Publikationer från Umeå universitet
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Effects of mosquito-proofing storm drains on adult and larvae mosquito abundance : protocol of the IDAlErt storm drAin randomiSed controlled trial (IDEAS)
No full textAedes and Culex mosquitoes, known for spreading arboviruses like dengue and West Nile, thrive in cities, posing health risks to urban populations. Climate change can create suitable climatic conditions for these vectors to spread further in Europe. Cities contain numerous landscape and infrastructure elements, such as storm drains, that allow stagnant water build-up facilitating mosquito breeding. Modifying urban infrastructure to prevent water accumulation can reduce mosquito populations, but evidence is limited. The Public Health Agency of Barcelona, Spain, introduced a structural modification of storm drains to prevent water accumulation. Together with the Agency, we designed a randomised controlled trial (RCT) to experimentally assess the effectiveness of these modifications on adult Aedes albopictus and Culex pipiens populations. It is a parallel-arm RCT with equal randomization of 44 drains to receive mosquito-proofing modifications (intervention) or not (control). Primary outcomes are adult mosquito counts and secondary outcomes are larvae and mosquito presence, assessed weekly at each drain until no mosquitoes are detected. Data analyses include generalised linear mixed models to estimate the time-averaged and highest intervention effects, subgroup and sensitivity analyses. The trial results will guide a city-wide expansion of the storm drain modifications and provide valuable evidence to enhance existing vector control measures
Chemical exposomics in biobanked plasma samples and associations with breast cancer risk factors
No full textBackground: The chemical exposome includes exposure to numerous environmental and endogenous molecules, many of which have been linked to reproductive outcomes due to their endocrine-disrupting properties. As several breast cancer risk factors, including age and parity, are related to reproduction, it is imperative to investigate the interplay between such factors and the chemical exposome prior to conducting large scale exposome-based breast cancer studies. Objective: This pilot study aimed to provide an overview of the chemical exposome in plasma samples from healthy women and identify associations between environmental exposures and three risk factors for breast cancer: age, parity, and age at menarche. Material and methods: Plasma samples (n = 161), were selected based on reproductive history from 100 women participating in the Northern Sweden Health and Disease Study, between 1987 and 2006. Samples were analyzed by liquid chromatography high-resolution mass spectrometry (LC-HRMS) for 77 priority target analytes including contaminants and hormones, with simultaneous untargeted profiling of the chemical exposome and metabolome. Linear mixed effects models were applied to test associations between risk factors and chemical levels. Results: Fifty-five target analytes were detected in at least one individual and over 94,000 untargeted features were detected across all samples. Among untargeted features, 430 could be annotated and were broadly classified as environmental (246), endogenous (167) or ambiguous (17). Applying mixed effect models to features detected in at least 70% of the samples (16,778), we found seven targeted analytes (including caffeine and various per- and poly-fluoroalkyl substances) and 38 untargeted features, positively associated with age. The directionality of these associations reversed for parity, decreasing with increasing births. Seven separate targeted analytes were associated with age at menarche. Significance: This study demonstrates how a comprehensive chemical exposome approach can be used to inform future research prioritization regarding associations between known and unknown substances, reproduction, and breast cancer risk. Impact statement: This study illustrates how chemical exposomics of long-term stored blood samples offers valuable insights to discover chemical exposures and their potential links to disease in humans, particularly those related to reproduction and breast cancer risk factors
Learning sites for health systems research : reflections on five programs in Africa, Asia, and Central America
No full textIntroduction: Learning sites have supported intervention development and testing in health care, but studies reflecting on lessons relating to their deployment for health policy and system research (HPSR) in low- and middle-income settings are limited. Methods: This experience report draws from learning over three continents and five research and community engagement programs—the oldest starting in 2010—to reflect on the challenges and benefits of doing embedded HPSR in learning sites, and how those have been managed. Its objective is to generate better understanding of their potential and constraints. The report draws from team members' experiential insights and program publications. Results: Challenges relating to initial engagement in the sites included building and maintaining trust, managing partner expectations, and negotiating