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Scientific Reports Jun 2024COVID-19 surveillance in Ukraine ceased after the Russian invasion of the country in 2022, on a background of low vaccination rates of 34.5% for two doses at this time....
COVID-19 surveillance in Ukraine ceased after the Russian invasion of the country in 2022, on a background of low vaccination rates of 34.5% for two doses at this time. We conducted a modelling study to estimate the epidemic trajectory of SARS-COV-2 in Ukraine after the start of the war. We use a COVID-19 deterministic Susceptible-Exposed-Infected-Recovered (SEIR) model for Ukraine to estimate the impact of increased vaccination coverage and masking as public health interventions. We fit the model output to case notification data between 6 January and 25 February 2022, then we forecast the COVID-19 epidemic trajectory in different scenarios of mask use and vaccine coverage. In the best-case scenario, 69% of the Ukrainian population would have been infected in the first half of 2022. Increasing mask use from 50 to 80% reduces cases and deaths by 17% and 30% respectively, while increasing vaccination rates to 60% and 9.6% for two and three doses respectively results in a 3% reduction in cases and 28% in deaths. However, if vaccination is increased to a higher coverage of 80% with two doses and 12.8% with three, or mask effectiveness is reduced to 40%, increasing vaccination coverage is more effective. The loss of health services, displacement, and destruction of infrastructure will amplify the risk of COVID-19 in Ukraine and make vaccine programs less feasible. Masks do not need the health infrastructure or cold-chain logistics required for vaccines and are more feasible for rapid epidemic control during war. However, increasing vaccine coverage will save more lives. Vaccination of refugees who have fled to other countries can be more feasibly achieved.
Topics: Ukraine; Humans; COVID-19; COVID-19 Vaccines; Vaccination Coverage; SARS-CoV-2; Masks; Vaccination
PubMed: 38926448
DOI: 10.1038/s41598-024-57447-7 -
BMJ Open Jun 2024Evidence-based psychological treatments for people with personality disorder usually involve attending group-based sessions over many months. Low-intensity psychological...
Clinical effectiveness and cost-effectiveness of Structured Psychological Support for people with probable personality disorder in mental health services in England: study protocol for a randomised controlled trial.
INTRODUCTION
Evidence-based psychological treatments for people with personality disorder usually involve attending group-based sessions over many months. Low-intensity psychological interventions of less than 6 months duration have been developed, but their clinical effectiveness and cost-effectiveness are unclear.
METHODS AND ANALYSIS
This is a multicentre, randomised, parallel-group, researcher-masked, superiority trial. Study participants will be aged 18 and over, have probable personality disorder and be treated by mental health staff in seven centres in England. We will exclude people who are: unwilling or unable to provide written informed consent, have a coexisting organic or psychotic mental disorder, or are already receiving psychological treatment for personality disorder or on a waiting list for such treatment. In the intervention group, participants will be offered up to 10 individual sessions of Structured Psychological Support. In the control group, participants will be offered treatment as usual plus a single session of personalised crisis planning. The primary outcome is social functioning measured over 12 months using total score on the Work and Social Adjustment Scale (WSAS). Secondary outcomes include mental health, suicidal behaviour, health-related quality of life, patient-rated global improvement and satisfaction, and resource use and costs. The primary analysis will compare WSAS scores across the 12-month period using a general linear mixed model adjusting for baseline scores, allocation group and study centre on an intention-to-treat basis. In a parallel process evaluation, we will analyse qualitative data from interviews with study participants, clinical staff and researchers to examine mechanisms of impact and contextual factors.
ETHICS AND DISSEMINATION
The study complies with the Helsinki Declaration II and is approved by the London-Bromley Research Ethics Committee (IRAS ID 315951). Study findings will be published in an open access peer-reviewed journal; and disseminated at national and international conferences.
TRIAL REGISTRATION NUMBER
ISRCTN13918289.
