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Abstract Background Compliance with standards of care is required for sustained improvement in the quality of delivery services. It thus represents a key challenge to improving maternal survival and meeting the Sustainable Development Goal (SDG) target of reducing the maternal mortality ratio to 70 deaths per 100,000 live births. This study examines the extent to which normal low-risk health facility deliveries in Nepal meet the standards of quality of care and assesses the effect of the standards of quality of care and various contextual factors on women’s satisfaction with the services they receive. Methods Drawing on the 2021 Nepal Health Facility Survey, the sample comprised 320 women who used health facilities for normal, low-risk delivery services. A weighted one-sample t-test was applied to examine the proportion of deliveries meeting the eight standards of care. Women’s overall satisfaction level was computed from seven satisfaction variables measured on a Likert scale, using principal component analysis. The composite measure was then dichotomized. Binary logistic regression was used to analyze the determinants of women’s satisfaction with delivery care services. Results Deliveries complying with the eight standards of care and its 53 indicators varied widely; output indicators were more frequently met than input indicators. Of the eight standards of care, the “functional referral system” performed highest (92.0%), while “competent, motivated human resources” performed the least (52.4%). Women who were attended by a provider when they called for support (AOR: 5.29; CI: 1.18, 23.64), who delivered in health facilities that displayed health statistics (AOR 3.16; CI: 1.87, 5.33), who experienced caring behaviors from providers (AOR: 2.59; CI: 1.06, 6.30) and who enjoyed audio-visual privacy (AOR 2.13; CI: 1.04, 4.38) had higher satisfaction levels compared to their counterparts. The implementation of the Maternity Incentive Scheme and presence of a maternal waiting room in health facilities, however, were associated with lower satisfaction levels. Conclusions Nepal performed moderately well in meeting the standards of care for normal, low-risk deliveries. To meet the SDG target Nepal must accelerate progress. It needs to focus on people-centered quality improvement to routinely assess the standards of care, mobilize available resources, improve coordination among the three tiers of government, and implement high-impact programs.

Abstract Background Nepal is committed to achieving the Sustainable Development Goal (SDG) 2030 target 3.1 of reducing the maternal mortality ratio to 70 deaths per 100,000 live births. Along with increasing access to health facility (HF)-based delivery services, improving HF readiness is critically important. The majority of births in Nepal are normal low-risk births and most of them take place in public HFs, as does the majority of maternal deaths. This study aims to assess changes in HF readiness in Nepal between 2015 and 2021, notably, if HF readiness for providing high-quality services for normal low-risk deliveries improved; if the functionality of basic emergency obstetric and neonatal care (BEmONC) services increased; and if infection prevention and control improved. Methods Cross-sectional data from two nationally representative HF-based surveys in 2015 and 2021 were analyzed. This included 457 HFs in 2015 and 804 HFs in 2021, providing normal low-risk delivery services. Indices for HF readiness for normal low-risk delivery services, BEmONC service functionality, and infection prevention and control were computed. Independent sample T-test was used to measure changes over time. The results were stratified by public versus private HFs. Results Despite a statistically significant increase in the overall HF readiness index for normal low-risk delivery services, from 37.9% in 2015 to 43.7%, in 2021, HF readiness in 2021 remained inadequate. The availability of trained providers, essential medicines for mothers, and basic equipment and supplies was high, while that of essential medicines for newborns was moderate; availability of delivery care guidelines was low. BEmONC service functionality did not improve and remained below five percent facility coverage at both time points. In private HFs, readiness for good quality obstetrical care was higher than in public HFs at both time points. The infection prevention and control index improved over time; however, facility coverage in 2021 remained below ten percent. Conclusions The slow progress and sub-optimal readiness for normal, low-risk deliveries and infection prevention and control, along with declining and low BEmONC service functionality in 2021 is reflective of poor quality of care and provides some proximate explanation for the moderately high maternal mortality and the stagnation of neonatal mortality in Nepal. To reach the SDG 2030 target of reducing maternal deaths, Nepal must hasten its efforts to strengthen supply chain systems to enhance the availability and utilization of essential medicines, equipment, and supplies, along with guidelines, to bolster the human resource capacity, and to implement mechanisms to monitor quality of care. In general, the capacity of local governments to deliver basic healthcare services needs to be increased.

