Comparison of Generic and Proprietary Sodium Stibogluconate for the Treatment of Visceral Leishmaniasis in Kenya.

OBJECTIVE: To compare the use of generic and proprietary sodium stibogluconate for the treatment of visceral leishmaniasis (kala-azar). METHODS: A total of 102 patients with confirmed kala-azar were treated in a mission hospital in West Pokot region, Kenya, with sodium stibogluconate (20 mg/kg/day for 30 days)--either as Pentostam (PSM) or generic sodium stibogluconate (SSG); 51 patients were allocated alternately to each treatment group. FINDINGS: There were no significant differences in baseline demographic characteristics or disease severity, or in events during treatment. There were 3 deaths in the PSM group and 1 in the SSG group; 2 patients defaulted in each group. Only 1 out of 80 test-of-cure splenic aspirates was positive for Leishmania spp.; this patient was in the SSG group. Follow-up after > or = 6 months showed that 6 out of 58 patients had relapsed, 5 in the SSG group and 1 in the PSM group. No outcome variable was significantly different between the two groups. CONCLUSION: The availability of cheaper generic sodium stibogluconate, subject to rigid quality controls, now makes it possible for the health authorities in kala-azar endemic areas to provide treatment to many more patients in Africa

Influenza season influence on outcome of new nodules in the NELSON study

We evaluated the impact of the influenza season on outcome of new lung nodules in a LDCT lung cancer screening trial population. NELSON-trial participants with ≥ 1 new nodule detected in screening rounds two and three were included. Outcome (resolution or persistence) of new nodules detected per season was calculated and compared. Winter (influenza season) was defined as 1st October to 31st March, and compared to the summer (hay-fever season), 1st April to 30th September. Overall, 820 new nodules were reported in 529 participants. Of the total new nodules, 482 (59%) were reported during winter. When considering the outcome of all new nodules, there was no statistically significant association between summer and resolving nodules (OR 1.07 [CI 1.00-1.15], p = 0.066), also when looking at the largest nodule per participant (OR 1.37 [CI 0.95-1.98], p = 0.094). Similarly, there was no statistically significant association between season and screen detected cancers (OR 0.47 [CI 0.18-1.23], p = 0.123). To conclude, in this lung cancer screening population, there was no statistically significant association between influenza season and outcome of new lung nodules. Hence, we recommend new nodule management strategy is not influenced by the season in which the nodule is detected.</p

You escaped! How did you learn during gameplay?

