bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual-, family- and school-based interventions to prevent multiple risk behaviours relating to alcohol, tobacco and drug use in young people aged 8-25 years: a systematic review and meta-analysis
Authors: Tinner Laura , Palmer Jennifer C , Lloyd E. Caitlin , Caldwell Deborah M , MacArthur Georgie J , Dias Kaiseree , Langford Rebecca , Redmore James , Wittkop Linda , Watkins Sarah Holmes , Hickman Matthew , Campbell Rona
Published: June 2022

Background

Engagement in multiple substance use risk behaviours such as tobacco smoking, alcohol and drug use during adolescence can result in adverse health and social outcomes. The impact of interventions that address multiple substance use risk behaviours, and the differential impact of universal versus targeted approaches, is unclear given findings from systematic reviews have been mixed. Our objective was to assess effects of interventions targeting multiple substance use behaviours in adolescents.

Methods

Eight databases were searched to October 2019. Individual and cluster randomised controlled trials were included if they addressed two or more substance use behaviours in individuals aged 8-25 years. Data were pooled in random-effects meta-analyses, reported by intervention and setting. Quality of evidence was assessed using GRADE. Heterogeneity was assessed using between-study variance, τ2 and Ι2, and the p-value of between-study heterogeneity statistic Q. Sensitivity analyses were undertaken using the highest and lowest intra-cluster correlation coefficient (ICC).

Results

Of 66 included studies, most were universal (n=52) and school-based (n=41). We found moderate quality evidence that universal school-based interventions are likely to have little or no short-term benefit (up to 12 months) in relation to alcohol use (OR 0.94, 95% CI: 0.84, 1.04), tobacco use (OR 0.98, 95% CI: 0.83, 1.15), cannabis use (OR 1.06, 95% CI: 0.86, 1.31) and other illicit drug use (OR 1.09, 95% CI: 0.85, 1.39). For targeted school-level interventions, there was low quality evidence of no or a small short-term benefit: alcohol use (OR 0.90, 95% CI: 0.74-1.09), tobacco use (OR 0.86, 95% CI: 0.66, 1.11), cannabis use (OR 0.84, 95% CI: 0.66-1.07) and other illicit drug use (OR 0.79, 95% CI 0.62-1.02). There were too few family-level (n=4), individual-level (n=2) and combination level (n=5) studies to draw confident conclusions. Sensitivity analyses of ICC did not change results.

Conclusions

There is low to moderate quality evidence that universal and targeted school-level interventions have no or a small beneficial effect for preventing substance use multiple risk behaviours in adolescents. Higher quality trials and study reporting would allow better evidence syntheses, which is needed given small benefit of universal interventions can have high public health benefit.

Trial registration

Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD011374. DOI: 10.1002/14651858.CD011374.
Translation and cross-cultural adaptation of the risk assessment instrument TilThermometer for a Swedish version – patient handling in the healthcare sector
Authors: Buck Sebastian , Sandqvist Jan , Nilsing Strid Emma , Knibbe Hanneke J. J. , Enthoven Paul , Wåhlin Charlotte
Published: June 2022

Background

Work-related musculoskeletal disorders are common in the healthcare sector due to exposure of physical demanding work tasks. Risk assessment is necessary to prevent injuries and promote a safety culture. The TilThermometer has proved to be useful in the Netherlands for assessing healthcare workers’ physical exposure to patient handling. The aim of this study was to translate the risk assessment instrument TilThermometer from Dutch to Swedish, perform cross-cultural adaptation, and evaluate its linguistic validity to a Swedish healthcare context.

Methods

Translation and validation process was performed according to following eight steps: 1) Translation (two translators), 2) Synthesis, 3) Back-translation (two back-translators), 4) Synthesis, 5) Linguistic review (one bilingual reviewer), 6) fifteen experts in a panel review according to Delphi-method, 7) Semi-structured interviewing eleven informants, analyzed using qualitative content analysis and step 8) discussion and input from creators of the instrument.

Results

A new Swedish version, the TilThermometer, was provided through the translation process (steps 1–5). The linguistic validity and usefulness were confirmed thru step 6 and 7. Consensus was reached in the expert review after two rounds, comments were analyzed and grouped into five groups. The qualitative content analyses of the interviews emerged in to three categories: 1) “User-friendly and understandable instrument”, 2) “Further development”, and 3) “Important part of the systematic work-environment management”.

Conclusion

In this study, the cross-cultural adaption and translation performed of the Swedish version of TilThermometer assured linguistic validity. This is this first phase before further testing the psychometrics aspects, inter-rater reliability and feasibility of TilThermometer. In the second phase TilThermometer will be implemented and evaluated together with other measures in the Swedish healthcare sector.
Medical school curriculum in the digital age: perspectives of clinical educators and teachers
Authors: Zainal Humairah , Xin Xiaohui , Thumboo Julian , Fong Kok Yong
Published: June 2022

Background

There is a need to reexamine Singapore’s medical school curricula in light of the increasing digitalization of healthcare. Notwithstanding Singapore’s digital competitiveness, there is a perceived gap in preparing its medical students for the digital age. Furthermore, limited research has evaluated the extent to which skills in using digital technologies should be taught to medical students in Asian medical schools to prepare them for future clinical practice- a gap that is filled by this study. Using Singapore as a case study, it explores the views of some local clinical educators and teachers towards the need to impart skills in digital technologies to medical students. It also offers recommendations on ways to balance the clinicians’ concerns about these technologies with the digital competencies needed for clinical practice.