NSG (NOD/Scid IL2Rγnull) mice reconstituted with PBMCs donated by patients with ulcerative colitis or Crohn’s disease highly reflect the respective pathological phenotype. To determine whether these findings could be applicable to atopic dermatitis (AD) and psoriasis vulgaris (PV), PBMCs isolated from patients with AD and PV were first subjected to immunological profiling. Subsequently, NSG mice were reconstituted with these PBMCs. Hierarchical clustering and network analysis revealed a distinct profile of patients with AD and PV with activated CD4+ T cells (CD69, CD25) occupying a central position in the AD network and CD4+ CD134+ cells acting as the main hub in the PV network. After dermal application of DMSO, both NSG mice reconstituted with PBMCs from donors with AD (ie, NSG-AD mice) and NSG mice reconstituted with PBMCs from donors with PV (ie, NSG-PV mice) exhibited increased clinical, skin, and histological scores. Immunohistochemical analysis, frequencies of splenic human leukocytes, and cytokine expression levels indicated that CD4+ CD69+ cells, M1 and TSLP receptor–expressing monocytes, switched B cells, and monocyte chemoattractant protein 3 were the driving factors of inflammation in NSG-AD mice. In contrast, inflammation in NSG-PV mice was characterized by an increase in fibroblasts in the epidermis, frequencies of CD1a-expressing monocytes, and IL-17 levels. Therefore, the pathological phenotypes of NSG-AD mice and NSG-PV mice differ and partially reflect the respective human diseases.

A growing body of evidence suggests an increased prevalence of anxiety and depression among teachers during the COVID-19 pandemic. However, there is little evidence in research documenting the extent of anxiety and depression in the university teacher population and how these relate to feelings of loneliness. This study aims to explore the prevalence of anxiety and depression symptoms among university teachers, identify differences, and further examine the relationships between loneliness and symptoms of anxiety and depression. The study participants included university teachers in the College of Health and Medical Sciences from four purposefully selected public universities who completed a survey questionnaire consisting of items that measured anxiety and depressive symptoms as well as loneliness. The final sample included 148 participants (45 participants [30.4%] located in the center or capital; 125 (83.1%) men; and 90 [62.5%] taught both online and face-to-face). The university teachers’ sample mean age = 39.07 had an SD = 7.67. As per the findings of this study, the prevalence of anxiety and depression symptoms was significant (11% and 12.3%) among university teachers in Ethiopia during the COVID-19 pandemic. Also, this study found a significant association between these symptoms and loneliness. Therefore, incorporating relevant strategies to promote mental well-being and targeting individuals who felt lonely were essential for overcoming health-related burdens. Universities should equip teachers with resources to prevent mental health issues and offer need-based counseling services to alleviate them.

Background: Entrustable Professional Activities (EPAs) are units of professional practice that are defined as tasks or responsibilities that are entrusted to an unsupervised execution by a trainee. In 2021, a framework of 29 EPAs was developed for surgical residency training programs in Ethiopia, with the goal of residents being able to perform independently by the time they graduate. However, studies show that surgical residents lack confidence and are unable to execute EPAs autonomously upon graduation, and concerns have been raised about graduate competencies in EPA execution. The goal of this research is to assess how surgical team members judge/perceive residents' performance in executing these EPAs autonomously at the time of graduation and how residents rate their own capability and autonomy in executing EPAs in order to systematically introduce and implement EPAs in Ethiopian medical education Methods: A survey was conducted in the Departments of Surgery at four residency training institutions in Ethiopia. All eligible surgical team members and final-year general surgery residents were invited to participate. Surgical team members were asked to rate the observed performance of a group of graduating surgical residents in each of the 29 EPAs, and residents were asked to rate their own capability in executing EPAs. The analysis focused on variations in performance ratings between surgical team members and residents, as well as across surgical team members. Results: A total of 125 surgical team members and 49 residents participated in this study. Residents rate their competence in performing these EPAs higher than surgical team members, mean 4.2 (SD = 0.63) vs. 3.7 (SD = 0.9). A statistically significant difference in perceptions of capability, autonomy, and expectations in executing EPAs was observed between the two groups of study (p = 0.03, CI: 0.51–0.95), as well as within surgical team members (p

Abstract Background Cinemeducation courses are used to supplement more standard teaching formats at medical schools and tend to emphasise biopsychosocial aspects of health. The purpose of this paper is to explore why medical students attend the cinemeducation course M23 Cinema (M23C) at LMU Munich and whether a film screening with a subsequent expert and peer discussion benefits their studies and their future careers as medical doctors. Methods An exploratory sequential mixed methods study design was used. Qualitative research, i.e. three focus groups, four expert interviews, one group interview and one narrative interview, was conducted to inform a subsequent quantitative survey. Qualitative data was analysed using qualitative content analysis and quantitative data was analysed descriptively. The findings were integrated using the “following a thread” protocol. Results In total, 28 people were interviewed and 503 participants responded to the survey distributed at seven M23C screenings. Participants perceive the M23C as informal teaching where they learn about perspectives on certain health topics through the combination of film and discussion while spending time with peers. The reasons for and reported benefits of participation varied with educational background, participation frequency and gender. On average, participants gave 5.7 reasons for attending the M23C. The main reasons for participating were the film, the topic and the ability to discuss these afterwards as well as to spend an evening with peers. Attending the M23C was reported to support the students’ memory with regards to certain topics addressed in the M23C when the issues resurface at a later stage, such as during university courses, in the hospital, or in their private life. Conclusions The M23C is characterised by its unique combination of film and discussion that encourages participants to reflect upon their opinions, perspectives and experiences. Participating in the M23C amplified the understanding of biopsychosocial aspects of health and illness in students. Thus, cinemeducative approaches such as the M23C may contribute to enabling health professionals to develop and apply humane, empathetic and relational skills.

