Search results for: C. Meier
59 Levels and Trends of Under-Five Mortality in South Africa from 1998 to 2012
Authors: T. Motsima, K. Zuma, E Rapoo
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Childhood mortality is a key sign of the coverage of child survival interventions, social and economic progressions. Although the level of under-five mortality has been declining, it is still unacceptably high. The primary aim of this paper is to establish and analyse the levels and trends of under-five mortality for the periods 1998, 2003 and 2012 in South Africa. Methods: The data used for analysis came from the 1998 SADHS, the 2003 SADHS and the 2012 SABSSM which collected information on the survival status of children. The Kaplan-Meier estimate of the survival function method was used to determine the probabilities of failure (death) from birth up to 59 months. Results and Conclusion: The overall U5MR declined by 28.2% from 53.1 in 1998 to 38.1 in 2012. The U5MR of male children declined from 59.2 in 1998 to 46.2 in 2003 and dropped further to 41.4 in 2012. The U5MR of children of mothers aged 40 years and older increased from 64.0 in 1998 to 89.0 in 2003 and rose further to 129.9 in 2012. The U5MR of children of mothers with education level of 12 years or more increased from 32.2 in 1998 to 35.2 in 2003 and declined substantially to 17.5 in 2012.Keywords: demographic and health survey, Kaplan-Meier, levels and trends, under-five mortality
Procedia PDF Downloads 13658 Early Versus Delayed Antiretroviral Therapy in HIV‐positive People with Tuberculosis
Authors: Mohhamed El Habib Labdouni
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Introduction: Co-infection with VIH and tuberculosis poses one of the major ongoing challenges for global TB and AIDS prevention and control. The objective of this study is to raise the issue of the resurgence of TB, in People living with VIH supported in a referent center in western Algeria. Its epidemiological, clinical, biological and radiological new trends, and to compare the mortality rate between early and delayed ART. Methods: It was a prospective study, during 36 months from the 01st/01/2012 to 31st/12/2014, by identifying and analyzing cases of TB-VIH co-infection. Our population was devised in two groups/ early ART and delayed ART. The primary and secondary endpoints were analyzed with Kaplan-Meier curves and log-rank test the period of follow up, which was fixed at 300 weeks. Results: Sixty cases of co-infection TB -VIH were enrolled in our study: 78.3% had pulmonary tuberculosis associated with extra-pulmonary, 13.3% had only pulmonary tuberculosis and 08.3% presented strictly extra-pulmonary TB. The clinical particularity of this co-infection is the frequency of serious localization such us: pleural 23.3%, peritoneal 31.7%, and meningeal suffusion 13.3%.y-.biologicaly we notice the predominance both of pancytopenia and leucoanemia, hyponatremia in 38,6% and hypokalemia in 19,3%. By analyzing Kaplan-Meier survival curves, we notice that early ART initiation is associated with a significant reduction of all-cause mortality (p = 0,000), and we have identified several prognostic factors such as hypokalemia hyponatremia, leukocytosis thrombopenemia leucothrombopenia (p = 0,005). Conclusion: Our study confirms most of the results reported in the literature. Early ART initiation reduces the rate of all-cause mortality, despite the probability of the occurrence of TB-IRIS.Keywords: TB-HIV co-infection, early ART, hyponatremia, extrapulmonary tuberculosis
Procedia PDF Downloads 18257 Predictor Factors for Treatment Failure among Patients on Second Line Antiretroviral Therapy
Authors: Mohd. A. M. Rahim, Yahaya Hassan, Mathumalar L. Fahrni
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Second line antiretroviral therapy (ART) regimen is used when patients fail their first line regimen. There are many factors such as non-adherence, drug resistance as well as virological and immunological failure that lead to second line highly active antiretroviral therapy (HAART) regimen treatment failure. This study was aimed at determining predictor factors to treatment failure with second line HAART and analyzing median survival time. An observational, retrospective study was conducted in Sungai Buloh Hospital (HSB) to assess current status of HIV patients treated with second line HAART regimen. Convenience sampling was used and 104 patients were included based on the study’s inclusion and exclusion criteria. Data was collected for six months i.e. from July until December 2013. Data was then analysed using SPSS version 18. Kaplan-Meier and Cox regression analyses were used to measure median survival times and predictor factors for treatment failure. The study population consisted mainly of male subjects, aged 30-45 years, who were heterosexual, and had HIV infection for less than 6 years. The most common second line HAART regimen given was lopinavir/ritonavir (LPV/r)-based combination. Kaplan-Meier analysis showed that patients on LPV/r demonstrated longer median survival times than patients on indinavir/ritonavir (IDV/r) based combination (p<0.001). The commonest reason for a treatment to fail with second line HAART was non-adherence. Based on Cox regression analysis, other predictor factors for treatment failure with second line HAART regimen were age and mode of HIV transmission.Keywords: adherence, antiretroviral therapy, second line, treatment failure
Procedia PDF Downloads 26256 Comparative Efficacy of Angiotensin Converting Enzymes Inhibitors and Angiotensin Receptor Blockers in Patients with Heart Failure in Tanzania: A Prospective Cohort Study
Authors: Mark P. Mayala, Henry Mayala, Khuzeima Khanbhai
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Background: Heart failure has been a rising concern in Tanzania. New drugs have been introduced, including the group of drugs called Angiotensin receptor Neprilysin Inhibitor (ARNI), but due to their high cost, angiotensin-converting enzymes inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) have been mostly used in Tanzania. However, according to our knowledge, the efficacy comparison of the two groups is yet to be studied in Tanzania. The aim of this study was to compare the efficacy of ACEIs and ARBs among patients with heart failure. Methodology: This was a hospital-based prospective cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Tanzania, from June to December 2020. Consecutive enrollment was done until fulfilling the inclusion criteria. Clinical details were measured at baseline. We assessed the relationship between ARBs and ACEIs users with N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels at admission and at 1-month follow-up using a chi-square test. A Kaplan-Meier curve was used to estimate the survival time of the two groups. Results: 155 HF patients were enrolled, with a mean age of 48 years, whereby 52.3% were male, and their mean left ventricular ejection fraction (LVEF) was 37.3%. 