Musculoskeletal Diseases in Marfan Syndrome – A Nationwide Registry Study.

Abstract BackgroundMarfan syndrome is associated with abnormalities in the musculoskeletal system including scoliosis, pectus deformities, protrusio acetabuli, and foot deformities. Over a life span, many patients with Marfan syndrome will need treatment; however, the musculoskeletal morbidity over a life span is not well described. The aim of the present study was to assess the overall burden of musculoskeletal disease in patients with Marfan syndrome.Materials and MethodsA registry-based, nationwide epidemiological study of patients with a Ghent II verified Marfan syndrome diagnosis from 1977-2014. Each patient was matched on age, and sex with up to 100 controls from the background population.ResultsWe identified 407 patients with Marfan syndrome and 40,700 controls and compared their musculoskeletal diagnoses and surgical treatments using Cox proportional hazards regression (HR). The risk of a registration of a musculoskeletal diagnosis in patients with Marfan syndrome was significantly increased compared to controls (HR: 1.94 (1.69-2.24). One out of six with Marfan syndrome was registered with scoliosis (HR: 36.7 (27.5-48.9). Scoliosis was more common in women with Marfan syndrome compared to men (HR: 4.30 (1.73-1.08)). One out of 11 were registered with a pectus deformity HR: 40.8 (28.1-59.3), and one out of three with a deformity of the foot (HR: 1.9 (1.6-2.3)). The proportion of patients with Marfan syndrome (94/407) that underwent musculoskeletal surgery was also significantly higher (HR: 1.76 (1.43-2.16)). The major areas of surgery were the spine, pectus correction, and surgery of the foot/ancle. Ten patients with Marfan syndrome had elective orthopedic surgery without being recognized and diagnosed with Marfan syndrome until later in life. None of these had scoliosis, pectus deformity or a foot deformity.Among patients with an aortic dissection, the age at dissection was 34.3 years in those with at least one major musculoskeletal abnormality. In patients without a major abnormality the age at dissection was 45.1 years (p<0.01).ConclusionsThe extend of musculoskeletal disease is quite significant in Marfan syndrome and many will need corrective surgery during their life span. Surgeons should be aware of undiagnosed patients with Marfan syndrome when treating patients with a Marfan syndrome like-phenotype.

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Serious infection risk in rheumatoid arthritis compared with non-inflammatory rheumatic and musculoskeletal diseases: a US national cohort study

RMD Open ◽

10.1136/rmdopen-2019-000935 ◽

2019 ◽

Vol 5 (1) ◽

pp. e000935 ◽

Cited By ~ 20

Author(s):

Bella Mehta ◽

Sofia Pedro ◽

Gulsen Ozen ◽

Andre Kalil ◽

Frederick Wolfe ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Bacterial Infections ◽

Proportional Hazards ◽

Musculoskeletal Diseases ◽

Bloodstream Infections ◽

Infection Risk ◽

Cox Proportional Hazards ◽

Joint Infections ◽

Serious Infection

ObjectivesTo identify serious infection (SI) risk by aetiology and site in patients with rheumatoid arthritis (RA) compared with those with non-inflammatory rheumatic and musculoskeletal diseases (NIRMD).MethodsPatients participating in FORWARD from 2001 to 2016 were assessed for SIs; defined by infections requiring hospitalisation, intravenous antibiotics or followed by death. SIs were categorised by aetiology and site. SI risk was assessed through Cox proportional hazards models. Best models were selected using machine learning Least Absolute Shrinkage and Selection Operator (LASSO) methodology.ResultsAmong 20 361 patients with RA and 6176 patients with NIRMD, 1600 and 276 first SIs were identified, respectively. Incidence of SIs was higher in RA compared with NIRMD (IRR = 1.5; 95% CI 1.2 to 1.5). The risk persisted after adjusting using the LASSO model (HR 1.7; 95% CI 1.5 to 1.8), but attenuated when additionally adjusted for glucocorticoid use (HR 1.3; 95% CI 1.2 to 1.5). SI risk was significantly higher in RA versus NIRMD for bacterial infections as well as for respiratory, skin, bone, joint, bloodstream infections and sepsis irrespective of glucocorticoid use. Compared with NIRMD, SI risk was significantly increased in patients with RA who were in moderate and high disease activity but was similar to those in low disease activity/remission (p trend < 0.001).ConclusionsThe risk of all SIs, particularly bacterial, respiratory, bloodstream, sepsis, skin, bone and joint infections are significantly increased in patients with RA compared with patients with NIRMD. This infection risk appears to be greatest in those with higher RA disease activity.