Topics: Humans; Cost-Benefit Analysis; England; Mental Health Services; Personality Disorders; Quality of Life; Treatment Outcome; Multicenter Studies as Topic; Adult; Psychosocial Intervention
PubMed: 38925701
DOI: 10.1136/bmjopen-2024-086593 -
Ibrain 2024This review comprehensively assesses the epidemiology, interaction, and impact on patient outcomes of perioperative sleep disorders (SD) and perioperative neurocognitive... (Review)
Review
This review comprehensively assesses the epidemiology, interaction, and impact on patient outcomes of perioperative sleep disorders (SD) and perioperative neurocognitive disorders (PND) in the elderly. The incidence of SD and PND during the perioperative period in older adults is alarmingly high, with SD significantly contributing to the occurrence of postoperative delirium. However, the clinical evidence linking SD to PND remains insufficient, despite substantial preclinical data. Therefore, this study focuses on the underlying mechanisms between SD and PND, underscoring that potential mechanisms driving SD-induced PND include uncontrolled central nervous inflammation, blood-brain barrier disruption, circadian rhythm disturbances, glial cell dysfunction, neuronal and synaptic abnormalities, impaired central metabolic waste clearance, gut microbiome dysbiosis, hippocampal oxidative stress, and altered brain network connectivity. Additionally, the review also evaluates the effectiveness of various sleep interventions, both pharmacological and nonpharmacological, in mitigating PND. Strategies such as earplugs, eye masks, restoring circadian rhythms, physical exercise, noninvasive brain stimulation, dexmedetomidine, and melatonin receptor agonists have shown efficacy in reducing PND incidence. The impact of other sleep-improvement drugs (e.g., orexin receptor antagonists) and methods (e.g., cognitive-behavioral therapy for insomnia) on PND is still unclear. However, certain drugs used for treating SD (e.g., antidepressants and first-generation antihistamines) may potentially aggravate PND. By providing valuable insights and references, this review aimed to enhance the understanding and management of PND in older adults based on SD.
PubMed: 38915944
DOI: 10.1002/ibra.12167 -
Implementation Science Communications Jun 2024Implementation research generally assumes established evidence-based practices and prior piloting of implementation strategies, which may not be feasible during a public...
BACKGROUND
Implementation research generally assumes established evidence-based practices and prior piloting of implementation strategies, which may not be feasible during a public health emergency. We describe the use of a simulation model of the effectiveness of COVID-19 mitigation strategies to inform a stakeholder-engaged process of rapidly designing a tailored intervention and implementation strategy for individuals with serious mental illness (SMI) and intellectual/developmental disabilities (ID/DD) in group homes in a hybrid effectiveness-implementation randomized trial.
METHODS
We used a validated dynamic microsimulation model of COVID-19 transmission and disease in late 2020/early 2021 to determine the most effective strategies to mitigate infections among Massachusetts group home staff and residents. Model inputs were informed by data from stakeholders, public records, and published literature. We assessed different prevention strategies, iterated over time with input from multidisciplinary stakeholders and pandemic evolution, including varying symptom screening, testing frequency, isolation, contact-time, use of personal protective equipment, and vaccination. Model outcomes included new infections in group home residents, new infections in group home staff, and resident hospital days. Sensitivity analyses were performed to account for parameter uncertainty. Results of the simulations informed a stakeholder-engaged process to select components of a tailored best practice intervention and implementation strategy.
RESULTS
The largest projected decrease in infections was with initial vaccination, with minimal benefit for additional routine testing. The initial level of actual vaccination in the group homes was estimated to reduce resident infections by 72.4% and staff infections by 55.9% over the 90-day time horizon. Increasing resident and staff vaccination uptake to a target goal of 90% further decreased resident infections by 45.2% and staff infections by 51.3%. Subsequent simulated removal of masking led to a 6.5% increase in infections among residents and 3.2% among staff. The simulation model results were presented to multidisciplinary stakeholders and policymakers to inform the "Tailored Best Practice" package for the hybrid effectiveness-implementation trial.
CONCLUSIONS
Vaccination and decreasing vaccine hesitancy among staff were predicted to have the greatest impact in mitigating COVID-19 risk in vulnerable populations of group home residents and staff. Simulation modeling was effective in rapidly informing the selection of the prevention and implementation strategy in a hybrid effectiveness-implementation trial. Future implementation may benefit from this approach when rapid deployment is necessary in the absence of data on tailored interventions.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04726371.
PubMed: 38915130
DOI: 10.1186/s43058-024-00593-w -
Proceedings of the National Academy of... Jul 2024Predicting which proteins interact together from amino acid sequences is an important task. We develop a method to pair interacting protein sequences which leverages the...
Predicting which proteins interact together from amino acid sequences is an important task. We develop a method to pair interacting protein sequences which leverages the power of protein language models trained on multiple sequence alignments (MSAs), such as MSA Transformer and the EvoFormer module of AlphaFold. We formulate the problem of pairing interacting partners among the paralogs of two protein families in a differentiable way. We introduce a method called Differentiable Pairing using Alignment-based Language Models (DiffPALM) that solves it by exploiting the ability of MSA Transformer to fill in masked amino acids in multiple sequence alignments using the surrounding context. MSA Transformer encodes coevolution between functionally or structurally coupled amino acids within protein chains. It also captures inter-chain coevolution, despite being trained on single-chain data. Relying on MSA Transformer without fine-tuning, DiffPALM outperforms existing coevolution-based pairing methods on difficult benchmarks of shallow multiple sequence alignments extracted from ubiquitous prokaryotic protein datasets. It also outperforms an alternative method based on a state-of-the-art protein language model trained on single sequences. Paired alignments of interacting protein sequences are a crucial ingredient of supervised deep learning methods to predict the three-dimensional structure of protein complexes. Starting from sequences paired by DiffPALM substantially improves the structure prediction of some eukaryotic protein complexes by AlphaFold-Multimer. It also achieves competitive performance with using orthology-based pairing.
