Search results for: survival and development
Commenced in January 2007
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Edition: International
Paper Count: 16307

Search results for: survival and development

16277 Parathyroid Hormone Receptor 1 as a Prognostic Indicator in Canine Osteosarcoma

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

Abstract:

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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16276 Response Development of larvae Portunus pelagicus to Artificial Feeding Predigest

Authors: Siti Aslamyah, Yushinta Fujaya, Okto Rimaldi

Abstract:

One of the problems faced in the crab hatchery operations is the reliance on the use of natural feed. This study aims to analyze the response of larval development and determine the initial stages crab larvae begin to fully able to accept artificial feeding predigest with the help of probiotic Bacillus sp. The experiment was conducted in June 2014 through July 2014 at the location of the scale backyard hatcheries, Bojo village Mallusettasi sub-district, district Barru. This study was conducted in two stages larval rearing. The first stage is designed in a completely randomized design with 5 treatments and each with 3 repetitions, ie, without the use of artificial feeding; predigest feed given from zoea 1 - megalopa; predigest feed given since zoea 2 - megalopa; predigest feed given from zoea 3 - megalopa; and feed predigest given since zoea 4 - megalopa. The second stage of the two treatments, i.e. comparing artificial feeding without and with predigest. The results showed that the artificial feeding predigest able to replace the use of natural feed started zoea 3 generated based on the survival rate. Artificial feeding predigest provide a higher survival rate (16%) compared to artificial diets without predigest only 10.8%. However, feed predigest not give a different effect on the rate of development of stadia. Cell activity in larvae that received artificial feed predigest higher with RNA-DNA ratio of 8.88 compared with no predigest only 5:36. This research is very valuable information for crab hatchery hatchery scale households have limitations in preparing natural food.

Keywords: artificial feeding, development of stadia, larvae Portunus pelagicus, predigest

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16275 Influence of Farnesol on Growth and Development of Dysdercus koenigii

Authors: Shailendra Kumar, Kamal Kumar Gupta

Abstract:

Dysdercus koenigii is an economically important pest of cotton worldwide. The pest damages the crop by sucking sap, staining lint, reducing the oil content of the seeds and deteriorating the quality of cotton. Plant possesses a plethora of secondary metabolites which are used as defense mechanism against herbivores. One of the important categories of such chemicals is insect growth regulators and the intermediates in their biosynthesis. Farnesol belongs to sesquiterpenoid. It is an intermediate in Juvenile hormone biosynthetic pathway in insects has been widely reported in the variety of plants. This chemical can disrupt the normal metabolic function and therefore, affects various life processes of the insects. Present study tested the efficacy of farnesol against Dysdercus koenigii. 2μl of 5% (100µg) and 10% (200µg) of the farnesol was applied topically on the dorsum of thoracic region of the newly emerged fifth instar nymphs of Dysdercus. The treated insects were observed daily for their survival, weight gain, and developmental anomalies for a period of ten days. The results indicated that treatment with 200µg farnesol decreased survival of the insects to 70% after 24h of exposure. At lower doses, no significant decrease in the survival was observed. However, the surviving nymphs showed alteration in growth, development, and metamorphosis. The weight gain in the treated nymphs showed deviation from control. The treated nymphs showed an increase in mortality during subsequent days and increase in the nymphal duration. The number of nymphs undergoing metamorphosis decreased to 46% and 88% in the treatments with the dose of 200µg and 100µg respectively. Severe developmental anomalies were also observed in the treated nymphs. The treated nymphs moulted into supernumerary nymphs, adultoids, adults with exuviae attached and adults with wing deformities. On treatment with 200µg; 26% adultoid, 4% adults with exuviae attached and 12% adults with wing deformed were produced. Treatment with 100µg resulted in production of 34% adultoid, 26% adults with deformed wing and 4% adults with exuviae attached. Many of the treated nymphs did not metamorphose into adults, remained in nymphal stage and died. Our results indicated potential application plant-derived secondary metabolites like farnesol in the management of Dysdercus population.

Keywords: development, Dysdercus koenigii, farnesol, survival

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16274 Predictors of Survival of Therapeutic Hypothermia Based on Analysis of a Consecutive American Inner City Population over 4 Years

Authors: Jorge Martinez, Brandon Roberts, Holly Payton Toca

Abstract:

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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16273 Survival Analysis after a First Ischaemic Stroke Event: A Case-Control Study in the Adult Population of England.