priority topics and stakeholders. Once the embedded research was underway, sustaining engagement, and managing power dynamics within the group, supporting all participants in developing new skills and managing rapidly changing settings were important. Finally, the complexity of reflecting on action and assessing impact are outlined, along with potential approaches to managing all of these challenges and the variety of gains that have been noted across the programs. Conclusions: We highlight the potential of learning sites to develop relationships, capacities, and local innovations which can strengthen health systems in the long term and some lessons in relation to how to do that, including the importance of stable, long-term funding as well as developing and recognizing facilitation skills among researchers. Supporting spaces for learning is particularly important when health systems face resource constraints and everyday or acute stressors and shocks.First published online: 04 December 2024</p
Short-term effect of temperature and precipitation on the incidence of West Nile neuroinvasive disease in Europe : a multi-country case-crossover analysis
No full textBackground: In recent years, Europe has experienced several outbreaks of West Nile Virus (WNV), a mosquito-borne pathogen. This study aims to quantify the impact of weekly mean temperature and cumulative precipitation on human cases of West Nile Neuroinvasive Disease (WNND), to assess the feasibility of climate-informed early warning systems for severe forms of WNV infection. Methods: Using a space-time-stratified case-crossover design, the short-term effects of meteorological factors on WNND cases reported in Europe from 2014 to 2022 were examined. Distributed lag nonlinear models were implemented in conditional logistic regressions to assess the delayed and nonlinear effects of temperature and precipitation on WNND risk as well as to estimate the Attributable Fraction (AF) of cases to extreme values of the two meteorological factors. Findings: Between 2014 and 2022, Europe reported 3437 WNND cases. Both meteorological factors recorded in the 8 weeks before symptom onset showed positive and delayed effects on WNND risk. The strongest effect was found for weekly mean temperatures at 2 weeks lag (Odds Ratio (OR): 1.15; 95% Confidence Interval (CI) 1.12–1.19) and for weekly cumulative precipitation at 3 weeks lag (OR: 1.12; 95% CI 1.09–1.16). Of all WNND cases analyzed, 36.4% (95% CI, 31.3%–40.3%) could be attributed to weekly mean temperatures exceeding the 25 °C, while 13.1% (95% CI, 9.5%–16.4%) to weekly cumulative precipitations exceeding 40 mm. Interpretation: These findings emphasize the significance of short-term variations in temperature and precipitation in driving WNND incidence in Europe. Meteorological factors can be used to operationalize early warning systems to reduce the disease burden from WNV infections, which are continually increasing across the continent
Changes in the provision and utilisation of health care services for chronic health conditions during the COVID-19 pandemic in rural northeast South Africa : an interrupted time series analysis
No full textBackground: The COVID-19 pandemic has impacted the provision and utilisation of health care services with varying magnitude across settings due to spatial temporal variation in the burden of COVID-19 cases and the roll-out of local COVID-19 response policies. This study assesses changes in the provision and utilisation of health care services for three major chronic health conditions (HIV/AIDS, hypertension, and diabetes) over the pre-COVID-19 and COVID-19 pandemic periods in a rural South African sub-district of Agincourt. Methods: Segmented interrupted time series regression models are applied to assess changes in the number of medication collection visits and new diagnoses for HIV/AIDS, hypertension, and diabetes from 1 January 2018 to 30 September 2021 covering the pre- COVID-19 period and the first three waves of the COVID-19 pandemic. Results: The number of medication collection visits for HIV/AIDS, hypertension, and diabetes dropped following the imposition of level 5 lockdown. Despite some improvements over the course of the pandemic, by the end of the third wave in September 2021, visits remained below the pre-COVID-19 era. The number of clinic visits for new diagnoses of HIV/AIDS and hypertension also fell after the introduction of level 5 lockdown. Although the number of new visits for HIV/AIDS bounced back to the pre-COVID-19 trends by the end of the third wave, the number of visits for new hypertension diagnoses remained significantly lower than expected. Referrals for collection of medications from the Central Chronic Medicines Dispensing and Distribution (CCMDD) programme, as an alternative to collection from clinics, increased exponentially over the course of the pandemic. Conclusions: Although the increased adoption of the CCMDD programme can in part account for decreased medication collection visits which persisted well after lockdown measures were lifted, marked reductions in the number of newly diagnosed cases of hypertension warrant concern. A deeper assessment of the appropriateness of referrals to the CCMDD programme as well as the longer-term effects on morbidity and mortality of missed treatment and/or delayed diagnosis is needed for a more granular understanding of the true ramifications of the COVID-19 pandemic and associated lockdown policies in the Agincourt subdistrict and other rural African settings