52 (33.5%) heart failure patients were on ACEIs, 57 (36.8%) on ARBs, and 46 (29.7%) were neither using ACEIs nor ARBs. At least half of the patients did not receive a guideline-directed medical therapy (GDMT), with only 82 (52.9%) receiving a GDMT. A drop in NT pro-BNP levels was observed during admission and at 1-month follow-up on both groups, from 6389.2 pg/ml to 4000.1 pg/ml for ARB users and 5877.7 pg/ml to 1328.2 pg/ml for the ACEIs users. There was no statistical difference between the two groups when estimated by the Kaplan-Meier curve, though more deaths were observed in those who were neither on ACEIs nor ARBs, with a calculated P value of 0.01. Conclusion: This study demonstrates that ACEIs have more efficacy and overall better clinical outcome than ARBs, but this should be taken under the patient-based case, considering the side effects of ACEIs and patients’ adherence.Keywords: angiotensin converting enzymes inhibitors, angiotensin receptor blockers, guideline direct medical therapy, N-terminal pro-brain natriuretic peptide
Procedia PDF Downloads 8555 Evaluating the Probability of Foreign Tourists' Return to the City of Mashhad, Iran
Authors: Mohammad Rahim Rahnama, Amir Ali Kharazmi, Safiye Rokni
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The tourism industry will be the most important unlimited, sustainable source of income after the oil and automotive industries by 2020 and not only countries, but cities are striving to apprehend its various facets. In line with this objective, the present descriptive-analytical study, through survey and using a questionnaire, seeks to evaluate the probability of tourists’ return and their recommendation to their countrymen to travel to Mashhad, Iran. The population under study is a sample of 384 foreign tourists who, in 2016, arrived at Mashhad, the second metropolis in Iran and its biggest religious city. The Kaplan-Meier estimator was used to analyze the data. Twenty-six percent of the tourists are female and 74% are male. On average, each tourist has had 3.02 trips abroad and 2.1 trips to Mashhad. Tourists from 14 different countries have arrived at Mashhad. Kuwait (15.9%), Armenia (15.6%), and Iraq (10.9%) were the countries where most tourists originated. Seventy-six percent of the tourists traveled with family and 90% of the tourists arrived at Mashhad via airplane. Major purposes of tourists’ trip include pilgrimage (27.9%), treatment (22.1%) followed by pilgrimage and treatment combined (35.4%). Major issues for tourists, in the order of priority, include quality of goods and services (30.2%), shopping (18%), and inhabitants’ treatment of foreigners (15.9%). Main tourist attractions, in addition to the Holy Shrine of Imam Reza, include Torqabeh and Shandiz (Torqabeh 40.9% and Shandiz 29.9%), Neyshabour (18.2%) followed by Kalat, 4.4%. The average willingness to return among tourists is 3.13, which is higher than the mean 3, indicating satisfaction with the stay in Mashhad. Similarly, the average for tourists’ recommending to their countrymen to visit Mashhad is 3.42, which is also an indicator of tourists’ satisfaction with their presence in Mashhad. According to the findings of the Kaplan-Meier estimator, an increase in the number of tourists’ trips to Mashhad, and an increase in the number of tourists’ foreign trips, reduces the probability of recommending a trip to Mashhad by tourists. Similarly, willingness to return is higher among those who stayed at a relatives’ home compared with other patterns of residence (hotels, self-catering accommodation, and pilgrim houses). Therefore, addressing the issues raised by tourists is essential for their return and their recommendation to others to travel to Mashhad.Keywords: international tourist, probability of return, satisfaction, Mashhad
Procedia PDF Downloads 16854 Surface Topography Measurement by Confocal Spectral Interferometry
Authors: A. Manallah, C. Meier
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Confocal spectral interferometry (CSI) is an innovative optical method for determining microtopography of surfaces and thickness of transparent layers, based on the combination of two optical principles: confocal imaging, and spectral interferometry. Confocal optical system images at each instant a single point of the sample. The whole surface is reconstructed by plan scanning. The interference signal generated by mixing two white-light beams is analyzed using a spectrometer. In this work, five ‘rugotests’ of known standard roughnesses are investigated. The topography is then measured and illustrated, and the equivalent roughness is determined and compared with the standard values.Keywords: confocal spectral interferometry, nondestructive testing, optical metrology, surface topography, roughness
Procedia PDF Downloads 27553 Building a Hierarchical, Granular Knowledge Cube
Authors: Alexander Denzler, Marcel Wehrle, Andreas Meier
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A knowledge base stores facts and rules about the world that applications can use for the purpose of reasoning. By applying the concept of granular computing to a knowledge base, several advantages emerge. These can be harnessed by applications to improve their capabilities and performance. In this paper, the concept behind such a construct, called a granular knowledge cube, is defined, and its intended use as an instrument that manages to cope with different data types and detect knowledge domains is elaborated. Furthermore, the underlying architecture, consisting of the three layers of the storing, representing, and structuring of knowledge, is described. Finally, benefits as well as challenges of deploying it are listed alongside application types that could profit from having such an enhanced knowledge base.Keywords: granular computing, granular knowledge, hierarchical structuring, knowledge bases
Procedia PDF Downloads 49652 Low SPOP Expression and High MDM2 expression Are Associated with Tumor Progression and Predict Poor Prognosis in Hepatocellular Carcinoma
Authors: Chang Liang, Weizhi Gong, Yan Zhang