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Age at Exposure to Parental Suicide and the Subsequent Risk of Suicide in Young People

Crisis ◽

10.1027/0227-5910/a000468 ◽

2018 ◽

Vol 39 (1) ◽

pp. 27-36 ◽

Cited By ~ 5

Author(s):

Kuan-Ying Lee ◽

Chung-Yi Li ◽

Kun-Chia Chang ◽

Tsung-Hsueh Lu ◽

Ying-Yeh Chen

Keyword(s):

Young People ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Birth Registry ◽

Data Set ◽

Parental Suicide ◽

The Impact ◽

Age At Exposure

Abstract. Background: We investigated the age at exposure to parental suicide and the risk of subsequent suicide completion in young people. The impact of parental and offspring sex was also examined. Method: Using a cohort study design, we linked Taiwan's Birth Registry (1978–1997) with Taiwan's Death Registry (1985–2009) and identified 40,249 children who had experienced maternal suicide (n = 14,431), paternal suicide (n = 26,887), or the suicide of both parents (n = 281). Each exposed child was matched to 10 children of the same sex and birth year whose parents were still alive. This yielded a total of 398,081 children for our non-exposed cohort. A Cox proportional hazards model was used to compare the suicide risk of the exposed and non-exposed groups. Results: Compared with the non-exposed group, offspring who were exposed to parental suicide were 3.91 times (95% confidence interval [CI] = 3.10–4.92 more likely to die by suicide after adjusting for baseline characteristics. The risk of suicide seemed to be lower in older male offspring (HR = 3.94, 95% CI = 2.57–6.06), but higher in older female offspring (HR = 5.30, 95% CI = 3.05–9.22). Stratified analyses based on parental sex revealed similar patterns as the combined analysis. Limitations: As only register-based data were used, we were not able to explore the impact of variables not contained in the data set, such as the role of mental illness. Conclusion: Our findings suggest a prominent elevation in the risk of suicide among offspring who lost their parents to suicide. The risk elevation differed according to the sex of the afflicted offspring as well as to their age at exposure.

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Proliferation-dominant high-grade astrocytoma: survival benefit associated with extensive resection of FLAIR abnormality region

Journal of Neurosurgery ◽

10.3171/2018.12.jns182775 ◽

2020 ◽

Vol 132 (4) ◽

pp. 998-1005 ◽

Cited By ~ 4

Author(s):

Haihui Jiang ◽

Yong Cui ◽

Xiang Liu ◽

Xiaohui Ren ◽

Mingxiao Li ◽

...

Keyword(s):

Survival Benefit ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Characteristic Curve ◽

Extent Of Resection ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

High Grade ◽

Extensive Resection ◽

High Grade Astrocytoma

OBJECTIVEThe aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).METHODSClinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.RESULTSBoth the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WIwith a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078–1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p=0.86).CONCLUSIONSVFLAIR/VCE-T1WIis an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.

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Adaptive metabolic and inflammatory responses identified using accelerated aging metrics are linked to adverse outcomes in severe SARS-CoV-2 infection

The Journals of Gerontology Series A ◽

10.1093/gerona/glab078 ◽

2021 ◽

Author(s):

Alejandro Márquez-Salinas ◽

Carlos A Fermín-Martínez ◽

Neftalí Eduardo Antonio-Villa ◽

Arsenio Vargas-Vázquez ◽

Enrique C. Guerra ◽

...

Keyword(s):

Critical Illness ◽

Proportional Hazards ◽

Inflammatory Responses ◽

Age Groups ◽

Accelerated Aging ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Adaptive Responses ◽