Methods

Findings were drawn from individual interviews with 33 clinical educators and teachers from Singapore’s public and private healthcare sectors. They were recruited using purposive sampling. Data were interpreted using qualitative thematic analysis.

Results

Participants included vice deans of education from all three local medical schools and senior consultants from a wide variety of disciplines. Overall, they acknowledged two benefits of equipping students with skills in digital technologies including promoting the culture of innovation and improving work efficiency. However, they also highlighted four main concerns of imparting these skills: (i) erosion of basic clinical skills, (ii) neglect of a generalist approach to healthcare characterized by holistic management of patients, inter-professional collaboration, and commitment to breadth of practice within each specialty, (iii) rapid pace of technological advances, and (iv) de-personalisation by technology.

Conclusions

The findings show that medical students in Singapore would benefit from a curriculum that teaches them to use digital technologies alongside core clinical skills.
Performance of a rule-based semi-automated method to optimize chart abstraction for surveillance imaging among patients treated for non-small cell lung cancer
Authors: Byrd Catherine , Ajawara Ureka , Laundry Ryan , Radin John , Bhandari Prasha , Leung Ann , Han Summer , Asch Stephen M. , Zeliadt Steven , Harris Alex H. S. , Backhus Leah
Published: June 2022

Background

We aim to develop and test performance of a semi-automated method (computerized query combined with manual review) for chart abstraction in the identification and characterization of surveillance radiology imaging for post-treatment non-small cell lung cancer patients.

Methods

A gold standard dataset consisting of 3011 radiology reports from 361 lung cancer patients treated at the Veterans Health Administration from 2008 to 2016 was manually created by an abstractor coding image type, image indication, and image findings. Computerized queries using a text search tool were performed to code reports. The primary endpoint of query performance was evaluated by sensitivity, positive predictive value (PPV), and F1 score. The secondary endpoint of efficiency compared semi-automated abstraction time to manual abstraction time using a separate dataset and the Wilcoxon rank-sum test.

Results

Query for image type demonstrated the highest sensitivity of 85%, PPV 95%, and F1 score 0.90. Query for image indication demonstrated sensitivity 72%, PPV 70%, and F1 score 0.71. The image findings queries ranged from sensitivity 75–85%, PPV 23–25%, and F1 score 0.36–0.37. Semi-automated abstraction with our best performing query (image type) improved abstraction times by 68% per patient compared to manual abstraction alone (from median 21.5 min (interquartile range 16.0) to 6.9 min (interquartile range 9.5), p < 0.005).

Conclusions

Semi-automated abstraction using the best performing query of image type improved abstraction efficiency while preserving data accuracy. The computerized query acts as a pre-processing tool for manual abstraction by restricting effort to relevant images. Determining image indication and findings requires the addition of manual review for a semi-automatic abstraction approach in order to ensure data accuracy.
Association between dexamethasone treatment and the host response in COVID-19 patients admitted to the general ward
Authors: de Brabander Justin , Michels Erik H. A. , van Linge Christine C. A. , Chouchane Osoul , Douma Renée A. , Reijnders Tom D. Y. , Schuurman Alex R. , van Engelen Tjitske S. R. ,   Amsterdam UMC COVID-19 biobank study group, van Agtmael Michiel A. , Algera Anne Geke , Appelman Brent , van Baarle Frank E. H. P. , Bax Diane J. C. , Beudel Martijn , Bogaard Harm Jan , Bomers Marije , Bonta Peter I. , Bos Lieuwe D. J. , Botta Michela , de Brabander Justin , de Bree Godelieve J. , de Bruin Sanne , Bugiani Marianne , Bulle Esther B. , Chouchane Osoul , Cloherty Alex P. M. , Buis David T. P. , de Rotte Maurits C. F. J. , Dijkstra Mirjam , Dongelmans Dave A. , Dujardin Romein W. G. , Elbers Paul E. , Fleuren Lucas M. , Geerlings Suzanne E. , Geijtenbeek Theo B. H. , Girbes Armand R. J. , Goorhuis Bram , Grobusch Martin P. , Hafkamp Florianne M. J. , Hagens Laura A. , Hamann Jörg , Harris Vanessa C. , Hemke Robert , Hermans Sabine M. , Heunks Leo M. A. , Hollmann Markus W. , Horn Janneke , Hovius Joppe W. , de Jong Menno D. , Koning Rutger , Lim Endry H. T. , van Mourik Niels , Nellen Jeannine , Nossent Esther J. , Paulus Frederique , Peters Edgar , Piña-Fuentes Dan A. I. , van der Poll Tom , Preckel Bennedikt , Prins Jan M. , Raasveld Jorinde , Reijnders Tom D. Y. , Schinkel Michiel , Schrauwen Femke A. P. , Schultz Marcus J. , Schuurman Alex R. , Schuurmans Jaap , Sigalof Kim , Slim Marleen A. , Smeele Patrick , Smit Marry R. , Stijnis Cornelis S. , Teunissen Charlotte E. , Thoral Patrick , Tsonas Anissa M. , Tuinman Pieter R. , van der Valk Marc , Veelo Denise P. , Volleman Carolien , de Vries Heder , Vught Lonneke A. , van Vugt Michèle , Wouters Dorien , Zwinderman Koos , Brouwer Matthijs C. , Wiersinga W. Joost , Vlaar Alexander P. J. , van de Beek Diederik , Wiersinga W. Joost , van der Poll Tom
Published: June 2022