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Purpose: Hepatocellular carcinoma (HCC) is a malignant tumor with a high mortality rate and poor prognosis worldwide. Murine double minute 2 (MDM2) regulates the tumor suppressor p53, increasing cancer risk and accelerating tumor progression. Speckle-type POX virus and zinc finger protein (SPOP), a key of subunit of Cullin-Ring E3 ligase, inhibits tumor genesis and progression by the ubiquitination of its downstream substrates. This study aimed to clarify whether SPOP and MDM2 are mutually regulated in HCC and the correlation between SPOP and MDM2 and the prognosis of HCC patients. Methods: First, the expression of SPOP and MDM2 in HCC tissues were detected by TCGA database. Then, 53 paired samples of HCC tumor and adjacent tissues were collected to evaluate the expression of SPOP and MDM2 using immunohistochemistry. Chi-square test or Fisher’s exact test were used to analyze the relationship between clinicopathological features and the expression levels of SPOP and MDM2. In addition, Kaplan‒Meier curve analysis and log-rank test were used to investigate the effects of SPOP and MDM2 on the survival of HCC patients. Last, the Multivariate Cox proportional risk regression model analyzed whether the different expression levels of SPOP and MDM2 were independent risk factors for the prognosis of HCC patients. Results: Bioinformatics analysis revealed the low expression of SPOP and high expression of MDM2 were related to worse prognosis of HCC patients. The relationship between the expression of SPOP and MDM2 and tumor stem-like features showed an opposite trend. The immunohistochemistry showed the expression of SPOP protein was significantly downregulated while MDM2 protein significantly upregulated in HCC tissue compared to that in para-cancerous tissue. Tumors with low SPOP expression were related to worse T stage and Barcelona Clinic Liver Cancer (BCLC) stage, but tumors with high MDM2 expression were related to worse T stage, M stage, and BCLC stage. Kaplan–Meier curves showed HCC patients with high SPOP expression and low MDM2 expression had better survival than those with low SPOP expression and high MDM2 expression (P < 0.05). A multivariate Cox proportional risk regression model confirmed that a high MDM2 expression level was an independent risk factor for poor prognosis in HCC patients (P <0.05). Conclusion: The expression of SPOP protein was significantly downregulated, while the expression of MDM2 significantly upregulated in HCC. The low expression of SPOP and high expression. of MDM2 were associated with malignant progression and poor prognosis of HCC patients, indicating a potential therapeutic target for HCC patients.Keywords: hepatocellular carcinoma, murine double minute 2, speckle-type POX virus and zinc finger protein, ubiquitination
Procedia PDF Downloads 14351 Achieving Better Security by Using Nonlinear Cellular Automata as a Cryptographic Primitive
Authors: Swapan Maiti, Dipanwita Roy Chowdhury
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Nonlinear functions are essential in different cryptoprimitives as they play an important role on the security of the cipher designs. Rule 30 was identified as a powerful nonlinear function for cryptographic applications. However, an attack (MS attack) was mounted against Rule 30 Cellular Automata (CA). Nonlinear rules as well as maximum period CA increase randomness property. In this work, nonlinear rules of maximum period nonlinear hybrid CA (M-NHCA) are studied and it is shown to be a better crypto-primitive than Rule 30 CA. It has also been analysed that the M-NHCA with single nonlinearity injection proposed in the literature is vulnerable against MS attack, whereas M-NHCA with multiple nonlinearity injections provide maximum length cycle as well as better cryptographic primitives and they are also secure against MS attack.Keywords: cellular automata, maximum period nonlinear CA, Meier and Staffelbach attack, nonlinear functions
Procedia PDF Downloads 31250 Preserved Relative Differences between Regions of Different Thermal Scans
Authors: Tahir Majeed, Michael Handschuh, René Meier
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Rheumatoid arthritis patients have swelling and pain at the joints of the hand. The regions where the patient feels pain also show increased body temperature. Thermal cameras can be used to detect the rise in temperature of the affected regions. To monitor the disease progression of rheumatoid arthritis patients, they must visit the clinic regularly for scanning and examination. After scanning and evaluation, the dosage of the medicine is regulated accordingly. To monitor the disease progression over time, the correlation between the images between different visits must be established. It has been observed that by using low-cost thermal cameras, the thermal measurements do not remain the same over time, even within a single scanning. In some situations, temperatures can vary as much as 2°C within the same scanning sequence. In this paper, it has been shown that although the absolute temperature varies over time, the relative difference between the different regions remains similar. Results have been computed over four scanning sequences and are presented.Keywords: relative thermal difference, rheumatoid arthritis, thermal imaging, thermal sensors
Procedia PDF Downloads 19649 The Comparison of Primary B-Cell and NKT-Cell Non-Hodgkin Lymphomas in Nasopharynx, Nasal Cavity, and Paranasal Sinuses
Authors: Jiajia Peng, Jianqing Qiu, Jianjun Ren, Yu Zhao
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Background: We aimed to compare clinical and survival differences between B-cell (B-NHL) and NKT-cell non-Hodgkin lymphomas (NKT-NHL) located in the nasal cavity, nasopharynx and paranasal sinuses, which are always categorized as one sinonasal type. Methods: Patients diagnosed with primary B-NHL and NKT-NHL in the nasal cavity, nasopharynx, and paranasal sinuses from the SEER database were included. We identified these patients based on histological types and anatomical sites and subsequently conducted univariate and multivariate Cox regression and Kaplan–Meier analyses to examine cancer-special survival (CSS) outcomes. Results: Overall, most B-NHL cases originated from the nasopharynx, while the majority of NKT-NHL cases occurred in the nasal cavity. Notably, the CSS outcomes improved significantly in all sinonasal B-NHL cases over time, whereas no such improvement trend was observed in each sinonasal NKT-NHL type. Additionally, increasing age was linked with an elevated risk of death in B-NHL, particularly in the nasal cavity (HR:3.37), rather than in NKT-NHL. Compared with B-NHL, the adverse effect of the higher stage on CSS was more evident in NKT-NHL, particularly in its nasopharynx site (HR: 5.12). Furthermore, radiotherapy was beneficial for survival in patients with sinonasal B-NHL and NKT-NHL, except in those with NKT-NHL in the nasopharynx site. However, chemotherapy has only been beneficial for CSS in patients with B-NHL in paranasal sinuses (HR: 0.42) since 2010, rather than in other types of B-NHL or NKT-NHL. Conclusions: Although B-NHL and NKT-NHL in the nasal cavity, nasopharynx and paranasal sinuses have similar anatomical locations, their clinic demographics and prognoses are largely different and should be treated and studied as distinct diseases.Keywords: B-cell non-Hodgkin lymphomas, NKT-cell non-Hodgkin lymphomas, nasal cavity lymphomas, nasal sinuses lymphomas, nasopharynx lymphomas
Procedia PDF Downloads 10548 High-Dose-Rate Brachytherapy for Cervical Cancer: The Effect of Total Reference Air Kerma on the Results of Single-Channel and Tri-Channel Applicators
Authors: Hossain A., Miah S., Ray P. K.
