Obstetric complications predict treatment response in first-episode schizophrenia

1999 ◽  
Vol 29 (3) ◽  
pp. 621-627 ◽  
Author(s):  
J. M. J. ALVIR ◽  
M. G. WOERNER ◽  
H. GUNDUZ ◽  
G. DEGREEF ◽  
J. A. LIEBERMAN
Keyword(s):  
Treatment Response ◽  
Proportional Hazards ◽  
Poor Response ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Obstetric Complications ◽  
Response To Treatment ◽  
First Episode ◽  
Ventricle Volume ◽  
First Episode Of Schizophrenia

Background. Understanding the role of obstetric complications (OCs) in schizophrenia could potentially shed light on the heterogeneity in the aetiology and course of schizophrenia. Many investigators have reported an association between OCs and schizophrenia, but few have examined the association between OCs and treatment outcome. We investigated this question in a sample of patients studied during their first episode of schizophrenia, schizoaffective or schizophreniform disorder.Method. OC histories were obtained for 59 patients participating in the Hillside First Episode Study. Cox proportional hazards regression analysis was used to estimate the effect of OCs on treatment response during the first episode of schizophrenia.Results. Twelve of the 59 patients (20%) had positive histories of OCs. This group exhibited lower rates of treatment response than those with negative OC histories (hazard ratio controlling for sex = 0·28; 95% CI = 0·13, 0·62). The positive OC group also had significantly greater lateral ventricle volume, baseline disorganization and number of live births. The effect of OC history on treatment response held when these three variables were controlled for.Conclusion. A history of obstetric complications predicted poor response to treatment in the first episode of schizophrenia. This large effect was based on a small sample of 59 patients. Thus, replication is called for.

Fibroblast growth factor receptor alteration (FGFRa) status and progression outcomes of patients with advanced or metastatic urothelial cancer (mUC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4530-4530
Author(s):  
Sarah Fleming ◽  
Dina Gifkins ◽  
Waleed Shalaby ◽  
Jianjun Gao ◽  
Philip Rosenberg ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Prognostic Impact ◽  
Patient Records ◽  
Front Line ◽  
Convenience Sample ◽  
Adjusted Risk ◽  
Metastatic Urothelial Cancer

4530 Background: FGFRa appear in approximately 15% of cases of mUC. Data on whether FGFRa in mUC have a prognostic impact or predictive benefit for particular treatments have been limited by small sample sizes. The objective of this study was to evaluate the association between tumor FGFRa and clinical outcomes of patients with advanced UC or mUC regardless of therapy type and status. Methods: A convenience sample of oncologists and urologists across the United States provided patient level data on 400 patients with stage IIIb or IV UC via a standardized questionnaire over a 1-month period (August 17, 2020 – September 20, 2020). Study design enriched for FGFRa by requiring physicians to provide ≥1 FGFRa patient record. The questionnaire included physician characteristics, patient demographic information, FGFR status, therapy given, response, and clinical and radiographic measures of progression. Patient records were eligible for inclusion if they were identified and treated during July 1, 2017, to June 30, 2019. Cox proportional hazards models were used to estimate adjusted risk of disease progression by FGFR status. Results: A total of 104 physicians (58.7% medical oncologists, 31.7% hematologic oncologists, and 9.6% urologic oncologists) contributed 414 patient records Overall, 73.9% of the patients were male and the average age was 64.5 years (SD ±10.6). Median follow-up was 15 months. Of the 414 patients, 218 (52.7%) had FGFRa and 196 (47.3%) had FGFR wild-type ( FGFRwt) mUC . Of the 218 patients with FGFRa, 47.2% were treated with front-line chemo, 27.5% with a programmed death-ligand 1 inhibitor (PD-L1), 11.5% with chemo + PD-L1, and 13.8% with other treatments. Of the 196 FGFRwt patients, 63.2% were treated with front-line chemo, 21.9% with PD-L1, 12.2% with chemo + PD-L1, and 2.6% with other treatments. There was no difference in response or progression status for those receiving front-line chemo (HR, 1.15; 95% CI, 0.86-1.55). Among 97 patients (55 FGFRa and 42 FGFRwt) who received PD-L1 alone as front-line therapy, those who had FGFRa had an adjusted risk of progression 2 times higher than their FGFRwt counterparts (HR, 2.12; 95% CI, 1.13-4.00). Conclusions: Patients with FGFRa mUC progressed earlier than FGFRwt patients treated with front-line PDL-1 inhibitors; however, there was no difference in progression in patients treated with chemo based upon FGFR status. This real-world study using a survey design efficiently generated a relatively large FGFRa dataset, mitigating a core limitation of other studies assessing the patient population with FGFRa. Further work is warranted to validate these results and determine the optimal strategy for treating the patient with FGFRa mUC. Gene expression profiling of FGFRa mUC samples from clinical trials will help determine the potential impact of subtype or other features that may associate with benefit from therapy.

