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Frontiers in Aging Neuroscience 2024The lack of cognitive awareness, anosognosia, is a clinical deficit in Alzheimer's disease (AD) dementia. However, an increased awareness of cognitive function,...
INTRODUCTION
The lack of cognitive awareness, anosognosia, is a clinical deficit in Alzheimer's disease (AD) dementia. However, an increased awareness of cognitive function, hypernosognosia, may serve as a marker in the preclinical stage. Subjective cognitive decline (SCD) might correspond to the initial symptom in the dynamic trajectory of awareness, but SCD might be absent along with low awareness of actual cognitive performance in the preclinical stage. We hypothesized that distinct meta-cognitive profiles, both hypernosognosia and anosognosia, might be identified in preclinical-AD. This research evaluated the association between cerebrospinal fluid (CSF) AD biomarkers and the awareness of episodic memory, further exploring dyadic (participant-partner) SCD reports, in the preclinical Alzheimer's continuum.
METHODS
We analyzed 314 cognitively unimpaired (CU) middle-aged individuals (mean age: 60, SD: 4) from the ALFA+ cohort study. Episodic memory was evaluated with the delayed recall from the Memory Binding Test (MBT). Awareness of episodic memory, meta-memory, was defined as the normalized discrepancy between objective and subjective performance. SCD was defined using self-report, and dyadic SCD profiles incorporated the study partner's report using parallel SCD-Questionnaires. The relationship between CSF Aβ42/40 and CSF p-tau181 with meta-memory was evaluated with multivariable regression models. The role of SCD and the dyadic contingency was explored with the corresponding stratified analysis.
RESULTS
CSF Aβ42/40 was non-linearly associated with meta-memory, showing an increased awareness up to Aβ-positivity and a decreased awareness beyond this threshold. In the non-SCD subset, the non-linear association between CSF Aβ42/40 and meta-memory persisted. In the SCD subset, higher Aβ-pathology was linearly associated with increased awareness. Individuals presenting only study partner's SCD, defined as unaware decliners, exhibited higher levels of CSF p-tau181 correlated with lower meta-memory performance.
DISCUSSION
These results suggested that distinct meta-cognitive profiles can be identified in preclinical-AD. While most individuals might experience an increased awareness associated with the entrance in the AD continuum, hypernosognosia, some might be already losing insight and stepping into the anosognosic trajectory. This research reinforced that an early anosognosic profile, although at increased risk of AD-related decline, might be currently overlooked considering actual diagnostic criteria, and therefore its medical attention delayed.
PubMed: 38872632
DOI: 10.3389/fnagi.2024.1394460 -
Heliyon Jun 2024The aim of this study was to investigate the effects of temporal instability and possible heterogeneity on pedestrian accident severity, 48786 accident data from 2018 to...
The aim of this study was to investigate the effects of temporal instability and possible heterogeneity on pedestrian accident severity, 48786 accident data from 2018 to 2021 in the UK STATS database were used as the study object, and accident severity was used as the dependent variable, and 49 accident characteristics were selected as independent variables from 6 characteristics of accident pedestrian, driver, vehicle, road, environment and time to construct the pedestrian accident mean heterogeneity random-parameter logit model and examined its temporal stability. The results of model estimation and likelihood ratio tests indicate that the variables affecting pedestrian injury severity are highly variable and not stable over the years. And further demonstrates the potential of models that address unobserved heterogeneity for significant relationships in pedestrian accident severity analyses.
PubMed: 38867994
DOI: 10.1016/j.heliyon.2024.e32013 -
Frontiers in Medicine 2024Human Immunodeficiency Virus (HIV) remains a global health challenge, and novel approaches to improve HIV control are significantly important. The cell and gene therapy...
Human Immunodeficiency Virus (HIV) remains a global health challenge, and novel approaches to improve HIV control are significantly important. The cell and gene therapy product AGT103-T was previously evaluated (NCT04561258) for safety, immunogenicity, and persistence in seven patients for up to 180 days post infusion. In this study, we sought to investigate the impact of AGT103-T treatment upon analytical treatment interruptions (ATIs). Six patients previously infused with AGT103-T were enrolled into an ATI study (NCT05540964), wherein they suspended their antiretroviral therapy (ART) until their viral load reached 100,000 copies/mL in two successive visits, or their CD4 count was reduced to below 300 cells/μL. During the ATI, all patients experienced viral rebound followed by a notable expansion in HIV specific immune responses. The participants demonstrated up to a five-fold increase in total CD8 counts over baseline approximately 1-2 weeks followed by the peak viremia. This coincided with a rise in HIV-specific CD8 T cells, which was attributed to the increase in antigen availability and memory recall. Thus, the protocol was amended to include a second ATI with the first ATI serving as an "auto-vaccination." Four patients participated in a second ATI. During the second ATI, the Gag-specific CD8 T cells were either maintained or rose in response to viral rebound and the peak viremia was substantially decreased. The patients reached a viral set point ranging from 7,000 copies/mL to 25,000 copies/mL. Upon resuming ART, all participants achieved viral control more rapidly than during the first ATI, with CD4 counts remaining within 10% of baseline measurements and without any serious adverse events or evidence of drug resistance. In summary, the rise in CD8 counts and the viral suppression observed in 100% of the study participants are novel observations demonstrating that AGT103-T gene therapy when combined with multiple ATIs, is a safe and effective approach for achieving viral control, with viral setpoints consistently below 25,000 copies/mL and relatively stable CD4 T cell counts. We conclude that HIV cure-oriented cell and gene therapy trials should include ATI and may benefit from designs that include multiple ATIs when induction of CD8 T cells is required to establish viral control.
