Search results for: survival model

Authors: A. Bere, H. G. Sithuba, K. Kyei, C. Sigauke

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We employ a discrete logit survival model to investigate the risk factors for early alcohol intake among students at two tertiary institutions in Thohoyandou, South Africa. Data were collected from a sample of 744 students using a self-administered questionnaire. Significant covariates were arrived at through a regularization algorithm implemented using the glmmLasso package. The tuning parameter was determined using a five-fold cross-validation algorithm. The baseline hazard was modelled as a smooth function of time through the use of spline functions. The results show that the hazard of initial alcohol intake peaks at the age of about 16 years and that at any given time, being of a male gender, prior use of other drugs, having drinking peers, having experienced negative life events and physical abuse are associated with a higher risk of alcohol intake debut.

Keywords: cross-validation, discrete hazard model, LASSO, smooth baseline hazard

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Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

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An estimating equation technique is an alternative method of the widely used maximum likelihood methods, which enables us to ease some complexity due to the complex characteristics of time-varying covariates. In the situations, when both the time-varying covariates and left-truncation are considered in the model, the maximum likelihood estimation procedures become much more burdensome and complex. To ease the complexity, in this study, the modified estimating equations those have been given high attention and considerations in many researchers under semiparametric transformation model was proposed. The purpose of this article was to develop the modified estimating equation under flexible and general class of semiparametric transformation models for left-truncated and right censored survival data with time-varying covariates. Besides the commonly applied Cox proportional hazards model, such kind of problems can be also analyzed with a general class of semiparametric transformation models to estimate the effect of treatment given possibly time-varying covariates on the survival time. The consistency and asymptotic properties of the estimators were intuitively derived via the expectation-maximization (EM) algorithm. The characteristics of the estimators in the finite sample performance for the proposed model were illustrated via simulation studies and Stanford heart transplant real data examples. To sum up the study, the bias for covariates has been adjusted by estimating density function for the truncation time variable. Then the effect of possibly time-varying covariates was evaluated in some special semiparametric transformation models.

Keywords: EM algorithm, estimating equation, semiparametric transformation models, time-to-event outcomes, time varying covariate

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Authors: S. Thaiudom, W. Toommuangpak

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Yoghurt ice cream (YIC) containing prebiotics and probiotics seems to be much more recognized among consumers who concern for their health. Not only can it be a benefit on consumers’ health but also its taste and freshness provide people easily accept. However, the survival of such probiotic especially Bifidobacterium longum, found in human gastrointestinal tract and to be benefit to human gut, was still needed to study in the severe condition as whipping and freezing in ice cream process. Low and full-fat yoghurt ice cream containing 2 and 10% (w/w) fat content (LYIC and FYIC), respectively was produced by mixing 20% yoghurt containing B. longum into milk ice cream mix. Fructo-oligosaccharides (FOS) or galacto-oligosaccharides (GOS) at 0, 1, and 2% (w/w) were separately used as prebiotic in order to improve the survival of B. longum. Survival of this bacteria as a function of ice cream storage time and ice cream properties were investigated. The results showed that prebiotic; especially FOS could improve viable count of B. longum. The more concentration of prebiotic used, the more is the survival of B. Longum. These prebiotics could prolong the survival of B. longum up to 60 days, and the amount of survival number was still in the recommended level (106 cfu per gram). Fat content and prebiotic did not significantly affect the total acidity and the overrun of all samples, but an increase of fat content significantly increased the fat particle size which might be because of partial coalescence found in FYIC rather than in LYIC. However, addition of GOS or FOS could reduce the fat particle size, especially in FYIC. GOS seemed to reduce the hardness of YIC rather than FOS. High fat content (10% fat) significantly influenced on lowering the melting rate of YIC better than 2% fat content due to the 3-dimension networks of fat partial coalescence theoretically occurring more in FYIC than in LYIC. However, FOS seemed to retard the melting rate of ice cream better than GOS. In conclusion, GOS and FOS in YIC with different fat content can enhance the survival of B. longum and affect physical and chemical properties of such yoghurt ice cream.

Keywords: Bifidobacterium longum, prebiotic, survival, yoghurt ice cream

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Authors: Wendu Pang, Yaxin Luo, Junhong Li, Yu Zhao, Danni Cheng, Yufang Rao, Minzi Mao, Ke Qiu, Yijun Dong, Fei Chen, Jun Liu, Jian Zou, Haiyang Wang, Wei Xu, Jianjun Ren

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We aimed to compare the prognostic prediction value of positive lymph node number (PLNN) to the American Joint Committee on Cancer (AJCC) tumor, lymph node, and metastasis (TNM) staging system for patients with hypopharyngeal squamous cell carcinoma (HPSCC). A total of 826 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004–2015) were identified and split into two independent cohorts: training (n=461) and validation (n=365). Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects of PLNN in patients with HPSCC. We further applied six Cox regression models to compare the survival predictive values of the PLNN and AJCC TNM staging system. PLNN showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P < 0.001) in both univariate and multivariable analyses, and was divided into three groups (PLNN 0, PLNN 1-5, and PLNN>5). In the training cohort, multivariate analysis revealed that the increased PLNN of HPSCC gave rise to significantly poor OS and CSS after adjusting for age, sex, tumor size, and cancer stage; this trend was also verified by the validation cohort. Additionally, the survival model incorporating a composite of PLNN and TNM classification (C-index, 0.705, 0.734) performed better than the PLNN and AJCC TNM models. PLNN can serve as a powerful survival predictor for patients with HPSCC and is a surrogate supplement for cancer staging systems.

Keywords: hypopharyngeal squamous cell carcinoma, positive lymph nodes number, prognosis, prediction models, survival predictive values

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Authors: Xinyuan Y. Song, Kai Kang

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Joint models for analyzing longitudinal and survival data are widely used to investigate the relationship between a failure time process and time-variant predictors. A common assumption in conventional joint models in the survival analysis literature is that all predictors are observable. However, this assumption may not always be supported because unobservable traits, namely, latent variables, which are indirectly observable and should be measured through multiple observed variables, are commonly encountered in the medical, behavioral, and financial research settings. In this study, a joint modeling approach to deal with this feature is proposed. The proposed model comprises three parts. The first part is a dynamic factor analysis model for characterizing latent variables through multiple observed indicators over time. The second part is a random coefficient trajectory model for describing the individual trajectories of latent variables. The third part is a proportional hazard model for examining the effects of time-invariant predictors and the longitudinal trajectories of time-variant latent risk factors on hazards of interest. A Bayesian approach coupled with a Markov chain Monte Carlo algorithm to perform statistical inference. An application of the proposed joint model to a study on the Alzheimer's disease neuroimaging Initiative is presented.