scholarly journals Context and contact: a comparison of patient and family engagement with early intervention services for psychosis in India and Canada

2020 ◽  
pp. 1-10
Author(s):  
Srividya N. Iyer ◽  
Ashok Malla ◽  
Aarati Taksal ◽  
Anika Maraj ◽  
Greeshma Mohan ◽  
...  
Keyword(s):  
Early Intervention ◽  
Family Involvement ◽  
Proportional Hazards ◽  
Family Engagement ◽  
Cox Proportional Hazards ◽  
First Episode ◽  
Early Intervention Services ◽  
Service Engagement ◽  
Intervention Services ◽  
Family Contact

Abstract Background It is unknown whether patient disengagement from early intervention services for psychosis is as prevalent in low- and middle-income countries (LMICs) like India, as it is in high-income countries (HICs). Addressing this gap, we studied two first-episode psychosis programs in Montreal, Canada and Chennai, India. We hypothesized lower service disengagement among patients and higher engagement among families in Chennai, and that family engagement would mediate cross-site differences in patient disengagement. Methods Sites were compared on their 2-year patient disengagement and family engagement rates conducting time-to-event analyses and independent samples t tests on monthly contact data. Along with site and family involvement, Cox proportional hazards regression included known predictors of patient disengagement (e.g. gender). Results The study included data about 333 patients (165 in Montreal, 168 in Chennai) and their family members (156 in Montreal, 168 in Chennai). More Montreal patients (19%) disengaged before 24 months than Chennai patients (1%), χ2(1, N = 333) = 28.87, p < 0.001. Chennai families had more contact with clinicians throughout treatment (Cohen's d = −1.28). Family contact significantly predicted patient disengagement in Montreal (HR = 0.87, 95% CI 0.81–0.93). Unlike in Chennai, family contact declined over time in Montreal, with clinicians perceiving such contact as not necessary (Cohen's d = 1.73). Conclusions This is the first investigation of early psychosis service engagement across a HIC and an LMIC. Patient and family engagement was strikingly higher in Chennai. Maintaining family contact may benefit patient engagement, irrespective of context. Findings also suggest that differential service utilization may underpin cross-cultural variations in psychosis outcomes.

scholarly journals What Is the Role for Metronidazole in the Treatment of Clostridium difficile Infection? Results From a National Cohort Study of Veterans With Initial Mild Disease

2018 ◽  
Vol 69 (8) ◽  
pp. 1288-1295 ◽  
Author(s):  
Haley J Appaneal ◽  
Aisling R Caffrey ◽  
Kerry L LaPlante
Keyword(s):  
Clostridium Difficile ◽  
Clinical Outcomes ◽  
Clostridium Difficile Infection ◽  
Proportional Hazards ◽  
Therapeutic Option ◽  
Cox Proportional Hazards ◽  
First Episode ◽  
Mild Disease ◽  
All Cause Mortality ◽  
National Cohort

Abstract Background Metronidazole may still be an appropriate therapeutic option for mild Clostridium difficile infection (CDI) in select patients, but data are limited to guide clinicians in identifying these patients. Methods Our 2-stage study included a national cohort of Veterans with a first episode of mild CDI (2010–2014). First, among those treated with metronidazole, we identified predictors of success, defined as absence of all-cause mortality or recurrence 30 days posttreatment, using multivariable unconditional logistic regression. Second, among a subgroup of patients with characteristics predictive of success identified in the first stage, we compared clinical outcomes among those treated with metronidazole compared with vancomycin, using Cox proportional hazards models for time to 30-day all-cause mortality, CDI recurrence, and failure. Results Among 3656 patients treated with metronidazole, we identified 3282 patients with success and 374 patients without success (failure). Younger age was the only independent predictor of success. Age ≤65 years was associated with an odds of success 1.63 times higher (95% confidence interval [CI], 1.29–2.06) than age >65 years. Among 115 propensity score–matched pairs ≤65 years of age, no significant differences were observed between metronidazole and vancomycin (reference) for all-cause mortality (hazard ratio [HR], 0.29 [95% CI, .06–1.38]), CDI recurrence (HR, 0.62 [95% CI, .26–1.49]), or failure (HR, 0.50 [95% CI, .23–1.07]). Conclusions Among patients ≤65 years of age with initial mild CDI, clinical outcomes were similar with metronidazole and vancomycin. These data suggest that metronidazole may be considered for the treatment of initial mild CDI among patients 65 years of age or younger.

scholarly journals Days gained response discriminates treatment response in patients with recurrent glioblastoma receiving bevacizumab-based therapies

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Kyle W Singleton ◽  
Alyx B Porter ◽  
Leland S Hu ◽  
Sandra K Johnston ◽  
Kamila M Bond ◽  
...  
Keyword(s):  
Treatment Response ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Recurrent Glioblastoma ◽  
Response To Therapy ◽  
Cytotoxic Therapy ◽  
Kaplan Meier ◽  
Recurrent Gbm

Abstract Background Accurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze days gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies. Methods DG response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N = 62). Kaplan–Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM. Results In patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan–Meier analysis showed significant differences in OS and PFS at DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy patients. Conclusion DG has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.

