red blood cells, total hemoglobin concentration, and packed cell volumes decreased when hemolysis progressed. Furthermore, an increase in plasma hemoglobin concentration and reticulocyte counts was observed. The onset of hemolysis induced by IPE was faster than that after PhE administration. The hemolytic activity of IPE was about tenfold higher in comparison with PhE. CONCLUSIONS: It is likely that the lower hemolytic activity of PhE is associated with inhibitory effect of aryl group on hemolytic action of this compound. Phenyl group, in contrast with alkyl moiety, represents electron acceptor system which exerts resonance and inductive effects and leads to changes in acid strength, also in case of phenoxyacetic acid, a metabolite of PhE.

Anemia, Hemolytic↗

PubMed2000

Association models for a multivariate binary response.

Models for a multivariate binary response are parameterized by univariate marginal probabilities and dependence ratios of all orders. The w-order dependence ratio is the joint success probability of w binary responses divided by the joint success probability assuming independence. This parameterization supports likelihood-based inference for both regression parameters, relating marginal probabilities to explanatory variables, and association model parameters, relating dependence ratios to simple and meaningful mechanisms. Five types of association models are proposed, where responses are (1) independent given a necessary factor for the possibility of a success, (2) independent given a latent binary factor, (3) independent given a latent beta distributed variable, (4) follow a Markov chain, and (5) follow one of two first-order Markov chains depending on the realization of a binary latent factor. These models are illustrated by reanalyzing three data sets, foremost a set of binary time series on auranofin therapy against arthritis. Likelihood-based approaches are contrasted with approaches based on generalized estimating equations. Association models specified by dependence ratios are contrasted with other models for a multivariate binary response that are specified by odds ratios or correlation coefficients.

Antirheumatic Agents↗

PubMed1991

Multivariate analysis of metastasis risk in laryngeal carcinoma. II. Immune response.

The presence of inflammatory reaction, plasma cells, and eosinophils in peritumoral connective tissue and in neoplastic stroma was evaluated with morphometrical method in 181 patients affected by laryngeal carcinoma. A logistic multiple regression model was applied making it with the use of an independent variable represented by the "infiltrating" or "expansive" types of tumor growth, in order to evaluate the probability of nodal metastatsis of each parameter. The results suggest an inverse correlationship between plasma cells and inflammatory infiltration and incidence of nodal metastatsis only in the comparison of the extreme conditions: those with scarce infiltration versus the ones with large infiltration. Inflammatory or plasmacellular infiltration may represent both a defense mechanism against cancer and an aspecific or allergic reaction. The eosinophilic infiltration shows no value in the prevention of nodal involvement.

Eosinophils↗

PubMed1991

Estimating equations for parameters in means and covariances of multivariate discrete and continuous responses.

Generalized estimating equations are introduced in an ad hoc fashion for the covariance matrix of a multivariate response. These equations are to be solved jointly with score equations from a generalized linear model for mean parameters. A class of quadratic exponential models is used to develop joint estimating equations for mean and covariance parameters in a more systematic fashion, and proposals for the use of such equations are developed. Comments on the relative merits of the ad hoc and model-based approaches to estimation are given and a regression illustration with a bivariate response is provided.

Anticonvulsants↗

PubMed2006

Does the Banff rejection activity index predict outcome in patients with early acute cellular rejection following liver transplantation?

The Banff schema incorporates a semiquantitative scoring system for grading of acute cellular rejection (ACR) of the liver allograft. The Banff rejection activity index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation (E); bile duct damage (B); and portal inflammation (P); the scores are combined to an overall score (the RAI). The purpose of this research was to determine the prognostic value of the Banff RAI score in predicting the response to increased immunosuppression and the long-term outcome of the graft. A retrospective study was done of patients undergoing primary liver transplantation between January 2000 and October 2004 with tacrolimus-based immunosuppression; 495 patients were included, 231 had histologically-confirmed ACR, 193 responded to 1 cycle of high-dose steroids. There was no correlation between the total RAI score and response to steroids, resistant rejection, development of chronic rejection, or graft survival. The E score was related to patient survival, a lower score being associated with a worse outcome (P = 0.048). In multivariable analysis, serum bilirubin, serum aspartate aminotransferase, and E score were significant predictors of death (P = 0.012). In univariable analysis, B score and bilirubin were significantly related to "resistant rejection" (P = 0.018 and 0.002, respectively), but only bilirubin was significant in multivariable analysis (logistic regression). In conclusion, although the Banff RAI score is a useful marker of the severity of rejection, neither the total RAI score nor any of the individual components correlated with response to steroids or graft survival.