Keywords: Bayesian analysis, joint model, longitudinal data, time-to-event data

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Authors: Sopit Tubtimhin, Chaliya Wamaloon, Anchalee Supattagorn

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Background and Significance: Breast cancer is the most frequently diagnosed and leading cause of cancer death among women. This study aims to determine factors potentially predicting recurrence and long-term survival after the first recurrence in surgically treated patients between postmenopausal and younger women. Methods and Analysis: A retrospective cohort study was performed on 498 Thai women with invasive breast cancer, who had undergone mastectomy and been followed-up at Ubon Ratchathani Cancer Hospital, Thailand. We collected based on a systematic chart audit from medical records and pathology reports between January 1, 2002, and December 31, 2011. The last follow-up time point for surviving patients was December 31, 2016. A Cox regression model was used to calculate hazard ratios of recurrence and death. Findings: The median age was 49 (SD ± 9.66) at the time of diagnosis, 47% was post-menopausal women ( ≥ 51years and not experienced any menstrual flow for a minimum of 12 months), and 53 % was younger women ( ˂ 51 years and have menstrual period). Median time from the diagnosis to the last follow-up or death was 10.81 [95% CI = 9.53-12.07] years in younger cases and 8.20 [95% CI = 6.57-9.82] years in postmenopausal cases. The recurrence-free survival (RFS) for younger estimates at 1, 5 and 10 years of 95.0 %, 64.0% and 58.93% respectively, appeared slightly better than the 92.7%, 58.1% and 53.1% for postmenopausal women [HRadj = 1.25, 95% CI = 0.95-1.64]. Regarding overall survival (OS) for younger at 1, 5 and 10 years were 97.7%, 72.7 % and 52.7% respectively, for postmenopausal patients, OS at 1, 5 and 10 years were 95.7%, 70.0% and 44.5 respectively, there were no significant differences in survival [HRadj = 1.23, 95% CI = 0.94 -1.64]. Multivariate analysis identified five risk factors for negatively impacting on survival were triple negative [HR= 2.76, 95% CI = 1.47-5.19], Her2-enriched [HR = 2.59, 95% CI = 1.37-4.91], luminal B [HR = 2.29, 95 % CI=1.35-3.89], not free margin [HR = 1.98, 95%CI=1.00-3.96] and patients who received only adjuvant chemotherapy [HR= 3.75, 95% CI = 2.00-7.04]. Statistically significant risks of overall cancer recurrence were Her2-enriched [HR = 5.20, 95% CI = 2.75-9.80], triple negative [HR = 3.87, 95% CI = 1.98-7.59], luminal B [HR= 2.59, 95% CI = 1.48-4.54,] and patients who received only adjuvant chemotherapy [HR= 2.59, 95% CI = 1.48-5.66]. Discussion and Implications: Outcomes from this studies have shown that postmenopausal women have been associated with increased risk of recurrence and mortality. As the results, it provides useful information for planning the screening and treatment of early-stage breast cancer in the future.

Keywords: breast cancer, menopause status, recurrence-free survival, overall survival

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Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer occupies the first place among the cancer in women in the world. It is urgent today to study the role of molecular markers which are capable of predicting the dynamics and outcome of the disease. The aim of this study is to define the prognostic value of the content of estrogen receptor (ER), progesterone receptor (PgR), and amplification of HER-2 / neu oncoprotein by studying 3 and 5-year overall and relapse-free survival in 470 patients with primary operable and 280 patients with locally–advanced breast cancer. Materials and methods: Study results of 3 and 5-year overall and relapse-free survival, depending on the content of RE, PgR in primary operable patients showed that ER positive (+) and PgR (+) survival was 100 (96.2%) and 97.3 (94.6%), for ER negative (-) and PgR (-) - 69.2 (60.3%) and 65.4 (57.7%), for ER positive (+) and negative PgR (-) 87.4 (80.1%) and 81.5 (79.3%), for ER negative (-) and positive PgR (+) - 97.4 (93.4%) and 90.4 (88.5%), respectively. Survival results depended also on the level of HER-2 / neu expression. In patients with HER-2 / neu negative the survival rates were as follows: 98.6 (94.7%) and 96.2 (92.3%). In group of patients with the level of HER-2 / neu (2+) expression these figures were: 45.3 (44.3%) and 45.1 (40.2%), and in group of patients with the level of HER-2 / neu (3+) expression - 41.2 (33.1%) and 34.3 (29.4%). The combination of ER negative (-), PgR (-), HER-2 / neu (-) they were 27.2 (25.4%) and 19.5 (15.3%), respectively. In patients with locally-advanced breast cancer the results of 3 and 5-year OS and RFS for ER (+) and PgR (+) were 76.3 (69.3%) and 62.2 (61.4%), for ER (-) and RP (-) 29.1 (23.7%) and 18.3 (12.6%), for ER (+) and PgR (-) 61.2 (47.2%) and 39.4 (25.6%), for ER (-) and PgR (+) 54.3 (43.1%) and 41.3 (18.3%), respectively. The level of HER-2 / neu expression also affected the survival results. Therefore, in HER-2/ neu negative patients the survival rate was 74.1 (67.6%) and 65.1 (57.3%), with the level of expression (2+) 20.4 (14.2%) and 8.6 (6.4%), with the level of expression (3+) 6.2 (3.1%) and 1.2 (1.5%), respectively. The combination for ER, PgR, HER-2 / neu negative was 22.1 (14.3%) and 8.4 (1.2%). Conclusion: Thus, the presence of steroid hormone receptors in breast tumor tissues at primary operable and locally- advanced process as the lack of HER-2/neu oncoprotein correlates with the highest rates of 3- and 5-year overall and relapse-free survival. The absence of steroid hormone receptors as well as of HER-2/neu overexpression in malignant breast tissues significantly degrades the 3- and 5-year overall and relapse-free survival. Tumors with ER, PgR and HER-2/neu negative have the most unfavorable prognostics.