ColotypeR gene signature predicts response to cetuximab in colorectal cancer metastases.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 599-599
Author(s):  
Steven Allen Buechler ◽  
Yesim Gokmen-Polar ◽  
Sunil S. Badve
Keyword(s):  
Colorectal Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Cox Proportional Hazards Model ◽  
Response To Treatment ◽  
Molecular Characteristics ◽  
Wild Type

599 Background: The consensus molecular subtypes (CMS1-4) partition primary colorectal cancer (CRC) into subgroups with distinct molecular characteristics. We previously reported a 20-genes ColotypeR-CMS signature that accurately defines CMS subtypes for primary CRC tumor samples. The utility of CMS subtyping in defining response to treatment of CRC metastases remains to be established. Here, we report the ability of ColotypeR scores to predict differential response to cetuximab among CMS subtypes in CRC metastases. Methods: The role of ColotypeR-CMS signature scores was assessed in CRC metastasis samples (GSE5851, N = 68, Affymetrix microarray) in predicting response to cetuximab. Progression-free survival (PFS) was the primary endpoint. The predictive significance of ColotypeR-CMS scores relative to KRAS mutation status was also studied using multivariate Cox proportional hazards models. Results: ColotypeR-CMS scores were computed in GSE5851 using the algorithm developed in primary tumor samples. Higher values of ColotypeR-CMS CMS2 score were significantly predictive of longer PFS (p = 5 x 10-5for the score test in Cox proportional hazards model; hazard ratio 0.20 (95%CI 0.09-0.44) in CRC metastases samples (GSE5851, N = 68) treated with cetuximab. PFS was independent of CMS1,3, 4 scores. KRAS wild type tumors had significantly longer PFS (p = 0.01; hazard ratio 0.49 (95%CI 0.28-0.86). In multivariate survival analysis, ColotypeR-CMS CMS2 score added to the significance of KRAS status (p = 0.012) and ColotypeR-CMS CMS2 score was predictive of longer PFS in KRAS wild type tumors (p = 0.009; hazard ratio 0.20 (95%CI 0.06-0.69)). Conclusions: We showed that in CRC metastasis samples, the ColotypeR CMS2 score was highly predictive of sensitivity to cetuximab treatment, while no increase in PFS was observed for higher values of CMS1, 3, 4 scores.

First-episode schizophrenia

1998 ◽  
Vol 172 (S33) ◽  
pp. 77-83 ◽  
Author(s):  
Richard Jed Wyatt ◽  
L. Michelle Damiani ◽  
Ioline D. Henter
Keyword(s):  
Early Intervention ◽  
Response To Treatment ◽  
First Episode ◽  
Antipsychotic Medications ◽  
First Episode Schizophrenia ◽  
First Episode Of Schizophrenia

BackgroundThe concept that early intervention with antipsychotic medications improves the long-term course of schizophrenia is discussed.MethodThis report reviews the literature concerning early intervention with antipsychotic medications for people with firstepisodes, and how it affects long-term morbidity. It also studies the effects of discontinuing antipsychotic medications on relapse for people with first episodes.ResultsEarly intervention with antipsychotic medications appears to decrease the long-term morbidity of schizophrenia.ConclusionsEarly intervention with antipsychotic medications should be encouraged for people experiencing their first episode of schizophrenia. This report proposes that studying the various phases of subject response to treatment can be helpful in elucidating when antipsychotic medications should be tapered or withdrawn.

scholarly journals Exposure to Vitamin D Fortification Policy in Prenatal Life and the Risk of Childhood Asthma: Results From the D-Tect Study

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 924
Author(s):  
Thorsteinsdottir ◽  
Maslova ◽  
Jacobsen ◽  
Frederiksen ◽  
Keller ◽  
...  
Keyword(s):  
Vitamin D ◽  
Study Design ◽  
Childhood Asthma ◽  
Proportional Hazards ◽  
Epidemiological Studies ◽  
Vitamin D Insufficiency ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Increased Risk ◽  
Small Sample Sizes