This study investigates the influence of the educational game design elements immersion, collaboration and debriefing, on fostering learning with educational escape rooms. We based the design of the escape room on an educational game design framework that aligns the learning goal and the game goal, that is, escaping from the room. One-hundred-and-twenty-six students, aged between 16 and 20 played the escape room. Measures for learning were pre-and post-tests. The game experience was measured through questionnaires, classroom observations and interviews with students and teachers. The results show a knowledge gain between pre-and post-test. Correlational analysis showed that all three design elements contributed to students' appreciation of the escape room, whereas only immersion had a direct contribution to knowledge gain. Based on the qualitative data it appeared that the used escape boxes contributed most to perceived immersion. Immersion helps students focus on each other and the tasks. Also, a narrative with distinct roles for each student helped to evoke immersion. Unexpectedly, these roles also scaffolded collaboration except for students in the school that engaged in a collaborative learning pedagogy. The study confirms the usability of the framework for game designs, based on theories for the design of physical and hybrid educational games. Practitioner notes What is already known about this topic The escape room as a learning environment appeals to teachers of different disciplines, ages, gender and teaching experiences. Teachers implement escape rooms to create active (hybrid) learning spaces, where learners need a combination of knowledge and skills to solve the subject-based activities. Students and teachers perceive that while participating in escape rooms, students are more engaged, active and learn more compared to regular classes. The assumption is that escape rooms support collaboration and automatically collaborative learning. Review studies on educational escape rooms show that a systematic evaluation is usually absent, disputable or indicates no knowledge gain. Teachers design their educational escape rooms based on digital escape games and/or their experience as players of escape rooms. For digital educational games, important game design aspects are researched. Three main challenges in designing educational games are (1) the participants' transition from the real world to the game world, (2) the alignment of game design aspects and educational aspects and (3) the transfer from attained experiences and knowledge back into the real world. What this paper adds This paper evaluates an educational game design framework for escape rooms, focussing on the above-mentioned main challenges in designing educational games. It investigates the influence of the educational game design elements immersion, collaboration and debriefing, on fostering learning with a hybrid educational escape room. It informs that all three design elements contributed to students' appreciation of the escape room, whereas only immersion had a direct contribution to knowledge gain. The used hybrid escape boxes contributed most to the immersion; scaffolding students to focus on each other and the tasks. Students' collaboration was successfully fostered. However, it scarcely led to collaborative learning during gameplay, due to lack of discussion and reflection needed for deeper understanding. Implications for practice and/or policy The educational escape game framework would help educators creating immersive games, which not only confront learners with meaningful contexts but also give learning gains. The educational escape game framework would help researchers focussing on important and difficult aspects of designing and implementing educational escape rooms to develop and research more effective escape rooms. In guidelines on creating immersion in educational escape games, the notion of physical objects is lacking. In this hybrid escape room, the physical objects such as escape boxes were the most powerful in creating immersion. In addition, the use of sound design in escape games in classrooms seems overrated. Debriefing after the gameplay is perceived necessary to discuss common misunderstandings, to make connections between the topics in various puzzles and to add more content to interest high-achieving students

PHP48 COST SENSITIVENESS AND PHYSICIAN TREATMENT CHOICES

Objectives To explore the relationship between nodule count and lung cancer probability in baseline low-dose CT lung cancer screening. Materials and Methods Included were participants from the NELSON trial with at least one baseline nodule (3392 participants [45% of screen-group], 7258 nodules). We determined nodule count per participant. Malignancy was confirmed by histology. Nodules not diagnosed as screen-detected or interval cancer until the end of the fourth screening round were regarded as benign. We compared lung cancer probability per nodule count category. Results 1746 (51.5%) participants had one nodule, 800 (23.6%) had two nodules, 354 (10.4%) had three nodules, 191 (5.6%) had four nodules, and 301 (8.9%) had > 4 nodules. Lung cancer in a baseline nodule was diagnosed in 134 participants (139 cancers; 4.0%). Median nodule count in participants with only benign nodules was 1 (Inter-quartile range [IQR]: 1–2), and 2 (IQR 1–3) in participants with lung cancer (p = NS). At baseline, malignancy was detected mostly in the largest nodule (64/66 cancers). Lung cancer probability was 62/1746 (3.6%) in case a participant had one nodule, 33/800 (4.1%) for two nodules, 17/354 (4.8%) for three nodules, 12/191 (6.3%) for four nodules and 10/301 (3.3%) for > 4 nodules (p = NS). Conclusion In baseline lung cancer CT screening, half of participants with lung nodules have more than one nodule. Lung cancer probability does not significantly change with the number of nodules. Baseline nodule count will not help to differentiate between benign and malignant nodules. Each nodule found in lung cancer screening should be assessed separately independent of the presence of other nodules

Influenza season influence on outcome of new nodules in the NELSON study

We evaluated the impact of the influenza season on outcome of new lung nodules in a LDCT lung cancer screening trial population. NELSON-trial participants with ≥ 1 new nodule detected in screening rounds two and three were included. Outcome (resolution or persistence) of new nodules detected per season was calculated and compared. Winter (influenza season) was defined as 1st October to 31st March, and compared to the summer (hay-fever season), 1st April to 30th September. Overall, 820 new nodules were reported in 529 participants. Of the total new nodules, 482 (59%) were reported during winter. When considering the outcome of all new nodules, there was no statistically significant association between summer and resolving nodules (OR 1.07 [CI 1.00-1.15], p = 0.066), also when looking at the largest nodule per participant (OR 1.37 [CI 0.95-1.98], p = 0.094). Similarly, there was no statistically significant association between season and screen detected cancers (OR 0.47 [CI 0.18-1.23], p = 0.123). To conclude, in this lung cancer screening population, there was no statistically significant association between influenza season and outcome of new lung nodules. Hence, we recommend new nodule management strategy is not influenced by the season in which the nodule is detected

Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation

Canonical Wnt signaling has been implicated in various aspects of hematopoiesis. Its role is controversial due to different outcomes between various inducible Wnt-signaling loss-of-function models and also compared with gain-of-function systems. We therefore studied a mouse deficient for a Wnt gene that seemed to play a nonredundant role in hematopoiesis. Mice lacking Wnt3a die prenatally around embryonic day (E) 12.5, allowing fetal hematopoiesis to be studied using in vitro assays and transplantation into irradiated recipient mice. Here we show that Wnt3a deficiency leads to a reduction in the numbers of hematopoietic stem cells (HSCs) and progenitor cells in the fetal liver (FL) and to severely reduced reconstitution capacity as measured in secondary transplantation assays. This deficiency is irreversible and cannot be restored by transplantation into Wnt3a competent mice. The impaired long-term repopulation capacity of Wnt3a-/- HSCs could not be explained by altered cell cycle or survival of primitive progenitors. Moreover, Wnt3a deficiency affected myeloid but not B-lymphoid development at the progenitor level, and affected immature thymocyte differentiation. Our results show that Wnt3a signaling not only provides proliferative stimuli, such as for immature thymocytes, but also regulates cell fate decisions of HSC during hematopoiesis

Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial

BACKGROUND There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers. METHODS A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants. RESULTS Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 personyears in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9. CONCLUSIONS In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and others; NELSON Netherlands Trial Register number, NL580.)

Relationship between the number of new nodules and lung cancer probability in incidence screening rounds of CT lung cancer screening: The NELSON study

Background: New nodules are regularly found after the baseline round of low-dose computed tomography (LDCT) lung cancer screening. The relationship between a participant's number of new nodules and lung cancer probability is unknown. Methods: Participants of the ongoing Dutch-Belgian Randomized Lung Cancer Screening (NELSON) Trial with (sub)solid nodules detected after baseline and registered as new by the NELSON radiologists were included. The correlation between a participant's new nodule count and the largest new nodule size was assessed using Spearman's rank correlation. To evaluate the new nodule count as predictor for new nodule lung cancer together with largest new nodule size, a multivariable logistic regression analysis was performed. Results: In total, 705 participants with 964 new nodules were included. In 48% (336/705) of participants no nodule had been found previously during baseline screening and in 22% (154/705) of participants >1 new nodule was detected (range 1–12 new nodules). Eventually, 9% (65/705) of the participants had lung cancer in a new nodule. In 100% (65/65) of participants with new nodule lung cancer, the lung cancer was the largest or only new nodule at initial detection. The new nodule lung cancer probability did not differ significantly between participants with 1 (10% [56/551], 95%CI 8–13%) or >1 new nodule (6% [9/154], 95%CI 3–11%, P =.116). An increased number of new nodules positively correlated with a participant's largest nodule size (P < 0.001, Spearman's rho 0.177). When adjusted for largest new nodule size, the new nodule count had a significant negative association with lung cancer (odds ratio 0.59, 0.37–0.95, P =.03). Conclusion: A participant's new nodule count alone only has limited association with lung cancer. However, a higher new nodule count correlates with an increased largest new nodule size, while the lung cancer probability remains equivalent, and may improve lung cancer risk prediction by size only

Protocol of the Healthy Brain Study: An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context

The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods. https://www.trialregister.nl/trial/795