Keywords: breast cancer, estrogen receptor, oncoprotein, progesterone receptor

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Authors: Latifa Hamoudi-Belarbi, L'Hadi Nouri, Khaled Belkacemi

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The effect of three methods of drying (traditional drying, freeze-drying and spray-drying) on the survival of concentrated cultures of Geotrichum fragrans and Wickerhamomyces anomalus was studied. The survival of yeast cultures was initially compared immediately after freeze-drying using HES 12%(w/v)+Sucrose 7% (w/v) as protectant, traditional drying in dry rice cakes and finally spray-drying with whey proteins. The survival of G. fragrans and W. anomalus was studied during 4 months of storage at 4°C and 25°C, in the darkness, under vacuum and at 0% relative humidity. The results demonstrated that high survival was obtained using traditional method of preservation in rice cakes (60% for G. fragrans and 65% for W. anomalus) and freeze-drying in (68% for G. fragrans and 74% for W. anomalus). However, poor survival was obtained by spray-drying method in whey protein with 20% for G. fragrans and 29% for W. anomalus. During storage at 25°C, yeast cultures of G. fragrans and W. anomalus preserved by traditional and freeze-drying methods showed no significant loss of viable cells up to 3 months of storage. Spray-dried yeast cultures had the greatest loss of viable count during the 4 months of storage at 25°C. During storage at 4°C, preservation of yeasts cultures using traditional method of preservation provided better survival than freeze-drying. This study demonstrated the effectiveness of the traditional method to preserve yeasts cultures compared to the high cost methods like freeze-drying and spray-drying.

Keywords: freeze-drying, traditional drying, spray drying, yeasts

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Authors: Daniel P. Kisangau, Ken M. Hosea, Herbert V. M. Lyaruu, Cosam C. Josep, Zakaria H. Mbwambo, Pax J. Masimba

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Crude extracts of Dracaena steudneri bark (DSB), Sapium ellipticum bark (SEB) and Capparis erythrocarpos root (CER) were investigated for their antifungal activity in immunocompromised mice infected with Candida albicans in an in vivo mice infection model. The results revealed a substantial dose dependency in all treatments given, with mice survival to the end of the experiment correlating well to the dose levels. At a dose of 400 mg/kg, C. erythrocarpos was the most effective with mice survival of 60% and organ burden clearance ranging from 64.0%-99.9% (P<0.0001) in all treatments. At the same dose, the least effective plant was S. ellipticum which had a mice survival of 20% and organ burden clearance ranging from 78.0%-96.6 (P>0.05). Mice survival for D. steudneri was 30% with organ burden clearance ranging from 89.0%-99.9% (P<0.05). All mice receiving no active treatment died before ten days post infection. In all treatment groups, there was a steady decline in mean weights of mice immediately after immunosuppression followed by gradual recovery in some cases which appeared to be dose dependent a few days post infection. Thus, extracts of D. steudneri and C. erythrocarpos portrayed the most significant potential as sources of antifungal drugs.

Keywords: antifungal activity, medicinal plants, candida albicans, East Africa

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Authors: Mekni Sabrine, Nouira Mariem

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Background and aim: Allogeneic hematopoietic stem cell transplantation is a curative treatment for several hematological diseases; however, it has a non-negligible morbidity and mortality depending on several prognostic factors, including pre-transplant hyperferritinemia. The aim of our study was to estimate the impact of hyperferritinemia on survivals and on the occurrence of post-transplant complications. Methods: It was a longitudinal study conducted over 8 years and including all patients who had a first allograft. The impact of pretransplant hyperferritinemia (ferritinemia ≥1500) on survivals was studied using the Kaplan Meier method and the COX model for uni- and multivariate analysis. The Khi-deux test and binary logistic regression were used to study the association between pretransplant ferritinemia and post-transplant complications. Results: One hundred forty patients were included with an average age of 26.6 years and a sex ratio (M/F)=1.4. Hyperferritinemia was found in 33% of patients. It had no significant impact on either overall survival (p=0.9) or event -free survival (p=0.6). In multivariate analysis, only the type of disease was independently associated with overall survival (p=0.04) and event-free survival (p=0.002). For post-allograft complications: The occurrence of early documented infections was independently associated with pretransplant hyperferritinemia (p=0.02) and the presence of acute graft versus host disease( GVHD) (p<10-3). The occurrence of acute GVHD was associated with early documented infection (p=0.002) and Cytomegalovirus reactivation (p<10-3). The occurrence of chronic GVHD was associated with the presence of Cytomegalovirus reactivation (p=0.006) and graft source (p=0.009). Conclusion: Our study showed the significant impact of pre-transplant hyperferritinemia on the occurrence of early infections but not on survivals. Early and more accurate assessment iron overload by other tests such as liver magnetic resonance imaging with initiation of chelating treatment could prevent the occurrence of such complications after transplantation.

Keywords: allogeneic, transplants, ferritin, survival

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Authors: Junhong Li, Danni Cheng, Yaxin Luo, Xiaowei Yi, Ke Qiu, Wendu Pang, Minzi Mao, Yufang Rao, Yao Song, Jianjun Ren, Yu Zhao

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Background: The number of multiple cancer patients was increasing, and the impact of prior cancer history on salivary gland cancer patients remains unclear. Methods: Clinical, demographic and pathological information on salivary gland cancer patients were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017, and the characteristics and prognosis between patients with a prior cancer and those without prior caner were compared. Univariate and multivariate cox proportional regression models were used for the analysis of prognosis. A risk score model was established to exam the impact of treatment on patients with a prior cancer in different risk groups. Results: A total of 9098 salivary gland cancer patients were identified, and 1635 of them had a prior cancer history. Salivary gland cancer patients with prior cancer had worse survival compared with those without a prior cancer (p<0.001). Patients with a different type of first cancer had a distinct prognosis (p<0.001), and longer latent time was associated with better survival (p=0.006) in the univariate model, although both became nonsignificant in the multivariate model. Salivary gland cancer patients with a prior cancer were divided into low-risk (n= 321), intermediate-risk (n=223), and high-risk (n=62) groups and the results showed that patients at high risk could benefit from surgery, radiation therapy, and chemotherapy, and those at intermediate risk could benefit from surgery. Conclusion: Prior cancer history had an adverse impact on the survival of salivary gland cancer patients, and individualized treatment should be seriously considered for them.

Keywords: prior cancer history, prognosis, salivary gland cancer, SEER

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Authors: Hanei Son

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Since the beginning of the 2010s, ‘start-up boom’ has continued with the creation of many new enterprises in Korea. Such tendency was led by various changes in society such as emergence and diffusion of smartphones. Especially, the Korean government has been interested in start-ups and entrepreneurship as an alternative engine for Korea's economic growth. With strong support from the government, as a result, many new enterprises have been established for recent years and the Korean government seems to have achieved its goal: expanding the basis of start-ups. However, it is unclear which factors affect the survival and growth of these new enterprises after their creation. Therefore, this study aims to identify which start-ups from early 2010s survived and which factors influenced their survival and growth. The study will strongly focus on which industries the new enterprises were in, as environmental elements are expected to be critical factors for business of start-ups in Korean context. For this purpose, 105 companies which were introduced as high potential start-ups from 2010 to 2012 were considered in the analysis. According to their current status, dead or alive, the start-ups were categorized by their industries and service area. Through this analysis, it was observed that many start-ups that are still in business are in internet or mobile platform businesses and four major sectors. In each group, a representative case has been studied to reveal its survival and growth factors. The results point to the importance of industrial characteristics for the survival and success of Korean startups and offer political implications in which sector and business more potentials for start-ups in Korea lie in.

