Non-parametric competing risks with multivariate frailty models

This research focuses on two theories: (i) competing risks and (ii) random eect (frailty) models. The theory of competing risks provides a structure for inference in problems where cases are subject to several types of failure. Random eects in competing risk models consist of two underlying distributions: the conditional distribution of the response variables, given the random eect, depending on the explanatory variables each with a failure type specic random eect; and the distribution of the random eect. In this situation, the distribution of interest is the unconditional distribution of the response variable, which may or may not have a tractable form. The parametric competing risk model, in which it is assumed that the failure times are coming from a known distribution, is widely used such as Weibull, Gamma and other distributions. The Gamma distribution has been widely used as a frailty distribution, perhaps due to its simplicity since it has a closed form expression of the unconditional hazard function. However, it is unrealistic to believe that a few parametric models are suitable for all types of failure time. This research focuses on a distribution free of the multivariate frailty models. Another approach used to overcome this problem is using nite mixture of parametric frailty especially those who have a closed form of unconditional survival function. In addition, the advantages and disadvantages of a parametric competing risk models with multivariate parametric and/or non-parametric frailty (correlated random eects) are investigated. In this research, four main models are proposed: rst, an application of a new computation and analysis of a multivariate frailty with competing risk model using Cholesky decomposition of the Lognormal frailty. Second, a correlated Inverse Gaussian frailty in the presence of competing risks model. Third, a non-parametric multivariate frailty with parametric competing risk model is proposed. Finally, a simulation study of nite mixture of Inverse Gaussian frailty showed the ability of this model to t dierent frailty distribution. One main issue in multivariate analysis is the time it needs to t the model. The proposed non-parametric model showed a signicant time decrease in estimating the model parameters (about 80% less time compared the Log-Normal frailty with nested loops). A real data of recurrence of breast cancer is used as the applications of these models

Lessons learned from COVID-19 Lockdown: An ASPED/MENA Study on Lifestyle Changes and Quality of Life during Ramadan Fasting in Children and Adolescents living with Type 1 Diabetes

Background: Lockdown was a unique experience that affected many aspects of life, particularly during the challenge of Ramadan fasting (RF). Studying this can increase understanding of the effects of lifestyle changes on quality of life (QoL) for children with type 1 diabetes (T1D) during RF. Methods: A cross-sectional study that assessed the effect of lockdown on lifestyle and QoL on fasting children living with T1D during Ramadan in the Middle East and North Africa region (2020-2021). We compared the child (self) and parent (proxy) reports using PEDQoL v3.0 disease specific questionnaire during lockdown and non-lockdown periods, and assessed correlations with lifestyle changes using regression and gap analyses. Results: A total of 998 reports from 499 children with T1D aged 8-18 years (study=276, control=223), and their parents during RF in lockdown and non-lockdown periods. Fathers were more involved in their children’s care during lockdown (p=0.019). Patients had better compliance with treatment (p= 0.002), a reversed sleep pattern (p= 0.033), increased food intake (p=<0.001) and less exercise (p<0.001). Children and parents perceived better QoL during lockdown (p=<0.001) with no differences between their reports in “Diabetes Symptoms”, “Treatment Adherence” and “Communication” domains. Self and proxy reports were different in all domains during non-lockdown (p-values <0.001- 0.009). In gap analysis, although not statistically significant, the gap was approximated between children’s and parents’ perceptions in all domains during lockdown. Conclusion: COVID-19 lockdown had a positive impact on QoL of children living with T1D during RF, possibly due to lifestyle changes and superior psychosocial family dynamics

24. Psycho-social impact of prosthetic heart valves on young Saudi females

Many patients with prosthetic heart valves (PHV) in Saudi Arabia fall at young age. Females in the reproductive age may encounter a significant amount of emotional stress due to struggling between own health, natural desires, husbands demands and societal expectations. Different types of PHV may impose variable degrees of psychological disturbances and family disruptions. Objectives: The aim of this study is to evaluate presence and magnitude of psycho-social effects of PHVs in young Saudi females. Methods: Seventy-five Saudi females with PHV (18–50 y) and their age and marital status-matched controls were included in the study. Self-administered questionnaire, that includes short-form Depression, Anxiety, and Stress Scale (DASS) was used to obtain data. Results: Mechanical valve (MV) group (n = 49) were 6.5 y older (P = 0.001), more illiterate (p < 0.001) and less employed (p = 0.031) than biological valve (BV) group. Mean marital duration was 22.6 y in MV group and 12.6 y in BV group (p < 0.001). Depression was least frequently observed in the MV group (P = 0.022), while a trend of higher DASS domains was observed in the BV group (p = NS). Predictors of lower depression rate include; living outside Riyadh city, lower level of education, being unemployed and having a supportive husband. Conclusion: Patients with MV have the most stable psychological status, probably as a result of stronger spousal relationship. Recommendation: Counselling husbands may strengthen spousal relationship and improve psychological wellbeing of patients with PHV

The Role of Interleukin-1 cytokine family (IL-1β, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis.

Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients' demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1β and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection's duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression

The implication of <it>dihydrofolate reductase </it>and <it>dihydropteroate synthetase </it>gene mutations in modification of <it>Plasmodium falciparum </it>characteristics

Abstract Background The Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) are enzymes of central importance in parasite metabolism. The dhfr and dhps gene mutations are known to be associated with sulphadoxine/pyrimethamine (SP) resistance. Objective To investigate the effects of dhfr/dhps mutations on parasite characteristics other than SP resistance. Method Parasite infections obtained from 153 Sudanese patients with uncomplicated falciparum malaria treated with SP or SP + chloroquine, were successfully genotyped at nine codons in the dhfr/dhps genes by PCR-ELISA. Results & conclusion Mutations were detected in dhfr at N51I, S108N and C59R, and in at dhps at A/S436F, A437G, K540E and A581G, the maximum number of mutations per infection were five. Based on number of mutant codons per infection (multiplicity of mutation, MOM), the infections were organized into six grades: wild-types (grade 0; frequency, 0.03) and infections with MOM grades of 1 to 5, with the following cumulative frequency; 0.97, 0.931, 0.866, 0.719, 0.121, respectively. There was no significant association between the MOM and SP response. Importantly, immunity, using age as a surrogate marker, contributed significantly to the clearance of parasites with multiple dhfr/dhps mutations. However, these mutations have a survival advantage as they were associated with increased gametocytogenesis. The above implications of dhfr/dhps mutations were associated with MOM 2 to 5, regardless of the gene/codon locus.</p

The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of <em>Plasmodium falciparum</em> characteristics

BACKGROUND: The Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) are enzymes of central importance in parasite metabolism. The dhfr and dhps gene mutations are known to be associated with sulphadoxine/pyrimethamine (SP) resistance. OBJECTIVE: To investigate the effects of dhfr/dhps mutations on parasite characteristics other than SP resistance. METHOD: Parasite infections obtained from 153 Sudanese patients with uncomplicated falciparum malaria treated with SP or SP + chloroquine, were successfully genotyped at nine codons in the dhfr/dhps genes by PCR-ELISA. RESULTS & CONCLUSION: Mutations were detected in dhfr at N51I, S108N and C59R, and in at dhps at A/S436F, A437G, K540E and A581G, the maximum number of mutations per infection were five. Based on number of mutant codons per infection (multiplicity of mutation, MOM), the infections were organized into six grades: wild-types (grade 0; frequency, 0.03) and infections with MOM grades of 1 to 5, with the following cumulative frequency; 0.97, 0.931, 0.866, 0.719, 0.121, respectively. There was no significant association between the MOM and SP response. Importantly, immunity, using age as a surrogate marker, contributed significantly to the clearance of parasites with multiple dhfr/dhps mutations. However, these mutations have a survival advantage as they were associated with increased gametocytogenesis. The above implications of dhfr/dhps mutations were associated with MOM 2 to 5, regardless of the gene/codon locus

Bieten Visiten eine effektive Lehre und Ausbildung? Hindernisse für das Lernen, und was macht eine gute Lehre an einem großen Krankenhaus der Tertiärversorgung aus Sicht von Ärzt*innen in der Ausbildung aus