PubMed: 38808136
DOI: 10.3389/fmed.2024.1342476 -
BMJ Open May 2024Radiologist shortages threaten the sustainability of breast cancer screening programmes. Artificial intelligence (AI) products that can interpret mammograms could...
Protocol for evaluating the fitness for purpose of an artificial intelligence product for radiology reporting in the BreastScreen New South Wales breast cancer screening programme.
INTRODUCTION
Radiologist shortages threaten the sustainability of breast cancer screening programmes. Artificial intelligence (AI) products that can interpret mammograms could mitigate this risk. While previous studies have suggested this technology has accuracy comparable to radiologists most have been limited by using 'enriched' datasets and/or not considering the interaction between the algorithm and human readers. This study will address these limitations by comparing the accuracy of a workflow using AI alongside radiologists on a large consecutive cohort of examinations from a breast cancer screening programme. The study will combine the strengths of a large retrospective design with the benefit of prospective data collection. It will test this technology without risk to screening programme participants nor the need to wait for follow-up data. With a sample of 2 years of consecutive screening examinations, it is likely the largest test of this technology to date. The study will help determine whether this technology can safely be introduced into the BreastScreen New South Wales (NSW) population-based screening programme to address radiology workforce risks without compromising cancer detection rates or increasing false-positive recalls.
METHODS AND ANALYSIS
A retrospective, consecutive cohort of digital mammography screens from 658 207 examinations from BreastScreen NSW will be reinterpreted by the Lunit Insight MMG AI product. The cohort includes 4383 screen-detected and 1171 interval cancers. The results will be compared with radiologist single reading and the AI results will also be used to replace the second reader in a double-reading model. New adjudication reading will be performed where the AI disagrees with the first reader. Recall rates and cancer detection rates of combined AI-radiologist reading will be compared with the rates obtained at the time of screening.
ETHICS AND DISSEMINATION
This study has ethical approval from the NSW Health Population Health Services Research Ethics Committee (2022/ETH02397). Findings will be published in peer-reviewed journals and presented at conferences. The findings of this evaluation will be provided to programme managers, governance bodies and other stakeholders in Australian breast cancer screening programmes.
Topics: Humans; Breast Neoplasms; Female; Mammography; Artificial Intelligence; New South Wales; Early Detection of Cancer; Retrospective Studies; Mass Screening; Middle Aged; Research Design
PubMed: 38806433
DOI: 10.1136/bmjopen-2023-082350 -
Foods (Basel, Switzerland) May 2024This paper presents the first assessment of dietary exposure to aflatoxin M1 (AFM1) and associated health risks through milk and dairy product consumption in Armenia....
This paper presents the first assessment of dietary exposure to aflatoxin M1 (AFM1) and associated health risks through milk and dairy product consumption in Armenia. Data on AFM1 in raw milk were obtained from an annual residue monitoring program. Additionally, commonly consumed dairy products (pasteurized milk, cheese, sour cream, curd cheese) were sampled, considering the sources of raw milk used by dairy companies. Per capita consumption of raw milk was sourced from national food balance databases, while individual consumption data for dairy products was collected via a 24 h recall survey with 1400 adult respondents. Detectable levels of AFM1 were observed in 7.14% of raw milk samples (up to 0.334 μg/kg) and, albeit at lower amounts (up to 0.009 µg/kg), in 30% and 40% of sour cream and curd cheese, respectively. The AFM1 levels were lower than the national maximum permitted level (0.5 μg/kg); however, levels in raw milk exceeded the EU ML (0.05 μg/kg). The estimated margin of exposure values for dairy products indicated no significant risk, whereas a reasonable worst-case estimate, using the measurable levels of AFM1 in raw milk consumption indicated a potential public health concern. This study provides a scientific basis for evaluating aflatoxin issues in the Caucasus area.