Keywords: government support for start-ups, industrial characteristics, Korean start-ups, survival of start-ups

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Authors: Geir Kirkebøen

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Most patients with serious diagnoses want to know their prognosis, in particular their expected survival time. As part of the informed consent process, physicians are legally obligated to communicate such information to patients. However, there is no established (evidence based) ‘best practice’ for how to do this. The two questions explored in this study are: How do physicians communicate expected survival time to patients, and how should it be done? We explored the first, descriptive question in a study with Norwegian oncologists as participants. The study had a scenario and a survey part. In the scenario part, the doctors should imagine that a patient, recently diagnosed with a serious cancer diagnosis, has asked them: ‘How long can I expect to live with such a diagnosis? I want an honest answer from you!’ The doctors should assume that the diagnosis is certain, and that from an extensive recent study they had optimal statistical knowledge, described in detail as a right-skewed survival curve, about how long such patients with this kind of diagnosis could be expected to live. The main finding was that very few of the oncologists would explain to the patient the variation in survival time as described by the survival curve. The majority would not give the patient an answer at all. Of those who gave an answer, the typical answer was that survival time varies a lot, that it is hard to say in a specific case, that we will come back to it later etc. The survey part of the study clearly indicates that the main reason why the oncologists would not deliver the mortality prognosis was discomfort with its uncertainty. The scenario part of the study confirmed this finding. The majority of the oncologists explicitly used the uncertainty, the variation in survival time, as a reason to not give the patient an answer. Many studies show that patients want realistic information about their mortality prognosis, and that they should be given hope. The question then is how to communicate the uncertainty of the prognosis in a realistic and optimistic – hopeful – way. Based on psychological research, our hypothesis is that the best way to do this is by explicitly describing the variation in survival time, the (usually) right skewed survival curve of the prognosis, and emphasize to the patient the (small) possibility of being a ‘lucky outlier’. We tested this hypothesis in two scenario studies with lay people as participants. The data clearly show that people prefer to receive expected survival time as a median value together with explicit information about the survival curve’s right skewedness (e.g., concrete examples of ‘positive outliers’), and that communicating expected survival time this way not only provides people with hope, but also gives them a more realistic understanding compared with the typical way expected survival time is communicated. Our data indicate that it is not the existence of the uncertainty regarding the mortality prognosis that is the problem for patients, but how this uncertainty is, or is not, communicated and explained.

Keywords: cancer patients, decision psychology, doctor-patient communication, mortality prognosis

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Authors: Narendra Kumar

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This study uses data from the ‘National Family Health Survey (NFHS-3) 2005-06’ to investigate the predictors of infant and child mortality among low economic households in East and Northeast region. The cross tabulation, life table survival estimates and Cox proportional hazard model techniques have been used to estimate the predictors of infant and child mortality. The life table survival estimates for infant and child mortality shows that infant mortality in female child is lower in comparison to male child but with child mortality, the rates are higher for female in comparison to male child and the Cox proportional hazard model also give highly significant in female in comparison to male child. The infant and child mortality rates among poor households highest in the Central region followed by North and Northeast region and the lowest in South region in comparison to all regions of India. Education of respondent has been found a significant characteristics in both analyzes, further birth interval, respondent occupation, caste/tribe and place of delivery has substantial impact on infant and child mortality among low economic households in East and Northeast region. Finally these findings specified that an increase in parents’ education, improve health care services and improve socioeconomic conditions of low economic households which should in turn raise infant and child survival and should decrease child mortality among low economic households in India.

Keywords: infant, child, mortality, socio-economic, India

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Authors: Getahun Nigusie Demise

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Background; antiretroviral treatment reduce HIV-related morbidity, and prolonged survival of patients however, there is lack of up-to-date information concerning the treatment long term effect on the survival of HIV positive children especially in the study area. Objective: The aim of this study is to assess the incidence and predictors of mortality among HIV positive children on antiretroviral therapy (ART) in public hospitals of Harer town who were enrolled from 2011 to 2021. Methodology: Institution based retrospective cohort study was conducted among 429 HIV positive children enrolled in ART clinic from January 1st 2011 to December30th 2021. Data were collected from medical cards by using a data extraction form, Descriptive analyses were used to Summarized the results, and life table was used to estimate survival probability at specific point of time after introduction of ART. Kaplan Meier survival curve together with log rank test was used to compare survival between different categories of covariates, and Multivariate Cox-proportional hazard regression model was used to estimate adjusted Hazard rate. Variables with p-values ≤0.25 in bivariable analysis were candidates to the multivariable analysis. Finally, variables with p-values < 0.05 were considered as significant variables. Results: The study participants had followed for a total of 2549.6 child-years (30596 child months) with an overall mortality rate of 1.5 (95% CI: 1.1, 2.04) per 100 child-years. Their median survival time was 112 months (95% CI: 101–117). There were 38 children with unknown outcome, 39 deaths, and 55 children transfer out to different facility. The overall survival at 6, 12, 24, 48 months were 98%, 96%, 95%, 94% respectively. being in WHO clinical Stage four (AHR=4.55, 95% CI:1.36, 15.24), having anemia(AHR=2.56, 95% CI:1.11, 5.93), baseline low absolute CD4 count (AHR=2.95, 95% CI: 1.22, 7.12), stunting (AHR=4.1, 95% CI: 1.11, 15.42), wasting (AHR=4.93, 95% CI: 1.31, 18.76), poor adherence to treatment (AHR=3.37, 95% CI: 1.25, 9.11), having TB infection at enrollment (AHR=3.26, 95% CI: 1.25, 8.49),and no history of change their regimen(AHR=7.1, 95% CI: 2.74, 18.24), were independent predictors of death. Conclusion: more than half of death occurs within 2 years. Prevalent tuberculosis, anemia, wasting, and stunting nutritional status, socioeconomic factors, and baseline opportunistic infection were independent predictors of death. Increasing early screening and managing those predictors are required.