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

Abstract:

Stroke is associated with a significant risk of morbidity and mortality. There is scarcity of research on the long-term survival after first-ever ischaemic stroke (IS) events in England with regards to effects of different medical therapies and comorbidities. The objective of this study was to model the all-cause mortality after an IS diagnosis in the adult population of England. Using a retrospective case-control design, we extracted the electronic medical records of patients born prior to or in year 1960 in England with a first-ever ischaemic stroke diagnosis from January 1986 to January 2017 within the Health and Improvement Network (THIN) database. Participants with a history of ischaemic stroke were matched to 3 controls by sex and age at diagnosis and general practice. The primary outcome was the all-cause mortality. The hazards of the all-cause mortality were estimated using a Weibull-Cox survival model which included both scale and shape effects and a shared random effect of general practice. The model included sex, birth cohort, socio-economic status, comorbidities and medical therapies. 20,250 patients with a history of IS (cases) and 55,519 controls were followed up to 30 years. From 2008 to 2015, the one-year all-cause mortality for the IS patients declined with an absolute change of -0.5%. Preventive treatments to cases increased considerably over time. These included prescriptions of statins and antihypertensives. However, prescriptions for antiplatelet drugs decreased in the routine general practice since 2010. The survival model revealed a survival benefit of antiplatelet treatment to stroke survivors with hazard ratio (HR) of 0.92 (0.90 – 0.94). IS diagnosis had significant interactions with gender and age at entry and hypertension diagnosis. IS diagnosis was associated with high risk of all-cause mortality with HR= 3.39 (3.05-3.72) for cases compared to controls. Hypertension was associated with poor survival with HR = 4.79 (4.49 - 5.09) for hypertensive cases relative to non-hypertensive controls, though the detrimental effect of hypertension has not reached significance for hypertensive controls, HR = 1.19(0.82-1.56). This study of English primary care data showed that between 2008 and 2015, the rates of prescriptions of stroke preventive treatments increased, and a short-term all-cause mortality after IS stroke declined. However, stroke resulted in poor long-term survival. Hypertension, a modifiable risk factor, was found to be associated with poor survival outcomes in IS patients. Antiplatelet drugs were found to be protective to survival. Better efforts are required to reduce the burden of stroke through health service development and primary prevention.

Keywords: general practice, hazard ratio, health improvement network (THIN), ischaemic stroke, multiple imputation, Weibull-Cox model.

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16272 The Modeling and Effectiveness Evaluation for Vessel Evasion to Acoustic Homing Torpedo

Authors: Li Minghui, Min Shaorong, Zhang Jun

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This paper aims for studying the operational efficiency of surface warship’s motorized evasion to acoustic homing torpedo. It orderly developed trajectory model, self-guide detection model, vessel evasion model, as well as anti-torpedo error model in three-dimensional space to make up for the deficiency of precious researches analyzing two-dimensionally confrontational models. Then, making use of the Monte Carlo method, it carried out the simulation for the confrontation process of evasion in the environment of MATLAB. At last, it quantitatively analyzed the main factors which determine vessel’s survival probability. The results show that evasion relative bearing and speed will affect vessel’s survival probability significantly. Thus, choosing appropriate evasion relative bearing and speed according to alarming range and alarming relative bearing for torpedo, improving alarming range and positioning accuracy and reducing the response time against torpedo will improve the vessel’s survival probability significantly.

Keywords: acoustic homing torpedo, vessel evasion, monte carlo method, torpedo defense, vessel's survival probability

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16271 Significant Factor of Magnetic Resonance for Survival Outcome in Rectal Cancer Patients Following Neoadjuvant Combined Chemotherapy and Radiation Therapy: Stratification of Lateral Pelvic Lymph Node

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

Abstract:

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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16270 Survival and Hazard Maximum Likelihood Estimator with Covariate Based on Right Censored Data of Weibull Distribution

Authors: Al Omari Mohammed Ahmed

Abstract:

This paper focuses on Maximum Likelihood Estimator with Covariate. Covariates are incorporated into the Weibull model. Under this regression model with regards to maximum likelihood estimator, the parameters of the covariate, shape parameter, survival function and hazard rate of the Weibull regression distribution with right censored data are estimated. The mean square error (MSE) and absolute bias are used to compare the performance of Weibull regression distribution. For the simulation comparison, the study used various sample sizes and several specific values of the Weibull shape parameter.

