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The COVID-19 pandemic caused a major economic downturn that disproportionally affected university students. This empirical research investigated effects and risk factors of the pandemic on students' economic situation with focus on financial distress and financial limitations. Data was collected using an online survey in May and June 2020 from students (n = 917) enrolled at universities in Germany. 80.6% were enrolled in bachelor programs (n = 738), the mean semester was 3.8 (standard deviation (SD = 2.0) and students' mean age was 23.1 years (SD = 4.1). 51.8% (n = 472) were female and 47.4% (n = 432) male. 56.7% (n = 506) of students worked before the pandemic. More than one third reported a decrease in income (36.5%; n = 334) and an increase in financial constraints (38.7%; n = 354). A multivariate logistic regression analysis showed that students with regular income were less likely to experience financial distress compared to those without (odds ratio (OR) = 0.456; p = 0.014). Furthermore, working part-time as associated with a higher financial distress compared to those without part-time employment (OR = 1.811; p = 0.003). Students who worked part-time before the pandemic also had a higher probability of increased financial restriction (or constraint) compared to those who did not work part-time (OR = 2.094; p < 0.001). University students were disproportionally affected by the economic consequences of the COVID-19 pandemic, which increased students' economic uncertainty. To offset such problems, financial aid schemes for students need to be made available to alleviate distress and to allow students to focus on their studies but should not compound problems by leading to financial hardship at a later point in time., Competing Interests: The authors have declared that no competing interests exist.

Artemisinin resistance is threatening global efforts for malaria control and elimination. Primaquine (PQ) and methylene blue (MB) are gametocytocidal drugs that can be combined with artemisinin-based combination therapy (ACT) to reduce malaria transmission, including resistant strains. Children (6-59 months) with uncomplicated falciparum malaria in Burkina Faso were treated with artesunate-amodiaquine (AS-AQ) and randomized to MB (15 mg/kg/day for 3 days) or PQ (0.25 mg/kg at day 2) with the aim to show non-inferiority of the MB regimen with regard to haematological recovery at day 7 (primary endpoint). MB-AS-AQ could not be shown to be non-inferior to PQ-AS-AQ (mean Hb difference between treatment groups on day 7 was -0.352, 95% CI -0.832-0.128, p = 0.0767), however, haemoglobin recovery following treatment was alike in the two study arms (day 7: mean 0.2±1.4 g/dl vs. 0.5±0.9 g/dl, p = 0.446). Occurrence of adverse events was similar in both groups, except for vomiting, which was more frequent in the MB than in the PQ arm (20/50 vs 7/50, p = 0.003). Adequate clinical and parasitological response was above 95% in both groups, but significantly more asexual parasites were cleared in the MB arm compared to the PQ arm already on day 1 (48/50, 96%, vs 40/50, 80%, p = 0.014). Moreover, P. falciparum gametocyte prevalence and density were lower in the MB arm than in the PQ arm, which reached statistical significance on day 2 (prevalence: 2/50, 4%, vs 15/49, 31%, p<0.001; density: 9.6 vs 41.1/μl, p = 0.024). However, it should be considered that PQ was given only on day 2. MB-ACT appears to be an interesting alternative to PQ-ACT for the treatment of falciparum malaria. While there is a need to further improve MB formulations, MB-ACT may already be considered useful to reduce falciparum malaria transmission intensity, to increase treatment efficacy, and to reduce the risk for resistance development and spread. Trial registration: ClinicalTrials.gov NCT02851108., Competing Interests: The authors have declared that no competing interests exist.

Purpose: This study aimed to assess the effectiveness of a care management intervention in improving self-management behavior in multimorbid patients with type 2 diabetes; care was delivered by medical assistants in the context of a primary care network (PCN) in Germany., Methods: This study is an 18-month, multi-center, two-armed, open-label, patient-randomized parallel-group superiority trial (ISRCTN 83908315). The intervention group received the care management intervention in addition to the usual care. The control group received usual care only. The primary outcome was the change in self-care behavior at month 9 compared to baseline. The self-care behavior was measured with the German version of the Summary of Diabetes Self-Care Activities Measure (SDSCA-G). A multilevel regression analysis was applied., Results: We assigned 495 patients to intervention (n = 252) and control (n = 243). At baseline, the mean age was 68 ±11 years, 47.8% of the patients were female and the mean HbA1c was 7.1±1.2%. The primary analysis showed no statistically significant effect, but a positive trend was observed (p = 0.206; 95%-CI = -0.084; 0.384). The descriptive analysis revealed a significantly increased sum score of the SDSCA-G in the intervention group over time (P = 0.012) but not in the control group (p = 0.1973)., Conclusion: The sum score for self-care behavior markedly improved in the intervention group over time. However, the results of our primary analysis showed no statistically significant effect. Possible reasons are the high baseline performance in our sample and the low intervention fidelity. The implementation of this care management intervention in PCNs has the potential to improve self-care behavior of multimorbid patients with type 2 diabetes., Competing Interests: The authors have declared that no competing interests exist.