Abstract Introduction Crohn's disease (CD) is characterized by pronounced intestinal fibrosis and severe mucosal damage and conventional animal models are limited to reflect these pathological manifestations. The aim of this study was to examine whether the combination of patient immune‐profiling and preclinical studies in a mouse model based on NOD/scid IL‐2Rγnull (NSG) reconstituted with peripheral blood mononuclear cells (PBMC) from CD patients has the capacity to harmonize ex vivo human and in vivo animal studies. Methods Immunological profiles of CD (n = 24) and ulcerative colitis (UC) patients (n = 47) were established by flow cytometry of subgroups of immune cells and subjected to hierarchical cluster and estimation graphics analyses. Pathological phenotypes of NSG mice, which were reconstituted with PBMC from CD, UC, and non‐IBD donors (NSG‐CD, NSG‐UC, and NSG‐non‐IBD) were compared. Readouts were the clinical, colon, and histological scores; subtypes of immune cells from spleen and colon; and levels of inflammatory markers, such as c‐reactive protein (CRP), monocyte chemotactic protein (MCP)‐3, transforming growth factor‐beta (TGFß), and hepatocyte growth factor (HGF). Fibrocytes were identified by immunohistochemistry in colonic sections. Results CD patients were significantly clustered in a group characterized by increased levels of TH1, TH2 cells, and decreased levels of CD14+ CD163+ monocytes (p = .003). In contrast to NSG‐UC mice, NSG‐CD mice exhibited an immune‐remodeling phenotype characterized by enhanced collagen deposition, elevated levels of CD14+ CD163+ monocytes, HGF, and TGFß. This phenotype was further corroborated by the presence of human fibrocytes as components of fibrotic areas. Conclusion The NSG‐CD model partially reflects the human disease and allows for studying the development of fibrosis.

Abstract Background Simulation-based learning with virtual patients is a highly effective method that could potentially be further enhanced by including reflection phases. The effectiveness of reflection phases for learning to diagnose has mainly been demonstrated for problem-centered instruction with text-based cases, not for simulation-based learning. To close this research gap, we conducted a study on learning history-taking using virtual patients. In this study, we examined the added benefit of including reflection phases on learning to diagnose accurately, the associations between knowledge and learning, and the diagnostic process. Methods A sample of N = 121 medical students completed a three-group experiment with a control group and pre- and posttests. The pretest consisted of a conceptual and strategic knowledge test and virtual patients to be diagnosed. In the learning phase, two intervention groups worked with virtual patients and completed different types of reflection phases, while the control group learned with virtual patients but without reflection phases. The posttest again involved virtual patients. For all virtual patients, diagnostic accuracy was assessed as the primary outcome. Current hypotheses were tracked during reflection phases and in simulation-based learning to measure diagnostic process. Results Regarding the added benefit of reflection phases, an ANCOVA controlling for pretest performance found no difference in diagnostic accuracy at posttest between the three conditions, F(2, 114) = 0.93, p = .398. Concerning knowledge and learning, both pretest conceptual knowledge and strategic knowledge were not associated with learning to diagnose accurately through reflection phases. Learners’ diagnostic process improved during simulation-based learning and the reflection phases. Conclusions Reflection phases did not have an added benefit for learning to diagnose accurately in virtual patients. This finding indicates that reflection phases may not be as effective in simulation-based learning as in problem-centered instruction with text-based cases and can be explained with two contextual differences. First, information processing in simulation-based learning uses the verbal channel and the visual channel, while text-based learning only draws on the verbal channel. Second, in simulation-based learning, serial cue cases are used to gather information step-wise, whereas, in text-based learning, whole cases are used that present all data at once.