Keywords: weibull regression distribution, maximum likelihood estimator, survival function, hazard rate, right censoring

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16269 The Clinical and Survival Differences between Primary B-Cell and T/NK-Cell Non-Hodgkin Lymphomas in the Nasopharynx, Nasal Cavity, and Nasal Sinus: A Population-Based Study of 3839 Cases in the Seer Database

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

Abstract:

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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16268 Fecundity and Egg Laying in Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae): Model Development and Field Validation

Authors: Muhammad Noor Ul Ane, Dong-Soon Kim, Myron P. Zalucki

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Models can be useful to help understand population dynamics of insects under diverse environmental conditions and in developing strategies to manage pest species better. Adult longevity and fecundity of Helicoverpa armigera (Hübner) were evaluated against a wide range of constant temperatures (15, 20, 25, 30, 35 and 37.5ᵒC). The modified Sharpe and DeMichele model described adult aging rate and was used to estimate adult physiological age. Maximum fecundity of H. armigera was 973 egg/female at 25ᵒC decreasing to 72 eggs/female at 37.5ᵒC. The relationship between adult fecundity and temperature was well described by an extreme value function. Age-specific cumulative oviposition rate and age-specific survival rate were well described by a two-parameter Weibull function and sigmoid function, respectively. An oviposition model was developed using three temperature-dependent components: total fecundity, age-specific oviposition rate, and age-specific survival rate. The oviposition model was validated against independent field data and described the field occurrence pattern of egg population of H. armigera very well. Our model should be a useful component for population modeling of H. armigera and can be independently used for the timing of sprays in management programs of this key pest species.

Keywords: cotton bollworm, life table, temperature-dependent adult development, temperature-dependent fecundity

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16267 Bayesian Using Markov Chain Monte Carlo and Lindley's Approximation Based on Type-I Censored Data

Authors: Al Omari Moahmmed Ahmed

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These papers describe the Bayesian Estimator using Markov Chain Monte Carlo and Lindley’s approximation and the maximum likelihood estimation of the Weibull distribution with Type-I censored data. The maximum likelihood method can’t estimate the shape parameter in closed forms, although it can be solved by numerical methods. Moreover, the Bayesian estimates of the parameters, the survival and hazard functions cannot be solved analytically. Hence Markov Chain Monte Carlo method and Lindley’s approximation are used, where the full conditional distribution for the parameters of Weibull distribution are obtained via Gibbs sampling and Metropolis-Hastings algorithm (HM) followed by estimate the survival and hazard functions. The methods are compared to Maximum Likelihood counterparts and the comparisons are made with respect to the Mean Square Error (MSE) and absolute bias to determine the better method in scale and shape parameters, the survival and hazard functions.

Keywords: weibull distribution, bayesian method, markov chain mote carlo, survival and hazard functions

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16266 Factors Associated with Recurrence and Long-Term Survival in Younger and Postmenopausal Women with Breast Cancer

Authors: Sopit Tubtimhin, Chaliya Wamaloon, Anchalee Supattagorn

Abstract:

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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16265 Evaluation of Growth Performance and Survival Rate of African Catfish (Clarias gariepinus) Fed with Graded Levels of Egg Shell Substituted Ration

Authors: A. Bello-Olusoji, M. O. Sodamola, Y. A. Adejola, D. D Akinbola

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An eight (8) weeks study was carried out on Four hundred and five (405) African catfish (Clarias gariepinus) juveniles to examine the effect of graded levels of egg shell on their growth performance and survival rates. They were acclimatized for two (2) weeks after which they were weighed and allotted into five dietary treatments of three (3) replicates each and 27 fishes per replicate making a total number of eighty-one (81) fishes per treatment. The dietary treatments contained 0, 25, 50, 75 and 100(%) egg shell inclusion from treatment one to treatment five respectively. Parameter on daily feed intake, weekly weight gain, and daily mortalities were recorded. The result of the experiment indicated that treatment four (4) with 75% inclusion of egg shell was the best in terms of weight gain and survival rates and was significantly different (P<0.05) when compared with the other treatments. For Catfish farming to remain viable in the nearest future, lower feed cost and increased profit are required; it is therefore recommended that diets of African catfish (Clarias gariepinus) be supplemented with well processed egg shell at 75% level of inclusion to achieve this.