Dexamethasone improves clinical outcomes in COVID-19 patients requiring supplementary oxygen. We investigated possible mechanisms of action by comparing sixteen plasma host response biomarkers in general ward patients before and after implementation of dexamethasone as standard of care. 48 patients without and 126 patients with dexamethasone treatment were sampled within 48 h of admission. Endothelial cell and coagulation activation biomarkers were comparable. Dexamethasone treatment was associated with lower plasma interleukin (IL)-6 and IL-1 receptor antagonist levels, whilst other inflammation parameters were not affected. These data argue against modification of vascular-procoagulant responses as an early mechanism of action of dexamethasone in COVID-19.
Cardiovascular benefits of SGLT2 inhibitors in type 2 diabetes, interaction with metformin and role of erythrocytosis: a self-controlled case series study
Authors: Wong Carlos King Ho , Lau Kristy Tsz Kwan , Tang Eric Ho Man , Lee Chi Ho , Lee Carmen Yu Yan , Woo Yu Cho , Au Ivan Chi Ho , Tan Kathryn Choon Beng , Lui David Tak Wai
Published: June 2022

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have proven cardiovascular benefits in patients with type 2 diabetes (T2D). This self-controlled case series study aims to evaluate whether metformin use and SGLT2i-associated erythrocytosis influence its cardiovascular benefits.

Methods

T2D patients with metformin and/or SGLT2i prescriptions between 2015 and 2020 were identified from the Hong Kong population. Study outcomes were composite cardiovascular diseases (CVD), coronary heart disease (CHD), hospitalisation for heart failure (HHF), stroke, and erythrocytosis. Risk periods were patient-time divided into four mutually exclusive windows: (i) ‘baseline period’ of metformin use without SGLT2i; (ii) pre-SGLT2i period; (iii) exposure to SGLT2i without metformin; and (iv) exposure to the drug combination. Another SCCS model was applied to evaluate the association between erythrocytosis and cardiovascular outcomes regarding SGLT2i exposure. Four mutually exclusive risk periods included (i) SGLT2i exposure with erythrocytosis; (ii) SGLT2i exposure without erythrocytosis; (iii) absence of SGLT2i exposure with erythrocytosis; and (iv) absence of SGLT2i exposure without erythrocytosis. Incidence rate ratios (IRR) of events at different risk periods were estimated using conditional Poisson regression model.

Results

Among 20,861 patients with metformin and/or SGLT2i prescriptions, 2575 and 1700 patients with events of composite CVD and erythrocytosis were identified, respectively. Compared to metformin use without SGLT2i, SGLT2i initiation was associated with lower risks of composite CVD, CHD, and HHF—regardless of the presence (CVD: IRR = 0.43, 95% CI 0.37–0.51; CHD: IRR = 0.44, 95% CI 0.37–0.53; HHF: IRR = 0.29, 95% CI 0.22–0.40; all p < 0.001) and absence of concomitant metformin (CVD: IRR = 0.31, 95% CI 0.20–0.48; CHD: IRR = 0.38, 95% CI 0.25–0.59; HHF: IRR = 0.17, 95% CI 0.09–0.31; all p < 0.001); while SGLT2i was neutral on stroke risk. Compared to metformin-SGLT2i combination, exposure to SGLT2i alone was associated with comparable risks of all cardiovascular outcomes (all p > 0.05). Incidence rates of erythrocytosis at baseline, SGLT2i without and with metformin use periods were 0.75, 3.06 and 3.27 per 100 person-years, respectively. SGLT2i users who developed erythrocytosis had lower risk of HHF (IRR = 0.38, 95% CI 0.14–0.99, p = 0.049) than those who did not.

Conclusions

Our real-world data suggested that SGLT2i-associated cardiovascular benefits were not attenuated by metformin use. Further studies will delineate the role of erythrocytosis as a surrogate marker of SGLT2i-associated cardiovascular benefit in reducing HHF.
Impact of red cell distribution width and red cell distribution width/albumin ratio on all-cause mortality in patients with type 2 diabetes and foot ulcers: a retrospective cohort study
Authors: Hong Jing , Hu Xiang , Liu Wenyue , Qian Xuehua , Jiang Feifei , Xu Zeru , Shen Feixia , Zhu Hong
Published: June 2022

Background

Red blood cell distribution width (RDW) has emerged as a prognostic factor for mortality in various diseases. Up to now, few studies have focused on the prognostic value of RDW in patients with diabetic foot ulcers (DFUs). This retrospective cohort study aimed to investigate the impact of RDW and RDW/albumin (ALB) ratio on all-cause mortality in patients with DFUs.

Methods

This study included 860 patients with DFUs in a tertiary academic hospital. The associations of RDW and RDW/ALB with all-cause mortality were assessed by multivariable cox regression analyses. The pairwise comparisons of receiver operating characteristic (ROC) curves were performed to compare the predictive performance of RDW and RDW/ALB ratio. Harrell’s concordance index, integrated discrimination improvement, and net reclassification improvement were used to estimate the improvements in risk discrimination.

