Estimating Monotonic Hazard Ratio Functions of Time

2021 ◽  
Author(s):  
Anthony Y.C. Kuk
Keyword(s):  
Hazard Ratio

Gamma Knife surgery as sole treatment for multiple brain metastases: 2-center retrospective review of 1508 cases meeting the inclusion criteria of the JLGK0901 multi-institutional prospective study

2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 48-52 ◽  
Author(s):  
Toru Serizawa ◽  
Masaaki Yamamoto ◽  
Yasunori Sato ◽  
Yoshinori Higuchi ◽  
Osamu Nagano ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Gamma Knife ◽  
Class Ii ◽  
Hazard Ratio ◽  
Gamma Knife Surgery ◽  
Inclusion Criteria ◽  
Primary Tumors ◽  
Poor Prognostic Factor ◽  
Group A ◽  
Group B

Object The authors retrospectively reviewed the results of Gamma Knife surgery (GKS) used as the sole treatment for brain metastases in patients who met the eligibility criteria for the ongoing JLGK0901 multi-institutional prospective trial. They also discuss the anticipated results of the JLGK0901 study. Methods Data from 1508 consecutive cases were analyzed. All of the patients were treated at the Gamma Knife House of Chiba Cardiovascular Center or the Mito Gamma House of Katsuta Hospital between 1998 and 2007 and met the following JLGK0901 inclusion criteria: 1) newly diagnosed brain metastases, 2) 1–10 brain lesions, 3) less than 10 cm3 volume of the largest tumor, 4) no more than 15 cm3 total tumor volume, 5) no findings of CSF dissemination, and 6) no impairment of activities of daily living (Karnofsky Performance Scale score < 70) due to extracranial disease. At the initial treatment, all visible lesions were irradiated with GKS without upfront whole-brain radiation therapy. Thereafter, gadolinium-enhanced MR imaging was performed every 2–3 months, and new distant lesions were appropriately retreated with GKS. Patients were divided into groups according to numbers of tumors: Group A, single lesions (565 cases); Group B, 2–4 tumors (577 cases); and Group C, 5–10 tumors (366 cases). The differences in overall survival (OS) were compared between groups. Results The median age of the patients was 66 years (range 19–96 years). There were 963 men and 545 women. The primary tumors were in the lung in 1114 patients, gastrointestinal tract in 179, breast in 105, urinary tract in 66, and other sites in 44. The overall mean survival time was 0.78 years (0.99 years for Group A, 0.68 years for Group B, and 0.62 years for Group C). The differences between Groups A and B (p < 0.0001) and between Groups B and C (p = 0.0312) were statistically significant. Multivariate analysis revealed significant prognostic factors for OS to be sex (poor prognostic factor: male, p < 0.0001), recursive partitioning analysis class (Class I vs Class II and Class II vs III, both p < 0.0001), primary site (lung vs breast, p = 0.0047), and number of tumors (Group A vs Group B, p < 0.0001). However, no statistically difference was detected between Groups B and C (p = 0.1027, hazard ratio 1.124, 95% CI 0.999–1.265). Conclusions The results of this retrospective analysis revealed an upper CI of 1.265 for the hazard ratio, which was lower than the 1.3 initially set by the JLGK0901 study. The JLGK0901 study is anticipated to show noninferiority of GKS as sole treatment for patients with 5–10 brain metastases compared with those with 2–4 in terms of OS.

Does Perioperative Hemoglobin A1c Level Affect the Incidence, Pattern and Mortality of Lower Extremity Amputation?

2019 ◽  
Vol 17 (4) ◽  
pp. 354-364
Author(s):  
Hassan Al-Thani ◽  
Moamena El-Matbouly ◽  
Maryam Al-Sulaiti ◽  
Noora Al-Thani ◽  
Mohammad Asim ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Lower Extremity ◽  
Hazard Ratio ◽  
Lower Extremity Amputation ◽  
Group 4 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2 ◽  
Extremity Amputation ◽  
Group 1

Background: We hypothesized that perioperative HbA1c influenced the pattern and outcomes of Lower Extremity Amputation (LEA). Methods: A retrospective analysis was conducted for all patients who underwent LEA between 2000 and 2013. Patients were categorized into 5 groups according to their perioperative HbA1c values [Group 1 (<6.5%), Group 2 (6.5-7.4%), Group 3 (7.5-8.4%), Group 4 (8.5-9.4%) and Group 5 (≥9.5%)]. We identified 848 patients with LEA; perioperative HbA1c levels were available in 547 cases (Group 1: 18.8%, Group 2: 17.7%, Group 3: 15.0%, Group 4: 13.5% and Group 5: 34.9%). Major amputation was performed in 35%, 32%, 22%, 10.8% and 13.6%, respectively. Results: The overall mortality was 36.5%; of that one quarter occurred during the index hospitalization. Mortality was higher in Group 1 (57.4%) compared with Groups 2-5 (46.9%, 38.3%, 36.1% and 31.2%, respectively, p=0.001). Cox regression analysis showed that poor glycemic control (Group 4 and 5) had lower risk of mortality post-LEA [hazard ratio 0.57 (95% CI 0.35-0.93) and hazard ratio 0.46 (95% CI 0.31-0.69)]; this mortality risk persisted even after adjustment for age and sex but was statistically insignificant. The rate of LEA was greater among poor glycemic control patients; however, the mortality was higher among patients with tight control. Conclusion: The effects of HbA1c on the immediate and long-term LEA outcomes and its therapeutic implications need further investigation.