Keywords: African catfish, egg shell, performance, performance, survival rate, weight gain

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16264 Impact of Mammographic Screening on Ethnic Inequalities in Breast Cancer Stage at Diagnosis and Survival in New Zealand

Authors: Sanjeewa Seneviratne, Ian Campbell, Nina Scott, Ross Lawrenson

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Introduction: Indigenous Māori women experience a 60% higher breast cancer mortality rate compared with European women in New Zealand. We explored the impact of difference in the rate of screen detected breast cancer between Māori and European women on more advanced disease at diagnosis and lower survival in Māori women. Methods: All primary in-situ and invasive breast cancers diagnosed in screening age women (as defined by the New Zealand National Breast Cancer Screening Programme) between 1999 and 2012 in the Waikato area were identified from the Waikato Breast Cancer Register and the national screening database. Association between screen versus non-screen detection and cancer stage at diagnosis and survival were compared by ethnicity and socioeconomic deprivation. Results: Māori women had 50% higher odds of being diagnosed with more advance staged cancer compared with NZ European women, a half of which was explained by the lower rate of screen detected cancer in Māori women. Significantly lower breast cancer survival rates were observed for Māori compared with NZ European and most deprived compared with most affluent socioeconomic groups for symptomatically detected breast cancer. No significant survival differences by ethnicity or socioeconomic deprivation were observed for screen detected breast cancer. Conclusions: Low rate of screen detected breast cancer appears to be a major contributor for more advanced stage disease at diagnosis and lower breast cancer survival in Māori compared with NZ European women. Increasing screening participation for Māori has the potential to substantially reduce breast cancer mortality inequity between Māori and NZ European women.

Keywords: breast cancer, screening, ethnicity, inequity

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16263 Winter – Not Spring - Climate Drives Annual Adult Survival in Common Passerines: A Country-Wide, Multi-Species Modeling Exercise

Authors: Manon Ghislain, Timothée Bonnet, Olivier Gimenez, Olivier Dehorter, Pierre-Yves Henry

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Climatic fluctuations affect the demography of animal populations, generating changes in population size, phenology, distribution and community assemblages. However, very few studies have identified the underlying demographic processes. For short-lived species, like common passerine birds, are these changes generated by changes in adult survival or in fecundity and recruitment? This study tests for an effect of annual climatic conditions (spring and winter) on annual, local adult survival at very large spatial (a country, 252 sites), temporal (25 years) and biological (25 species) scales. The Constant Effort Site ringing has allowed the collection of capture - mark - recapture data for 100 000 adult individuals since 1989, over metropolitan France, thus documenting annual, local survival rates of the most common passerine birds. We specifically developed a set of multi-year, multi-species, multi-site Bayesian models describing variations in local survival and recapture probabilities. This method allows for a statistically powerful hierarchical assessment (global versus species-specific) of the effects of climate variables on survival. A major part of between-year variations in survival rate was common to all species (74% of between-year variance), whereas only 26% of temporal variation was species-specific. Although changing spring climate is commonly invoked as a cause of population size fluctuations, spring climatic anomalies (mean precipitation or temperature for March-August) do not impact adult survival: only 1% of between-year variation of species survival is explained by spring climatic anomalies. However, for sedentary birds, winter climatic anomalies (North Atlantic Oscillation) had a significant, quadratic effect on adult survival, birds surviving less during intermediate years than during more extreme years. For migratory birds, we do not detect an effect of winter climatic anomalies (Sahel Rainfall). We will analyze the life history traits (migration, habitat, thermal range) that could explain a different sensitivity of species to winter climate anomalies. Overall, we conclude that changes in population sizes for passerine birds are unlikely to be the consequences of climate-driven mortality (or emigration) in spring but could be induced by other demographic parameters, like fecundity.

Keywords: Bayesian approach, capture-recapture, climate anomaly, constant effort sites scheme, passerine, seasons, survival

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16262 Application of Gamma Frailty Model in Survival of Liver Cirrhosis Patients

Authors: Elnaz Saeedi, Jamileh Abolaghasemi, Mohsen Nasiri Tousi, Saeedeh Khosravi