Results

Patients with high RDW and RDW/ALB had lower overall survival rates (all P < 0.001). The multivariable Cox regression revealed that high RDW [adjusted hazard ratio (HR) 2.426, 95% confidence interval (CI): 1.557–3.778, P < 0.001] and high RDW/ALB (adjusted HR 2.360, 95% CI: 1.414–3.942, P = 0.001) were independent associated with high all-cause mortality. In subgroup analyses, the comparative analysis of ROC curves revealed that the discriminating ability of the RDW/ALB ratio was significantly superior to RDW in patients with no severe DFUs or no severe peripheral artery disease, or in young and middle-aged patients (all P < 0.05). Adding RDW and RDW/ALB ratio to base models improved discrimination and risk reclassification for all-cause mortality.

Conclusions

RDW and RDW/ALB ratio are robust and independent prognostic markers in patients with DFUs. The RDW/ALB ratio appears to be of more predictive value for mortality in younger and less severely ill patients with DFUs. Both RDW and RDW/ALB ratio can provide incremental predictive value for all-cause mortality over traditional risk factors. RDW and RDW/ALB ratio can be used to identify high-risk patients with DFUs.
Multiple Plasmodium falciparum drug resistance polymorphisms identified in a pregnant woman with severe malaria and a concomitant spontaneous abortion in Cross River, Nigeria, West Africa
Authors: Oboh Mary Aigbiremo , Faal Fatou , Adeniji Oluwagbemisola Elizabeth , Correa Simon , Amawu Anthony Uyimulam , Ogban Ekon , Heinz Eva , Hughes Grant , Meremikwu Martin M. , Amambua-Ngwa Alfred
Published: June 2022

Background

The development of resistance by Plasmodium falciparum to anti-malarial drugs impedes any benefits of the drug. In addition, absence or delayed availability of current anti-malarial drugs in remote areas has the potential to results to parasite escape and continuous transmission.

Case presentation

The case of a 29-year old pregnant woman from Biase Local Government Area in Cross River State Nigeria presenting with febrile illness and high body temperature of 38.7 °C was reported. She looked pale and vomited twice on arrival at the health facility. Her blood smear on the first day of hospitalization was positive for P. falciparum by RDT, microscopy (21,960 parasite/µl) and real-time PCR, with a PCV of 18%. She was treated with 600 mg intravenous quinine in 500 ml of 5% Dextrose/0.9% Saline 8-hourly for 24 h. On the second day of hospitalization, she complained of weakness, persistent high-grade fever and vaginal bleeding. A bulging amnion from an extended cervix was observed. Following venous blood collection for laboratory investigations, 600 µg of misoprostol was inserted into the posterior fornix of her vagina as part of her obstetric care. Parenteral quinine was discontinued, and she was given full therapeutic regimen of artemether-lumefantrine 80/480 mg tablets to be taken for 3 days beginning from the second day. Her blood samples on the second and third day of hospitalization remained positive for P. falciparum by all three diagnostic methods. Single nucleotide polymorphism (SNP) assay on all three P. falciparum isolates revealed the presence of variants associated with multiple drug resistant markers.

Discussion

Infecting P. falciparum isolates may have been resistant to initial quinine treatment resulting from parasite cross-resistance with other quinoline associated resistant markers such as 86Y and 184 F.

Conclusions

Therefore, the likely transmission of similarly resistant parasites in the study area calls for reinforcement of interventions and adherence to current World Health Organization guidelines in administering only approved drugs to individuals in order to mitigate parasite escape and eventual transmission to other susceptible individuals.
Using Bayesian state-space models to understand the population dynamics of the dominant malaria vector, Anopheles funestus in rural Tanzania
Authors: Ngowo Halfan S. , Okumu Fredros O. , Hape Emmanuel E. , Mshani Issa H. , Ferguson Heather M. , Matthiopoulos Jason
Published: June 2022

Background

It is often assumed that the population dynamics of the malaria vector Anopheles funestus, its role in malaria transmission and the way it responds to interventions are similar to the more elaborately characterized Anopheles gambiae. However, An. funestus has several unique ecological features that could generate distinct transmission dynamics and responsiveness to interventions. The objectives of this work were to develop a model which will: (1) reconstruct the population dynamics, survival, and fecundity of wild An. funestus populations in southern Tanzania, (2) quantify impacts of density dependence on the dynamics, and (3) assess seasonal fluctuations in An. funestus demography. Through quantifying the population dynamics of An. funestus, this model will enable analysis of how their stability and response to interventions may differ from that of An. gambiae sensu lato.

Methods

A Bayesian State Space Model (SSM) based on mosquito life history was fit to time series data on the abundance of female An. funestus sensu stricto collected over 2 years in southern Tanzania. Prior values of fitness and demography were incorporated from empirical data on larval development, adult survival and fecundity from laboratory-reared first generation progeny of wild caught An. funestus. The model was structured to allow larval and adult fitness traits to vary seasonally in response to environmental covariates (i.e. temperature and rainfall), and for density dependency in larvae. The effects of density dependence and seasonality were measured through counterfactual examination of model fit with or without these covariates.

Results

The model accurately reconstructed the seasonal population dynamics of An. funestus and generated biologically-plausible values of their survival larval, development and fecundity in the wild. This model suggests that An. funestus survival and fecundity annual pattern was highly variable across the year, but did not show consistent seasonal trends either rainfall or temperature. While the model fit was somewhat improved by inclusion of density dependence, this was a relatively minor effect and suggests that this process is not as important for An. funestus as it is for An. gambiae populations.