Keywords: human immunodeficiency virus-positive children, anti-retroviral therapy, survival, treatment, Ethiopia

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Authors: R. O. B. Bitencourt, F. S. Farias, M. C. Freitas, C. J. R. Balduino, E.S. Mesquita, A. R. C. Corval, P. S. Gôlo, E. G. Pontes, V. R. E. P. Bittencourt, I. C. Angelo

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Aedes aegypti larval survival rate was assessed after exposure to blastopores or conidia (mineral oil-in-water formulation or aqueous suspension) of Beauveria bassiana CG 479 propagules (blastospores or conidia). Here, mineral oil was used in the fungal formulation to control Aedes aegypti larvae. 1%, 0.5% or 0.1% mineral oil-in-water solutions were used to evaluate mineral oil toxicity for mosquito larvae. In the oil toxicity test, 0.1% mineral oil solution reduced only 4.5% larval survival; accordingly, this concentration was chosen for fungal oil-in-water formulations. Aqueous suspensions were prepared using 0.01% Tween 80^® in sterile dechlorinated water. A. aegypti larvae (L₂) were exposed in aqueous suspensions or mineral oil-in-water fungal formulations at 1×107 propagules mL^-1; the survival rate (assessed daily, for 7 days) and the median survival time (S₅₀) were calculated. Seven days after the treatment, mosquito larvae survival rates were 8.56%, 16.22%, 58%, and 42.56% after exposure to oil-in-water blastospores, oil-in-water conidia, blastospores aqueous suspension and conidia aqueous suspension (respectively). Larvae exposed to 0.01% Tween 80^® had 100% survival rate and the ones treated with 0.1% mineral oil-in-water had 95.11% survival rate. Larvae treated with conidia (regardless the presence of oil) or treated with blastospores formulation had survival median time (S₅₀) ranging from one to two days. S₅₀ was not determined (ND) when larvae were exposed to blastospores aqueous suspension, 0.01% Tween 80^® (aqueous control) or 0.1% mineral oil-in-water formulation (oil control). B. bassiana conidia and blastospores (mineral oil-in-water formulated or suspended in water) had potential to control A. aegypti mosquito larvae, despite mineral oil-in-water formulation yielded better results in comparison to aqueous suspensions. Here, B. bassiana CG 479 isolate is suggested as a potential biocontrol agent of A. aegypti mosquito larvae.

Keywords: blastospores, formulation, mosquitoes, conidia

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Authors: Ugbor Raphael Oluchukwu

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Focusing on liquidity comes more naturally to a Chief Executive Officer than an Accountant who is trained to practice accrual accounting. When business is just commencing, it is essentially run on a cheque book (cash accounting) and for as long as there is cash in the accounts, the business is solvent. When complexity sets in and the business adopts financial accounting, the effect of liquidity and cash management becomes more pronounced. The management of cash no doubts impacts positively on the survival and growth of firms. What is in doubt is the amount of cash to be held by a firm as enough cash to enable the firm stay “afloat”. The focus of this paper is to determine liquidity and cash management in business, the Nigerian case. The specific objectives of the study are to do a theoretical review of the amount of cash to be held by a firm as enough cash to enable it stay afloat and to do a theoretical analysis to show the effect of cash flow on the survival and growth of firms in Nigeria.

Keywords: cash, firm survival, growth, liquidity management

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Authors: Sujata Chaturvedi, Ishita Pant, Deepak Kumar Jha, Vinod Kumar Singh Gautam, Chandra Bhushan Tripathi

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Objective: To describe clinical, histopathological and immunohistochemical profile of glioblastoma in patients and to correlate these findings with patient survival. Material and methods: 30 cases of histopathologically diagnosed glioblastomas were included in this study. These cases were analysed in detail for certain clinical and histopathological parameters. Immunohistochemical staining for p53, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), mouse double minute 2 homolog (MDM2) and Ki67 was done and scores were calculated. Results of these findings were correlated with patient survival. Results: A retrospective analysis of the histopathology records and clinical case files was done in 30 cases of glioblastoma (WHO grade IV). The mean age of presentation was 50.6 years with a male predilection. The most common involved site was the frontal lobe. Amongst the clinical parameters, age of the patient and extent of surgical resection showed a significant correlation with the patient survival. Histopathological parameters showed no significant correlation with the patient survival, while amongst the immunohistochemical parameters expression of MDM2 showed a significant correlation with the patient survival. Conclusion: In this study incorporating clinical, histopathological and basic panel of immunohistochemistry, age of the patient, extent of the surgical resection and expression of MDM2 showed significant correlation with the patient survival.

Keywords: glioblastoma, p53, EGFR, VEGF, MDM2, Ki67

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Authors: Danni Cheng

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Purpose:Surgicallyinclusive treatment(SIT)isthemajor treatment fororopharyngealsquamouscellcarcinoma (OPSCC) in Eastern countries, while nonsurgical treatments(NSTs) are the priority treatment in Western countries. The preferred treatmentsforOPSCC patients remaindebated. Methods:Atotalof 153 consecutive OPSCC casesdiagnosed between 2009 and 2019inWCH, and 15,400 OPSCC cases from SEER database (2000-2017) were obtained. Clinical characteristics, treatments, and survival outcomes were retrospectively collected. We conductedKaplan-Meier curves univariate and multivariate analysis to compare the prognosis of OPSCC patients in WCH, SEER Asian, and SEER all ethnic population by different treatment modalities,HPVstatus, ages, and TNM stages. Results: The 5-year overall survival rate was 59% in WCH, 64% in the SEER all ethnic and 67% in SEER Asian group. In both univariate and multivariate analysis, SIT was observed as a consistent benefit factor for OPSCC patients in all three populations when classified by genders, tumor stages, and HPV status. Patients who underwent SIT had significantly better survival outcomes than those who received NSTsin WCH, SEER Asian, and SEER all ethnic groups. HPV positive status was the beneficial factor of OPSCC patients in all three groups. Besides, male patients had worse survival outcomes in both WCH and SEER Asian group, whereas male patients had better outcomes in the SEER all ethnic group. Conclusion: In contrast to nowadaysNSTs are the first-line therapiesfor OPSCC, our ten-year real-world data and SEER data indicated that OPSCC patients who underwent SIT had better prognosis than NSTs.

Keywords: OPSCC, survival outcome, SEER, treatment modalities

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Authors: Chettou Souhaila, Soufi Omar, Roumia Mohammed Ammar

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Protecting the environment is to preserve the survival and future of humanity. Indeed, the environment is our source of food and drinking water, the air is our source of oxygen, the climate allows our survival and biodiversity are a potential drug reservoir. Preserving the environment is, therefore, a matter of survival. The objective of this project is to familiarize the general public with environmental problems not only with the theme of environmental protection, but also with the concept of biodiversity in different ecosystems. For it, the aim of our project was to create the Ecorium which is a place that preserves many species of plants of different ecosystems, schools, malls, buildings, offices, ecological transports, gardens, and many familial activities that participated in the ecosystems development, strategic biodiversity and sustainable development.