Predictive Capacity ◽

Risk Of Death

Abstract Background Chronological age (CA) is a predictor of adverse COVID-19 outcomes; however, CA alone does not capture individual responses to SARS-CoV-2 infection. Here, we evaluated the influence of aging metrics PhenoAge and PhenoAgeAccel to predict adverse COVID-19 outcomes. Furthermore, we sought to model adaptive metabolic and inflammatory responses to severe SARS-CoV-2 infection using individual PhenoAge components. Methods In this retrospective cohort study, we assessed cases admitted to a COVID-19 reference center in Mexico City. PhenoAge and PhenoAgeAccel were estimated using laboratory values at admission. Cox proportional hazards models were fitted to estimate risk for COVID-19 lethality and adverse outcomes (ICU admission, intubation, or death). To explore reproducible patterns which model adaptive responses to SARS-CoV-2 infection, we used k-means clustering using PhenoAge components. Results We included 1068 subjects of whom 222 presented critical illness and 218 died. PhenoAge was a better predictor of adverse outcomes and lethality compared to CA and SpO2 and its predictive capacity was sustained for all age groups. Patients with responses associated to PhenoAgeAccel>0 had higher risk of death and critical illness compared to those with lower values (log-rank p<0.001). Using unsupervised clustering we identified four adaptive responses to SARS-CoV-2 infection: 1) Inflammaging associated with CA, 2) metabolic dysfunction associated with cardio-metabolic comorbidities, 3) unfavorable hematological response, and 4) response associated with favorable outcomes. Conclusions Adaptive responses related to accelerated aging metrics are linked to adverse COVID-19 outcomes and have unique and distinguishable features. PhenoAge is a better predictor of adverse outcomes compared to CA.

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Adapting the Default Weighted Survival Analysis Modelling Approach to Model IFRS 9 LGD

Risks ◽

10.3390/risks9060103 ◽

2021 ◽

Vol 9 (6) ◽

pp. 103

Author(s):

Morne Joubert ◽

Tanja Verster ◽

Helgard Raubenheimer ◽

Willem D. Schutte

Keyword(s):

Survival Analysis ◽

Financial Reporting ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Survival Curve ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Reporting Standard ◽

International Financial Reporting Standard ◽

Ifrs 9

Survival analysis is one of the techniques that could be used to predict loss given default (LGD) for regulatory capital (Basel) purposes. When using survival analysis to model LGD, a proposed methodology is the default weighted survival analysis (DWSA) method. This paper is aimed at adapting the DWSA method (used to model Basel LGD) to estimate the LGD for International Financial Reporting Standard (IFRS) 9 impairment requirements. The DWSA methodology allows for over recoveries, default weighting and negative cashflows. For IFRS 9, this methodology should be adapted, as the estimated LGD is a function of in the expected credit losses (ECL). Our proposed IFRS 9 LGD methodology makes use of survival analysis to estimate the LGD. The Cox proportional hazards model allows for a baseline survival curve to be adjusted to produce survival curves for different segments of the portfolio. The forward-looking LGD values are adjusted for different macro-economic scenarios and the ECL is calculated for each scenario. These ECL values are probability weighted to produce a final ECL estimate. We illustrate our proposed IFRS 9 LGD methodology and ECL estimation on a dataset from a retail portfolio of a South African bank.

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Perioperative Geriatric Assessment as A Predictor of Long-Term Hepatectomy Outcomes in Elderly Patients with Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers13040842 ◽

2021 ◽

Vol 13 (4) ◽

pp. 842

Author(s):

Masaki Kaibori ◽

Hideyuki Matsushima ◽

Morihiko Ishizaki ◽

Hisashi Kosaka ◽

Kosuke Matsui ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Geriatric Assessment ◽

Proportional Hazards ◽

Prognostic Indicator ◽

Cox Proportional Hazards ◽

Rate Of Change ◽

Score Change ◽

Comorbidity Burden ◽

Reduction Group

This retrospective study recorded pertinent baseline geriatric assessment variables to identify risk factors for recurrence-free survival (RFS) and overall survival (OS) after hepatectomy in 100 consecutive patients aged ≥70 years with hepatocellular carcinoma. Patients had geriatric assessments of cognition, nutritional and functional statuses, and comorbidity burden, both preoperatively and at six months postoperatively. The rate of change in each score between preoperative and postoperative assessments was calculated by subtracting the preoperative score from the score at six months postoperatively, then dividing by the score at six months postoperatively. Patients with score change ≥0 comprised the maintenance group, while patients with score change <0 comprised the reduction group. The change in Geriatric 8 (G8) score at six months postoperatively was the most significant predictive factor for RFS and OS among the tested geriatric assessments. Five-year RFS rates were 43.4% vs. 6.7% (maintenance vs. reduction group; HR, 0.19; 95%CI, 0.11–0.31; p < 0.001). Five-year OS rates were 73.8% vs. 17.8% (HR, 0.12; 95%CI, 0.06–0.25; p < 0.001). Multivariate Cox proportional hazards analysis showed that perioperative maintenance of G8 score was an independent prognostic indicator for both RFS and OS. Perioperative changes in G8 scores can help forecast postoperative long-term outcomes in these patients.