Conclusion

The model's ability to accurately reconstruct the dynamics and demography of An. funestus could potentially be useful in simulating the response of these populations to vector control techniques deployed separately or in combination. The observed and simulated dynamics also suggests that An. funestus could be playing a role in year-round malaria transmission, with any apparent seasonality attributed to other vector species.
A comparison of malaria prevention behaviours, care-seeking practices and barriers between malaria at-risk worksite migrant workers and villagers in Northern Shan State, Myanmar—a mixed method study
Authors: Aung Ye Kyaw , Zin Su Su , Tesfazghi Kemi , Paudel Mahesh , Thet May Me , Thein Si Thu
Published: June 2022

Background

Migrant populations are at an increased risk of exposure to malaria due to their nature of work and seasonal migration. This study aimed to compare malaria prevention behaviours and care-seeking practices among worksite migrant workers and villagers in the malaria-at-risk areas of Eastern Myanmar close to the China border.

Methods

A mixed method study was conducted in March 2019. The malaria-at-risk worksites in the four targeted townships, and villages located the nearest to these worksites were approached. Key stakeholders, such as worksite managers and village leaders, were interviewed.

Results

A total of 23 worksites, which employed 880 migrants and 447 locals, and 20 villages, which were homes for 621 migrants and 9731 locals, were successfully interviewed. Regarding malaria prevention behaviours, sleeping under a bed net was common among both worksites (74%) and villages (85%). In contrast, insecticide-treated nets/long-lasting insecticidal nets (ITN/LLIN) usage was much lower in the worksites than in the villages (39% vs 80%). Regarding care-seeking practices for febrile illness, self-medication was a popular choice for both worksite workers and villagers owing to the easy availability of western medicine. Moreover, local-belief-driven traditional practices were more common among villagers. For occasions in which fever was not relieved, both would seek health care from rural health centres, private clinics, or public hospitals. As for barriers, villagers mostly cited language barriers, which often lead to misunderstanding between health providers and them. In contrast, most of the worksites cited logistics issues as they were in remote areas with devastated road conditions and the routes to formal health facilities were not secure due to frequent armed conflicts.

Conclusion

This study demonstrated that site-workers and villagers had different malaria prevention behaviours and care-seeking practices even though they resided in the same geographic area. Hence, it is important to recognize such differences for more effective intervention approaches.
Regional heterogeneity of malaria prevalence and associated risk factors among children under five in Togo: evidence from a national malaria indicators survey
Authors: Kombate Gountante , Gmakouba Wakpaouyare , Scott Susana , Azianu Komi Ameko , Ekouevi Didier Koumavi , van der Sande Marianne A. B.
Published: June 2022

Background

Malaria remains a major cause of morbidity and death among children less than 5 years of age. In Togo, despite intensification of malaria control interventions, malaria remained highly prevalent, with significant heterogeneity from one region to another. The aim of this study is to explore further such regional differences in malaria prevalence and to determine associated risk factors.

Methods

Data from a 2017 cross-sectional nationally representative malaria indicator survey was used. Children aged 6–59 months in selected households were tested for malaria using a rapid diagnostic test (RDT), confirmed by microscopy. Univariate and multivariate logistic regression analysis were performed using Generalized Linear Models.

Results

A total of 2131 children aged 6–59 months (1983 in rural areas, 989 in urban areas) were enrolled. Overall 28% of children tested positive for malaria, ranging from 7.0% in the Lomé Commune region to 4% 7.1 in the Plateaux region. In multivariate analysis, statistically significant differences between regions persisted. Independent risk factors identified were higher children aged (aOR = 1.46, 95% CI [1.13–1.88]) for those above 24 months compared to those below; households wealth quintile (aOR = 0.22, 95% CI [0.11–0.41]) for those richest compared to those poorest quintiles; residence in rural areas (aOR = 2.02, 95% CI [1.32–3.13]).

Conclusion

Interventions that target use of combined prevention measures should prioritise on older children living in poorest households in rural areas, particularly in the regions of high malaria prevalence.
Motivators and demotivators to accessing malaria in pregnancy interventions in sub-Saharan Africa: a meta-ethnographic review
Authors: Aberese-Ako Matilda , Doegah Phidelia , Acquah Evelyn , Magnussen Pascal , Ansah Evelyn , Ampofo Gifty , Agyei Dominic Dankwah , Klu Desmond , Mottey Elsie , Balen Julie , Doumbo Safiatou , Mbacham Wilfred , Gaye Ouma , Gyapong Margaret , Owusu-Agyei Seth , Tagbor Harry
Published: June 2022

Background

Despite the introduction of efficacious interventions for malaria control, sub-Saharan Africa continues to bear the highest burden of malaria and its associated effects on vulnerable populations, such as pregnant women and children. This meta-ethnographic review contributes to literature on malaria in pregnancy interventions in sub-Saharan Africa by offering insights into the multiple factors that motivate or demotivate women from accessing MiP interventions.