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Goals and Objectives: A typical analysis of survival data involves the modeling of time-to-event data, such as the time till death. A frailty model is a random effect model for time-to-event data, where the random effect has a multiplicative influence on the baseline hazard function. This article aims to investigate the use of gamma frailty model with concomitant variable in order to individualize the prognostic factors that influence the liver cirrhosis patients’ survival times. Methods: During the one-year study period (May 2008-May 2009), data have been used from the recorded information of patients with liver cirrhosis who were scheduled for liver transplantation and were followed up for at least seven years in Imam Khomeini Hospital in Iran. In order to determine the effective factors for cirrhotic patients’ survival in the presence of latent variables, the gamma frailty distribution has been applied. In this article, it was considering the parametric model, such as Exponential and Weibull distributions for survival time. Data analysis is performed using R software, and the error level of 0.05 was considered for all tests. Results: 305 patients with liver cirrhosis including 180 (59%) men and 125 (41%) women were studied. The age average of patients was 39.8 years. At the end of the study, 82 (26%) patients died, among them 48 (58%) were men and 34 (42%) women. The main cause of liver cirrhosis was found hepatitis 'B' with 23%, followed by cryptogenic with 22.6% were identified as the second factor. Generally, 7-year’s survival was 28.44 months, for dead patients and for censoring was 19.33 and 31.79 months, respectively. Using multi-parametric survival models of progressive and regressive, Exponential and Weibull models with regard to the gamma frailty distribution were fitted to the cirrhosis data. In both models, factors including, age, bilirubin serum, albumin serum, and encephalopathy had a significant effect on survival time of cirrhotic patients. Conclusion: To investigate the effective factors for the time of patients’ death with liver cirrhosis in the presence of latent variables, gamma frailty model with parametric distributions seems desirable.

Keywords: frailty model, latent variables, liver cirrhosis, parametric distribution

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16261 The Prognostic Prediction Value of Positive Lymph Nodes Numbers for the Hypopharyngeal Squamous Cell Carcinoma

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

Abstract:

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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16260 Place of Radiotherapy in the Treatment of Intracranial Meningiomas: Experience of the Cancer Center Emir Abdelkader of Oran Algeria

Authors: Taleb L., Benarbia M., Boutira F. M., Allam H., Boukerche A.

Abstract:

Introduction and purpose of the study: Meningiomas are the most common non-glial intracranial tumors in adults, accounting for approximately 30% of all central nervous system tumors. The aim of our study is to determine the epidemiological, clinical, therapeutic, and evolutionary characteristics of a cohort of patients with intracranial meningioma treated with radiotherapy at the Emir Abdelkader Cancer Center in Oran. Material and methods: This is a retrospective study of 44 patients during the period from 2014 to 2020. The overall survival and relapse-free survival curves were calculated using the Kaplan-Meier method. Results and statistical analysis: The median age of the patients was 49 years [21-76 years] with a clear female predominance (sex ratio=2.4). The average diagnostic delay was seven months [2 to 24 months], the circumstances of the discovery of which were dominated by headaches in 54.5% of cases (n=24), visual disturbances in 40.9% (n=18), and motor disorders in 15.9% (n=7). The seat of the tumor was essentially at the level of the base of the skull in 52.3% of patients (n=23), including 29.5% (n=13) at the level of the cavernous sinus, 27.3% (n=12) at the parasagittal level and 20.5% (n=9) at the convexity. The diagnosis was confirmed surgically in 36 patients (81.8%) whose anatomopathological study returned in favor of grades I, II, and III in respectively 40.9%, 29.5%, and 11.4% of the cases. Radiotherapy was indicated postoperatively in 45.5% of patients (n=20), exclusive in 27.3% (n=12) and after tumor recurrence in 27.3% of cases (n=18). The irradiation doses delivered were as follows: 50 Gy (20.5%), 54 Gy (65.9%), and 60 Gy (13.6%). With a median follow-up of 69 months, the probabilities of relapse-free survival and overall survival at three years are 93.2% and 95.4%, respectively, whereas they are 71.2% and 80.7% at five years. Conclusion: Meningiomas are common primary brain tumors. Most often benign but can also progress aggressively. Their treatment is essentially surgical, but radiotherapy retains its place in specific situations, allowing good tumor control and overall survival.

Keywords: diagnosis, meningioma, surgery, radiotherapy, survival

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16259 ICT: Ensuring the Survival of Voluntary Organisations in Ireland

Authors: T. J. McDonald

Abstract:

This paper explores the adoption and usage of ICT by 3 specific types of voluntary organisations in Ireland: Sporting, Community and Rural & Agricultural. It explores the problems that these organisations are facing and examines some of the concerns expressed by their members. The paper outlines how various forms of ICT are being slowly adopted and diffused among its membership to help solve these problems and address their members concerns and in doing so, perhaps ensure the survival of the organisation into the future.