Adolescent↗

PubMed1993

Transsphenoidal adenomectomy for growth hormone-secreting pituitary adenomas in acromegaly: outcome analysis and determinants of failure.

The results of transsphenoidal adenomectomy for growth hormone (GH)-secreting pituitary adenomas in acromegaly performed over a 17-year period were analyzed retrospectively to determine which preoperative factors significantly influenced the long-term surgical outcome. These variables were then used to develop a logistic regression model to determine the probability of surgical failure. The series consisted of 103 patients. Long-term follow-up study (mean duration 102 +/- 64 months) was performed to derive outcome analysis and determinants of failure. Surgical control was defined as a long-term postoperative serum basal GH level of less than 5 micrograms/liter, a long-term postoperative serum somatomedin C (SM-C) level of less than 2.2 U/ml, and a favorable clinical response. Eighteen (17.5%) patients did not meet these criteria. The overall control rate by the GH criteria was 81.3% and by the SM-C criteria 76.2%. By multivariate logistic regression analysis, tumor stage was the strongest predictor of outcome (p < 0.05). The preoperative GH level, tumor grade, and preoperative SM-C level were significant univariate predictors (p < 0.05). There were statistically significant differences in mean preoperative GH and SM-C levels (p < 0.05, t-test) and tumor stage (p < 0.05, chi-squared test) between patients whose acromegaly was controlled by surgery and those whose acromegaly was not. Furthermore, estimates were derived of the probability of surgical failure based on preoperative GH level, preoperative SM-C level, and tumor grade and stage. The authors believe these findings will enhance clinical decision-making for neurosurgeons considering transsphenoidal microsurgery in patients with acromegaly.

Acromegaly↗

PubMed2002

Histopathologic effects of neoadjuvant therapies for advanced squamous cell carcinoma of the esophagus: multivariate analysis of predictive factors and p53 overexpression.

In 97 patients (60, chemotherapy; 22, chemoradiotherapy; 15, radiotherapy), histopathologic effects were evaluated microscopically, and histologic response rates were compared among three neoadjuvant treatment modalities. Predictive factors for neoadjuvant therapies were analyzed by logistic regression, including the results of p53 immunohistochemical staining. In the chemoradiotherapy group, the pathologic response rate was 86.4%, and was significantly higher than that for chemotherapy (P < 0.0001) or for radiotherapy (P = 0.0031). In patients with normal p53 protein expression, the histopathologic response rate to chemotherapy was 20.0%, a higher rate than that for patients with abnormal p53 overexpression. In the chemoradiotherapy or radiotherapy group, however, the response rates were almost the same, irrespective of p53 oncoprotein status. From multivariate analysis, the neoadjuvant treatment modality itself was identified as the most powerful predictive factor for the effect. Chemoradiotherapy had the most powerful effect on advanced esophageal cancer, and p53 status did not influence the clinical outcome in this group.

Adult↗

PubMed2005

An index of local sensitivity to nonignorable drop-out in longitudinal modelling.

In longitudinal studies with potentially nonignorable drop-out, one can assess the likely effect of the nonignorability in a sensitivity analysis. Troxel et al. proposed a general index of sensitivity to nonignorability, or ISNI, to measure sensitivity of key inferences in a neighbourhood of the ignorable, missing at random (MAR) model. They derived detailed formulas for ISNI in the special case of the generalized linear model with a potentially missing univariate outcome. In this paper, we extend the method to longitudinal modelling. We use a multivariate normal model for the outcomes and a regression model for the drop-out process, allowing missingness probabilities to depend on an unobserved response. The computation is straightforward, and merely involves estimating a mixed-effects model and a selection model for the drop-out, together with some simple arithmetic calculations. We illustrate the method with three examples.

Animal Feed↗

PubMed2006

Factors influencing implementation of the Coordinated Approach to Child Health (CATCH) Eat Smart School Nutrition Program in Texas.