Topics: Sequence Alignment; Proteins; Amino Acid Sequence; Algorithms; Sequence Analysis, Protein; Computational Biology; Databases, Protein
PubMed: 38913900
DOI: 10.1073/pnas.2311887121 -
PLoS Computational Biology Jun 2024Carbohydrates and glycoproteins modulate key biological functions. However, experimental structure determination of sugar polymers is notoriously difficult....
Carbohydrates and glycoproteins modulate key biological functions. However, experimental structure determination of sugar polymers is notoriously difficult. Computational approaches can aid in carbohydrate structure prediction, structure determination, and design. In this work, we developed a glycan-modeling algorithm, GlycanTreeModeler, that computationally builds glycans layer-by-layer, using adaptive kernel density estimates (KDE) of common glycan conformations derived from data in the Protein Data Bank (PDB) and from quantum mechanics (QM) calculations. GlycanTreeModeler was benchmarked on a test set of glycan structures of varying lengths, or "trees". Structures predicted by GlycanTreeModeler agreed with native structures at high accuracy for both de novo modeling and experimental density-guided building. We employed these tools to design de novo glycan trees into a protein nanoparticle vaccine to shield regions of the scaffold from antibody recognition, and experimentally verified shielding. This work will inform glycoprotein model prediction, glycan masking, and further aid computational methods in experimental structure determination and refinement.
PubMed: 38913746
DOI: 10.1371/journal.pcbi.1011895 -
Medical Research Archives May 2024Respiratory fluid dynamics is integral to comprehending the transmission of infectious diseases and the effectiveness of interventions such as face masks and social...
On the efficacy of facial masks to suppress the spreading of pathogen-carrying saliva particles during human respiratory events: Insights gained via high-fidelity numerical modeling.
Respiratory fluid dynamics is integral to comprehending the transmission of infectious diseases and the effectiveness of interventions such as face masks and social distancing. In this research, we present our recent studies that investigate respiratory particle transport via high-fidelity large eddy simulation coupled with the Lagrangian particle tracking method. Based on our numerical simulation results for human respiratory events with and without face masks, we demonstrate that facial masks could significantly suppress particle spreading. The studied respiratory events include coughing and normal breathing through mouth and nose. Using the Lagrangian particle tracking simulation results, we elucidated the transport pathways of saliva particles during inhalation and exhalation of breathing cycles, contributing to our understanding of respiratory physiology and potential disease transmission routes. Our findings underscore the importance of respiratory fluid dynamics research in informing public health strategies to reduce the spread of respiratory infections. Combining advanced mathematical modeling techniques with experimental data will help future research on airborne disease transmission dynamics and the effectiveness of preventive measures such as face masks.
PubMed: 38911991
DOI: 10.18103/mra.v12i5.5441 -
Diabetes, Metabolic Syndrome and... 2024The prevalence of obesity continues to rise. People with obesity are at increased risk of several diseases. We tested an algorithm-based screening program for people...
PURPOSE
The prevalence of obesity continues to rise. People with obesity are at increased risk of several diseases. We tested an algorithm-based screening program for people with a BMI above 30 kg/m and present data on the prevalence of previously undiagnosed obesity-related diseases.
PATIENTS AND METHODS
Seven hundred and sixty-nine persons with BMI > 30 kg/m and age 18-60 years were screened for diabetes (assessed by glycosylated hemoglobin and oral glucose tolerance test at HbA1c 43-48 mmol/mol), sleep apnea (screened by questionnaires and assessed by cardiorespiratory monitoring at indication of sleep disorder), liver steatosis or liver fibrosis (assessed by biochemistry and fibroscan) and arterial hypertension (assessed by both office and 24-hour blood pressure measurement). A reference group of people with a BMI of 18.5-29.9 kg/m was established.
RESULTS
Of those referred, 73.0% were women. We identified new diabetes in 4.2%, prediabetes in 9.1%, moderate-to-severe sleep apnea in 25.1%, increased liver fat and increased liver stiffness in 68.1% and 17.4%, respectively, and hypertension or masked hypertension in 19.0%. The prevalence of diseases was much higher among men and increased with BMI. Except for hypertension, we found few participants with undiagnosed disease in the reference group.