Keywords: ecological system, ecorium, environment, sustainable development

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Authors: Kiumars Shahbazi, Salah Salimian, Abdolrahim Hashemi Dizaj

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Locating is one of the key elements in success and survival of industrial centers and has great impact on cost reduction of establishment and launching of various economic activities. In this study, streets with unequal length model have been used that is the classic extension of Spoke model; however with unlimited number of streets with uneven lengths. The results showed that the spoke model is a special case of streets with unequal length model. According to the results of this study, if the strategy of enterprises and firms is to select both price and location, there would be no balance in the game. Furthermore, increased length of streets leads to increased profit of enterprises and with increased number of streets, the enterprises choose locations that are far from center (the maximum differentiation), and the enterprises' output will decrease. Moreover, the enterprise production rate will incline toward zero when the number of streets goes to infinity, and complete competition outcome will be achieved.

Keywords: locating, Nash equilibrium, streets with unequal length model, streets with unequal length model

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Authors: Antonia Harold-Barry, Eugene Dempsey

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Background: The objective is to examine the survival and outcome of infants born under 26 weeks gestation in an Irish tertiary maternity hospital from 2007-2016 and to describe the survival and neurodevelopmental outcomes of these extremely preterm infants. Method: The population is 132 infants born at 23, 24, and 25 weeks in Cork University Maternity Hospital from 2007 to 2016. Ethical approval was granted by the Cork Clinical Research Ethics Committee. Patient details were obtained from the Vermont Oxford and Badger Networks. Survival rates and Bayley scores were calculated to assess neurodevelopmental outcomes. Statistical analysis with SPSS included frequencies, distributions, and comparisons between data from 2007-2011 and 2012-2016. Results: Overall survival rate was 63%. Of the surviving babies, 61% had Bayley scores calculated. Survival stood at 39% for delivery at 23 weeks, 50% at 24 weeks, and 83% at 25 weeks. The 2012 to 2016 cohort has shown further increases in survival, with 50% of babies at 23 weeks, 58% at 24 weeks, and 89% at 25 weeks. Corresponding figures for 2007-2011 are 20%, 39%, and 75%. Gestational age and incidence of periventricular leukomalacia were statistically significant, with a p-value of 0.022. Gestational age and delivery room deaths had a p-value of 0.025, as did gestational age and birth weight. A comparison of the two cohorts (2007-2011 and 2012-2016) with the administration of antenatal steroids showed a statistically significant p-value of 0.044. Conclusion: There is less morbidity and mortality in infants born at 25 than at 23 or 24 weeks. Survival of extremely premature infants has increased significantly over the past ten years. Survival rates with normal neurodevelopmental outcomes are comparable with international standards and reflect positive changes in attitude and practices in neonatal intensive care. This study will inform parents about the potential outcomes of extreme prematurity and policy regarding the management of extreme prematurity.

Keywords: extreme of viability, neurodevelopmental outcome, periventricular leukomalacia, prematurity

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Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

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In biomedical researches and randomized clinical trials, the most commonly interested outcomes are time-to-event so-called survival data. The importance of robust models in this context is to compare the effect of randomly controlled experimental groups that have a sense of causality. Causal estimation is the scientific concept of comparing the pragmatic effect of treatments conditional to the given covariates rather than assessing the simple association of response and predictors. Hence, the causal effect based semiparametric transformation model was proposed to estimate the effect of treatment with the presence of possibly time-varying covariates. Due to its high flexibility and robustness, the semiparametric transformation model which shall be applied in this paper has been given much more attention for estimation of a causal effect in modeling left-truncated and right censored survival data. Despite its wide applications and popularity in estimating unknown parameters, the maximum likelihood estimation technique is quite complex and burdensome in estimating unknown parameters and unspecified transformation function in the presence of possibly time-varying covariates. Thus, to ease the complexity we proposed the modified estimating equations. After intuitive estimation procedures, the consistency and asymptotic properties of the estimators were derived and the characteristics of the estimators in the finite sample performance of the proposed model were illustrated via simulation studies and Stanford heart transplant real data example. To sum up the study, the bias of covariates was adjusted via estimating the density function for truncation variable which was also incorporated in the model as a covariate in order to relax the independence assumption of failure time and truncation time. Moreover, the expectation-maximization (EM) algorithm was described for the estimation of iterative unknown parameters and unspecified transformation function. In addition, the causal effect was derived by the ratio of the cumulative hazard function of active and passive experiments after adjusting for bias raised in the model due to the truncation variable.

Keywords: causal estimation, EM algorithm, semiparametric transformation models, time-to-event outcomes, time-varying covariate

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Authors: Awf A. Al-Khan, Michael J. Day, Judith Nimmo, Mourad Tayebi, Stewart D. Ryan, Samantha J. Richardson, Janine A. Danks

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Osteosarcoma (OS) is the most common type of malignant primary bone tumour in dogs. In addition to their critical roles in bone formation and remodeling, parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) are involved in progression and metastasis of many types of tumours in humans. The aims of this study were to determine the localisation and expression levels of PTHrP and PTHR1 in canine OS tissues using immunohistochemistry and to investigate if this expression is correlated with survival time. Formalin-fixed, paraffin-embedded tissue samples from 44 dogs with known survival time that had been diagnosed with primary osteosarcoma were analysed for localisation of PTHrP and PTHR1. Findings showed that both PTHrP and PTHR1 were present in all OS samples. The dogs with high level of PTHR1 protein (16%) had decreased survival time (P<0.05) compared to dogs with less PTHR1 protein. PTHrP levels did not correlate with survival time (P>0.05). The results of this study indicate that the PTHR1 is expressed differently in canine OS tissues and this may be correlated with poor prognosis. This may mean that PTHR1 may be useful as a prognostic indicator in canine OS and could represent a good therapeutic target in OS.