Abstract With glucose being the preferred source of energy in activated T cells, targeting glycolysis has become an attractive therapeutic intervention point for chronic inflammatory bowel diseases (IBD). The switch to glycolysis is mediated by phosphoinositide‐3‐kinases (PI3K) which relay signals from surface receptors to the AKT pathway. We first confirmed by analysis of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) that metabolism is shifted towards glycolysis in IBD patients as compared to non‐IBD donors. In contrast to non‐IBD donors, OCR correlated with ECAR (IBD: cor = 0.79, p = 2E‐10; non‐IBD: cor = 0.37, p = n.s.), in IBD patients. Second, we tested the PI3K inhibitor copanlisib as a potential therapeutic. Ex vivo, copanlisib suppressed the ECAR significantly in T cells activated by anti‐CD3 antibodies and significantly decreased ECAR rates in the presence of copanlisib (anti‐CD3: 58.24 ± 29.06; copanlisib: 43.16 ± 20.23, p

Despite increasing focus on the importance of self–regulated learning for undergraduate students in universities in recent years, very little is known about its specific features in universities in developing countries, in general, and Ethiopia, in particular. This study examined the relationships of self-regulated learning strategies (SRLSs) with perceived learning and further assessed the relationships within the SRLS components in Ethiopian public universities. For this, the authors adopted Pintrich’s self-regulation theory as a guiding framework and used structural equation modeling (SEM) analysis. The sample used in the analysis pooled survey data from three randomly selected public universities and included volunteer undergraduate students having a major in Business and Economics and Engineering and Technology fields (n = 1142; male = 700 and female = 442), with mean age = 21.98 and SD = 2.50. The results indicated that the student SRLS and perceived learning gains scores were average values in terms of the magnitude of those measured variables. A two–step hierarchical regression analysis showed that the five components of SRLS that emerged from SEM analysis significantly predicted students’ perceived learning over and above the control variables (ΔR2 ≥ 0.38 and 39%) for the total samples. Moreover, the regression results showed that greater predictions were observed for the help–seeking component (0.35 ≤ β ≥ 0.47) than others, significantly positively predicting the perceived learning for the total samples. Overall, the findings of this study indicate that the SRLSs are relevant mechanisms to aid student success in higher education. The implications of the study are highlighted.

This study's aim was to demonstrate that the combination of patient immune profiling and testing in a humanized mouse model of ulcerative colitis (UC) might lead to patient stratification for treatment with oxelumab. First, immunological profiles of UC patients and non-UC donors were analyzed for CD4+ T cells expressing OX40 (CD134; also known as TNFRSF4) and CD14+ monocytes expressing OX40L (CD252; also known as TNFSF4) by flow cytometric analysis. A significant difference was observed between the groups for CD14+ OX40L+ (UC: n=11, 85.44±21.17, mean±s.d.; non-UC: n=5, 30.7±34.92; P=0.02), whereas no significant difference was detected for CD4+ OX40+. CD14+ OX40L+ monocytes were correlated significantly with T helper 1 and 2 cells. Second, NOD/Scid IL2Rγ null mice were reconstituted with peripheral blood mononuclear cells from UC donors exhibiting elevated levels of OX40L, and the efficacy of oxelumab was compared with that of adalimumab. The clinical, colon and histological scores and the serum concentrations of IL-6, IL-1β and glutamic acid were assessed. Treatment with oxelumab or adalimumab resulted in significantly reduced clinical, colon and histological scores, reduced serum concentrations of IL-6 and reduced frequencies of splenic human effector memory T cells and switched B cells. Comparison of the efficacy of adalimumab and oxelumab by orthogonal partial least squares discrimination analysis revealed that oxelumab was slightly superior to adalimumab; however, elevated serum concentrations of glutamic acid suggested ongoing inflammation. These results suggest that oxelumab addresses the pro-inflammatory arm of inflammation while promoting the remodeling arm and that patients exhibiting elevated levels of OX40L might benefit from treatment with oxelumab.

Purpose The aim of this study was to assess morbidity and mortality pattern of small for gestational age (SGA) preterm infants in comparison to appropriate for gestational age (AGA) preterm infants of similar gestational age.Method We compared neonatal outcomes of 1336, 1:1 matched, singleton SGA and AGA preterm infants based on their gestational age using data from the study ‘Causes of Illness and Death of Preterm Infants in Ethiopia (SIP)’. Data were analysed using SPSS V.23. ORs and 95% CIs and χ2 tests were done, p value of

Background . Patterns of fetal growth are largely influenced by environmental, nutritional, and socioeconomic factors more than differences in populations. The aim of this study was to assess anthropometric measurements of Ethiopian preterm infants at birth and compare the results with the international INTERGROWTH-21st data. Patients and methods. We analyzed anthropometric data on live-born singleton preterm infants enrolled in a hospital-based multicenter study of illness in preterm infants (SIP). Eligible newborns with gestational age of 28-36 weeks were included. Gestational age (GA) and sex-specific mean and standard deviations (SD), 10th, 50th, 90th, centile values for birth weight, length and head circumference (HC) were calculated and compared with INTERGROWTH-21st data. Result . A total of 2763 preterm infants were included in the study, 54% were male. The prevalence of small for GA (SGA) (90th percentile) were 10.8% and 9.9%, respectively. In all 3 parameters, the mean values of boys were higher than of girls. Birth weight centiles were comparable to international averages at lower GA, then after GA of 32 weeks the 10th, 50th, and 90th centile values were 100-500 g less than the international averages. The head circumference centiles were mostly comparable, and the 90th centile values were greater than the international averages across the GA and in both sexes. Conclusion. The infants’ birth weights were smaller at higher GA, which may indicate maternal undernutrition in the third trimester of pregnancy. Strengthening antenatal nutrition counseling and providing nutrition supplementation might improve the birth weight.