The purpose of this research was to evaluate factors influencing the implementation of the Coordinated Approach to Child Health (CATCH) Eat Smart School Nutrition Program in Texas using data from the CATCH dissemination study. A mail survey was sent to school foodservice personnel (N = 213) who attended a CATCH training from August 2000 through January 2002. A response rate of 40% (n = 85) was achieved. The mean score for the percentage of CATCH Eat Smart guidelines implemented was 80.44. Multivariate linear regression analysis revealed that, after adjusting for age and number of years employed in school foodservice, the following factors were significantly associated with the percentage of CATCH Eat Smart guidelines implemented: utility of CATCH and CATCH Eat Smart in meeting requirements for Coordinated School Health Programs (P = 0.006), school foodservice personnel's satisfaction with food made using the CATCH Eat Smart guidelines (P = 0.008), utility of CATCH in facilitating interschool communication about children's health (P = 0.019), and perceived student satisfaction with food made using the CATCH Eat Smart guidelines (P = 0.046). These results suggest that dissemination approaches for Coordinated School Health Programs should focus on ways to enhance program satisfaction, be consistent with legislated mandates, and increase interschool staff communication to increase program implementation by school foodservice personnel.

Adolescent↗

PubMed2006

Microbiologically documented nosocomial infections after coronary artery bypass surgery without cardiopulmonary bypass.

OBJECTIVE: This study was undertaken to evaluate the frequency, characteristics, and risk factors of microbiologically documented nosocomial infections after off-pump coronary artery bypass grafting. METHODS: A prospective cohort study was performed at Henry Dunant Hospital, Athens, Greece. It included all adult patients who underwent coronary artery bypass grafting with no valve surgery and without the use of cardiopulmonary bypass during a period of 3 years. Case patients were those with development of microbiologically documented nosocomial infections. Various variables were examined as possible risk factors for nosocomial infections. RESULTS: Twenty-one of 782 studied patients (2.7%) acquired 26 microbiologically documented nosocomial infections after off-pump coronary artery bypass grafting. Eight of 782 studied patients had pneumonia (1.02%), 7 of 782 (0.90%) had bacteremia, 4 of 782 (0.51%) had superficial wound infection at the sternotomy site, 4 of 782 (0.51%) had urinary tract infection, 2 of 782 (0.26%) had mediastinitis, and 1 of 782 (0.13%) had pressure sore infection. Twenty-one infections were monomicrobial, whereas 5 were polymicrobial. All polymicrobial infections were wound infections. There was a statistically significant difference in mortality between patients with and without nosocomial infection (23.8% vs 1.2%, P < .001). Clinical response of the infection to the treatment administered was observed in 21 of 26 episodes (80.8%) in 21 patients. A backward stepwise multivariable logistic regression model showed that independent risk factors (P < .05) associated with development of microbiologically documented nosocomial infection were arterial hypertension, previous vascular surgery, urgent operation, postoperative atrial fibrillation, number of inotropes used during and after operation, transfusion of fresh-frozen plasma during the intensive care unit stay, and intensive care unit stay until development of infection. CONCLUSION: Nosocomial infection after off-pump coronary artery bypass grafting is an uncommon but potentially life-threatening complication. The identification of independent risk factors, including arterial hypertension, associated with development of postoperative infection may help in the development of clinical strategies for the prevention, early diagnosis, and treatment of these infections.

Adult↗

PubMed2004

Salmonella Dublin infection in dairy cattle: risk factors for becoming a carrier.

Long-term Salmonella Dublin carrier animals harbor the pathogen in lymph nodes and internal organs and can periodically shed bacteria through feces or milk, and contribute to transmission of the pathogen within infected herds. Thus, it is of great interest to reduce the number of new carrier animals in cattle herds. An observational field study was performed to evaluate factors affecting the risk that dairy cattle become carrier animals after infection with Salmonella Dublin. Based on repeated sampling, cattle in 12 Danish dairy herds were categorized according to course of infection, as either carriers (n = 157) or transiently infected (n = 87). The infection date for each animal was estimated from fecal excretion and antibody responses. The relationship between the course of infection (carrier versus transiently infected) and risk factors were analyzed using a random effect multilevel, multivariable logistic regression model. The animals with the highest risk of becoming carriers were heifers infected between the age of 1 year and 1st calving, and cows infected around the time of calving. The risk was higher in the first two quarters of the year (late Winter to Spring), and when the prevalence of potential shedders in the herd was low. The risk also varied between herds. The herds with the highest risk of carrier development were herds with clinical disease outbreaks during the study period. These findings are useful for future control strategies against Salmonella Dublin, because they show the importance of optimized calving management and management of heifers, and because they show that even when the herd prevalence is low, carriers are still being produced. The results raise new questions about the development of the carrier state in cattle after infection with low doses of Salmonella Dublin.

Animals↗

PubMed1996

Long-term outcome, survival analysis, and risk stratification of dynamic cardiomyoplasty.