Keywords: Ireland, voluntary organisations, ICT, adoption and diffusion

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16258 Prognostic Impact of Pre-transplant Ferritinemia: A Survival Analysis Among Allograft Patients

Authors: Mekni Sabrine, Nouira Mariem

Abstract:

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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16257 Basil Plants Attract and Benefit Generalist Lacewing Predator Ceraeochrysa cubana Hagen (Neuroptera: Chrysopidae) by Providing Nutritional Resources

Authors: Michela C. Batista Matos, Madelaine Venzon, Elem F. Martins, Erickson C. Freitas, Adenir V. Teodoro, Maira C. M. Fonseca, Angelo Pallini

Abstract:

Aromatic plant species are capable of producing and releasing volatile organic compounds spontaneously, which can repel or attract beneficial insects such as generalist predators of herbivores. Attractive plants could be used as crop companion plants to promote biological control of pests. In order to select such plants for future use in horticulture fields, we assessed the attractiveness of the aromatic plants Ocimum basilicum L. (basil), Mentha piperita L. (peppermint), Melissa officinalis L. (lemon balm) and Cordia verbenacea DC (black sage) to adults of the generalist lacewing predator Ceraeochrysa cubana Hagen (Neuroptera: Chrysopidae). This predator is commonly found in agroecosystems in Brazil and it feeds on aphids, mites, small caterpillars, insect eggs and scales. We further tested the effect of these plant species on the survival, development and oviposition of C. cubana. Finally, we evaluated the survival of larvae and adults of C. cubana when only flowers of basil were offered. Females of C. cubana were attracted to basil but not to the remaining aromatic plants. Larvae survival was higher when individuals had access only to basil leaf than when they had access to peppermint, lemon balm, black sage or water. Adult survival on leaf treatments and on water was no longer than three days. Flowers of basil enhanced predator larvae survival, yet they did not reach adulthood. Adults fed on basil flowers lived longer compared with water, but they did not reproduce. Basil is a promising aromatic plant species to be considered for conservation biological control programs. Besides being attractive to adults of the generalist predator, it benefits larvae and adults by providing nutritional resources when prey or other resources are absent. Financial support: CNPq, FAPEMIG and CAPES (Brazil).

Keywords: basil, chrysopidae, conservation biological control, companion plants

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16256 Dental Implant Survival in Patients with Osteoporosis

Authors: Mohammad ASadian, Samira RajiAsadabadi

Abstract:

Osteoporosis is very common, particularly in post-menopausal women and is characterized by a decrease in bone mass and strength. Osteoporosis also affects the jawbone and it is considered a potential contraindication to the placement of dental implants. The present paper reviews the literature regarding the effect of osteoporosis on the osseointegration of implants. Experimental models have shown that osteoporosis affects the process of osseointegration, which can be reversed by treatment. However, studies in subjects with osteoporosis have shown no differences in the survival of the implants compared to healthy individuals. Therefore, osteoporosis cannot be considered a contraindication for implant placement. Oral bisphosphonates are the most commonly used pharmacological agents in the treatment of osteoporosis. Although there have been cases of osteonecrosis of the jaw in patients treated with bisphosphonates, they are very rare and it is more usually associated with intravenous bisphosphonates in patients with neoplasms or other serious diseases. Nevertheless, patients treated with bisphosphonates must be informed in writing about the possibility of this complication and must give informed consent. Ceasing to use of bisphosphonates before implant placement does not seem to be necessary.

Keywords: Osteoporosis, dental implant, bisphosphonates, survival

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16255 Eco-Biological Study of Artemia salina (Branchiopoda, Anostraca) in Sahline Salt Lake, Tunisia

Authors: Khalil Trigui, Rafik Ben Said, Fourat Akrout, Neji Aloui

Abstract:

In this study, we examined in the first part the eco-biology of Artemia (A.salina) collected from Sahline Salt Lake (governorate of Monastir: Tunisia) during an annual cycle. The correlations between environmental factors and some biological parameters of Artemia were determined. The results obtained showed that the environmental factors affected the biology of Artemia. The highest abundance was recorded in May (550 ± 2,16 ind/l) and all life history stages existed with different seasonal proportions. The Artemia population is bisexual with ovoviviparous reproduction at the beginning and oviparous at the end of the life cycle. We also recorded the dominance of males at the start and the females at the end of the cycle. During all the study period, the size of mature females is bigger than that of males. The fertility obtained resulted in a significant production of cysts compared to the nauplii. A negative correlation with highly significant effect was deduced between environmental factors (temperature and salinity) and the production of nauplii (ovoviviparity) in contrast with dissolved oxygen. In the second part of our work is consecrated to the mastery of breeding Artemia. For this, we tested the effect of five external factors (temperature, salinity, dissolved oxygen, light intensity and food) on the survival of this crustacean. Thereby, the survival rates of Artemia were affected by the different values of studied factors. The recorded results showed that Artemia salina has an optimum temperature ranged from 25 to 27°C with a survival rate ranging from 84 to 88%. The optimal salinity to breed Artemia salina was 37 psu (62 ± 0,23%). Nevertheless, this crustacean was able to survive and withstand the salinity of 0 psu (freshwater). The optimum concentration of dissolved oxygen was 7mg/l with a survival rate of 87,11 ± 0,04%. An optimum light intensity of 10 lux revealed a survival rate equal to 85,33 ± 0,01%. The results also showed that the preferred micro-algae by Artemia is Dunaliella salina with a maximum survival rate of the order of 80 ± 0,15%. There is a significant effect for all experienced parameters on the survival of Artemia reared except the nature of food.