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Introduction: Single channel and tri-channel applicators are used in the traditional treatment of cervical cancer. Total reference air kerma (TRAK) and treatment outcomes in high-dose-rate brachytherapy for cervical cancer using single-channel and tri-channel applicators were the main objectives of this retrospective study. Material and Methods: Patients in the radiotherapy division who received brachytherapy, chemotherapy, and external radiotherapy (EBRT) using single and tri-channel applicators were the subjects of a retrospective cohort study from 2016 to 2020. All brachytherapy parameters, including TRAK, were calculated in accordance with the international protocol. The Kaplan Meier method was used to analyze survival rates using a log-rank test. Results and Discussions: Based on treatment times of 15.34 (10-20) days and 21.35 (6.5-28) days, the TRAK for the tri-channel applicator was 0.52 cGy.m² and for the single-channel applicator was 0.34 cGy.m². Based on TRAK, the rectum, bladder, and tumor had respective Pearson correlations of 0.082, 0.009, and 0.032. The 1-specificity and sensitivity were 0.70 and 0.30, respectively. At that time, AUC was 0.71. The log-rank test showed that tri-channel applicators had a survival rate of 95% and single-channel applicators had a survival rate of 85% (p=0.565). Conclusions: The relationship between TRAK and treatment duration and Pearson correlation for the tumor, rectum, and bladder suggests that TRAK should be taken into account for the proper operation of single channel and tri-channel applicators.Keywords: single-channel, tri-channel, high dose rate brachytherapy, cervical cancer
Procedia PDF Downloads 10047 Survival Outcomes Related to Treatment Modalities in Patients with Oropharyngeal Squamous Cell Carcinoma
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
Procedia PDF Downloads 17446 Endovascular Aneurysm Repair (Evar) with Endoanchors: For Tandem Aortic Abdominal Aneurysm (Aaa) with Hostile Neck & Proximal Penetrating Atherosclerotic Ulcer
Authors: Von Jerick Tenorio, Jonald Lucero, Marivic Vestal, Edwin Tiempo
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In patients with hostile aortic neck anatomy, the risks of proximal seal complications and stent migration remain with EVAR despite improved endograft technology. This case report discusses how the technical challenges of the hostile neck anatomy, proximal penetrating atherosclerotic ulcer (PAU) and tortuous femoral access were addressed. The CT aortogram of a 63-year-old hypertensive and diabetic man with recurring abdominal discomfort revealed a fusiform infra-renal aneurysm measuring 8.8 cm in length and 5.7 cm in diameter. The proximal landing zone only has a 3 mm healthy neck with a conicity of > 10% and a thrombus of 4 mm thick. Proximal to the aneurysm is a PAU with a circumferential mural thrombus. The right femoral artery is tortuous with > 90o angulation. A 20% oversized Endurant II endograft and Aptus Heli-FX EndoAnchors were deployed as prophylaxis for type I endoleaks and endograft migration consequent to the conical neck and proximal aneurysm extension consequent to the PAU. A stiff Backup Meier guide wire facilitated the deployment of the endograft. Coil embolization of the right internal iliac artery was performed as prophylaxis for type II endoleaks. EndoAnchors can be used as an adjunct to EVAR as prophylaxis for proximal seal complications and stent migration in patients with hostile aortic aneurysm neck anatomy and concomitant proximal PAU.Keywords: endoAnchors, endoleaks, EVAR, hostile neck
Procedia PDF Downloads 20445 Prospective Study to Determine the Efficacy of Day Hospital Care to Improve Treatment Adherence for Hospitalized Schizophrenic Patients
Authors: Jin Hun Choi, So Hyun Ahn, Seong Keun Wang, Ik-Seung Chee, Jung Lan Kim, Sun Woo Lee
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Objectives: The purpose of the study is to investigate the effects of day hospital care in hospitalized schizophrenic patients in terms of treatment adherence and treatment outcomes. Methods: Among schizophrenic patients hospitalized between 2011 and 2012, 23 day hospital care patient and 40 control subjects were included in the study. All candidates underwent Beck Cognitive Insight Scale, Drug Attitude Inventory, World Health Organization Quality of Life Assessment and Psychological Well-Being Scale when their symptoms were stabilized during hospitalization, and after being discharged, 23 patients received day hospital care for two months and then changed to out-patient care while 40 patients received out-patient care immediately after discharge. At the point of two months of out-patient care, the treatment adherence of the two groups was evaluated; tracking observation was performed until February, 2013, and survival rates were compared between the two groups. Results: Treatment adherence was higher in the day hospital care group than in the control group. Kaplan-Meier survival analysis showed a higher survival rate for the day hospital care group compared to the control group. Levels of cognitive insight and quality of life were higher after day hospital care than before day hospital care in the day hospital care group. Conclusions: Through the study, it was confirmed that when hospitalized schizophrenic patients received continuous day hospital care after being discharged, they received further out-patient care more faithfully. The study is considered to aid in the understanding regarding schizophrenic patients’ treatment adherence issues and improvement of treatment outcomes.Keywords: schizophrenia, day hospital care, adherence, outcomes
Procedia PDF Downloads 35344 MAGE-A3 and PRAME Gene Expression and EGFR Mutation Status in Non-Small-Cell Lung Cancer
Authors: Renata Checiches, Thierry Coche, Nicolas F. Delahaye, Albert Linder, Fernando Ulloa Montoya, Olivier Gruselle, Karen Langfeld, An de Creus, Bart Spiessens, Vincent G. Brichard, Jamila Louahed, Frédéric F. Lehmann