scholarly journals The risk factors of local recurrence and distant metastasis on pT1/T2N0 mid-low rectal cancer after total mesorectal excision

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
I-Li Lai ◽  
Jeng-Fu You ◽  
Yih-Jong Chern ◽  
Wen-Sy Tsai ◽  
Jy-Ming Chiang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Rectal Cancer ◽  
Local Recurrence ◽  
Distant Metastasis ◽  
Resection Margin ◽  
Radical Resection ◽  
Hazard Ratio ◽  
Low Rectal Cancer ◽  
Distal Resection Margin ◽  
Lymph Node Yield

Abstract Background Radical resection is associated with good prognosis among patients with cT1/T2Nx rectal cancer. However, still some of the patients experienced cancer recurrence following radical resection. This study tried to identify the postoperative risk factors of local recurrence and distant metastasis separately. Methods This retrospective, single-center study comprised of 279 consecutive patients from Linkou branch of Chang Gung Memorial Hospital in 2005–2016 with rectal adenocarcinoma, pT1/T2N0M0 at distance from anal verge ≤ 8cm, who received curative radical resection. Results The study included 279 patients with pT1/pT2N0 mid-low rectal cancer with median follow-up of 73.5 months. Nineteen (6.8%) patients had disease recurrence in total. Nine (3.2%) of them had local recurrence, and fourteen (5.0%) of them had distant metastasis. Distal resection margin < 0.9 (cm) (hazard ratio = 4.9, p = 0.050) was the risk factor of local recurrence. Preoperative carcinoembryonic antigen (CEA) ≥ 5 ng/mL (hazard ratio = 9.3, p = 0.0003), lymph node yield (LNY) < 14 (hazard ratio = 5.0, p = 0.006), and distal resection margin < 1.4cm (hazard ratio = 4.0, p = 0.035) were the risk factors of distant metastasis. Conclusion For patients with pT1/pT2N0 mid-low rectal cancer, current multidisciplinary treatment brings acceptable survival outcome. Insufficient distal resection margin attracted the awareness of risk factors for local recurrence and distant metastasis as a foundation for future research.

Effectiveness, Durability, and Safety of Dolutegravir and Lamivudine Versus Dolutegravir, Lamivudine, and Abacavir in a Real-Life Cohort of HIV-Infected Adults

2021 ◽  
pp. 106002802110341
Author(s):  
Inés Mendoza ◽  
Alicia Lázaro ◽  
Miguel Torralba
Keyword(s):  
Viral Load ◽  
Safety Profile ◽  
Real Life ◽  
Hazard Ratio ◽  
Treatment Discontinuation ◽  
Treatment Naïve ◽  
Tn 4 ◽  
Risk Of Treatment ◽  
Hiv 1 ◽  
All Treatment

Background: Dolutegravir (DTG) plus lamivudine (2-DR) is suggested as an initial and switch option in HIV-1 treatment. Objective: To analyze the effectiveness, durability, and safety of 2-DR compared with DTG plus abacavir/lamivudine (3-DR). Methods: This was an observational, ambispective study that included all treatment-naïve (TN) and treatment-experienced (TE) patients who started 2-DR or 3-DR between July 1, 2018, and November 30, 2020. The primary end point was noninferiority, at 24 and 48 weeks, of 2-DR versus 3-DR regarding the percentage of patients with viral load (VL)≥50 and 200 copies/mL in TN (4% margin) and VL<50 and 200 copies/mL in TE (margin 12%). Durability of response, and safety were also measured. Results: 242 patients were included (53 TN and 189 TE). Two TN patients on 2-DR had VL≥50 copies/mL and 1 had VL≥200 copies/mL at week 24. In TE patients on 2-DR, 90.2% achieved VL<200 copies/mL at week 24 (difference: 3.8%; 95% CI = −6.3% to 14%) and 91.8% at week 48 (difference: 0.06%; 95% CI = −9% to 10%), meeting noninferiority criteria. Among the 53 TN patients, only 1 VF was observed in 2-DR. In TN patients, the risk of treatment discontinuation was similar between groups (hazard ratio [HR] = 0.37; P = 0.15); similar rates were also found in TE patients (HR = 0.94; P = 0.85). TE patients on 2-DR showed a better safety profile compared with 3-DR patients ( P<0.001). Conclusion and Relevance: Our results did not show noninferiority in terms of virological effectiveness. Nevertheless, all effectiveness measures support the use of 2-DR in a real-life cohort of TN and TE. Additionally, durability and safety of 2-DR were confirmed to be similar to that of 3-DR.