PubMed: 38790817
DOI: 10.3390/foods13101518 -
JAAD International Sep 2024Empirical decisions to select therapies for psoriasis (PSO) and atopic dermatitis (AD) can lead to delays in disease control and increased health care costs. However,...
BACKGROUND
Empirical decisions to select therapies for psoriasis (PSO) and atopic dermatitis (AD) can lead to delays in disease control and increased health care costs. However, routine molecular testing for AD and PSO are lacking.
OBJECTIVE
To examine (1) how clinicians choose systemic therapies for patients with PSO and AD without molecular testing and (2) to determine how often the current approach leads to patients switching medications.
METHODS
A 20-question survey designed to assess clinician strategies for systemic treatment of AD and PSO was made available to attendees of a national dermatology conference in 2022.
RESULTS
Clinicians participating in the survey (265/414, 64% response rate) ranked "reported efficacy" as the most important factor governing treatment choice ( < .001). However, 62% (165/265) of clinicians estimated that 2 or more systemic medications were typically required to achieve efficacy. Over 90% (239/265) of respondents would or would likely find a molecular test to guide therapeutic selection useful.
LIMITATIONS
To facilitate ease of recall, questions focused on systemic therapies as a whole and not individual therapies.
CONCLUSION
Clinicians want a molecular test to help determine the most efficacious drug for individual patients.
PubMed: 38774343
DOI: 10.1016/j.jdin.2024.03.019 -
Journal of Epidemiology and Global... May 2024Mammography (MG) has demonstrated its effectiveness in diminishing mortality and advanced-stage breast cancer incidences in breast screening initiatives. Notably,...
BACKGROUND
Mammography (MG) has demonstrated its effectiveness in diminishing mortality and advanced-stage breast cancer incidences in breast screening initiatives. Notably, research has accentuated the superior diagnostic efficacy and cost-effectiveness of digital breast tomosynthesis (DBT). However, the scope of evidence validating the cost-effectiveness of DBT remains limited, prompting a requisite for more comprehensive investigation. The present study aimed to rigorously evaluate the cost-effectiveness of DBT plus MG (DBT-MG) compared to MG alone within the framework of Taiwan's National Health Insurance program.
METHODS
All parameters for the Markov decision tree model, encompassing event probabilities, costs, and utilities (quality-adjusted life years, QALYs), were sourced from reputable literature, expert opinions, and official records. With 10,000 iterations, a 2-year cycle length, a 30-year time horizon, and a 2% annual discount rate, the analysis determined the incremental cost-effectiveness ratio (ICER) to compare the cost-effectiveness of the two screening methods. Probabilistic and one-way sensitivity analyses were also conducted to demonstrate the robustness of findings.
RESULTS
The ICER of DBT-MG compared to MG was US$5971.5764/QALYs. At a willingness-to-pay (WTP) threshold of US$33,004 (Gross Domestic Product of Taiwan in 2021) per QALY, more than 98% of the probabilistic simulations favored adopting DBT-MG versus MG. The one-way sensitivity analysis also shows that the ICER depended heavily on recall rates, biopsy rates, and positive predictive value (PPV2).
CONCLUSION
DBT-MG shows enhanced diagnostic efficacy, potentially diminishing recall costs. While exhibiting a higher biopsy rate, DBT-MG aids in the detection of early-stage breast cancers, reduces recall rates, and exhibits notably superior cost-effectiveness.
PubMed: 38748377
DOI: 10.1007/s44197-024-00239-z -
Euro Surveillance : Bulletin Europeen... May 2024is a bacterium widely distributed in the environment. Listeriosis is a severe disease associated with high hospitalisation and mortality rates. In April 2019,...
is a bacterium widely distributed in the environment. Listeriosis is a severe disease associated with high hospitalisation and mortality rates. In April 2019, listeriosis was diagnosed in two hospital patients in Finland. We conducted a descriptive study to identify the source of the infection and defined a case as a person with a laboratory-confirmed serogroup IIa sequence type (ST) 37. Six cases with ST 37 were notified to the Finnish Infectious Diseases Registry between 2015 and 2019. Patient interviews and hospital menus were used to target traceback investigation of the implicated foods. In 2021 and 2022, similar ST 37 was detected from samples of a ready-to-eat plant-based food product including fava beans. Inspections by the manufacturer and the local food control authority indicated that the food products were contaminated with after pasteurisation. Our investigation highlights the importance that companies producing plant-based food are subject to similar controls as those producing food of animal origin. Hospital menus can be a useful source of information that is not dependent on patient recall.
Topics: Humans; Listeria monocytogenes; Listeriosis; Disease Outbreaks; Finland; Food Microbiology; Female; Male; Foodborne Diseases; Middle Aged; Aged; Food Contamination; Adult; Fabaceae
PubMed: 38726694
DOI: 10.2807/1560-7917.ES.2024.29.19.2300488 -
Swiss Medical Weekly May 2024Listeriosis is a notifiable disease in Switzerland. In summer 2022, the Swiss Federal Office of Public Health noticed an increase in reports of listeriosis cases,...