MicroED structures of fluticasone furoate and fluticasone propionate provide new insights into their function
No full textThe detailed understanding of the conformational pathway of fluticasone, a widely prescribed medicine for allergic rhinitis, asthma, and chronic obstructive pulmonary disease (COPD), from formulation to its protein-bound state, has been limited due to a lack of access to its high-resolution structures. The three-dimensional (3D) structure of fluticasone furoate 1 remains unpublished, and the deposited structure of fluticasone propionate 2 could be further refined due to refinement against new data. We applied microcrystal electron diffraction (MicroED) to determine the 3D structures of 1 and 2 in their solid states. The preferred geometries in solution were predicted by using density functional theory (DFT) calculations. A comparative analysis of the structures of 1 and 2 across three states (in solid state, in solution, and protein-bound conformation) revealed the course of the conformational changes during the entire transition. Potential energy plots were calculated for the most dynamic bonds, uncovering their rotational barriers. This study underscores the combined use of MicroED and DFT calculations to provide a comprehensive understanding of conformational and energy changes during drug administration. The quantitative comparison also highlights the subtle structural differences that may lead to significant changes in the pharmaceutical properties
A scalable CRISPR-Cas9 gene editing system facilitates CRISPR screens in the malaria parasite Plasmodium berghei
No full textMany Plasmodium genes remain uncharacterized due to low genetic tractability. Previous large-scale knockout screens have only been able to target about half of the genome in the more genetically tractable rodent malaria parasite Plasmodium berghei. To overcome this limitation, we have developed a scalable CRISPR system called P. berghei high-throughput (PbHiT), which uses a single cloning step to generate targeting vectors with 100-bp homology arms physically linked to a guide RNA (gRNA) that effectively integrate into the target locus. We show that PbHiT coupled with gRNA sequencing robustly recapitulates known knockout mutant phenotypes in pooled transfections. Furthermore, we provide an online resource of knockout and tagging designs to target the entire P. berghei genome and scale-up vector production using a pooled ligation approach. This work presents for the first time a tool for high-throughput CRISPR screens in Plasmodium for studying the parasite’s biology at scale
Nurse anesthetists' experiences of nursing in the Beach Chair-position
No full textBakgrund: Beach Chair-position är en sittande position som används till patienter som ska operera exempelvis axlar och överarmar. Positionen är förenad med risker ur ett anestesiologiskt perspektiv. Flera allvarliga skador och dödsfall har rapporterats efter operationer i Beach Chair-position. Tidigare forskning visar att operationer i Beach Chair-position kan utföras under olika former av anestesier. Anestesisjuksköterskor förväntas kunna vårda patienter med individuella förutsättningar och i olika positioner, samt ha kunskap om risker och komplikationer som patienter kan utsättas för i olika positioner och utföra anestesiologisk omvårdnad utan att patienten kommer till skada. Motiv: Idag finns begränsad kunskap om anestesisjuksköterskors erfarenheter om att vårda patienter i Beach Chair-position. Anestesisjuksköterskor kan bidra med kunskap till vården i Beach Chair-position, vilket kan bidra till ökad patientsäkerhet och utveckling. Syfte: Att belysa anestesisjuksköterskors erfarenheter av att vårda i Beach Chair-position. Metod: Individuella semistrukturerade intervjuer genomfördes med 9 anestesisjuksköterskor som har erfarenhet av att vårda patienter i Beach Chair-position. Intervjuerna analyserades med kvalitativ innehållsanalys utifrån ett induktivt förhållningssätt. Resultat: Analysen resulterade i två kategorier. Anestesisjuksköterskorna beskrev (1) Vikten av att se Beach Chair-positionens förutsättningar genom att förbereda inför anestesi, göra riskbedömningar samt hantera luftvägen, och (2) Vikten av att samarbeta; genom att kommunicera med anestesiläkare, inkludera patienten samt vara en del av teamet. Konklusion: Genom att studien belyser anestesisjuksköterskor erfarenheter av att vårda i Beach Chair-position ökar kunskapen kring vikten av att ha tydliga strategier och planera inför anestesin, vikten av att samarbeta tvärprofessionellt, samt att känna igen de risker som är förknippade med Beach Chair-positionen med tanke på den patient som ska opereras. Studien belyser vikten av evidensbaserade riktlinjer för att bedriva säker vård för patienter. Background: The Beach Chair-position is a seated position used for patients undergoing surgeries on the shoulder and upper arm. This position is associated with risks from an anesthesiological