METHODS: To analyze the long-term outcome of dynamic cardiomyoplasty, we retrospectively studied 127 consecutive patients who underwent this procedure in Paris, France (n = 76), São Paulo, Brazil (n = 37), and Portland, Oregon (n = 14). Preoperative data were collected for patients operated on between January 1985 and June 1994 and examined with respect to effect on long-term survival. Patients had a mean age of 50 +/- 13 years and were predominantly male (82%). In 46% the cause of disease was ischemic. Concomitant operations were performed in 22 patients. RESULTS: Operative mortality was 12% (15/127). Kaplan-Meier survival +/- standard error at 1 through 5 years was 73% +/- 4%, 57% +/- 5%, 49% +/- 6%, 44% +/- 6%, and 40% +/- 7%, respectively. There was a distinct improvement at 6 months in New York Heart Association functional class (3.2 +/- 0.05 vs 1.7 +/- 0.07, p < 0.0001) and a small but significant increase in left ventricular ejection fraction (20% +/- 0.8% vs 23% +/- 1.5%, p = 0.04). Ninety-day mortality was associated with low right ventricular ejection fraction, a blunted hemodynamic response to exercise testing, and requirement for an intraaortic balloon pump at the time of the operation. Using a stepwise Cox regression method of multivariable survival analysis (n = 101), we determined that atrial fibrillation, New York Heart Association class IV, high pulmonary capillary wedge pressure, and balloon pump use were independent variables simultaneously associated with poor overall survival. When metabolic testing variables were added to this model, peak oxygen consumption eliminated both pulmonary capillary wedge pressure and functional class from the model, albeit with fewer (n = 74) patients. CONCLUSION: Dynamic cardiomyoplasty is an evolving therapy for symptomatic congestive heart failure, the results of which may be enhanced by intelligent, risk-sensitive patient selection.

Cardiomyoplasty↗

PubMed2006

(-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans.

Epidemiological and medical anthropological investigations suggest that flavanol-rich foods exert cardiovascular health benefits. Endothelial dysfunction, a prognostically relevant key event in atherosclerosis, is characterized by a decreased bioactivity of nitric oxide (NO) and impaired flow-mediated vasodilation (FMD). We show in healthy male adults that the ingestion of flavanol-rich cocoa was associated with acute elevations in levels of circulating NO species, an enhanced FMD response of conduit arteries, and an augmented microcirculation. In addition, the concentrations and the chemical profiles of circulating flavanol metabolites were determined, and multivariate regression analyses identified (-)-epicatechin and its metabolite, epicatechin-7-O-glucuronide, as independent predictors of the vascular effects after flavanol-rich cocoa ingestion. A mixture of flavanols/metabolites, resembling the profile and concentration of circulating flavanol compounds in plasma after cocoa ingestion, induced a relaxation in preconstricted rabbit aortic rings ex vivo, thus mimicking acetylcholine-induced relaxations. Ex vivo flavanol-induced relaxation, as well as the in vivo increases in FMD, were abolished by inhibition of NO synthase. Oral administration of chemically pure (-)-epicatechin to humans closely emulated acute vascular effects of flavanol-rich cocoa. Finally, the concept that a chronic intake of high-flavanol diets is associated with prolonged, augmented NO synthesis is supported by data that indicate a correlation between the chronic consumption of a cocoa flavanol-rich diet and the augmented urinary excretion of NO metabolites. Collectively, our data demonstrate that the human ingestion of the flavanol (-)-epicatechin is, at least in part, causally linked to the reported vascular effects observed after the consumption of flavanol-rich cocoa.

Administration, Oral↗

PubMed2003

Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols.

PURPOSE: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. PATIENTS AND METHODS: Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. RESULTS: With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. CONCLUSION: The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma.

Adolescent↗

PubMed1999

Factors associated with the sexual experiences of underprivileged Mexican adolescents.

This study investigated factors associated with the sexual experiences of 523 underprivileged Mexican adolescents. Approximately 41% of the males and 24% of the females were sexually active, with more than half not using contraceptives. Multivariate logistic regression analysis revealed that sexual activity was strongly associated with age, knowledge about sexually transmitted diseases, and attitudes toward sexuality. Positive affective responsiveness in the family was associated with sexual activity and number of sexual partners. Family problem solving and roles were also associated with sexual activity. The use of contraceptives was negatively related to affective involvement between parents, and being a victim of sexual abuse was negatively associated with number of persons in the family. These findings support the notion that affective environment within the family is a factor in adolescent sexuality.

Adolescent↗