Background . In low-income countries, preterm nutrition is often inadequately addressed. The aim of the study was to assess the patterns of feeding and associated clinical outcomes of preterm neonates admitted to neonatal intensive care units in Ethiopia. Method . This was a multicenter, prospective study. Infants’ clinical characteristics at birth, daily monitoring of feeding history, and weight measurements were collected. An outcome assessment was completed at 28 days. Result . For this analysis, 2560 infants (53% male) were eligible. The mean (SD) gestational age was 33.1 (2.2) weeks. During the hospital stay the proportion of infants on breast milk only, preterm formula, term formula, and mixed feeding was 58%, 27.4%, 1.6%, and 34.1%, respectively. Delay in enteral feeding was associated with increased risk of death (odds ratio [OR] = 1.92, 95% confidence interval [CI] = 1.33-2.78; P < .001) and (OR = 5.06, 95% CI = 3.23-7.87; P < .001) for 1 to 3 and 4 to 6 days of delay in enteral feeding, respectively, after adjusting for possible confounders. The length of delay in enteral feeding was associated with increased risk of hypoglycemia (OR = 1.2, 95% CI = 1.1-1.2; P = .005). The mortality rate was lower in hospitals providing preterm formula more often ( P = .04). Half of the infants continued losing weight at the time of discharge. Conclusion . Delayed enteral feeding significantly increases the risk of mortality before discharge and hypoglycemia in preterm infants in resource-limited settings. Ensuring adequate nutritional support of preterm infants is highly needed.

Background Preterm infants have high risk of developing growth restriction and long-term complications. Enteral feeding is often delayed in neonatal intensive care units (NICUs) for the fear of feeding intolerance and the associated necrotising enterocolitis, and recent advances in nutritional support are unavailable in low-income countries.Objective The aim of this study was to assess the incidence and associated factors of extrauterine growth restriction (EUGR) among preterm infants in selected NICUs in Ethiopia.Method This was a cross-sectional study involving a subgroup analysis of preterm infants admitted to hospitals, from a multicentre descriptive study of cause of illness and death in preterm infants in Ethiopia, conducted from 2016 to 2018. EUGR was defined as weight at discharge Z-scores

To date, no comprehensive analysis of autoantibodies in sera of patients with ulcerative colitis has been conducted. To analyze the spectrum of autoantibodies and to elucidate their role serum-IgG from UC patients (n = 49) and non-UC donors (n = 23) were screened by using a human protein microarray. Screening yielded a remarkable number of 697 differentially-reactive at the nominal 0·01 significance level (FDR

Abstract Background Ulcerative colitis (UC) is a highly progressive inflammatory disease that requires the interaction of epithelial, immune, endothelial and muscle cells and fibroblasts. Previous studies suggested two inflammatory conditions in UC-patients: ‘acute’ and ‘remodeling’ and that the design of a disease network might improve the understanding of the inflammatory processes. The objective of the study was to design and validate a disease network in the NOD-SCID IL2rγnull (NSG)-UC mouse model to get a better understanding of the inflammatory processes. Methods Leukocytes were isolated from the spleen of NSG-UC mice and subjected to flow cytometric analysis. RT-PCR and RNAseq analysis were performed from distal parts of the colon. Based on these analyses and the effects of interleukins, chemokines and growth factors described in the literature, a disease network was designed. To validate the disease network the effect of infliximab and pitrakinra was tested in the NSG-UC model. A clinical- and histological score, frequencies of human leukocytes isolated from spleen and mRNA expression levels from distal parts of the colon were determined. Results Analysis of leukocytes isolated from the spleen of challenged NSG-UC mice corroborated CD64, CD163 and CD1a expressing CD14+ monocytes, CD1a expressing CD11b+ macrophages and HGF, TARC, IFNγ and TGFß1 mRNA as inflammatory markers. The disease network suggested that a proinflammatory condition elicited by IL-17c and lipids and relayed by cytotoxic T-cells, Th17 cells and CD1a expressing macrophages and monocytes. Conversely, the remodeling condition was evoked by IL-34 and TARC and promoted by Th2 cells and M2 monocytes. Mice benefitted from treatment with infliximab as indicated by the histological- and clinical score. As predicted by the disease network infliximab reduced the proinflammatory response by suppressing M1 monocytes and CD1a expressing monocytes and macrophages and decreased levels of IFNγ, TARC and HGF mRNA. As predicted by the disease network inflammation aggravated in the presence of pitrakinra as indicated by the clinical and histological score, elevated frequencies of CD1a expressing macrophages and TNFα and IFNγ mRNA levels. Conclusions The combination of the disease network and the NSG-UC animal model might be developed into a powerful tool to predict efficacy or in-efficacy and potential mechanistic side effects.