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Background: The RNA-expression levels of cancer-testis antigens MAGE A3 and PRAME were determined in resected tissue from patients with primary non-small-cell lung cancer (NSCLC) and related to clinical outcome. EGFR, KRAS and BRAF mutation status was determined in a subset to investigate associations with MAGE A3 and PRAME expression. Methods: We conducted a single-centre, uncontrolled, retrospective study of 1260 tissue-bank samples from stage IA-III resected NSCLC. The prognostic value of antigen expression (qRT-PCR) was determined by hazard-ratio and Kaplan-Meier curves. Results: Thirty-seven percent (314/844) of tumours expressed MAGE-A3, 66% (723/1092) expressed PRAME and 31% (239/839) expressed both. Respective frequencies in squamous-cell tumours and adenocarcinomas were 43%/30% for MAGE A3 and 80%/44% for PRAME. No correlation with stage, tumour size or patient age was found. Overall, no prognostic value was identified for either antigen. A trend to poorer overall survival was associated with MAGE-A3 in stage IIIB and with PRAME in stage IB. EGFR and KRAS mutations were found in 10.1% (28/311) and 33.8% (97/311) of tumours, respectively. EGFR (but not KRAS) mutation status was negatively associated with PRAME expression. Conclusion: No clear prognostic value for either PRAME or MAGE A3 was observed in the overall population, although some observed trends may warrant further investigation.Keywords: MAGE A3, PRAME, cancer-testis gene, NSCLC, survival, EGFR
Procedia PDF Downloads 38143 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
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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
Procedia PDF Downloads 18342 The Role of HPV Status in Patients with Overlapping Grey Zone Cancer in Oral Cavity and Oropharynx
Authors: Yao Song
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Objectives: We aimed to explore the clinicodemographic characteristics and prognosis of grey zone squamous cell cancer (GZSCC) located in the overlapping or ambiguous area of the oral cavity and oropharynx and to identify valuable factors that would improve its differential diagnosis and prognosis. Methods: Information of GZSCC patients in the Surveillance, Epidemiology, and End Results (SEER) database was compared to patients with an oral cavity (OCSCC) and oropharyngeal (OPSCC) squamous cell carcinomas with corresponding HPV status, respectively. Kaplan-Meier method with log-rank test and multivariate Cox regression analysis were applied to assess associations between clinical characteristics and overall survival (OS). A predictive model integrating age, gender, marital status, HPV status, and staging variables was conducted to classify GZSCC patients into three risk groups and verified internally by 10-fold cross validation. Results: A total of 3318 GZSCC, 10792 OPSCC, and 6656 OCSCC patients were identified. HPV-positive GZSCC patients had the best 5-year OS as HPV-positive OPSCC (81% vs. 82%). However, the 5-year OS of HPV-negative/unknown GZSCC (43%/42%) was the worst among all groups, indicating that HPV status and the overlapping nature of tumors were valuable prognostic predictors in GZSCC patients. Compared with the strategy of dividing GZSCC into two groups by HPV status, the predictive model integrating more variables could additionally identify a unique high-risk GZSCC group with the lowest OS rate. Conclusions: GZSCC patients had distinct clinical characteristics and prognoses compared with OPSCC and OCSCC; integrating HPV status and other clinical factors could help distinguish GZSCC and predict their prognosis.Keywords: GZSCC, OCSCC, OPSCC, HPV
Procedia PDF Downloads 7541 Survival Pattern of Under-five Mortality in High Focus States in India
Authors: Rahul Kumar
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Background: Under-FiveMortality Rate(U5MR)ofanationiswidelyacceptedandlong-standing indicators of well-beingofherchildren.They measuredtheprobability of dying before theageoffive(expressedper1000livebirths).TheU5MRisanappropriate indicator of the cumulative exposure totheriskofdeathduringthefirstfiveyearsoflife, and accepted globalindicator ofthehealthandsocioeconomicstatusofagiven population.Itisalsousefulforassessing theimpactofvariousintervention programmes aimed at improving child survival.Under-fivemortalitytrendsconstitutealeadingindicatorofthelevel ofchildhealthandoveralldevelopmentincountries. Objectives: The first aim of our research is to study the level, trends, and Pattern of Under-five mortality using different sources of data. The second objective is to examine the survival pattern of Under-five mortality by different background characteristics. Data Source and Methodology: SRS and NFHS data have been used forobservingthelevelandtrendofUnder-Five mortality rate. Kaplan Meier Estimate has been used to understand the survival Pattern of Under-five mortality. Result: WefindthatallmostallthestatesmadesomeprogressbyreducingU5MRin recent decades.During1992-93highestU5MR(per thousand live birth) was observed in Assam(142)followed by up(141),Odisha(131),MP(130),andBihar(127.5).While the least U5MR(perthousandlive birth)wasobservedinRajasthan(102). The highestU5MR(per thousandlive birth)isobservedinUP(78.1), followed by MP(64.9)and Chhattisgarh(63.7)which are far away from the national level(50). Among them, Uttarakhand(46.7)hadleastU5MR(perthousandlivebirth), followed by Odisha(48.6). TheU5MR(perthousandlivebirth)ofcombinedhighfocusstateis63.7whichisfar away fromthenationallevel(50). Weidentified thatthesurvivalprobability ofunder-fivechildrenfromadolescentmotherislessin comparisontootherchildrenbornby differentagegroupofmothers. thatduringneonatalperiodusually male mortality exceedsthefemale mortality butthisdifferentialreversedinthepostneonatalperiod. Astheirageincreasesand approachingtofiveyears,weidentifiedthatthesurvivalprobability ofbothsexdecreasesbut female’s survival probabilitydecrement is more than male as their ageincreases. The poorer children’s survival probability is minimum. Children using improved toilet facility has more survival probability throughout thefiveyearsthan who uses unimproved. The survival probability of children under five who got Full ANCis more than the survival probability of children under five who doesn’t get any ANC. Conclusions: Improvement of maternal education is an urgent need to improve their health seeking behavior and thus the health of their children. Awareness on reproductive health and environmental sanitation should be strengthened.Keywords: under-five mortality, survival pattern, ANC, trend
Procedia PDF Downloads 13140 Predicting High-Risk Endometrioid Endometrial Carcinomas Using Protein Markers