Keywords: dog, expression, osteosarcoma, parathyroid hormone receptor 1 (PTHR1), parathyroid hormone-related protein (PTHrP), survival

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Authors: Jorge Martinez, Brandon Roberts, Holly Payton Toca

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Background: Therapeutic hypothermia (TH) is the international standard of care for all comatose patients after cardiac arrest, but criticism focuses on poor outcomes. We sought to develop criteria to identify American urban patients more likely to benefit from TH. Methods: Retrospective chart review of 107 consecutive adults undergoing TH in downtown New Orleans from 2010-2014 yielded records for 99 patients with all 44 survivors or families contacted up to four years. Results: 69 males and 38 females with a mean age of 60.2 showed 63 dead (58%) and 44 survivors (42%). Presenting cardiac rhythm was divided into shockable (Pulseless Ventricular Tachycardia, Ventricular Fibrillation) and non-shockable (Pulseless Electrical Activity, Asystole). Presenting in shockable rhythms with ROSC <20 minutes were 21 patients with 15 (71%) survivors (p=.001). Time >20 minutes until ROSC in shockable rhythms had 5 patients with 3 survivors (78%, p=0.001). Presenting in non-shockable rhythms with ROSC <20 minutes were 54 patients with 18 survivors (33%, p=.001). ROSC >20 minutes in non-shockable rhythms had 19 patients with 2 survivors (8%, p=.001). Survivors of shockable rhythms showed 19 (100%) living post TH. 15 survivors (79%, n=19, p=.001) had CPC score 1 or 2 with 4 survivors (21%, n=19) having a CPC score of 3. A total of 25 survived non-shockable rhythm. Acute survival of patients with non-shockable rhythm showed 18 expired <72 hours (72%, n=25) with long-term survival of 4 patients (5%, n=74) and CPC scores of 1 or 2 (p=.001). Interestingly, patients with time to ROSC <20 minutes exhibiting more than one loss of sustained ROSC showed 100% mortality (p=.001). Patients presenting with shockable >20 minutes ROSC had overall survival of 70% (p=.001), but those undergoing >3 cardiac rhythm changes had 100% mortality (p=.001). Conclusion: Patients presenting with shockable rhythms undergoing TH had overall acute survival of 70% followed by long-term survival of 100% after 4 years. In contrast, patients presenting with non-shockable rhythm had long-term survival of 5%. TH is not recommended for patients presenting with non-shockable rhythm and requiring greater than 20 minutes for restoration of ROSC.

Keywords: cardiac rhythm changes, Pulseless Electrical Activity (PEA), Therapeutic Hypothermia (TH)

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Authors: Abdisalam Hassan Muse, Samuel Mwalili, Oscar Ngesa

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A generalized log-logistic distribution with variable shapes of the hazard rate was introduced and studied, extending the log-logistic distribution by adding an extra parameter to the classical distribution, leading to greater flexibility in analysing and modeling various data types. The proposed distribution has a large number of well-known lifetime special sub-models such as; Weibull, log-logistic, exponential, and Burr XII distributions. Its basic mathematical and statistical properties were derived. The method of maximum likelihood was adopted for estimating the unknown parameters of the proposed distribution, and a Monte Carlo simulation study is carried out to assess the behavior of the estimators. The importance of this distribution is that its tendency to model both monotone (increasing and decreasing) and non-monotone (unimodal and bathtub shape) or reversed “bathtub” shape hazard rate functions which are quite common in survival and reliability data analysis. Furthermore, the flexibility and usefulness of the proposed distribution are illustrated in a real-life data set and compared to its sub-models; Weibull, log-logistic, and BurrXII distributions and other parametric survival distributions with 3-parmaeters; like the exponentiated Weibull distribution, the 3-parameter lognormal distribution, the 3- parameter gamma distribution, the 3-parameter Weibull distribution, and the 3-parameter log-logistic (also known as shifted log-logistic) distribution. The proposed distribution provided a better fit than all of the competitive distributions based on the goodness-of-fit tests, the log-likelihood, and information criterion values. Finally, Bayesian analysis and performance of Gibbs sampling for the data set are also carried out.

Keywords: hazard rate function, log-logistic distribution, maximum likelihood estimation, generalized log-logistic distribution, survival data, Monte Carlo simulation

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Authors: Min Ju Kim, Beom Jin Park, Deuk Jae Sung, Na Yeon Han, Kichoon Sim

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Purpose: The purpose of this study is to determine the significant magnetic resonance (MR) imaging factors of lateral pelvic lymph node (LPLN) on the assessment of survival outcomes of neoadjuvant combined chemotherapy and radiation therapy (CRT) in patients with mid/low rectal cancer. Materials and Methods: The institutional review board approved this retrospective study of 63 patients with mid/low rectal cancer who underwent MR before and after CRT and patient consent was not required. Surgery performed within 4 weeks after CRT. The location of LPLNs was divided into following four groups; 1) common iliac, 2) external iliac, 3) obturator, and 4) internal iliac lymph nodes. The short and long axis diameters, numbers, shape (ovoid vs round), signal intensity (homogenous vs heterogenous), margin (smooth vs irregular), and diffusion-weighted restriction of LPLN were analyzed on pre- and post-CRT images. For treatment response using size, lymph node groups were defined as group 1) short axis diameter ≤ 5mm on both MR, group 2) > 5mm change into ≤ 5mm after CRT, and group 3) persistent size > 5mm before and after CRT. Clinical findings were also evaluated. The disease-free survival and overall survival rate were evaluated and the risk factors for survival outcomes were analyzed using cox regression analysis. Results: Patients in the group 3 (persistent size >5mm) showed significantly lower survival rates than the group 1 and 2 (Disease-free survival rates of 36.1% and 78.8, 88.8%, p < 0.001). The size response (group 1-3), multiplicity of LPLN, the level of carcinoembryonic antigen (CEA), patient’s age, T and N stage, vessel invasion, perineural invasion were significant factors affecting disease-free survival rate or overall survival rate using univariate analysis (p < 0.05). The persistent size (group 3) and multiplicity of LPLN were independent risk factors among MR imaging features influencing disease-free survival rate (HR = 10.087, p < 0.05; HR = 4.808, p < 0.05). Perineural invasion and T stage were shown as independent histologic risk factors (HR = 16.594, p < 0.05; HR = 15.891, p < 0.05). Conclusion: The persistent size greater than 5mm and multiplicity of LPLN on both pre- and post-MR after CRT were significant MR factors affecting survival outcomes in the patients with mid/low rectal cancer.