Background: For virtually every patient with colorectal cancer (CRC), hematoxylin-eosin (HE)-stained tissue slides are available. These images contain quantitative information, which is not routinely used to objectively extract prognostic biomarkers. In the present study, we investigated whether deep convolutional neural networks (CNNs) can extract prognosticators directly from these widely available images., Methods and Findings: We hand-delineated single-tissue regions in 86 CRC tissue slides, yielding more than 100,000 HE image patches, and used these to train a CNN by transfer learning, reaching a nine-class accuracy of >94% in an independent data set of 7,180 images from 25 CRC patients. With this tool, we performed automated tissue decomposition of representative multitissue HE images from 862 HE slides in 500 stage I-IV CRC patients in the The Cancer Genome Atlas (TCGA) cohort, a large international multicenter collection of CRC tissue. Based on the output neuron activations in the CNN, we calculated a "deep stroma score," which was an independent prognostic factor for overall survival (OS) in a multivariable Cox proportional hazard model (hazard ratio [HR] with 95% confidence interval [CI]: 1.99 [1.27-3.12], p = 0.0028), while in the same cohort, manual quantification of stromal areas and a gene expression signature of cancer-associated fibroblasts (CAFs) were only prognostic in specific tumor stages. We validated these findings in an independent cohort of 409 stage I-IV CRC patients from the "Darmkrebs: Chancen der Verhütung durch Screening" (DACHS) study who were recruited between 2003 and 2007 in multiple institutions in Germany. Again, the score was an independent prognostic factor for OS (HR 1.63 [1.14-2.33], p = 0.008), CRC-specific OS (HR 2.29 [1.5-3.48], p = 0.0004), and relapse-free survival (RFS; HR 1.92 [1.34-2.76], p = 0.0004). A prospective validation is required before this biomarker can be implemented in clinical workflows., Conclusions: In our retrospective study, we show that a CNN can assess the human tumor microenvironment and predict prognosis directly from histopathological images., Competing Interests: The authors have declared that no competing interests exist.

Background: Neglected tropical diseases (NTDs) account for a large disease burden in sub-Saharan Africa. While the general cost-effectiveness of NTD interventions to improve health outcomes has been assessed, few studies have also accounted for the financial and education gains of investing in NTD control., Methods: We built on extended cost-effectiveness analysis (ECEA) methods to assess the health gains (e.g. infections, disability-adjusted life years or DALYs averted), household financial gains (out-of-pocket expenditures averted), and education gains (cases of school absenteeism averted) for five NTD interventions that the government of Madagascar aims to roll out nationally. The five NTDs considered were schistosomiasis, lymphatic filariasis, and three soil-transmitted helminthiases (Ascaris lumbricoides, Trichuris trichiura, and hookworm infections)., Results: The estimated incremental cost-effectiveness for the roll-out of preventive chemotherapy for all NTDs jointly was USD125 per DALY averted (95% uncertainty range: 65-231), and its benefit-cost ratio could vary between 5 and 31. Our analysis estimated that, per dollar spent, schistosomiasis preventive chemotherapy, in particular, could avert a large number of infections (176,000 infections averted per $100,000 spent), DALYs (2,000 averted per $100,000 spent), and cases of school absenteeism (27,000 school years gained per $100,000 spent)., Conclusion: This analysis incorporates financial and education gains into the economic evaluation of health interventions, and therefore provides information about the efficiency of attainment of three Sustainable Development Goals (SDGs). Our findings reveal how the national scale-up of NTD control in Madagascar can help address health (SDG3), economic (SDG1), and education (SDG4) goals. This study further highlights the potentially large societal benefits of investing in NTD control in low-resource settings., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective: Knowledge about predictors of health-related quality of life for multimorbid patients with type 2 diabetes mellitus in primary care could help to improve quality and patient-centeredness of care in this specific group of patients. Thus, the aim of this study was to investigate the impact of several patient characteristics on health-related quality of life of multimorbid patients with type 2 diabetes mellitus in a community setting., Research Design and Methods: A cross-sectional study with 32 primary care practice teams in Mannheim, Germany, and randomly selected multimorbid patients with type 2 diabetes mellitus (N = 495) was conducted. In order to analyze associations of various patient characteristics with health-related quality of life (EQ-5D index) a multilevel analysis was applied., Results: After excluding patients with missing data, the cohort consisted of 404 eligible patients. The final multilevel model highlighted six out of 14 explanatory patient variables which were significantly associated with health-related quality of life: female gender (r = -0.0494; p = .0261), school education of nine years or less (r = -0.0609; p = .0006), (physical) mobility restrictions (r = -0.1074; p = .0003), presence of chronic pain (r = -0.0916; p = .0004), diabetes-related distress (r = -0.0133; p < .0001), and BMI (r = -0.0047; p = .0045)., Conclusion: The findings of this study suggest that increased diabetes-related distress, chronic pain, restrictions in (physical) mobility, female gender, as well as lower education and, increased BMI have a noteworthy impact on health-related quality of life in multimorbid patients with type 2 diabetes mellitus seen in primary care practices in a community setting. The highlighted aspects should gain much more attention when treating multimorbid patients with type 2 diabetes mellitus., Competing Interests: The authors have declared that no competing interests exist.