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PETCO2 gradient: a novel prognostic parameter in cardiopulmonary exercise testing

European Heart Journal ◽

10.1093/ehjci/ehaa946.1077 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

I.D Poveda Pinedo ◽

I Marco Clement ◽

O Gonzalez ◽

I Ponz ◽

A.M Iniesta ◽

...

Keyword(s):

Exercise Testing ◽

Proportional Hazards ◽

Cardiopulmonary Exercise Testing ◽

Cox Proportional Hazards ◽

Prognostic Parameter ◽

Cardiopulmonary Exercise ◽

Proportional Hazards Regression ◽

Kaplan Meier ◽

Baseline Characteristics ◽

The Difference

Abstract Background Previous parameters such as peak VO2, VE/VCO2 slope and OUES have been described to be prognostic in heart failure (HF). The aim of this study was to identify further prognostic factors of cardiopulmonary exercise testing (CPET) in HF patients. Methods A retrospective analysis of HF patients who underwent CPET from January to November 2019 in a single centre was performed. PETCO2 gradient was defined by the difference between final PETCO2 and baseline PETCO2. HF events were defined as decompensated HF requiring hospital admission or IV diuretics, or decompensated HF resulting in death. Results A total of 64 HF patients were assessed by CPET, HF events occurred in 8 (12.5%) patients. Baseline characteristics are shown in table 1. Patients having HF events had a negative PETCO2 gradient while patients not having events showed a positive PETCO2 gradient (−1.5 [IQR −4.8, 2.3] vs 3 [IQR 1, 5] mmHg; p=0.004). A multivariate Cox proportional-hazards regression analysis revealed that PETCO2 gradient was an independent predictor of HF events (HR 0.74, 95% CI [0.61–0.89]; p=0.002). Kaplan-Meier curves showed a significantly higher incidence of HF events in patients having negative gradients, p=0.002 (figure 1). Conclusion PETCO2 gradient was demonstrated to be a prognostic parameter of CPET in HF patients in our study. Patients having negative gradients had worse outcomes by having more HF events. Time to first event, decompensated heart Funding Acknowledgement Type of funding source: None

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Factors that contribute to urban–rural gradients in risk of schizophrenia: Comparing Danish and Western Australian registers

Australian & New Zealand Journal of Psychiatry ◽

10.1177/00048674211009615 ◽

2021 ◽

pp. 000486742110096

Author(s):

Oleguer Plana-Ripoll ◽

Patsy Di Prinzio ◽

John J McGrath ◽

Preben B Mortensen ◽

Vera A Morgan

Keyword(s):

Confidence Interval ◽

Western Australia ◽

Urban Areas ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Indigenous Status ◽

Increased Risk ◽

The Relationship ◽

Western Australian

Introduction: An association between schizophrenia and urbanicity has long been observed, with studies in many countries, including several from Denmark, reporting that individuals born/raised in densely populated urban settings have an increased risk of developing schizophrenia compared to those born/raised in rural settings. However, these findings have not been replicated in all studies. In particular, a Western Australian study showed a gradient in the opposite direction which disappeared after adjustment for covariates. Given the different findings for Denmark and Western Australia, our aim was to investigate the relationship between schizophrenia and urbanicity in these two regions to determine which factors may be influencing the relationship. Methods: We used population-based cohorts of children born alive between 1980 and 2001 in Western Australia ( N = 428,784) and Denmark ( N = 1,357,874). Children were categorised according to the level of urbanicity of their mother’s residence at time of birth and followed-up through to 30 June 2015. Linkage to State-based registers provided information on schizophrenia diagnosis and a range of covariates. Rates of being diagnosed with schizophrenia for each category of urbanicity were estimated using Cox proportional hazards models adjusted for covariates. Results: During follow-up, 1618 (0.4%) children in Western Australia and 11,875 (0.9%) children in Denmark were diagnosed with schizophrenia. In Western Australia, those born in the most remote areas did not experience lower rates of schizophrenia than those born in the most urban areas (hazard ratio = 1.02 [95% confidence interval: 0.81, 1.29]), unlike their Danish counterparts (hazard ratio = 0.62 [95% confidence interval: 0.58, 0.66]). However, when the Western Australian cohort was restricted to children of non-Aboriginal Indigenous status, results were consistent with Danish findings (hazard ratio = 0.46 [95% confidence interval: 0.29, 0.72]). Discussion: Our study highlights the potential for disadvantaged subgroups to mask the contribution of urban-related risk factors to risk of schizophrenia and the importance of stratified analysis in such cases.