Keywords: rectal cancer, MRI, lymph node, combined chemoradiotherapy

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Authors: Jiajia Peng, Danni Cheng, Jianqing Qiu, Yufang Rao, Minzi Mao, Ke Qiu, Junhong Li, Fei Chen, Feng Liu, Jun Liu, Xiaosong Mu, Wenxin Yu, Wei Zhang, Wei Xu, Yu Zhao, Jianjun Ren

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Background: Currently, primary B-cell non-Hodgkin lymphoma (B-NHL) and T/NK-cell non-Hodgkin lymphoma (NKT-NHL) originated from the nasal cavity (NC), nasopharynx (NP) and nasal sinus (NS) distinguished unclearly in the clinic. Objective: We sought to compare the clinical and survival differences of B-NHL and NKT-NHL that occurred in NC, NP, and NS, respectively. Methods: Retrospective data of patients diagnosed with nasal cavity lymphoma (NCL), nasopharyngeal lymphoma (NPL), and nasal sinus lymphoma (NSL) between 1975 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database were collected. We identified the B/NKT-NHL patients based on the histological type and performed univariate, multivariate, and Kaplan-Meier analyses to investigate the survival rates. Results: Of the identified 3,101 B-NHL and 738 NKT-NHL patients, those with B-NHL in NP were the majority (43%) and had better cancer-specific survival than those in NC and NS from 2010 to 2017 (5-year-CSS, NC vs. NP vs. NS: 81% vs. 83% vs. 82%). In contrast, most of the NKT-NHL originated from NC (68%) and had the highest CSS rate in the recent seven years (2010-2017, 5-year-CSS: 63%). Additionally, the survival outcomes of patients with NKT-NHL-NP (HR: 1.34, 95% CI: 0.62-2.89, P=0.460) who had received surgery were much worse than those of patients with NKT-NHL-NC (HR: 1.07, 95% CI: 0.75-1.52, P=0.710) and NKT-NHL-NS (HR: 1.11, 95% CI: 0.59-2.07, P=0.740). NKT-NHL-NS patients who had radiation performed (HR: 0.38, 95% CI: 0.19-0.73, P=0.004) showed the highest survival rates, while chemotherapy performed (HR: 1.01, 95% CI: 0.43-2.37, P=0.980) presented opposite results. Conclusions: Although B-NHL and NKT-NHL originating from NC, NP and NS had similar anatomical locations, their clinical characteristics, treatment therapies, and prognoses were different in this study. Our findings may suggest that B-NHL and NKT-NHL in NC, NP, and NS should be treated as different diseases in the clinic.

Keywords: nasopharyngeal lymphoma, nasal cavity lymphoma, nasal sinus lymphoma, B-cell non-Hodgkin lymphoma, T/NK-cell non-Hodgkin lymphoma

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Authors: Ella Tyuryumina, Alexey Neznanov

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This study is an attempt to obtain reliable data on the natural history of breast cancer growth. We analyze the opportunities for using classical mathematical models (exponential and logistic tumor growth models, Gompertz and von Bertalanffy tumor growth models) to try to describe growth of the primary tumor and the secondary distant metastases of human breast cancer. The research aim is to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoMPaS and corresponding software. We are interested in: 1) modelling the whole natural history of the primary tumor and the secondary distant metastases; 2) developing adequate and precise CoMPaS which reflects relations between the primary tumor and the secondary distant metastases; 3) analyzing the CoMPaS scope of application; 4) implementing the model as a software tool. The foundation of the CoMPaS is the exponential tumor growth model, which is described by determinate nonlinear and linear equations. The CoMPaS corresponds to TNM classification. It allows to calculate different growth periods of the primary tumor and the secondary distant metastases: 1) ‘non-visible period’ for the primary tumor; 2) ‘non-visible period’ for the secondary distant metastases; 3) ‘visible period’ for the secondary distant metastases. The CoMPaS is validated on clinical data of 10-years and 15-years survival depending on the tumor stage and diameter of the primary tumor. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer growth models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. The CoMPaS model and predictive software: a) fit to clinical trials data; b) detect different growth periods of the primary tumor and the secondary distant metastases; c) make forecast of the period of the secondary distant metastases appearance; d) have higher average prediction accuracy than the other tools; e) can improve forecasts on survival of breast cancer and facilitate optimization of diagnostic tests. The following are calculated by CoMPaS: the number of doublings for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases; tumor volume doubling time (days) for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases. The CoMPaS enables, for the first time, to predict ‘whole natural history’ of the primary tumor and the secondary distant metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on the primary tumor sizes. Summarizing: a) CoMPaS describes correctly the primary tumor growth of IA, IIA, IIB, IIIB (T1-4N0M0) stages without metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and inception of the secondary distant metastases.

Keywords: breast cancer, exponential growth model, mathematical model, metastases in lymph nodes, primary tumor, survival

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Authors: Padma Chutoo, Elena Kulinskaya, Ilyas Bakbergenuly, Nicholas Steel, Dmitri Pchejetski

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Transient ischaemic attacks (TIAs) are warning signs for future strokes. TIA patients are at increased risk of stroke and cardio-vascular events after a first episode. A majority of studies on TIA focused on the occurrence of these ancillary events after a TIA. Long-term mortality after TIA received only limited attention. We undertook this study to determine the long-term hazards of all-cause mortality following a first episode of a TIA using anonymised electronic health records (EHRs). We used a retrospective case-control study using electronic primary health care records from The Health Improvement Network (THIN) database. Patients born prior to or in year 1960, resident in England, with a first diagnosis of TIA between January 1986 and January 2017 were matched to three controls on age, sex and general medical practice. The primary outcome was all-cause mortality. The hazards of all-cause mortality were estimated using a time-varying Weibull-Cox survival model which included both scale and shape effects and a random frailty effect of GP practice. 20,633 cases and 58,634 controls were included. Cases aged 39 to 60 years at the first TIA event had the highest hazard ratio (HR) of mortality compared to matched controls (HR = 3.04, 95% CI (2.91 - 3.18)). The HRs for cases aged 61-70 years, 71-76 years and 77+ years were 1.98 (1.55 - 2.30), 1.79 (1.20 - 2.07) and 1.52 (1.15 - 1.97) compared to matched controls. Aspirin provided long-term survival benefits to cases. Cases aged 39-60 years on aspirin had HR of 0.93 (0.84 - 1.00), 0.90 (0.82 - 0.98) and 0.88 (0.80 - 0.96) at 5 years, 10 years and 15 years, respectively, compared to cases in the same age group who were not on antiplatelets. Similar beneficial effects of aspirin were observed in other age groups. There were no significant survival benefits with other antiplatelet options. No survival benefits of antiplatelet drugs were observed in controls. Our study highlights the excess long-term risk of death of TIA patients and cautions that TIA should not be treated as a benign condition. The study further recommends aspirin as the better option for secondary prevention for TIA patients compared to clopidogrel recommended by NICE guidelines. Management of risk factors and treatment strategies should be important challenges to reduce the burden of disease.

Keywords: dual antiplatelet therapy (DAPT), General Practice, Multiple Imputation, The Health Improvement Network(THIN), hazard ratio (HR), Weibull-Cox model

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