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

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.

scholarly journals Genotype characterization and delayed loss of ambulation by glucocorticoids in a large cohort of patients with Duchenne muscular dystrophy

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shu Zhang ◽  
◽  
Dongdong Qin ◽  
Liwen Wu ◽  
Man Li ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Hazard Ratio ◽  
Large Cohort ◽  
Muscle Disease ◽  
Clinical Progression ◽  
Large Deletions ◽  
The Mean ◽  
Lower Hazard

Abstract Background Duchenne muscular dystrophy (DMD) is the most common genetic muscle disease in human. We aimed to describe the genotype distribution in a large cohort of Chinese DMD patients and their delayed loss of ambulation by glucocorticoid (GC) treatments. This is to facilitate protocol designs and outcome measures for the emerging DMD clinical trials. Results A total of 1163 patients with DMD were recruited and genotyped. Genotype variations were categorized as large deletions, large duplications, and small mutations. Large deletions were further analyzed for those amenable to exon-skipping therapies. Participants aged 5 years or older were grouped into GC-treated and GC-naïve groups. Clinical progression among different genotypes and their responses to GC treatments were measured by age at loss of ambulation (LOA). Among the mutation genotypes, large deletions, large duplications, and small mutations accounted for 68.79%, 7.14%, and 24.07%, respectively. The mean age at diagnosis was 4.59 years; the median ages at LOA for the GC-naïve, prednisone/prednisolone-treated, and deflazacort-treated groups were 10.23, 12.02, and 13.95 years, respectively. The “deletion amenable to skipping exon 44” subgroup and the nonsense-mutation subgroup had older ages at LOA than the “other deletions” subgroup. Subgroups were further analyzed by both genotypes and GC status. All genotypes showed significant beneficial responses to GC treatment. Deletions amenable to skipping exon 44 showed a lower hazard ratio (0.155). The mean age at death was 18.57 years in this DMD group. Conclusion Genotype variation influences clinical progression in certain DMD groups. Beneficial responses to GC treatment were observed among all DMD genotypes. Compared with other genotypes, deletions amenable to skipping exon 44 had a lower hazard ratio, which may indicate a stronger protective effect of GC treatments on this subgroup. These data are valuable for designing future clinical trials, as clinical outcomes may be influenced by the genotypes.

Association Between the APOE ɛ2/ɛ4 Genotype and Alzheimer’s Disease and Mild Cognitive Impairment Among African Americans

2021 ◽  
pp. 1-6
Author(s):  
Dianxu Ren ◽  
Oscar L. Lopez ◽  
Jennifer H. Lingler ◽  
Yvette Conley
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
African Americans ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Increased Risk ◽  
Similar Risk

We examined the association between APOE ɛ2/ɛ4 with incident Alzheimer’s disease (AD) and mild cognitive impairment (MCI) among African Americans using the national dataset from the National Alzheimer’s Coordinating Center (NACC) from 2005 to September 2019. Compared to ɛ3/ɛ3 carriers, ɛ2/ɛ4 carriers exhibited a similar risk of incident AD (adjusted hazard ratio [aHR] = 0.85, 95% CI [0.39, 1.84]) among the AD cohort and similar risk of incident MCI (aHR = 0.88, 95% CI [0.51, 1.50]) among the MCI cohort. Our findings suggest that, unlike the increased risk of AD and MCI in non-Latino whites, APOE ɛ2/ɛ4 genotype is not associated with the incidence of AD and MCI among African Americans.

scholarly journals THE RELATIONSHIP BETWEEN INFLAMMATORY DIETARY PATTERN AND INCIDENCE OF PERIODONTITIS

2021 ◽  
pp. 1-36
Author(s):  
Ahmed A. Alhassani ◽  
Frank B. Hu ◽  
Bernard A. Rosner ◽  
Fred K. Tabung ◽  
Walter C. Willett ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Periodontal Disease ◽  
Secondary Analysis ◽  
Hazard Ratio ◽  
Reduced Rank Regression ◽  
Rank Regression ◽  
Increased Risk ◽  
Cox Proportional Hazard Models ◽  
Study Population