Keywords: Artemia salina, biology, breeding, ecology, Sahline salt lake

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16254 In vivo Anticandida Activity of Three Traditionally Used Medicinal Plants in East Africa

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

Abstract:

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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16253 A Modified Estimating Equations in Derivation of the Causal Effect on the Survival Time with Time-Varying Covariates

Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

Abstract:

a systematic observation from a defined time of origin up to certain failure or censor is known as survival data. Survival analysis is a major area of interest in biostatistics and biomedical researches. At the heart of understanding, the most scientific and medical research inquiries lie for a causality analysis. Thus, the main concern of this study is to investigate the causal effect of treatment on survival time conditional to the possibly time-varying covariates. The theory of causality often differs from the simple association between the response variable and predictors. A causal estimation is a scientific concept to compare a pragmatic effect between two or more experimental arms. To evaluate an average treatment effect on survival outcome, the estimating equation was adjusted for time-varying covariates under the semi-parametric transformation models. The proposed model intuitively obtained the consistent estimators for unknown parameters and unspecified monotone transformation functions. In this article, the proposed method estimated an unbiased average causal effect of treatment on survival time of interest. The modified estimating equations of semiparametric transformation models have the advantage to include the time-varying effect in the model. Finally, the finite sample performance characteristics of the estimators proved through the simulation and Stanford heart transplant real data. To this end, the average effect of a treatment on survival time estimated after adjusting for biases raised due to the high correlation of the left-truncation and possibly time-varying covariates. The bias in covariates was restored, by estimating density function for left-truncation. Besides, to relax the independence assumption between failure time and truncation time, the model incorporated the left-truncation variable as a covariate. Moreover, the expectation-maximization (EM) algorithm iteratively obtained unknown parameters and unspecified monotone transformation functions. To summarize idea, the ratio of cumulative hazards functions between the treated and untreated experimental group has a sense of the average causal effect for the entire population.

Keywords: a modified estimation equation, causal effect, semiparametric transformation models, survival analysis, time-varying covariate

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16252 Different Sampling Schemes for Semi-Parametric Frailty Model

Authors: Nursel Koyuncu, Nihal Ata Tutkun

Abstract:

Frailty model is a survival model that takes into account the unobserved heterogeneity for exploring the relationship between the survival of an individual and several covariates. In the recent years, proposed survival models become more complex and this feature causes convergence problems especially in large data sets. Therefore selection of sample from these big data sets is very important for estimation of parameters. In sampling literature, some authors have defined new sampling schemes to predict the parameters correctly. For this aim, we try to see the effect of sampling design in semi-parametric frailty model. We conducted a simulation study in R programme to estimate the parameters of semi-parametric frailty model for different sample sizes, censoring rates under classical simple random sampling and ranked set sampling schemes. In the simulation study, we used data set recording 17260 male Civil Servants aged 40–64 years with complete 10-year follow-up as population. Time to death from coronary heart disease is treated as a survival-time and age, systolic blood pressure are used as covariates. We select the 1000 samples from population using different sampling schemes and estimate the parameters. From the simulation study, we concluded that ranked set sampling design performs better than simple random sampling for each scenario.

Keywords: frailty model, ranked set sampling, efficiency, simple random sampling

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16251 Intelligent Prediction of Breast Cancer Severity

Authors: Wahab Ali, Oyebade K. Oyedotun, Adnan Khashman

Abstract:

Breast cancer remains a threat to the woman’s world in view of survival rates, it early diagnosis and mortality statistics. So far, research has shown that many survivors of breast cancer cases are in the ones with early diagnosis. Breast cancer is usually categorized into stages which indicates its severity and corresponding survival rates for patients. Investigations show that the farther into the stages before diagnosis the lesser the chance of survival; hence the early diagnosis of breast cancer becomes imperative, and consequently the application of novel technologies to achieving this. Over the year, mammograms have used in the diagnosis of breast cancer, but the inconclusive deductions made from such scans lead to either false negative cases where cancer patients may be left untreated or false positive where unnecessary biopsies are carried out. This paper presents the application of artificial neural networks in the prediction of severity of breast tumour (whether benign or malignant) using mammography reports and other factors that are related to breast cancer.

