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Cancers Jun 2024Despite treatment having improved through intensive surgical procedures and chemotherapy-and more recently, targeted therapies-ovarian cancer is the most fatal female...
BACKGROUND
Despite treatment having improved through intensive surgical procedures and chemotherapy-and more recently, targeted therapies-ovarian cancer is the most fatal female cancer. As such, we wanted to analyze age-specific survival trends for ovarian cancer in Denmark, Finland, Norway and Sweden over the past 50 years, with a special aim of comparing survival development between the age groups.
METHODS
We modelled survival data from the NORDCAN database for 1-, 5- and conditional 5/1-year relative (between years 1 and 5) survival for ovarian cancer from 1972 to 2021.
RESULTS
Young patients had a 70% 5-year survival while the survival was only 30% for the oldest patients. Conditional survival showed that survival between years 1 and 5 did not improve for patients older than 60 years throughout the 50-year period, during which time the gaps between the youngest and the oldest patients widened.
CONCLUSIONS
Improvement in 1-year survival was so large that it masked the modest development between years 1 and 5, resulting in a widening age disparity in 5-year survival. The current treatment practices, which appear increasingly effective for younger patients, have not helped remedy the large age differences in ovarian cancer survival. Early detection methods and therapeutic innovations are urgently needed, and aged patients need a special focus.
PubMed: 38927904
DOI: 10.3390/cancers16122198 -
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 -
Neurology(R) Neuroimmunology &... Sep 2024Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct CNS demyelinating disease. The rate of asymptomatic optic nerve enhancement on MRI...
BACKGROUND AND OBJECTIVES
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct CNS demyelinating disease. The rate of asymptomatic optic nerve enhancement on MRI has not been explored in patients with MOGAD. An improved understanding of this would guide clinical practice and assessment of treatment efficacy. We aimed to determine the frequency of asymptomatic optic nerve enhancement in MOGAD.
METHODS
This was a retrospective review of patients evaluated at Mayo Clinic with MOGAD between January 1, 2000, and August 1, 2021 (median follow-up 1.6 [range 1-19] years). MRI studies were reviewed by masked neuroradiologists. Scans performed within 30 days of ON attack were classified as attack scans. Images obtained for routine surveillance, before ON attack, or at the time of non-ON attack were classified as interattack scans.
RESULTS
Five hundred sixty-six MRIs (203 unique patients, 53% female) were included. Interattack MRIs represented 341 (60%) of the scans (median 36 days post-ON [range -1,032 to 6,001]). Of the interattack scans, 43 of 341 (13%), 30 unique patients, showed optic nerve enhancement. The enhancement was located at prior sites of ON in 35 of 43 (81%). Among the 8 patients with enhancement in new optic nerve areas, 6 had acute disseminated encephalomyelitis without an eye examination at the time of the MRI and 2 had preceding ON without imaging. Long-term visual outcomes showed no significant difference between those with and without asymptomatic enhancement, with improved visual acuity in most patients.
DISCUSSION
Asymptomatic optic nerve enhancement occurred in 13% of interattack MRIs, the majority in patients with prior ON and occurring at prior sites of optic nerve enhancement. New asymptomatic optic nerve enhancement in areas without prior ON was rare. These findings are important for understanding the natural history of MOGAD, the interpretation of symptoms or response to treatment, and the adjudication of attacks in clinical trials.
Topics: Humans; Female; Male; Adult; Myelin-Oligodendrocyte Glycoprotein; Retrospective Studies; Magnetic Resonance Imaging; Middle Aged; Young Adult; Optic Nerve; Adolescent; Aged; Child; Autoantibodies; Demyelinating Autoimmune Diseases, CNS; Child, Preschool; Asymptomatic Diseases; Aged, 80 and over
PubMed: 38924706
DOI: 10.1212/NXI.0000000000200277 -
Scandinavian Journal of Psychology Jun 2024Ethnicity plays a significant role in adolescents' everyday lives, but there is a limited understanding of adolescents' own experiences with how ethnicity is addressed...