Diagnosis is a prerequisite for successful professional problem-solving: A physician identifies an appropriate treatment based on a diagnosis of the patient’s disease, and a teacher selects an appropriate learning task based on an assessment of the student’s prior knowledge. Education in academic professions such as medicine or teaching is often focuses on the acquisition of conceptual knowledge from lectures and books; opportunities for students to engage in practical diagnostic situations are typically rare. However, applying such conceptual knowledge in diagnostic activities is regarded as necessary for developing diagnostic competences. In this article, we focus on simulations in which students can actively engage in practicing diagnostic activities concerning cases from professional practice. We review and link research perspectives on diagnostic competences, their components and their development. This is partly done by exploring the commonalities and differences in research on diagnostic competences in medicine and teaching. Then, we present approaches to simulation, followed by different types of instructional support in such simulations. In particular, we focus on different forms of scaffolding during problem-solving, and on the possibly complementary roles of expository forms of instruction in these kinds of environments. Building on the perspectives reviewed, we propose a framework for fostering diagnostic competences in simulations in higher education and outline an interdisciplinary research approach concerning the instructional design of such simulations.

BackgroundThe annual number of surgical operations performed is increasing throughout the world. With this rise in the number of surgeries performed, so too, the challenge of effectively managing postoperative pain. In Africa, there are scanty data available that make use of multi-center data to characterize the quality of postoperative pain management. In this study using a longitudinal data, we have attempted to characterize the quality of postoperative pain management; among patients scheduled for major elective orthopedic, gynecologic and general surgery.MethodsThis prospective longitudinal study evaluated the quality of postoperative pain management in patients undergoing elective general, gynecologic, and orthopedic surgery. We quantified the prevalence of moderate to severe postoperative pain with the International Pain Outcome Questionnaire and the corresponding adequacy of treatment with the pain management index. At four time points after surgery, we estimated pain severity, its physical and emotional interference, and patient satisfaction.ResultsModerate to severe postoperative pain was present in 88.2% of patients, and pain was inadequately treated in 58.4% of these patients. Chronic pain (β = 0.346, 95% CI: 0.212, 0.480) predicted patients' worst pain intensity. Gender was not associated with the worst pain intensity or percentage of time spent in severe pain. Patient's pain intensity did not predicted the level of satisfaction.ConclusionsThe prevalence of moderate to severe postoperative pain and its functional interference is high in Ethiopian patients. The treatment provided to patients is inadequate and not in line with international recommendations and standards.

BackgroundPostoperative pain remains a challenge in the developed world, but the consequences of inadequately treated postoperative pain are particularly severe in low- and middle-income countries. Since 2011, reports have drawn attention to the poor quality of postoperative pain management in Ethiopia; however, our multicenter qualitative study was the first to attempt to understand the factors that are barriers to and facilitators of quality pain managment in the country. To this aim, the study explored the perspectives of patients, healthcare professionals, and hospital officials. We expected that the results of this study would inform strategies to improve the provision of quality pain management in Ethiopia and perhaps even in other low- and middle-income countries.MethodsThis study used a qualitative, descriptive approach in which nine healthcare professionals, nine patients, and six hospital officials (i.e. executives in a managerial or leadership position in administration, nursing, or education) participated in face-to-face, semi-structured interviews. Thematic data analysis was conducted, and patterns were explained with the help of a theoretical framework.FindingsThe barriers identified ranged from healthcare professionals' lack of empathy to a positive social appraisal of patients' ability to cope with pain. They also included a lack of emphasis on pain and its management during early medical education, together with the absence of available resources. Enhancing the ability of healthcare professionals to create favorable rapport with patients and increasing the cultural competence of professionals are essential ingredients of future pain education interventions.ConclusionsBarriers to and facilitators of postoperative pain management do not exist independently but are reciprocally linked. This finding calls for holistic and inclusive interventions targeting healthcare professionals, patients, and hospital officials. The current situation is unlikely to improve if only healthcare professionals are educated about pain physiology, pharmacology, and management. Patients should also be educated, and the hospital environment should be modified to provide high-quality postoperative pain management.