Methods

A meta-ethnographic approach was used for the synthesis. Original qualitative research articles published from 2010 to November 2021 in English in sub-Saharan Africa were searched for. Articles focusing on WHO’s recommended interventions such as intermittent preventive treatment with sulfadoxine-pyrimethamine, long-lasting insecticidal nets and testing and treatment of Malaria in Pregnancy (MiP) were included. Selected articles were uploaded into Nvivo 11 for thematic coding and synthesis.

Results

Twenty-seven original qualitative research articles were included in the analysis. Main factors motivating uptake of MiP interventions were: (1) well organized ANC, positive attitudes of health workers and availability of MiP services; (2) Women’s knowledge of the effects of malaria in pregnancy, previous experience of accessing responsive ANC; (3) financial resources and encouragement from partners, relatives and friends and (4) favourable weather condition and nearness to a health facility. Factors that demotivated women from using MiP services were: (1) stock-outs, ANC charges and health providers failure to provide women with ample education on the need for MiP care; (2) perception of not being at risk and the culture of self-medication; (3) fear of being bewitched if pregnancy was noticed early, women’s lack of decision-making power and dependence on traditional remedies and (4) warm weather, long distances to health facilities and the style of construction of houses making it difficult to hang LLINs.

Conclusions

Health system gaps need to be strengthened in order to ensure that MiP interventions become accessible to women. Additionally, health managers need to involve communities in planning, designing and implementing malaria interventions for pregnant women. It is important that the health system engage extensively with communities to facilitate pregnant women and communities understanding of MiP interventions and the need to support pregnant women to access them.
Adherence to national malaria clinical management and testing guidelines in selected private clinics of Gambela Town, Gambela Region, Ethiopia: a mixed method study
Authors: Gindola Yamlak , Getahun Desalegn , Sugerman David , Tongren Eric , Tokarz Ryan , Wossen Mesfin , Demissie Kassahun , Zemelak Etsehiwot , Okugn Akuma , Wendimu Jimmawork , Hailu Girmay , Tegistu Mesfin , Begna Dumesa
Published: June 2022

Background

The World Health Organization World Malaria Report of 2019 indicated an estimated 228 million cases of malaria occurred worldwide in 2018. More than 75% of the total area of Ethiopia is malarious, making malaria a leading public health problem in Ethiopia. Adherence to clinical guidelines improves the quality of care received by patients, thus improving patient outcomes. This study investigates healthcare workers’ adherence to malaria testing and treatment guidelines in selected private clinics of Gambela Town, Ethiopia.

Methods

A mixed study design involving a retrospective review of 425 patient files and 20 healthcare worker interviews in private clinics was implemented. Data were collected using pre-tested data collection forms. The collected data were then cleaned and entered into statistical software for analysis, with a level of significance set at < 0.05. A qualitative analysis was also conducted using healthcare worker interviews to identify the existing barriers to guideline adherence.

Results

Among the 430 cases of suspected malaria, only 65% were tested for malaria. Of those tested, 75% tested positive and 25% tested negative. The most common co-morbidity in patients treated for malaria was anaemia (30%), followed by gastroenteritis (10%). Patients with co-morbidities were more likely to receive appropriate treatment (p = 0.03) compared to those without co-morbidities. All healthcare workers interviewed were aware of the existence of the malaria treatment guidelines. However, many were not aware of the contents of the guidelines and only 40% had been trained to understand the guidelines. Overall, 85% of the workers claimed to adhere to guidelines, with 15% claiming non-adherence.

Conclusion

The gap between knowledge of the malaria treatment guidelines and their application by healthcare workers remains wide. The level of knowledge of these guidelines was also low. Continuous training, follow-up, supportive supervision, and improved adherence to the malaria guidelines are therefore recommended.
M1-derived extracellular vesicles enhance photodynamic therapy and promote immunological memory in preclinical models of colon cancer
Authors: Huis in ‘t Veld Ruben V. , Lara Pablo , Jager Martine J. , Koning Roman I. , Ossendorp Ferry , Cruz Luis J.
Published: June 2022

Extracellular vesicles (EVs) are promising drug carriers of photosensitizers for photodynamic therapy (PDT) in cancer treatment, due to their ability to circulate in blood and enter cells efficiently. The therapeutic potential of EVs has been suggested to depend on the type and physiological state of their cell of origin. However, the effects of deriving EVs from various cells in different physiological states on their antitumor capacity are rarely evaluated. In the present study, we compared the antitumor efficacy of EV-mediated PDT by incorporating the photosensitizer Zinc Phthalocyanine (ZnPc) into EVs from multiple cells sources. ZnPc was incorporated by a direct incubation strategy into EVs derived from immune cells (M1-like macrophages and M2-like macrophages), cancer cells (B16F10 melanoma cancer cells) and external sources (milk). Our data show that all EVs are suitable carriers for ZnPc and enable efficient PDT in vitro in co-culture models and in vivo. We observed that EV-mediated PDT initiates immunogenic cell death through the release and exposure of damage associated molecular patterns (DAMPs) on cancer cells, which subsequently induced dendritic cell (DC) maturation. Importantly, of all ZnPc-EVs tested, in absence of light only M1-ZnPc displayed toxicity to MC38, but not to DC, in monoculture and in co-culture, indicating specificity for cancer over immune cells. In MC38 tumor-bearing mice, only M1-ZnPc induced a tumor growth delay compared to control in absence of light. Interestingly, M1- but not M2-mediated PDT, induced complete responses against MC38 tumors in murine models (100% versus 38% of cases, respectively), with survival of all animals up to at least 60 days post inoculation. Finally, we show that all cured animals are protected from a rechallenge with MC38 cells, suggesting the induction of immunological memory after EV-mediated PDT. Together, our data show the importance of the cell type from which the EVs are obtained and highlight the impact of the immunological state of these cells on the antitumor efficacy of EV-mediated PDT.