Prenatal vitamin D insufficiency may be associated with an increased risk of developing childhood asthma. Results from epidemiological studies are conflicting and limited by short follow-up and small sample sizes. The objective of this study was to examine if children born to women exposed to the margarine fortification policy with a small dose of extra vitamin D during pregnancy had a reduced risk of developing asthma until age 9 years, compared to children born to unexposed women. The termination of a Danish mandatory vitamin D fortification policy constituted the basis for the study design. We compared the risk of inpatient asthma diagnoses in all Danish children born two years before (n = 106,347, exposed) and two years after (n = 115,900, unexposed) the termination of the policy. The children were followed in the register from 0–9 years of age. Data were analyzed using Cox proportional hazards regression. The Hazard Ratio for the first inpatient asthma admission among exposed versus unexposed children was 0.96 (95%CI: 0.90–1.04). When stratifying by sex and age, 0–3 years old boys exposed to vitamin D fortification showed a lower asthma risk compared to unexposed boys (HR 0.78, 95%CI: 0.67–0.92). Prenatal exposure to margarine fortification policy with extra vitamin D did not affect the overall risk of developing asthma among children aged 0–9 years but seemed to reduce the risk among 0–3 years old boys. Taking aside study design limitations, this could be explained by different sensitivity to vitamin D from different sex-related asthma phenotypes in children with early onset, and sex differences in lung development or immune responses.

Gender disparities in hepatocellular cancer survival

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15517-e15517
Author(s):  
A. E. Hendifar ◽  
D. Yang ◽  
S. Iqbal ◽  
H. Lenz ◽  
A. El-Khoueiry
Keyword(s):  
Overall Survival ◽  
Cancer Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Premenopausal Women ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Response To Treatment ◽  
Cancer Specific Survival ◽  
Asian Ethnicity

e15517 Background: Recent reports suggest that estrogen mediated inhibition of IL-6 protects against the development of HCC and may explain the decreased risk of liver cancer in women. We investigated the relation-hip between gender, age, and survival for patients with localized HCC. Methods: We identified 11,097 patients with localized, histologically defined HCC, from 1988- 2003, using the Surveillance, Epidemiology, and End Results (SEER) registry. Age at diagnosis, sex, ethnicity, and overall survival were evaluated using Cox proportional hazards model. The models were adjusted for treatment modality, tumor differentiation, tumor size, lymph node involvement, and number of lesions; they were stratified by year of diagnosis and SEER registry site. Results: 8,111 (73%) patients were men and 2,986 (27%) were women. In univariate and multivariate analyses, female gender, young age (< 55 yo), and Asian ethnicity were all associated with improved overall survival (p<0.001). In patients less than 55 yo, women had a superior OS and cancer specific survival (CSS) when compared to men (OS: 18 months vs. 9, CSS: 31 months vs. 14, p<0.001). Conversely, in patients older than 55, there were no gender differences (OS: 8 months vs. 8, CSS 13 months vs. 11, p = 0.08). Local therapies, including, ablation (HR = 0.47 [0.43–0.53]), hepatectomy (HR = 0.40 [0.36–0.44]), radiation (HR = 0.67 [0.57–0.78]) and transplantation (HR = 0.17 [0.15–0.20]) were also associated with improved survival. There were no interactions identified between gender and treatment use. Conclusions: To our knowledge, this is the first report to highlight the superior outcome of premenopausal women with HCC compared to men. We postulate a potential role for estrogen in influencing the biology of HCC and the response to treatment. These observations are consistent with ones made in other gastrointestinal cancers and with reported preclinical data suggesting a protective role for estrogen. Further studies that confirm these observations and elucidate the biology of estrogen's influence on HCC are needed. [Table: see text] No significant financial relationships to disclose.

scholarly journals Risk factors of recurrent erysipelas in adult Chinese patients: a prospective cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ang Li ◽  
Ni Wang ◽  
Lingzhi Ge ◽  
Hongyan Xin ◽  
Wenfei Li
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Venous Insufficiency ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Chinese Patients ◽  
First Episode ◽  
Common Skin

Abstract Background Erysipelas is a common skin infection that is prone to recur. Recurrent erysipelas has a severe effect on the quality of life of patients. The present study aimed to investigate the risk factors of recurrent erysipelas in adult Chinese patients. Methods A total of 428 Chinese patients with erysipelas who met the inclusion criteria were studied. The patients were divided into the nonrecurrent erysipelas group and the recurrent erysipelas group. Clinical data were collected on the first episode and relapse of erysipelas. The patients were followed up every 3 months. Statistical analysis was performed to analyze and determine the risk factors of erysipelas relapse. Results Univariate analysis was performed to analyze the data, including surgery, types of antibiotics administered in the first episode, obesity, diabetes mellitus, venous insufficiency, lymphedema, and malignancy. The differences between the groups were statistically significant (p < 0.05). The Cox proportional hazards regression model analysis showed that the final risk factors included surgery, obesity, diabetes mellitus, venous insufficiency, and lymphedema. Conclusions Surgery, obesity, diabetes mellitus, venous insufficiency, and lymphedema are considered as risk factors for recurrent erysipelas.

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