Authors: Yuexin Liu, Gordon B. Mills, Russell R. Broaddus, John N. Weinstein
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The lethality of endometrioid endometrial cancer (EEC) is primarily attributable to the high-stage diseases. However, there are no available biomarkers that predict EEC patient staging at the time of diagnosis. We aim to develop a predictive scheme to help in this regards. Using reverse-phase protein array expression profiles for 210 EEC cases from The Cancer Genome Atlas (TCGA), we constructed a Protein Scoring of EEC Staging (PSES) scheme for surgical stage prediction. We validated and evaluated its diagnostic potential in an independent cohort of 184 EEC cases obtained at MD Anderson Cancer Center (MDACC) using receiver operating characteristic curve analyses. Kaplan-Meier survival analysis was used to examine the association of PSES score with patient outcome, and Ingenuity pathway analysis was used to identify relevant signaling pathways. Two-sided statistical tests were used. PSES robustly distinguished high- from low-stage tumors in the TCGA cohort (area under the ROC curve [AUC]=0.74; 95% confidence interval [CI], 0.68 to 0.82) and in the validation cohort (AUC=0.67; 95% CI, 0.58 to 0.76). Even among grade 1 or 2 tumors, PSES was significantly higher in high- than in low-stage tumors in both the TCGA (P = 0.005) and MDACC (P = 0.006) cohorts. Patients with positive PSES score had significantly shorter progression-free survival than those with negative PSES in the TCGA (hazard ratio [HR], 2.033; 95% CI, 1.031 to 3.809; P = 0.04) and validation (HR, 3.306; 95% CI, 1.836 to 9.436; P = 0.0007) cohorts. The ErbB signaling pathway was most significantly enriched in the PSES proteins and downregulated in high-stage tumors. PSES may provide clinically useful prediction of high-risk tumors and offer new insights into tumor biology in EEC.Keywords: endometrial carcinoma, protein, protein scoring of EEC staging (PSES), stage
Procedia PDF Downloads 22039 Interaction of Racial and Gender Disparities in Salivary Gland Cancer Survival in the United States: A Surveillance Epidemiology and End Results Study
Authors: Sarpong Boateng, Rohit Balasundaram, Akua Afrah Amoah
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Introduction: Racial and Gender disparities have been found to be independently associated with Salivary Gland Cancers (SGCs) survival; however, to our best knowledge, there are no previous studies on the interplay of these social determinants on the prognosis of SGCs. The objective of this study was to examine the joint effect of race and gender on the survival of SGCs. Methods: We analyzed survival outcomes of 13,547 histologically confirmed cases of SGCs using the Surveillance Epidemiology and End Results (SEER) database (2004 to 2015). Multivariable Cox regression analysis and Kaplan-Meier curves were used to estimate hazard ratios (HR) after controlling for age, tumor characteristics, treatment type and year of diagnosis. Results: 73.5% of the participants were whites, 8.5% were blacks, 10.1% were Hispanics and 58.5% were males. Overall, males had poorer survival than females (HR = 1.16, p=0.003). In the adjusted multivariable model, there were no significant differences in survival by race. However, the interaction of gender and race was statistically significant (p=0.01) in Hispanic males. Thus, compared to White females (reference), Hispanic females had significantly better survival (HR=0.53), whiles Hispanic males had worse survival outcomes (HR=1.82) for SGCs. Conclusions: Our results show significant interactions between race and gender, with racial disparities varying across the different genders for SGCs survival. This study indicates that racial and gender differences are crucial factors to be considered in the prognostic counseling and management of patients with SGCs. Biologic factors, tumor genetic characteristics, chemotherapy, lifestyle, environmental exposures, and socioeconomic and dietary factors are potential yet proven reasons that could account for racial and gender differences in the survival of SGCs.Keywords: salivary, cancer, survival, disparity, race, gender, SEER
Procedia PDF Downloads 20038 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.
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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
Procedia PDF Downloads 9937 Systematic Review and Meta-Analysis of Mid-Term Survival, and Recurrent Mitral Regurgitation for Robotic-Assisted Mitral Valve Repair
Authors: Ramanen Sugunesegran, Michael L. Williams
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Over the past two decades surgical approaches for mitral valve (MV) disease have evolved with the advent of minimally invasive techniques. Robotic mitral valve repair (RMVr) safety and efficacy has been well documented, however, mid- to long-term data are limited. The aim of this review was to provide a comprehensive analysis of the available mid- to long-term term data for RMVr. Electronic searches of five databases were performed to identify all relevant studies reporting minimum 5-year data on RMVr. Pre-defined primary outcomes of interest were overall survival, freedom from MV reoperation and freedom from moderate or worse mitral regurgitation (MR) at 5-years or more post-RMVr. A meta-analysis of proportions or means was performed, utilizing a random effects model, to present the data. Kaplan-Meier curves were aggregated using reconstructed individual patient data. Nine studies totaling 3,300 patients undergoing RMVr were identified. Rates of overall survival at 1-, 5- and 10-years were 99.2%, 97.4% and 92.3%, respectively. Freedom from MV reoperation at 8-years post RMVr was 95.0%. Freedom from moderate or worse MR at 7-years was 86.0%. Rates of early post-operative complications were low with only 0.2% all-cause mortality and 1.0% cerebrovascular accident. Reoperation for bleeding was low at 2.2% and successful RMVr was 99.8%. Mean intensive care unit and hospital stay were 22.4 hours and 5.2 days, respectively. RMVr is a safe procedure with low rates of early mortality and other complications. It can be performed with low complication rates in high volume, experienced centers. Evaluation of available mid-term data post-RMVr suggests favorable rates of overall survival, freedom from MV reoperation and freedom from moderate or worse MR recurrence.Keywords: mitral valve disease, mitral valve repair, robotic cardiac surgery, robotic mitral valve repair