CONCLUSION
An algorithm-based screening program is feasible and reveals undiagnosed obesity-related disease in a large proportion of the participants. The disproportional referral pattern calls for a tailored approach aiming to include more men with obesity.
TRIAL REGISTRATION
Inclusion of the non-obese group was approved by the Scientific Ethics Committee of The Region of Southern Denmark (project identification number: S-20210091), and the study was reported at clinicaltrials.gov (NCT05176132).
PubMed: 38910914
DOI: 10.2147/DMSO.S456028 -
The International Journal on Drug Policy Jun 2024Within Manitoba and Saskatchewan, pre-existing health inequities amongst Indigenous groups were intensified during the COVID-19 pandemic. Service disruptions in the...
BACKGROUND
Within Manitoba and Saskatchewan, pre-existing health inequities amongst Indigenous groups were intensified during the COVID-19 pandemic. Service disruptions in the health and social service sector-combined with the effects of intersectional stigma-disproportionately impacted Indigenous peoples living with HIV (IPLH). IPLH experience structural violence and necropolitical exclusion through systemic forms of stigma situated within Canada's expansive colonial history. Utilizing the theoretical foundations of structural violence and necropolitics, this qualitative study examines how the COVID-19 pandemic amplified preceding states of inequity for IPLH.
METHODS
Semi-structured interviews were conducted with 60 participants. The sample comprised of those with lived experience (n = 45) as well as those who provided services for IPLH (n = 15). Indigenous Storywork guided the data collection and analysis process. Topics explored within each interview included access to health and social services, harm reduction, substance use, and experiences in providing services during COVID-19 pandemic. Thematic analysis was used to identify common themes throughout each story.
RESULTS
Our results indicate that the COVID-19 pandemic exposed and amplified pre-existing forms of structural violence and necropolitical logics for IPLH within Manitoba and Saskatchewan. Specifically, we describe how structural violence and necropolitics are manifested via three main avenues- (i) restrictions and removal of care, (ii) bureaucracy and institutional care politics, and (iii) discrimination and systemic racism within the Canadian healthcare system.
CONCLUSION
The COVID-19 pandemic within Manitoba and Saskatchewan sparked massive changes in service provision within settler-colonial and neoliberal institutions of care. For those services that remained open to IPLH, masking requirements, questionnaire requirements, scheduling requirements, and a lack of in-person services acted as only some of the barriers described by community members as detrimental to care access. Increased experiences of discrimination in health care on the basis of substance use or HIV status further limited access to needed services.
PubMed: 38905942
DOI: 10.1016/j.drugpo.2024.104503 -
PLOS Global Public Health 2024Community Health Workers (CHWs) are a key human resource for health particularly in low- and middle-income countries. In many parts of the world, CHWs are known to have...
Community Health Workers (CHWs) are a key human resource for health particularly in low- and middle-income countries. In many parts of the world, CHWs are known to have played an instrumental role in controlling the COVID-19 pandemic. This study explored the involvement of CHWs in the COVID-19 response in Uganda. A qualitative study that involved 10 focus group discussions (FGDs) among CHWs was conducted. The study was carried out in 5 districts of Amuria, Karenga, Kamwenge, Bugiri and Pader. The FGD guide used explored the role of CHWs in the COVID-19 response in their communities including lived experiences, challenges, and coping mechanisms. The data were analyzed thematically with the support of NVivo version 12 pro (QSR International). CHWs were at the frontline of COVID-19 prevention interventions at households and in the community. CHWs raised awareness on prevention measures including wearing face masks, hand hygiene, and social distancing. They identified suspected cases such as new members entering the community, as well as individuals returning from abroad with signs and symptoms of COVID-19. CHWs mobilized the community and increased awareness on COVID-19 vaccination which played an important role in reducing misinformation. They also supported home-based management of mild COVID-19 cases through isolation of patients; provided health and nutritional guidance among patients in their homes; and referred suspected cases to health facilities for testing and management. Both monetary and non-monetary incentives were provided to support CHWs in the COVID-19 response. However, the adequacy and timing of the incentives were inadequate. Routine services of CHWs such as health promotion and treatment of childhood illnesses were disrupted during the pandemic. CHWs played an instrumental role in response to the pandemic especially on surveillance, risk communication, and observance of preventing measures. Strategies to ensure that routine services of CHWs are not disrupted during pandemics are needed.
PubMed: 38905244
DOI: 10.1371/journal.pgph.0003312