Graphical Abstract
Interfacing DNA nanotechnology and biomimetic photonic complexes: advances and prospects in energy and biomedicine
Authors: Zhou Xu , Lin Su , Yan Hao
Published: June 2022

Self-assembled photonic systems with well-organized spatial arrangement and engineered optical properties can be used as efficient energy materials and as effective biomedical agents. The lessons learned from natural light-harvesting antennas have inspired the design and synthesis of a series of biomimetic photonic complexes, including those containing strongly coupled dye aggregates with dense molecular packing and unique spectroscopic features. These photoactive components provide excellent features that could be coupled to multiple applications including light-harvesting, energy transfer, biosensing, bioimaging, and cancer therapy. Meanwhile, nanoscale DNA assemblies have been employed as programmable and addressable templates to guide the formation of DNA-directed multi-pigment complexes, which can be used to enhance the complexity and precision of artificial photonic systems and show the potential for energy and biomedical applications. This review focuses on the interface of DNA nanotechnology and biomimetic photonic systems. We summarized the recent progress in the design, synthesis, and applications of bioinspired photonic systems, highlighted the advantages of the utilization of DNA nanostructures, and discussed the challenges and opportunities they provide.

Graphical Abstract
Abplatin(IV) inhibited tumor growth on a patient derived cancer model of hepatocellular carcinoma and its comparative multi-omics study with cisplatin
Authors: Li Xing , Zhang Lingpu , Li Tuo , Li Shumu , Wu Wenjing , Zhao Lingyu , Xie Peng , Yang Jinqi , Li Peipei , Zhang Yangyang , Xiao Haihua , Yu Yingjie , Zhao Zhenwen
Published: June 2022

Background

Cisplatin, the alkylating agent of platinum(II) (Pt(II)), is the most common antitumor drug in clinic; however, it has many side effects, therefore it is higly desired to develop low toxicity platinum(IV) (Pt(IV)) drugs. Multi-omics analysis, as a powerful tool, has been frequently employed for the mechanism study of a certain therapy at the molecular level, which might be helpful for elucidating the mechanism of platinum drugs and facilitating their clinical application.

Methods

Strating form cisplatin, a hydrophobic Pt(IV) prodrug (CisPt(IV)) with two hydrophobic aliphatic chains was synthesized, and further encapsulated with a drug carrier, human serum albumin (HSA), to form nanoparticles, namely AbPlatin(IV). The anticancer effect of AbPlatin(IV) was investigated in vitro and in vivo. Moreover, transcriptomics, metabolomics and lipidomics were performed to explore the mechanism of AbPlatin(IV).

Results

Compared with cisplatin, Abplatin(IV) exhibited better tumor-targeting effect and greater tumor inhibition rate. Lipidomics study showed that Abplatin(IV) might induce the changes of BEL-7404 cell membrane, and cause the disorder of glycerophospholipids and sphingolipids. In addition, transcriptomics and metabolomics study showed that Abplatin(IV) significantly disturbed the purine metabolism pathway.

Conclusions

This research highlighted the development of Abplatin(IV) and the use of multi-omics for the mechanism elucidation of prodrug, which is the key to the clinical translation of prodrug.

Graphical Abstract
A clinical trial of super-stable homogeneous lipiodol-nanoICG formulation-guided precise fluorescent laparoscopic hepatocellular carcinoma resection
Authors: He Pan , Xiong Yongfu , Ye Jinfa , Chen Biaoqi , Cheng Hongwei , Liu Hao , Zheng Yating , Chu Chengchao , Mao Jingsong , Chen Aizheng , Zhang Yang , Li Jingdong , Tian Jie , Liu Gang
Published: June 2022

Background

Applying traditional fluorescence navigation technologies in hepatocellular carcinoma is severely restricted by high false-positive rates, variable tumor differentiation, and unstable fluorescence performance.

Results

In this study, a green, economical and safe nanomedicine formulation technology was developed to construct carrier-free indocyanine green nanoparticles (nanoICG) with a small uniform size and better fluorescent properties without any molecular structure changes compared to the ICG molecule. Subsequently, nanoICG dispersed into lipiodolviaa super-stable homogeneous intermixed formulation technology (SHIFT&nanoICG) for transhepatic arterial embolization combined with fluorescent laparoscopic hepatectomy to eliminate the existing shortcomings. A 52-year-old liver cancer patient was recruited for the clinical trial of SHIFT&nanoICG. We demonstrate that SHIFT&nanoICG could accurately identify and mark the lesion with excellent stability, embolism, optical imaging performance, and higher tumor-to-normal tissue ratio, especially in the detection of the microsatellite lesions (0.4 × 0.3 cm), which could not be detected by preoperative imaging, to realize a complete resection of hepatocellular carcinoma under fluorescence laparoscopy in a shorter period (within 2 h) and with less intraoperative blood loss (50 mL).