Procedia PDF Downloads 8236 Prognostic Impact of Pre-transplant Ferritinemia: A Survival Analysis Among Allograft Patients
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
Procedia PDF Downloads 6535 Exclusive Breastfeeding Abandonment among Adolescent Mothers: A Cohort Study
Authors: Maria I. Nuñez-Hernández, Maria L. Riesco
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Background: Exclusive breastfeeding (EBF) up to 6 months old infant have been considered one of the most important factors in the overall development of children. Nevertheless, as resources are scarce, it is essential to identify the most vulnerable groups that have major risk of EBF abandonment, in order to deliver the best strategies. Children of adolescent mothers are within these groups. Aims: To determine the EBF abandonment rate among adolescent mothers and to analyze the associated factors. Methods: Prospective cohort study of adolescent mothers in the southern area of Santiago, Chile, conducted in primary care services of public health system. The cohort was established from 2014 to 2015, with a sample of 105 adolescent mothers and their children at 2 months of life. The inclusion criteria were: adolescent mother from 14 to 19 years old; not twin babies; mother and baby leaving the hospital together after birthchild; correct attachment of the baby to the breast; no difficulty understanding the Spanish language or communicating. Follow-up was performed at 4 and 6 months old infant. Data were collected by interviews, considering EBF as breastfeeding only, without adding other milk, tea, juice, water or other product that not breast milk, except drugs. Data were analyzed by descriptive and inferential statistics, by Kaplan-Meier estimator and Log-Rank test, admitting the probability of occurrence of type I error of 5% (p-value = 0.05). Results: The cumulative EBF abandonment rate at 2, 4 and 6 months was 33.3%, 52.2% and 63.8%, respectively. Factors associated with EBF abandonment were maternal perception of the quality of milk as poor (p < 0.001), maternal perception that the child was not satisfied after breastfeeding (p < 0.001), use of pacifier (p < 0.001), maternal consumption of illicit drugs after delivery (p < 0.001), mother return to school (p = 0.040) and presence of nipple trauma (p = 0.045). Conclusion: EBF abandonment rate was higher in the first 4 months of life and is superior to the population of women who breastfeed. Among the EBF abandonment factors, one of them is related to the adolescent condition, and two are related to the maternal subjective perception.Keywords: adolescent, breastfeeding, midwifery, nursing
Procedia PDF Downloads 32134 The Importance of a Coating and Architecture of the Surface Metal on the Survival of Uncemented Total Knee Arthroplasty
Authors: Raymond Puijk, Rachid Rassir, Inger N. Sierevelt, Anneke Spekenbrink-Sporen, Bart G. C. W. Pijls, Rob G. H. H. Nelissen, Peter A. Nolte
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Background: Among uncemented total knee arthroplasty (TKA), a wide variety of metal surface structures (MSS) and coatings exist to enhance implants' biological properties (i.e., bone ingrowth). This study explores the variety of MSS-coating combinations and compares their mid-long-term survivorships with cemented TKAs, by using data from the Dutch Arthroplasty Register. Methods: A total of 235,500 cemented and 11,132 uncemented primary TKAs with a median follow-up of 5.1 years were included. MSS-coating combinations were (1) Porous-uncoated (n=8986), (2) Beaded-hydroxyapatite (HA)(n=1093), (3) Matte-uncoated (n=846), (4) Matte-Titanium-nitride (TiN) (n=207). Five- and 10-year revision-free survival for all-cause revisions, and aseptic loosening of the tibial component, were calculated and compared by using Kaplan-Meier, Log-rank tests, and multivariable Cox proportional hazard regression analyses. Results: Ten-year survival rates with all-cause revisions as an endpoint, were 94.2% for cement, and 94.7%, 96.3%, 92.1%, and 79.0% for porous-uncoated, beaded-HA, matte-uncoated, and Matte-TiN, respectively (p<0.01). Rates for aseptic loosening were 98.8% for cemented, and 98.7%, 99.8%, 97.2%, and 94.9% for the uncemented, respectively (p<0.01).The beaded-HA implants were half the risk for an all-cause revision compared to cemented implants (p<0.01). Matte-uncoated and matte-TiN implants were at more risk of an all-cause revision than cemented implants (p=0.01, p<0.01). Proportions of revisions for aseptic loosening were comparable among most groups. Conclusion: Based on Dutch registry data, four main MSS-coating combinations among uncemented TKAs were found. survivorships for all-cause revisions and aseptic release differed widely between groups. Beaded-HA and porous-uncoated implants had the best survival rates among the uncemented TKAs and were non-inferior to the cemented TKAs.Keywords: total knee arthroplasty, cement, uncemented, cementless;, metal surface structure, coating
Procedia PDF Downloads 15033 Combinational Therapeutic Targeting of BRD4 and CDK7 Synergistically Induces Anticancer Effects in Hepatocellular Carcinoma
Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan
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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.Keywords: BRD4, CDK7, cell proliferation, combined inhibition
Procedia PDF Downloads 5432 Role of P53, KI67 and Cyclin a Immunohistochemical Assay in Predicting Wilms’ Tumor Mortality
Authors: Ahmed Atwa, Ashraf Hafez, Mohamed Abdelhameed, Adel Nabeeh, Mohamed Dawaba, Tamer Helmy
