Obstetric Complications and Polygenic Risk Score: Which Role in Predicting a Severe Short-Term Outcome in Psychosis?
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ABSTRACT:
SUBMITTER: Tosato S
PROVIDER: S-EPMC8702213 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionTo establish a prognostic model for predicting 14-day mortality in ICU patients with severe sepsis overall and according to place of infection acquisition and to sepsis episode number.MethodsIn this prospective multicentre observational study on a multicentre database (OUTCOMEREA) including data from 12 ICUs, 2268 patients with 2737 episodes of severe sepsis were randomly divided into a training cohort (n = 1458) and a validation cohort (n = 810). Up to four consecutive severe sepsis episodes per patient occurring within the first 28 ICU days were included. We developed a prognostic model for predicting death within 14 days after each episode, based on patient data available at sepsis onset.ResultsIndependent predictors of death were logistic organ dysfunction (odds ratio (OR), 1.22 per point, P < 10-4), septic shock (OR, 1.40; P = 0.01), rank of severe sepsis episode (1 reference, 2: OR, 1.26; P = 0.10 >or= 3: OR, 2.64; P < 10-3), multiple sources of infection (OR; 1.45, P = 0.03), simplified acute physiology score II (OR, 1.02 per point; P < 10-4), McCabe score ([greater than or equal to]2) (OR, 1.96; P < 10-4), and number of chronic co-morbidities (1: OR, 1.75; P < 10-3, >or= 2: OR, 2.24, P < 10-3). Validity of the model was good in whole cohorts (AUC-ROC, 0.76; 95%CI, 0.74 to 0.79; and HL Chi-square: 15.3 (P = 0.06) for all episodes pooled).ConclusionsIn ICU patients, a prognostic model based on a few easily obtained variables is effective in predicting death within 14 days after the first to fourth episode of severe sepsis complicating community-, hospital-, or ICU-acquired infection.
| S-EPMC2717433 | biostudies-literature
Project description:BACKGROUND:The extent of weight loss among patients undergoing bariatric surgery is highly variable. Herein, we tested the contribution of genetic background to such interindividual variability after biliopancreatic diversion with duodenal switch. METHODS:Percentage of excess body weight loss (%EBWL) was monitored in 865 patients over a period of 48 months after bariatric surgery, and two polygenic risk scores were constructed with 186 and 11 (PRS186 and PRS11) single nucleotide polymorphisms previously associated with body mass index (BMI). RESULTS:The accuracy of the %EBWL logistic prediction model - including initial BMI, age, sex, and surgery modality, and assessed as the area under the receiver operating characteristics (ROC) curve adjusted for optimism (AUCadj = 0.867) - significantly increased after the inclusion of PRS186 (?AUCadj = 0.021; 95% CI of the difference [95% CIdiff] = 0.005-0.038) but not PRS11 (?AUCadj= 0.008; 95% CIdiff= -0.003-0.019). The overall fit of the longitudinal linear mixed model for %EBWL showed a significant increase after addition of PRS186 (-2 log-likelihood = 12.3; P = 0.002) and PRS11 (-2 log-likelihood = 9.9; P = 0.007). A significant interaction with postsurgery time was found for PRS186 (? = -0.003; P = 0.008) and PRS11 (? = -0.008; P = 0.03). The inclusion of PRS186 and PRS11 in the model improved the cost-effectiveness of bariatric surgery by reducing the percentage of false negatives from 20.4% to 10.9% and 10.2%, respectively. CONCLUSION:These results revealed that genetic background has a significant impact on weight loss after biliopancreatic diversion with duodenal switch. Likewise, the improvement in weight loss prediction after addition of polygenic risk scores is cost-effective, suggesting that genetic testing could potentially be used in the presurgical assessment of patients with severe obesity. FUNDING:Heart and Stroke Foundation of Canada (G-17-0016627) and Canada Research Chair in Genomics Applied to Nutrition and Metabolic Health (no. 950-231-580).