perspective. Several serious injuries and fatalities have been reported following surgeries performed in the Beach Chair-position. Previous research shows that surgeries in the Beach Chair-position can be performed under various forms of anesthesia. Nurse anesthetists are expected to care for patients with individual needs and in different positions. They should have knowledge of the risks and complications that patients may face in different positions and provide anesthesiological care without causing harm to the patient. Motive: There is currently a lack of knowledge regarding nurse anesthetists’ experiences in caring for patients in the Beach Chair-position. Nurse anesthetists can contribute valuable insights to the care of patients in this position, which could enhance patient safety and development. Aim: To explore nurse anesthetists' experiences in caring for patients in the Beach Chair-position. Methods: Individual semi-structured interviews were conducted with 9 nurse anesthetists experienced in caring for patients in the Beach Chair-position. The interviews were analyzed using qualitative content analysis based on an inductive approach. Result: The analysis resulted in two categories. The nurse anesthetists described: (1) the importance of understanding the Beach Chair-positions’ requirements by preparing for anesthesia, conducting risk assessments, and managing the airway and (2) the importance of collaboration through communication with anesthesiologists, including the patient, and being part of the team. Conclusion: By highlighting nurse anesthetists' experiences in caring for patients in the Beach Chair-position, the study enhances the understanding of the importance of having clear strategies and planning ahead for anesthesia. It also emphasizes the significance of interprofessional collaboration and recognizing the risks associated with the Beach Chair-position, considering the individual patient's needs and the surgical procedure. The study underscores the importance of evidence-based guidelines to provide safe care for patients
Navigating the human–robot interface : exploring human interactions and perceptions with social and telepresence robots
No full textThis study investigates user experiences of interactions with two types of robots: Pepper, a social humanoid robot, and Double 3, a self-driving telepresence robot. Conducted in a controlled setting with a specific participant group, this research aims to understand how the design and functionality of these robots influence user perception, interaction patterns, and emotional responses. The findings reveal diverse participant reactions, highlighting the importance of adaptability, effective communication, autonomy, and perceived credibility in robot design. Participants showed mixed responses to human-like emotional displays and expressed a desire for robots capable of more nuanced and reliable behaviors. Trust in robots was influenced by their perceived functionality and reliability. Despite limitations in sample size, the study provides insights into the ethical and social considerations of integrating AI in public and professional spaces, offering guidance for enhancing user-centered designs and expanding applications for social and telepresence robots in society
Open reduction and internal fixation offers lower hip-related complications compared to stem revision in Vancouver B2 fractures around cemented polished tapered femoral stems
No full textPURPOSE: Periprosthetic femoral fractures (PFFs) after total hip arthroplasty (THA) are increasing, particularly Vancouver B2 fractures around cemented polished tapered femoral stems. Open reduction and internal fixation (ORIF) are more frequently used in comparison to the traditional stem revision to deal with these complex fractures. This observational study aims to compare the outcomes of ORIF versus stem revision in the treatment of Vancouver B2. METHODS: A retrospective cohort study was conducted at Danderyd Hospital, Stockholm, from 2008 to 2022, including 157 patients (mean age 83.4 ± 7.0 years, 59% females) with a surgically treated Vancouver B2 fractures with an intact bone-cement interface. The study assessed the immediate and long-term outcomes of ORIF versus stem revision, examining post-operative complications, reoperation rates, and implant survivorship. RESULTS: Among the 157 patients, 37 were treated with ORIF and 120 with stem revision. The ORIF group, which consisted of older patients and had a higher prevalence of cognitive dysfunction, experienced no hip-related adverse events. In contrast, the revision group had a 17.8% incidence of adverse events. Mortality within 90 days was significantly higher in the ORIF group (24%) compared to the revision group (4%) (p = 0.0007). One-year mortality was also higher in the ORIF group (32%) than in the revision group (15%) (p = 0.03). CONCLUSIONS: ORIF presents as a viable option for managing Vancouver B2 fractures in the proximity of a polished tapered stem when anatomical reduction is possible. The less invasive surgery provides potential advantages in patient outcomes and resource utilization. Further research is warranted to aid in the development of treatment guidelines. LEVEL OF EVIDENCE: III