ABSTRACT The long-term inflammatory impact of diet could potentially elevate the risk of periodontal disease through modification of systemic inflammation. The aim of the present study was to prospectively investigate the associations between a food based, reduced rank regression (RRR) derived, empirical dietary inflammatory pattern (EDIP) and incidence of periodontitis. The study population was composed of 34,940 men from the Health Professionals Follow-Up Study, who were free of periodontal disease and major illnesses at baseline (1986). Participants provided medical and dental history through mailed questionnaires every 2 years, and dietary data through validated semi-quantitative food frequency questionnaires every 4 years. We used Cox proportional hazard models to examine the associations between EDIP scores and validated self-reported incidence of periodontal disease over a 24-year follow-up period. No overall association between EDIP and the risk of periodontitis was observed; the hazard ratio comparing the highest EDIP quintile (most proinflammatory diet) to the lowest quintile was 0.99 (95% confidence interval: 0.89 -1.10, p-value for trend = 0.97). A secondary analysis showed that among obese non-smokers (i.e. never and former smokers at baseline), the hazard ratio for periodontitis comparing the highest EDIP quintile to the lowest was 1.39 (95% confidence interval: 0.98 -1.96, p-value for trend = 0.03). In conclusion, no overall association was detected between EDIP and incidence of self-reported periodontitis in the study population. From the subgroups evaluated EDIP was significantly associated with increased risk of periodontitis only among nonsmokers who were obese. Hence, this association must be interpreted with caution.

scholarly journals preoperative right ventricular overwork is a major determinant of residual pulmonary arterial hypertension in patients with repaired arterial septal defect

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
M Suzuki ◽  
Y Tanaka ◽  
K Yamashita ◽  
A Shono ◽  
K Sumimoto ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Septal Defect ◽  
Hazard Ratio ◽  
Coupling Index ◽  
Pulmonary Arterial ◽  
Asd Closure ◽  
The Right ◽  
Postoperative Residual

Abstract Funding Acknowledgements Type of funding sources: None. Background The haemodynamic effect of atrial septal defect (ASD) is a chronic volume overload of the right heart and pulmonary vasculature. Pulmonary overcirculation is generally compensated for by the right ventricular (RV) and pulmonary arterial (PA) reserve. However, in a subset of patients, prolonged pulmonary overcirculation insidiously induces obstructive pulmonary vasculopathy, which results in postoperative residual pulmonary arterial hypertension (PAH) after ASD closure. Postoperative PAH is a major concern because it is closely associated with poor outcomes and impaired quality of life. However, to date, no clinically robust predictors of postoperative residual PAH have been clearly identified. Purpose This study sought to assess the haemodynamic characteristics of ASD patients in terms of mechano-energetic parameters and to identify the predictors of postoperative residual PAH in these patients. Methods A total of 120 ASD patients (age: 58 ± 17 years) and 46 normal controls were recruited. As previously reported, the simplified RV contraction pressure index (sRVCPI) was calculated as an index of RV external work by multiplying the tricuspid annular plane systolic excursion (TAPSE) by the pressure gradient between the RV and right atrium. RV- PA coupling was evaluated using TAPSE divided by PA systolic pressure as an index of the RV length-force relationship. These parameters were measured both at baseline and 6 months after ASD closure. Results As expected, baseline sRVCPI was significantly greater in patients with ASD than in controls (775 ± 298 vs. 335 ± 180 mm Hg • mm, P &lt; 0.01), which indicated significant "RV overwork". As a result, RV-PA coupling in ASD patients was significantly impaired compared to that in controls (0.9 ± 0.8 vs. 3.5 ± 1.7 mm/mm Hg, P &lt; 0.01). All 120 ASD patients underwent transcatheter or surgical shunt closure; 15 of them had residual PAH after closure. After 6 months, RV-PA coupling index significantly improved in patients without residual PAH, from 0.96 ± 0.81 to 1.27 ± 1.24 mm/mm Hg (P = 0.02). Furthermore, RV load was markedly reduced, with sRVCPI falling from 691 ± 258 to 434 ± 217 mm Hg • mm, P &lt; 0.01). However, in patients with residual PAH, RV-PA coupling index deteriorated from 0.64 ± 0.23 to 0.53 ± 0.12 mm/mm Hg (P &lt; 0.01). As a result, RV overload was not significantly relieved (sRVCPI; from 971 ± 382 to 783 ± 166 mm Hg • mm, P = 0.22). In a multivariate analysis, baseline pulmonary vascular resistance (hazard ratio 1.009; P &lt; 0.01) and preoperative sRVPCI (hazard ratio 1.003; P &lt; 0.01) revealed to be independent predictors of residual PAH. Conclusion In terms of mechano-energetic function, preoperative "RV overwork" can be used as a robust predictor of an impaired RV-PA relationship in ASD patients. Moreover, periodic assessment of sRVPCI may contribute to the better management for patients with unrepaired ASD. Abstract Figure.

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