| S-EPMC6171810 | biostudies-other
Project description:This study investigates the long term economic impact of severe obstetric complications for women and their children in Burkina Faso, focusing on measures of food security, expenditures and related quality of life measures. It uses a hospital based cohort, first visited in 2004/2005 and followed up four years later. This cohort of 1014 women consisted of two main groups of comparison: 677 women who had an uncomplicated delivery and 337 women who experienced a severe obstetric complication which would have almost certainly caused death had they not received hospital care (labelled a "near miss" event). To analyze the impact of such near miss events as well as the possible interaction with the pregnancy outcome, we compared household and individual level indicators between women without a near miss event and women with a near miss event who either had a live birth, a perinatal death or an early pregnancy loss. We used propensity score matching to remove initial selection bias. Although we found limited effects for the whole group of near miss women, the results indicated negative impacts: a) for near miss women with a live birth, on child development and education, on relatively expensive food consumption and on women's quality of life; b) for near miss women with perinatal death, on relatively expensive foods consumption and children's education and c) for near miss women who had an early pregnancy loss, on overall food security. Our results showed that severe obstetric complications have long lasting consequences for different groups of women and their children and highlighted the need for carefully targeted interventions.
| S-EPMC3818276 | biostudies-literature
Project description:BackgroundFunctional recovery of patients with clinical and subclinical psychosis is associated with clinical, neuropsychological and developmental factors. Less is known about how these factors predict functional outcomes in the same models. We investigated functional outcomes and their predictors in patients with first-episode psychosis (FEP) or a confirmed or nonconfirmed clinical high risk of psychosis (CHR-P vs. CHR-N).MethodsAltogether, 130 patients with FEP, 60 patients with CHR-P and 47 patients with CHR-N were recruited and extensively examined at baseline (T0) and 9 (T1) and 18 (T2) months later. Global Assessment of Functioning (GAF) at T0, T1 and T2 and psychotic, depression, and anxiety symptoms at T1 and T2 were assessed. Functional outcomes were predicted using multivariate repeated ANOVA.ResultsDuring follow-up, the GAF score improved significantly in patients with FEP and CHR-P but not in patients with CHR-N. A single marital status, low basic education level, poor work situation, disorganization symptoms, perceptual deficits, and poor premorbid adjustment in patients with FEP, disorganization symptoms and poor premorbid adjustment in patients with CHR-P, and a low basic education level, poor work situation and general symptoms in patients with CHR-N predicted poor functional outcomes. Psychotic symptoms at T1 in patients with FEP and psychotic and depression symptoms at T1 and anxiety symptoms at T2 in patients with CHR-P were associated with poor functioning.ConclusionsIn patients with FEP and CHR-P, poor premorbid adjustment and disorganization symptomatology are common predictors of the functional outcome, while a low education level and poor work situation predict worse functional outcomes in patients with FEP and CHR-N. Interventions aimed at improving the ability to work and study are most important in improving the functioning of patients with clinical or subclinical psychosis.
| S-EPMC8641211 | biostudies-literature
Project description:OBJECTIVE:To document the outcome and determine prognostic factors for patients with severe acute respiratory syndrome who require admission to an intensive care unit. DESIGN:Observational cohort study involving retrospective analysis of demographic, clinical, laboratory and radiological data. SETTING:Adult intensive care unit in a tertiary referral university hospital involved in a major outbreak of severe acute respiratory syndrome (SARS). PATIENTS:The first 54 patients admitted with SARS to an intensive care unit (ICU). All were treated with corticosteroids, ribavirin, broad spectrum antimicrobials and supportive therapy. INTERVENTIONS:None. MEASUREMENTS AND RESULTS:All patients were admitted for respiratory failure. The median APACHE II score was 11 (interquartile range 8-13). At 28 days 34 patients (63%; 95% CI 49.6-74.6) were alive and not mechanically ventilated. Six patients were alive but ventilated (11.3%; 95% confidence interval 5.3-22.6) and 14 had died (25.9%; CI 16.1-38.9). Seven of 27 ventilated patients developed evidence of barotrauma (25.9%; 95% CI 13.2-44.7). Median maximal multiple-organ dysfunction score was 5 (interquartile range 3.3-9). Median maximal respiratory dysfunction score was 3 (interquartile range 3-4). Increased age, severity of illness, lymphocyte count, decreased steroid dose, positive fluid balance, chronic disease or immunosuppression and nosocomial sepsis were associated with poor outcome on univariate analysis. Poor outcome was defined as death or need for mechanical ventilation at 28 days after ICU admission. CONCLUSIONS:Mortality amongst critically ill patients with SARS is high. It causes predominantly severe respiratory failure, with little other organ failure, and a high incidence of barotrauma amongst those requiring mechanical ventilation.