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Associations of Dietary Patterns with Incident Depression: The Maastricht Study

Nutrients ◽

10.3390/nu13031034 ◽

2021 ◽

Vol 13 (3) ◽

pp. 1034

Author(s):

Vincenza Gianfredi ◽

Annemarie Koster ◽

Anna Odone ◽

Andrea Amerio ◽

Carlo Signorelli ◽

...

Keyword(s):

Depressive Symptoms ◽

Dietary Patterns ◽

Proportional Hazards ◽

A Priori ◽

Preventive Measure ◽

Population Based ◽

Cox Proportional Hazards ◽

Healthy Diet ◽

Patient Health

Our aim was to assess the association between a priori defined dietary patterns and incident depressive symptoms. We used data from The Maastricht Study, a population-based cohort study (n = 2646, mean (SD) age 59.9 (8.0) years, 49.5% women; 15,188 person-years of follow-up). Level of adherence to the Dutch Healthy Diet (DHD), Mediterranean Diet, and Dietary Approaches To Stop Hypertension (DASH) were derived from a validated Food Frequency Questionnaire. Depressive symptoms were assessed at baseline and annually over seven-year-follow-up (using the 9-item Patient Health Questionnaire). We used Cox proportional hazards regression analyses to assess the association between dietary patterns and depressive symptoms. One standard deviation (SD) higher adherence in the DHD and DASH was associated with a lower hazard ratio (HR) of depressive symptoms with HRs (95%CI) of 0.78 (0.69–0.89) and 0.87 (0.77–0.98), respectively, after adjustment for sociodemographic and cardiovascular risk factors. After further adjustment for lifestyle factors, the HR per one SD higher DHD was 0.83 (0.73–0.96), whereas adherence to Mediterranean and DASH diets was not associated with incident depressive symptoms. Higher adherence to the DHD lowered risk of incident depressive symptoms. Adherence to healthy diet could be an effective non-pharmacological preventive measure to reduce the incidence of depression.

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Risk factors associated with major adverse cardiac and cerebrovascular events following percutaneous coronary intervention: a 10-year follow-up comparing random survival forest and Cox proportional-hazards model

BMC Cardiovascular Disorders ◽

10.1186/s12872-020-01834-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Maryam Farhadian ◽

Sahar Dehdar Karsidani ◽

Azadeh Mozayanimonfared ◽

Hossein Mahjub

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Coronary Intervention ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Cerebrovascular Events ◽

Long Term Follow Up ◽

Stent Length

Abstract Background Due to the limited number of studies with long term follow-up of patients undergoing Percutaneous Coronary Intervention (PCI), we investigated the occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) during 10 years of follow-up after coronary angioplasty using Random Survival Forest (RSF) and Cox proportional hazards models. Methods The current retrospective cohort study was performed on 220 patients (69 women and 151 men) undergoing coronary angioplasty from March 2009 to March 2012 in Farchshian Medical Center in Hamadan city, Iran. Survival time (month) as the response variable was considered from the date of angioplasty to the main endpoint or the end of the follow-up period (September 2019). To identify the factors influencing the occurrence of MACCE, the performance of Cox and RSF models were investigated in terms of C index, Integrated Brier Score (IBS) and prediction error criteria. Results Ninety-six patients (43.7%) experienced MACCE by the end of the follow-up period, and the median survival time was estimated to be 98 months. Survival decreased from 99% during the first year to 39% at 10 years' follow-up. By applying the Cox model, the predictors were identified as follows: age (HR = 1.03, 95% CI 1.01–1.05), diabetes (HR = 2.17, 95% CI 1.29–3.66), smoking (HR = 2.41, 95% CI 1.46–3.98), and stent length (HR = 1.74, 95% CI 1.11–2.75). The predictive performance was slightly better by the RSF model (IBS of 0.124 vs. 0.135, C index of 0.648 vs. 0.626 and out-of-bag error rate of 0.352 vs. 0.374 for RSF). In addition to age, diabetes, smoking, and stent length, RSF also included coronary artery disease (acute or chronic) and hyperlipidemia as the most important variables. Conclusion Machine-learning prediction models such as RSF showed better performance than the Cox proportional hazards model for the prediction of MACCE during long-term follow-up after PCI.

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