AIMS OF THE STUDY
Listeriosis is a notifiable disease in Switzerland. In summer 2022, the Swiss Federal Office of Public Health noticed an increase in reports of listeriosis cases, indicating a possible ongoing outbreak. Here we present the approaches applied for rapidly confirming the outbreak, detecting the underlying source of infection and the measures put in place to eliminate it and contain the outbreak.
METHODS
For close surveillance and early detection of outbreak situations with their possible sources, listeriosis patients in Switzerland are systematically interviewed about risk behaviours and foods consumed prior to the infection. Listeria monocytogenes isolates derived from patients in medical laboratories are sent to the National Reference Laboratory for Enteropathogenic Bacteria and Listeria, where they routinely undergo whole-genome sequencing. Interview and whole-genome sequencing data are continuously linked for comparison and analysis.
RESULTS
In summer 2022, 20 patient-derived L. monocytogenes serotype 4b sequence type 388 strains were found to belong to an outbreak cluster (≤10 different alleles between neighbouring isolates) based on core genome multilocus sequence typing analysis. Geographically, 18 of 20 outbreak cases occurred in northeastern Switzerland. The median age of patients was 77.4 years (range: 58.1-89.7), with both sexes equally affected. Rolling analysis of the interview data revealed smoked trout from a local producer as a suspected infection source, triggering an on-site investigation of the production facility and sampling of the suspected products by the responsible cantonal food inspection team on 15 July 2022. Seven of ten samples tested positive for L. monocytogenes and the respective cantonal authority ordered a ban on production and distribution as well as a product recall. The Federal Food Safety and Veterinary Office released a nationwide public alert covering the smoked fish products concerned. Whole-genome sequencing analysis confirmed the interrelatedness of the L. monocytogenes smoked trout product isolates and the patient-derived isolates. Following the ban on production and distribution and the product recall, reporting of new outbreak-related cases rapidly dropped to zero.
CONCLUSIONS
This listeriosis outbreak could be contained within a relatively short time thanks to identification of the source of contamination through the established combined approach of timely interviewing of every listeriosis patient or a representative and continuous molecular analysis of the patient- and food-derived L. monocytogenes isolates. These findings highlight the effectiveness of this well-established, joint approach involving the federal and cantonal authorities and the research institutions mandated to contain listeriosis outbreaks in Switzerland.
Topics: Humans; Switzerland; Disease Outbreaks; Listeria monocytogenes; Listeriosis; Whole Genome Sequencing; Male; Aged; Female; Aged, 80 and over; Multilocus Sequence Typing; Middle Aged; Food Microbiology; Foodborne Diseases; Interviews as Topic
PubMed: 38701492
DOI: 10.57187/s.3745 -
JRSM Open May 2024Commentators and professional organisations note that an expanding market in human milk-based products (HMBPs) could reduce breastfeeding, compromising maternal and...
OBJECTIVES
Commentators and professional organisations note that an expanding market in human milk-based products (HMBPs) could reduce breastfeeding, compromising maternal and infant health, and undermine public milk bank donations. We investigate whether English NHS trusts purchased these products and whether HMBP companies have marketed to them.
DESIGN
Freedom of Information (FOI) requests asking: (1) whether trusts obtained human milk; (2) if so, how; and (3) whether HMBP companies had approached them. We analysed trusts' responses qualitatively. In 2023, an FOI request to the Food Standards Authority (FSA) following a product recall.
SETTING
England.
PARTICIPANTS
One hundred and ninety-four NHS trusts, the FSA.
MAIN OUTCOME MEASURES
Obtaining human milk, approaches by companies, and trust responses to approaches.
RESULTS
One hundred and seventy-six trusts responded, 102 reporting human milk from milk banks. No trusts reported purchasing from companies in 2022. In 2023, the FSA confirmed six English hospitals used HMBPs from one company; an FOI for trusts' names was refused on law enforcement grounds. Two trusts reported participating in clinical trials funded by companies. Twenty-one reported approaches, using several strategies, including uninvited ward visits. Trusts rejected marketing based on guidance from: (1) trust dieticians or physicians; (2) regional regulatory bodies; (3) professional bodies; and (4) perceived application of an International Code on breastfeeding.
CONCLUSIONS
Companies market to trusts, adopting methods previously used by the formula industry. Trusts express confusion over whether this infringes agreements designed to promote breastfeeding. We encourage clarification and guidance for professionals and trusts to ensure safety, infant and maternal health, and protect public provision.
PubMed: 38699203
DOI: 10.1177/20542704241237658