| S-EPMC7080204 | biostudies-literature
Project description:Pregnancy poses a threat to women with aortopathy. Conclusive data on the obstetric and aortic outcome in this risk collective, especially when it comes to aortic complications in the long term, are still missing. This study offers a comparative analysis of pregnancy-associated outcome in 113 consecutive women with Marfan syndrome or bicuspid aortic valve disease, including 46 ever-pregnant and 37 never-pregnant women with Marfan syndrome, and 23 ever-pregnant and 7 never-pregnant females with bicuspid aortic valve disease. The overall obstetric outcome was comparable between ever-pregnant women with Marfan syndrome and with bicuspid aortic valve disease (p = 0.112). Pregnancy-associated aortic dissection occurred in two women with Marfan syndrome (3%) during a total of 62 completed pregnancies, whereas no single case of aortic event occurred in women with bicuspid aortic valve disease during a total of 36 completed pregnancies (p = 0.530). In the long-term follow-up, aortic dissection occurred in 21% of ever-pregnant women with Marfan syndrome, but in none of the women with bicuspid aortic valve disease (p = 0.022). Proximal aortic surgery was performed with similar frequency in ever-pregnant women with Marfan syndrome and with bicuspid aortic valve disease in the long term (p = 0.252). However, ever-pregnant women with Marfan syndrome were younger when surgery was performed (44 ± 9 vs. 59 ± 7 years; p = 0.041). In Marfan syndrome, long-term growth of the aorta was comparable between ever-pregnant and never-pregnant women. Pregnancy thus exhibited an increased immediate aortic risk only in women with Marfan syndrome, but not in women with bicuspid aortic valve disease. Previous pregnancy did not relate to an increased long-term risk of adverse aortic events in women with Marfan syndrome or with bicuspid aortic valve disease.
| S-EPMC7230569 | biostudies-literature
Project description:Bipolar disorder (BD) is highly heterogeneous in symptomatology. Narrowing the clinical phenotype may increase the power to identify risk genes that contribute to particular BD subtypes. This study was designed to test the hypothesis that genetic overlap between schizophrenia (SZ) and BD is higher for BD with a history of manic psychosis. Analyses were conducted using a Mayo Clinic Bipolar Biobank cohort of 957 bipolar cases (including 333 with history of psychosis during mania, 64 with history of psychosis only during depression, 547 with no history of psychosis, and 13 with unknown history of psychosis) and 778 controls. Polygenic risk score (PRS) analysis was performed by calculating a SZ-PRS for the BD cases and controls, and comparing the calculated SZ risk between different psychosis subgroups and bipolar types. The SZ-PRS was significantly higher for BD-I cases with manic psychosis than BD-I cases with depressive psychosis (Nagelkerke's R2?=?0.021; p?=?0.045), BD-I cases without psychosis (R2?=?0.015; p?=?0.007), BD-II cases without psychosis (R2?=?0.014; p?=?0.017), and controls (R2?=?0.065; p?=?2?×?10-13). No other significant differences were found. Our results show that BD-I with manic psychosis is genetically more similar to SZ than any other tested BD subgroup. Further investigations on genetics of distinct clinical phenotypes composing major psychoses may help refine the current diagnostic classification system.