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Introduction and Objective: Tumour staging and grading do not usually reflect the future behavior of Wilms' tumor (WT) regarding mortality. Therefore, in this study, P53, Ki67 and cyclin A immunohistochemistry were used in a trial to predict WT cancer-specific survival (CSS). Methods: In this nonconcurrent cohort study, patients' archived data, including age at presentation, gender, history, clinical examination and radiological investigations, were retrieved then the patients were reviewed at the outpatient clinic of a tertiary care center by history-taking, clinical examination and radiological investigations to detect the oncological outcome. Cases that received preoperative chemotherapy or died due to causes other than WT were excluded. Formalin-fixed, paraffin-embedded specimens obtained from the previously preserved blocks at the pathology laboratory were taken on positively charged slides for IHC with p53, Ki67 and cyclin A. All specimens were examined by an experienced histopathologist devoted to the urological practice and blinded to the patient's clinical findings. P53 and cyclin A staining were scored as 0 (no nuclear staining),1 (<10% nuclear staining), 2 (10-50% nuclear staining) and 3 (>50% nuclear staining). Ki67 proliferation index (PI) was graded as low, borderline and high. Results: Of the 75 cases, 40 (53.3%) were males and 35 (46.7%) were females, and the median age was 36 months (2-216). With a mean follow-up of 78.6±31 months, cancer-specific mortality (CSM) occurred in 15 (20%) and 11 (14.7%) patients, respectively. Kaplan-Meier curve was used for survival analysis, and groups were compared using the Log-rank test. Multivariate logistic regression and Cox regression were not used because only one variable (cyclin A) had shown statistical significance (P=.02), whereas the other significant factor (residual tumor) had few cases. Conclusions: Cyclin A IHC should be considered as a marker for the prediction of WT CSS. Prospective studies with a larger sample size are needed.Keywords: wilms’ tumour, nephroblastoma, urology, survival
Procedia PDF Downloads 6631 Cup-Cage Construct for Treatment of Severe Acetabular Bone Loss in Revision Total Hip Arthroplasty: Midterm Clinical and Radiographic Outcomes
Authors: Faran Chaudhry, Anser Daud, Doris Braunstein, Oleg Safir, Allan Gross, Paul Kuzyk
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Background: Acetabular reconstruction in the context of massive acetabular bone loss is challenging. In rare scenarios where the extent of bone loss precludes shell placement (cup-cage), reconstruction at our center consisted of a cage combined with highly porous metal augments. This study evaluates survivorship, complications, and functional outcomes using this technique. Methods: A total of 131 cup-cage implants (129 patients) were included in our retrospective review of revisions of total hip arthroplasty from January 2003 to January 2022. Among these cases, 100/131 (76.3%) were women, the mean age at surgery time was 68.7 years (range, 29.0 to 92.0; SD, 12.4), and the mean follow-up was 7.7 years (range, 0.02 to 20.3; SD, 5.1). Kaplan-Meier survivorship analysis was conducted with failure defined as revision surgery and/or failure of the cup-cage reconstruction. Results: A total of 30 implants (23%) reached the study endpoint involving all-cause revision. Overall survivorship was 74.8% at 10 years and 69.8% at 15 years. Reasons for revision included infection 12/131 (9.1%), dislocation 10/131 (7.6%), aseptic loosening of cup and/or cage 5/131 (3.8%), and aseptic loosening of the femoral stem 2/131 (1.5%). The mean LLD improved from 12.2 ± 15.9 mm to 3.9 ± 11.8 (p<0.05). The horizontal and vertical hip centres on plain film radiographs were significantly improved (p<0.05). Functionally, there was a decrease in the number of patients requiring the use of gait aids, with fewer patients (34, 25.9%) using a cane, walker, or wheelchair post-operatively compared to pre-operatively (58, 44%). There was a significant increase in the number of independent ambulators from 24 to 47 (36%). Conclusion: The cup-cage construct is a reliable treatment option for the treatment of various acetabular defects. There are favourable survivorship, clinical and radiographic outcomes, with a satisfactory complication rate.Keywords: revision total hip arthroplasty, acetabular defect, pelvic discontinuity, trabecular metal augment, cup-cage
Procedia PDF Downloads 6730 Real-World Comparison of Adherence to and Persistence with Dulaglutide and Liraglutide in UAE e-Claims Database
Authors: Ibrahim Turfanda, Soniya Rai, Karan Vadher
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Objectives— The study aims to compare real-world adherence to and persistence with dulaglutide and liraglutide in patients with type 2 diabetes (T2D) initiating treatment in UAE. Methods— This was a retrospective, non-interventional study (observation period: 01 March 2017–31 August 2019) using the UAE Dubai e-Claims database. Included: adult patients initiating dulaglutide/liraglutide 01 September 2017–31 August 2018 (index period) with: ≥1 claim for T2D in the 6 months before index date (ID); ≥1 claim for dulaglutide/liraglutide during index period; and continuous medical enrolment for ≥6 months before and ≥12 months after ID. Key endpoints, assessed 3/6/12 months after ID: adherence to treatment (proportion of days covered [PDC; PDC ≥80% considered ‘adherent’], per-group mean±standard deviation [SD] PDC); and persistence (number of continuous therapy days from ID until discontinuation [i.e., >45 days gap] or end of observation period). Patients initiating dulaglutide/liraglutide were propensity score matched (1:1) based on baseline characteristics. Between-group comparison of adherence was analysed using the McNemar test (α=0.025). Persistence was analysed using Kaplan–Meier estimates with log-rank tests (α=0.025) for between-group comparisons. This study presents 12-month outcomes. Results— Following propensity score matching, 263 patients were included in each group. Mean±SD PDC for all patients at 12 months was significantly higher in the dulaglutide versus the liraglutide group (dulaglutide=0.48±0.30, liraglutide=0.39±0.28, p=0.0002). The proportion of adherent patients favored dulaglutide (dulaglutide=20.2%, liraglutide=12.9%, p=0.0302), as did the probability of being adherent to treatment (odds ratio [97.5% CI]: 1.70 [0.99, 2.91]; p=0.03). Proportion of persistent patients also favoured dulaglutide (dulaglutide=15.2%, liraglutide=9.1%, p=0.0528), as did the probability of discontinuing treatment 12 months after ID (p=0.027). Conclusions— Based on the UAE Dubai e-Claims database data, dulaglutide initiators exhibited significantly greater adherence in terms of mean PDC versus liraglutide initiators. The proportion of adherent patients and the probability of being adherent favored the dulaglutide group, as did treatment persistence.Keywords: adherence, dulaglutide, effectiveness, liraglutide, persistence
Procedia PDF Downloads 125