Keywords: breast cancer, intelligent classification, neural networks, mammography

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16250 Assessment of Incidence and Predictors of Mortality Among HIV Positive Children on Art in Public Hospitals of Harer Town Who Were Enrolled From 2011 to 2021

Authors: Getahun Nigusie Demise

Abstract:

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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16249 Group Sequential Covariate-Adjusted Response Adaptive Designs for Survival Outcomes

Authors: Yaxian Chen, Yeonhee Park

Abstract:

Driven by evolving FDA recommendations, modern clinical trials demand innovative designs that strike a balance between statistical rigor and ethical considerations. Covariate-adjusted response-adaptive (CARA) designs bridge this gap by utilizing patient attributes and responses to skew treatment allocation in favor of the treatment that is best for an individual patient’s profile. However, existing CARA designs for survival outcomes often hinge on specific parametric models, constraining their applicability in clinical practice. In this article, we address this limitation by introducing a CARA design for survival outcomes (CARAS) based on the Cox model and a variance estimator. This method addresses issues of model misspecification and enhances the flexibility of the design. We also propose a group sequential overlapweighted log-rank test to preserve type I error rate in the context of group sequential trials using extensive simulation studies to demonstrate the clinical benefit, statistical efficiency, and robustness to model misspecification of the proposed method compared to traditional randomized controlled trial designs and response-adaptive randomization designs.

Keywords: cox model, log-rank test, optimal allocation ratio, overlap weight, survival outcome

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16248 Relatively High Heart-Rate Variability Predicts Greater Survival Chances in Patients with Covid-19

Authors: Yori Gidron, Maartje Mol, Norbert Foudraine, Frits Van Osch, Joop Van Den Bergh, Moshe Farchi, Maud Straus

Abstract:

Background: The worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-COV2), which began in 2019, also known as Covid-19, has infected over 136 million people and tragically took the lives of over 2.9 million people worldwide. Many of the complications and deaths are predicted by the inflammatory “cytokine storm.” One way to progress in the prevention of death is by finding a predictive and protective factor that inhibits inflammation, on the one hand, and which also increases anti-viral immunity on the other hand. The vagal nerve does precisely both actions. This study examined whether vagal nerve activity, indexed by heart-rate variability (HRV), predicts survival in patients with Covid-19. Method: We performed a pseudo-prospective study, where we retroactively obtained ECGs of 271 Covid-19 patients arriving at a large regional hospital in The Netherlands. HRV was indexed by the standard deviation of the intervals between normal heartbeats (SDNN). We examined patients’ survival at 3 weeks and took into account multiple confounders and known prognostic factors (e.g., age, heart disease, diabetes, hypertension). Results: Patients’ mean age was 68 (range: 25-95) and nearly 22% of the patients had died by 3 weeks. Their mean SDNN (17.47msec) was far below the norm (50msec). Importantly, relatively higher HRV significantly predicted a higher chance of survival, after statistically controlling for patients’ age, cardiac diseases, hypertension and diabetes (relative risk, H.R, and 95% confidence interval (95%CI): H.R = 0.49, 95%CI: 0.26 – 0.95, p < 0.05). However, since HRV declines rapidly with age and since age is a profound predictor in Covid-19, we split the sample by median age (40). Subsequently, we found that higher HRV significantly predicted greater survival in patients older than 70 (H.R = 0.35, 95%CI: 0.16 – 0.78, p = 0.01), but HRV did not predict survival in patients below age 70 years (H.R = 1.11, 95%CI: 0.37 – 3.28, p > 0.05). Conclusions: To the best of our knowledge, this is the first study showing that higher vagal nerve activity, as indexed by HRV, is an independent predictor of higher chances for survival in Covid-19. The results are in line with the protective role of the vagal nerve in diseases and extend this to a severe infectious illness. Studies should replicate these findings and then test in controlled trials whether activating the vagus nerve may prevent mortality in Covid-19.

Keywords: Covid-19, heart-rate Variability, prognosis, survival, vagal nerve

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