Ethnicity plays a significant role in adolescents' everyday lives, but there is a limited understanding of adolescents' own experiences with how ethnicity is addressed in different contexts. Three contexts of importance during adolescence are investigated in the present study: schools, social media, and sports. A closer contextual examination has the potential to provide insights into how multiple contexts shape experiences with ethnicity. The aim of the study was to understand more about adolescents' experiences of how ethnicity is addressed in schools, on social media, and in sports. Six focus groups with a total of 21 adolescents (M = 14.5, SD = 0.5, female = 76%) discussed their experiences. Data were transcribed verbatim and analyzed using a close-to-data, inductive thematic analysis. The analysis resulted in three main themes and seven subthemes, indicating that ethnicity was addressed differently in the three studied contexts. For the main theme of how ethnicity was addressed in schools, the subthemes were: Addressing ethnicity is important; Ethnicity is addressed through stereotypes and Everyday racism. The main theme of ethnicity on social media consisted of two subthemes: Sharing ethnic and cultural narratives and Hateful remarks. The main theme of ethnicity in sports also consisted of two subthemes: On equal terms and Clear consequences for racist behaviors. To better understand the multiple contexts, the results are discussed guided by the ecological systems theory. The adolescents highlighted that there are many benefits of addressing ethnicity and that it is important to do so in multiple contexts of adolescent life, just not in the same way. When ethnicity was addressed carelessly, such as through stereotypes or via racism masked as jokes, it had the potential to cause harm. When ethnicity was addressed with reflection, it instead had the potential to build understanding, lead to positive experiences, and provide learning opportunities.
PubMed: 38924590
DOI: 10.1111/sjop.13050 -
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 -
Aerospace Medicine and Human Performance Jul 2024While there are numerous factors that may affect pilot attentional performance, we hypothesize that an increased expiratory work of breathing experienced by fighter...
While there are numerous factors that may affect pilot attentional performance, we hypothesize that an increased expiratory work of breathing experienced by fighter pilots may impose a "distraction stimulus" by creating an increased expiratory effort sensation. Therefore, the purpose of this study was to determine the extent to which increasing expiratory pressure time product or expiratory effort sensation impacts attentional performance. Data was collected on 10 healthy participants (age: 29 ± 6 yr). Participants completed six repetitions of a modified Masked Conjunctive Continuous Performance Task protocol while breathing against four different expiratory threshold loads. Repeated measures analysis of variances and generalized additive mixed effects models were used to investigate the effects of expiratory threshold load conditions on expiratory pressure time product, expiratory effort sensation, and the influence of altered end tidal gases on Masked Conjunctive Continuous Performance Task scores. The overall median hit reaction times were significantly longer as the expiratory threshold loads increased. Specific shape-conjunctive and non-conjunctive median hit reaction times were longer with increased expiratory effort sensation. Additionally, increased expiratory effort sensation did not significantly change commission error rates, but did significantly increase omission error rates. The findings of our work suggest that both progressively greater expiratory threshold loads during spontaneous breathing and expiratory effort sensation may impair subjects' attentional performance due to longer reaction times and increased stimuli recognition error rates.
Topics: Humans; Adult; Attention; Male; Young Adult; Exhalation; Reaction Time; Female; Task Performance and Analysis; Pilots
PubMed: 38915161
DOI: 10.3357/AMHP.6383.2024 -
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 -
Expert Opinion on Drug Safety Jun 2024From 2009 to 2015, the IMI PROTECT conducted rigorous studies addressing questions about optimal implementation and significance of disproportionality analyses, leading... (Review)
Review
INTRODUCTION
From 2009 to 2015, the IMI PROTECT conducted rigorous studies addressing questions about optimal implementation and significance of disproportionality analyses, leading to the development of Good Signal Detection Practices. The ensuing period witnessed the independent exploration of research paths proposed by IMI PROTECT, accumulating valuable experience and insights that have yet to be seamlessly integrated.
AREAS COVERED
This state-of-the-art review integrates IMI PROTECT recommendations with recent acquisitions and evolving challenges. It deals with defining the object of study, disproportionality methods, subgrouping, masking, drug-drug interaction, duplication, expectedness, the debated use of disproportionality results as risk measures, integration with other types of data.
EXPERT OPINION
Despite the ongoing skepticism regarding the usefulness of disproportionality analyses and individual case safety reports, their ability to timely detect safety signals regarding rare and unpredictable adverse reactions remains unparalleled. Moreover, recent exploration into their potential for characterizing safety signals revealed valuable insights concerning potential risk factors and the patient's perspective. To fully realize their potential beyond hypothesis generation and achieve a comprehensive evidence synthesis with other kinds of data and studies, each with their unique limitations and contributions, we need to investigate methods for more transparently communicating disproportionality results and mapping and addressing pharmacovigilance biases.
PubMed: 38913869
DOI: 10.1080/14740338.2024.2368817