| S-EPMC6131184 | biostudies-literature
Project description:ObjectivePharmacogenomic studies of antipsychotics have typically examined effects of individual polymorphisms. By contrast, polygenic risk scores (PRSs) derived from genome-wide association studies (GWAS) can quantify the influence of thousands of common alleles of small effect in a single measure. The authors examined whether PRSs for schizophrenia were predictive of antipsychotic efficacy in four independent cohorts of patients with first-episode psychosis (total N=510).MethodAll study subjects received initial treatment with antipsychotic medication for first-episode psychosis, and all were genotyped on standard single-nucleotide polymorphism (SNP) arrays imputed to the 1000 Genomes Project reference panel. PRS was computed based on the results of the large-scale schizophrenia GWAS reported by the Psychiatric Genomics Consortium. Symptoms were measured by using total symptom rating scales at baseline and at week 12 or at the last follow-up visit before dropout.ResultsIn the discovery cohort, higher PRS significantly predicted higher symptom scores at the 12-week follow-up (controlling for baseline symptoms, sex, age, and ethnicity). The PRS threshold set at a p value <0.01 gave the strongest result in the discovery cohort and was used to replicate the findings in the other three cohorts. Higher PRS significantly predicted greater posttreatment symptoms in the combined replication analysis and was individually significant in two of the three replication cohorts. Across the four cohorts, PRS was significantly predictive of adjusted 12-week symptom scores (pooled partial r=0.18; 3.24% of variance explained). Patients with low PRS were more likely to be treatment responders than patients with high PRS (odds ratio=1.91 in the two Caucasian samples).ConclusionsPatients with higher PRS for schizophrenia tended to have less improvement with antipsychotic drug treatment. PRS burden may have potential utility as a prognostic biomarker.
| S-EPMC6461047 | biostudies-literature
Project description:ObjectiveTo develop and validate an expanded obstetric comorbidity score for predicting severe maternal morbidity that can be applied consistently across contemporary U.S. patient discharge data sets.MethodsDischarge data from birth hospitalizations in California during 2016-2017 were used to develop the score. The outcomes were severe maternal morbidity, defined using the Centers for Disease Control and Prevention index, and nontransfusion severe maternal morbidity (excluding cases where transfusion was the only indicator of severe maternal morbidity). We selected 27 potential patient-level risk factors for severe maternal morbidity, identified using International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes. We used a targeted causal inference approach integrated with machine learning to rank the risk factors based on adjusted risk ratios (aRRs). We used these results to assign scores to each comorbidity, which sum to a single numeric score. We validated the score in California and national data sets and compared the performance to that of a previously developed obstetric comorbidity index.ResultsAmong 919,546 births, the rates of severe maternal morbidity and nontransfusion severe maternal morbidity were 168 and 74 per 10,000 births, respectively. The highest risk comorbidity was placenta accreta spectrum (aRR of 30.5 for severe maternal morbidity and 54.7 for nontransfusion severe maternal morbidity) and the lowest was gestational diabetes mellitus (aRR of 1.06 for severe maternal morbidity and 1.12 for nontransfusion severe maternal morbidity). Normalized scores based on the aRR were developed for each comorbidity, which ranged from 1 to 59 points for severe maternal morbidity and from 1 to 36 points for nontransfusion severe maternal morbidity. The overall performance of the expanded comorbidity scores was good (C-statistics were 0.78 for severe maternal morbidity and 0.84 for nontransfusion severe maternal morbidity in California data and 0.82 and 0.87, respectively, in national data) and improved on prior comorbidity indices developed for obstetric populations. Calibration plots showed good concordance between predicted and actual risks of the outcomes.ConclusionWe developed and validated an expanded obstetric comorbidity score to improve comparisons of severe maternal morbidity rates across patient populations with different comorbidity case mixes.
| S-EPMC7523732 | biostudies-literature
Project description:Women who survive severe obstetric complications (SOC) have health and well-being issues even up to 1 year postpartum and have challenges in their quality-of-life (QoL). However, little is known about their predicaments. This study aimed to describe the impact of severe obstetric complications on women's QoL and well-being after surviving severe obstetric complications. Using the WHO standards for near-miss, twelve (12) women who survived severe obstetric complications were recruited between January and March 2019. The study adopted a qualitative approach with an exploratory descriptive design to explore the experiences of women who survived SOC in Southern Ghana. The participants were purposively sampled and were interviewed face to face in their homes and healthcare facility after discharge from the Hospital. Recorded interviews were transcribed and analyzed. Two (2) major themes and nine (9) sub-themes emerged. The findings revealed that women who suffered SOC are unable to perform functional activities, have financial constraints, residual hypertension, signs and symptoms of anaemia, pain, and mostly have difficulty in sleeping due to fear of death when they fall asleep. Anxiety, sadness, and emotional trauma was a common phenomenon. The study findings offer insights and directions on measures to improve the care and QoL of women who have survived severe obstetric complications in Ghana.
| S-EPMC8928636 | biostudies-literature