Introduction: Ethiopia is a rapidly developing country in Eastern Africa. In total, 43.2% of the population are younger than 15. In contrast, until a few years ago, pediatric surgery was only available in Addis Ababa. Now, Ethiopia is making great efforts to improve the care of children who require surgery. JimmaChild was established to set up a pediatric surgery in Jimma. Material and methods: JimmaChild developed from a scientific collaboration between Jimma University (JU) and Ludwig-Maximilians-University. The project was developed and realized by Ethiopian and German colleagues. A curriculum was written for this purpose. The pediatric surgical training of the fellows was carried out on-site by German pediatric surgeons. Results: A new pediatric surgery was established at JU with its own operating room, ward, and staff. After two and a half years, two fellows completed their final examinations as pediatric surgeons. Among others, 850 elective surgeries were performed, 82% assisted by the German colleagues. The German colleagues rated the preparation for the trip, the on-site support, and the professional progress of the fellows mostly as good to very good. Reported problems in the program flow were also recognized and solved in part. Conclusions: The best possible integration of the project into existing structures was achieved by close cooperation of Ethiopian and German colleagues during the project development. Problems were identified and addressed early on by external monitoring. As the project responsibility was mainly with the Ethiopian colleagues, a department was created that now exists independently of external funding and trains its own fellows.

Animal models reflective of ulcerative colitis (UC) remain a major challenge, and yet are crucial to understand mechanisms underlying the onset of disease and inflammatory characteristics of relapses and remission. Mouse models in which colitis-like symptoms are induced through challenge with toxins such as oxazolone, dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) have been instrumental in understanding the inflammatory processes of UC. However, these neither reflect the heterogeneous symptoms observed in the UC-affected population nor can they be used to test the efficacy of inhibitors developed against human targets where high sequence and structural similarity of the respective ligands is lacking. In an attempt to overcome these problems, we have developed a mouse model that relies on NOD-scid IL2R γnull mice reconstituted with peripheral blood mononuclear cells derived from UC-affected individuals. Upon challenge with ethanol, mice developed colitis-like symptoms and changes in the colon architecture, characterized by influx of inflammatory cells, edema, crypt loss, crypt abscesses and epithelial hyperplasia, as previously observed in immune-competent mice. TARC, TGFβ1 and HGF expression increased in distal parts of the colon. Analysis of human leucocytes isolated from mouse spleen revealed an increase in frequencies of CD1a+, CD64+, CD163+ and TSLPR+ CD14+ monocytes, and antigen-experienced CD44+ CD4+ and CD8+ T-cells in response to ethanol. Analysis of human leucocytes from the colon of challenged mice identified CD14+ monocytes and CD11b+ monocytes as the predominant populations. Quantitative real-time PCR (RT-PCR) analysis from distal parts of the colon indicated that IFNγ might be one of the cytokines driving inflammation. Treatment with infliximab ameliorated symptoms and pathological manifestations, whereas pitrakinra had no therapeutic benefit. Thus, this model is partially reflective of the human disease and might help to increase the translation of animal and clinical studies.

Glucose is the preferred source of energy in activated inflammatory cells. Glucose uptake into the cell is ensured by a family of glucose uptake transporters (GLUTs), which have been identified as off-target molecules of the HIV protease inhibitor ritonavir. In this study, we examined the effect of ritonavir on inflammation in vitro and in vivo. Peripheral blood mononuclear cells (PBMCs) were activated with anti-CD3 in the presence or absence of ritonavir and analyzed by flow cytometric analysis. Frequencies of CD4+ cells were significantly affected by ritonavir (CD69+ P=3E-05; CD134 P=4E-06; CD25+ P=E-07; central memory P=0.02; effector P=6E-03; effector memory P=6E-05). To corroborate that inflammation has a metabolic effect in vivo, a mouse model was used that is based on immunocompromised NOD-scid IL-2Rγ null mice reconstituted with PBMCs from patients with ulcerative colitis (UC). Inflammation had a significant effect on amino acid (AA) levels (Glu P=1E-07, Asp P=1E-04). Principal component analysis (PCA) discriminated between unchallenged and challenged groups. Finally, the efficacy of ritonavir was tested in the same mouse model. Dependent variables were clinical and histological scores, frequencies of human leukocytes isolated from spleen and colon, and levels of AA in sera of mice. Mice benefited from treatment with ritonavir as indicated by significantly decreased colon (P=7E-04) and histological (P=1E-04) scores, frequencies of M2 monocytes (CD14+ CD163; P=0.02), and Glu levels (P=2E-05). PCA discriminated between control and challenged groups (P=0.026). Thus, inhibition of glucose uptake might be a promising therapeutic intervention point for active UC.