Background: Ward rounds (WR) have been integral to the process of teaching and learning medicine and also provides a vital opportunity to communicate with the patient, their relatives, and other healthcare professionals. Yet in recent years trainees' perception of the educational value of WRs seems to have declined. Objectives: The aim of this study to assess trainees' perception of the educational value of WRs at King Abdulaziz Medical City(KAMC), Riyadh, a 1500 bed academic hospital in Saudi Arabia.Methods: A self-administered, paper-based survey was distributed to physicians in training at KAMC between October and December 2019. All residents who attended WRs were invited to participate. The questionnaire was adapted from a survey used in a previous study. The demographic section requested details of the respondent's age, gender, specialty, and seniority. The second and third sections asked about the logistics of current ward round practices. It included several questions on the structure as well as the duration and frequency of ward rounds. The fourth and fifth sections asked for participant's perception of the opportunities for, and the obstacles to, learning on ward rounds. The subsequent sections asked several questions onward round structure and the clinical teacher. Responses were requested on a 5-point Likert-type scale (strongly disagree, disagree, neutral, agree, strongly agree). The last section asked the participant for general comments and feedbackResult: The study targeted 250 residents in specialties that routinely performed WRs. Only 166 residents returned the questionnaire (response rate of 66.4%). Male 89 (53.6%), medical 108 (65.1%), surgical 58 (34.9%), resident in first year 81 (48.8%). The overall average time spent on WR was 13 (± 11 SD) hours per week. The WR was perceived as a good opportunity to learn about diagnostic investigation 138 (83%) and patient management 133(80.1%), history taking114 (68.7%) physical examination 103 (62.0%), and time management skills 86 (51.8%). The majority of our trainees felt that the WR was educationally very useful to 86 (52%) and attribute to at least a third of the education they receive during their training. They also reported that about the quarter of the time spent on WRs is devoted to teaching. The good teacher described as enthusiastic to teach 137 (82.5%), provide feedback to trainees 135 (81%), do not rush 139(83.7), communicate to trainee 144 (86.7), and consultant level,101 (60.8). Trainees also identify a few factors that hinder their training such as lack of time 130 (79%), and the number of patients 129 (78.3). Conclusion: This study identifies the strengths and weaknesses of WR in our institution. Finding will help training supervisors in addressing and rectifying these shortcoming and factors hinder training.Hintergrund: Visiten sind ein integrativer Bestandteil des Lehrprozesses und des Lernens in der Medizin und bieten zudem eine sehr wichtige Möglichkeit, um mit Patient*innen, deren Verwandten und anderem Gesundheitspersonal zu kommunizieren. Und trotzdem scheint in den letzten Jahren der Ausbildungswert von Visiten in der Wahrnehmung der Ärzt*innen in der Ausbildung nachzulassen. Ziele: Ziel dieser Studie ist es, die Wahrnehmung der Ärzt*innen in der Ausbildung hinsichtlich des Ausbildungswertes von Visiten in König Abdulaziz Medical City (KAMC), Riad, einem akademischen Lehrkrankenhaus mit 1.500 Betten in Saudi-Arabien, zu untersuchen.Methoden: Unter den Ärzt*innen in der Ausbildung am KAMC wurde zwischen Oktober und Dezember 2019 eine selbsterstellte Umfrage in Papierform verteilt. Alle Assistenzärzt*innen, die an Visiten teilnahmen, wurden zur Beteiligung aufgerufen. Der Fragebogen wurde anhand einer Umfrage erstellt, die bei einer früheren Studie verwendet wurde. Der demografische Teil erfragte Angaben zu Alter, Geschlecht, Fachrichtung und Dienstalter der Befragten. Der zweite und dritte Teil fragte nach der Logistik der gegenwärtigen Visitenpraxis. Sie umfassten verschiedene Fragen zu Struktur sowie Dauer und Häufigkeit von Visiten. Der vierte und fünfte Teil befragte die Teilnehmer*innen nach ihrer Wahrnehmung der Möglichkeiten und Hindernisse von Visiten für das Lernen. Die nachfolgenden Abschnitte stellten verschiedene Fragen zu Visitenstruktur und klinischen Ausbildern. Antworten wurden in Form einer 5-Punkte Likert-Skala erbeten (stimme überhaupt nicht zu, stimme nicht zu, unentschieden, stimme zu, stimme völlig zu). Der letzte Teil bat die Teilnehmer*innen um allgemeine Anmerkungen, Hinweise und FeedbackErgebnis: Die Studie richtete sich an 250 Assistenzärzt*innen in Fachrichtungen, die routinemäßig Visiten durchführen. Nur 166 Assistenzärzt*innen reichten den Fragebogen wieder ein (Rücklaufquote von 66,4%), davon: männliche (89; 53,6%), innere (108; 65,1%), chirurgische (58; 34,9%), Assistenzärzt*innen im ersten Ausbildungsjahr (81; 48,8%). Die Gesamtdurchschnittszeit, die für Visiten aufgewendet wurde, lag bei 13 (± 11 SD) Stunden pro Woche. Die Visiten wurden als gute Möglichkeit angesehen, um etwas über diagnostische Untersuchung (138; 83%) und Patientenmanagement (133; 80,1%), Anamnese (114; 68,7%), körperliche Untersuchung (103; 62,0%) und Zeitmanagementfähigkeiten (86; 51,8%) zu lernen. Die Mehrzahl unserer Ärzt*innen in der Ausbildung hatten den Eindruck, dass die Visiten für ihre Ausbildung sehr nützlich sind (86; 52%) und zu mindestens einem Drittel der Ausbildung, die sie während ihres Studiums erhalten, beitragen. Sie berichteten auch, dass etwa ein Viertel der bei Visiten verbrachten Zeit auf die Lehre verwendet wird. Gute Ausbilder*innen wurden beschrieben als engagierte Lehrer*innen (137; 82,5%), jemand, der den Lernenden Feedback gibt (135; 81%), sie nicht antreibt (139; 83,7%), mit den Lernenden kommuniziert (144; 86,7%) und ihnen beratend zur Seite steht (101; 60,8%). Die Ärzt*innen in der Ausbildung identifizierten auch einige Faktoren, die ihre Ausbildung behindern, wie z. B. Zeitmangel (130; 79%) und die Anzahl der Patient*innen (129; 78,3%). Schlussfolgerung: Diese Studie identifiziert die Stärken und Schwächen von Visiten in unserer Einrichtung. Die Ergebnisse werden den Ausbildungsbetreuer*innen dabei helfen, diese Mängel und Faktoren, die die Ausbildung behindern, anzugehen und zu korrigieren