Conclusions

This simple and effective strategy integrates the diagnosis and treatment of hepatocellular carcinoma, and thus, it has great potential in various clinical applications.
Cyclosporine A loaded brain targeting nanoparticle to treat cerebral ischemia/reperfusion injury in mice
Authors: Liu Daozhou , Ji Qifeng , Cheng Ying , Liu Miao , Zhang Bangle , Mei Qibing , Huan Menglei , Zhou Siyuan
Published: June 2022

Background

Ischemic stroke is one of the main causes of death and disability in the world. The treatment for ischemic stroke is to restore blood perfusion as soon as possible. However, when ischemic brain tissue is re-perfused by blood, the mitochondrial permeability transition pore (mPTP) in neuron and microglia is excessively opened, resulting in the apoptosis of neuron and nerve inflammation. This aggravates nerve injury. Cyclosporine A (CsA) inhibits the over-opening of mPTP, subsequently reducing the release of ROS and the apoptosis of cerebral ischemia/reperfusion injured neuron and microglia. However, CsA is insoluble in water and present in high concentrations in lymphatic tissue. Herein, cerebral infarction tissue targeted nanoparticle (CsA@HFn) was developed to treat cerebral ischemia/reperfusion injury.

Results

CsA@HFn efficiently penetrated the blood-brain barrier (BBB) and selectively accumulated in ischemic area, inhibiting the opening of mPTP and ROS production in neuron. This subsequently reduced the apoptosis of neuron and the damage of BBB. Consequently, CsA@HFn significantly reduced the infarct area. Moreover, CsA@HFn inhibited the recruitment of astrocytes and microglia in ischemic region and polarized microglia into M2 type microglia, which subsequently alleviated the nerve inflammation.

Conclusions

CsA@HFn showed a significant therapeutic effect on cerebral ischemia/reperfusion injury by alleviating the apoptosis of neuron, nerve inflammation and the damage of BBB in ischemic area. CsA@HFn has great potential in the treatment of ischemic stroke.

Graphical Abstract
Development of a digital platform to improve community response to overdose and prevention among harm reduction organizations
Authors: Claborn Kasey , Creech Suzannah , Conway Fiona N. , Clinton Nina M. , Brinkley Katlyn T. , Lippard Elizabeth , Ramos Tristan , Samora Jake , Miri Aaron , Benzer Justin
Published: June 2022

The overdose crisis in the USA remains a growing and urgent public health concern. Over 108,000 people died due to overdose during 2021. Fatal and non-fatal overdoses are under-reported in the USA due to current surveillance methods. Systemic gaps in overdose data limit the opportunity for data-driven prevention efforts and resource allocation. This study aims to improve overdose surveillance and community response through developing a digital platform for overdose reporting and response among harm reduction organizations. We used a community-engaged, user-center design research approach. We conducted qualitative interviews with N = 44 overdose stakeholders including people who use drugs and harm reductionists. Results highlighted the need for a unified, multilingual reporting system uniquely tailored for harm reduction organizations. Anonymity, data transparency, protection from legal repercussions, data accuracy, and community-branded marketing emerged as key themes for the overdose platform. Emergent themes included the need for real-time data in a dashboard designed for community response and tailored to first responders and harm reduction organizations. This formative study provides the groundwork for improving overdose surveillance and data-driven response through the development of an innovative overdose digital platform.
Assessment of health state utilities in dermatology: an experimental time trade-off value set for the dermatology life quality index
Authors: Ruzsa Gábor , Rencz Fanni , Brodszky Valentin
Published: June 2022

Background

Dermatology Life Quality Index (DLQI) scores are used in many countries as access and reimbursement criteria for costly dermatological treatments. In this study we examined how time trade-off (TTO) utility valuations made by individuals from the general population are related to combinations of DLQI severity levels characterizing dermatologically relevant health states, with the ultimate purpose of developing a value set for the DLQI.

Methods

We used data from an online cross-sectional survey conducted in Hungary in 2020 (n = 842 after sample exclusions). Respondents were assigned to one of 18 random blocks and were asked to provide 10-year TTO valuations for the corresponding five hypothetical health states. To analyze the relationship between DLQI severity levels and utility valuations, we estimated linear, censored, ordinal, and beta regression models, complemented by two-part scalable models accommodating heterogeneity effects in respondents’ valuation scale usage. Successive severity levels (0–3) of each DLQI item were represented by dummy variables. We used cross-validation methods to reduce the initial set of 30 dummy variables and improve model robustness.

Results

Our final, censored linear regression model with 13 dummy variables had R2 = 0.136, thus accounting for 36.9% of the incremental explanatory power of a maximal (full-information) benchmark model (R2 = 0.148) over the uni-dimensional model (R2 = 0.129). Each DLQI item was found to have a negative effect on the valuation of health states, yet this effect was largely heterogeneous across DLQI items, and the relative contribution of distinctive severity levels also varied substantially. Overall, we found that the social/interpersonal consequences of skin conditions (in the areas of social and leisure activities, work and school, close personal relationships, and sexuality) had roughly twice as large disutility impact as the physical/practical aspects.

Conclusions

We have developed an experimental value set for the DLQI, which could prospectively be used for quantifying the quality-adjusted life years impact of dermatological treatments and serve as a basis for cost-effectiveness analyses. We suggest that, after validation of our main results through confirmatory studies, population-specific DLQI value sets could be developed and used for conducting cost-effectiveness analyses and developing financing guidelines in dermatological care.