BACKGROUND:The recent genome-wide association studies (GWAS) in inflammatory bowel disease (IBD) suggest significant genetic overlap with complex mycobacterial diseases like tuberculosis or leprosy. TLR variants have previously been linked to susceptibility for mycobacterial diseases. Here we investigated the contribution to IBD risk of two TLR2 polymorphisms, the low-prevalence variant Arg753Gln and the GTn microsatellite repeat polymorphism in intron 2. We studied association with disease, possible correlations with phenotype and gene-gene interactions. METHODOLOGY/PRINCIPAL FINDINGS:We conducted a large study in 843 patients with Crohn's disease, 426 patients with ulcerative colitis and 805 healthy, unrelated controls, all of European origin. Overall, the frequency for carriers of shorter GTn repeats in intron 2 of the TLR2 gene, which have previously been associated with low TLR2 expression and high IL-10 production, was slightly elevated in Crohn's disease and ulcerative colitis compared to healthy controls (16.0% resp. 16.7% vs. 12.8%). The highest frequency of short GTn carriers was noted among IBD patients on anti TNF-alpha therapy. However, none of these differences was significant in the multivariate analysis. The Arg753Gln polymorphism showed no association with any clinical subtype of IBD, including extensive colitis, for which such an association was previously described. We found no association with specific phenotypic disease subgroups. Also, epistasis analysis revealed no significant interactions between the two TLR2 variants and confirmed IBD susceptibility genes. CONCLUSIONS:The two functional relevant polymorphisms in TLR2, the GTn microsatellite repeat polymorphism in intron 2 and the Arg753Gln variant do not seem to play a role in the susceptibility to Crohn's disease or ulcerative colitis.

SUMMARY Animal models mimicking human diseases have been used extensively to study the pathogenesis of autoimmune diseases and the efficacy of potential therapeutics. They are, however, limited with regard to their similarity to the human disease and cannot be used if the antagonist and its cognate receptor require high similarity in structure or binding. Here, we examine the induction of oxazolone-mediated features of atopic dermatitis (AD) in NOD-scid IL2Rγnull mice engrafted with human peripheral blood mononuclear cells (PBMC). The mice developed the same symptoms as immunocompetent BALB/c mice. Histological alterations induced by oxazolone were characterized by keratosis, epithelial hyperplasia and influx of inflammatory cells into the dermis and epidermis. The cellular infiltrate was identified as human leukocytes, with T cells being the major constituent. In addition, oxazolone increased human serum IgE levels. The response, however, required the engraftment of PBMC derived from patients suffering from AD, which suggests that this model reflects the immunological status of the donor. Taken together, the model described here has the potential to evaluate the efficacy of therapeutics targeting human lymphocytes in vivo and, in addition, might be developed further to elucidate molecular mechanisms inducing and sustaining flares of the disease.

This study focused on the difference between perceived and desired physician empathy (pPE and dPE) in the eye of patients with inflammatory bowel disease (IBD). It was investigated if a discrepancy (ΔPE) correlates with trust and satisfaction of patients. At the same time the aim was to gain detailed information about the subjective burden of disease and the resources of IBD patients, in order to better understand them.A modified version of the German Version of the Consultation and Relational Empathy (CARE) measure was completed as a paper-and-pencil questionnaire by IBD patients attending our facility (n = 32) and as an online survey by IBD patients at other locations throughout Germany (n = 89). Patients were in average 36.3±12 years old.The mean (SD) rating of pPE was 3.93 (0.96) on a scale of 1 to 5 ("poor" to "excellent"); however, the mean (SD) dPE was 4.38 (0.48) on the same scale. ΔPE correlated with perceived empathy and with patients' satisfaction with treatment and trust in their health care providers. Patients reported quite a high subjective burden (mean [SD]: 2.93 [.63]) and named family, friends, and support groups as resources.Rather than assessing patient satisfaction with treatment and trust in their physician only with perceived PE, we suggest ΔPE as a useful additional parameter.

Professional knowledge is highlighted as an important prerequisite of both medical doctors and teachers. Based on recent conceptions of professional knowledge in these fields, knowledge can be differentiated within several aspects. However, these knowledge aspects are currently conceptualized differently across different domains and projects. Thus, this paper describes recent frameworks for professional knowledge in medical and educational sciences, which are then integrated into an interdisciplinary two-dimensional model of professional knowledge that can help to align terminology in both domains and compare research results. The models’ two dimensions differentiate between cognitive types of knowledge and content-related knowledge facets and introduces a terminology for all emerging knowledge aspects. The models’ applicability for medical and educational sciences is demonstrated in the context of diagnosis by describing prototypical diagnostic settings for medical doctors as well as for teachers, which illustrate how the framework can be applied and operationalized in these areas. Subsequently, the role of the different knowledge aspects for acting and the possibility of transfer between different content areas are discussed. In conclusion, a possible extension of the model along a “third dimension„ that focuses on the effects of growing expertise on professional knowledge over time is proposed and issues for further research are outlined.