-
Patient Education and Counseling Jun 2024This study aimed to evaluate a theory-based website to support people with dementia and their families in the advance care planning (ACP) process.
OBJECTIVE
This study aimed to evaluate a theory-based website to support people with dementia and their families in the advance care planning (ACP) process.
METHODS
We conducted an eight-week evaluation study with a convergent parallel mixed-methods design involving people with mild to moderate dementia and their family caregivers who used the website at their convenience. Interviews were conducted at baseline and after 8 weeks to evaluate usability, acceptability, feasibility, experiences, and effects on ACP knowledge, attitudes, perceived barriers to engaging in ACP, self-efficacy and skills to engage in ACP.
RESULTS
We included 52 participants (21 people with dementia and 31 family caregivers). In the interviews, all participants considered the website useful and valued the ACP content. Morever, participants reported that family caregivers mostly used the website alone or with the person with dementia. Participants' ACP knowledge, self-efficacy, and skills improved after 8 weeks compared the beginning of the study.
CONCLUSION
The website may be an ideal introduction for those wanting to start ACP, providing user-friendly content and features for initiating and exploring ACP.
PRACTICAL IMPLICATIONS
ACP in dementia requires a tailored approach. Extra support is crucial for website adoption, emphasising the role of family caregivers while respecting individuals' autonomy.
PubMed: 38943816
DOI: 10.1016/j.pec.2024.108357 -
Molekuliarnaia Biologiia 2024Many viruses, including SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, enter host cells through a process of cell-viral membrane fusion that is...
Many viruses, including SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, enter host cells through a process of cell-viral membrane fusion that is activated by proteolytic enzymes. Typically, these enzymes are host cell proteases. Identifying the proteases that activate the virus is not a simple task but is important for the development of new antiviral drugs. In this study, we developed a bioinformatics method for identifying proteases that can cleave viral envelope glycoproteins. The proposed approach involves the use of predictive models for the substrate specificity of human proteases and the application of a structural analysis method for predicting the vulnerability of protein regions to proteolysis based on their 3D structures. Specificity models were constructed for 169 human proteases using information on their known substrates. A previously developed method for structural analysis of potential proteolysis sites was applied in parallel with specificity models. Validation of the proposed approach was performed on the SARS-CoV-2 spike protein, whose proteolysis sites have been well studied.
Topics: Spike Glycoprotein, Coronavirus; Humans; SARS-CoV-2; Computational Biology; Proteolysis; Substrate Specificity; Peptide Hydrolases; COVID-19; Pandemics; Models, Molecular; Betacoronavirus
PubMed: 38943589
DOI: No ID Found -
Health Technology Assessment... Jun 2024Gallstone disease is a common gastrointestinal disorder in industrialised societies. The prevalence of gallstones in the adult population is estimated to be... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Gallstone disease is a common gastrointestinal disorder in industrialised societies. The prevalence of gallstones in the adult population is estimated to be approximately 10-15%, and around 80% remain asymptomatic. At present, cholecystectomy is the default option for people with symptomatic gallstone disease.
OBJECTIVES
To assess the clinical and cost-effectiveness of observation/conservative management compared with laparoscopic cholecystectomy for preventing recurrent symptoms and complications in adults presenting with uncomplicated symptomatic gallstones in secondary care.
DESIGN
Parallel group, multicentre patient randomised superiority pragmatic trial with up to 24 months follow-up and embedded qualitative research. Within-trial cost-utility and 10-year Markov model analyses. Development of a core outcome set for uncomplicated symptomatic gallstone disease.
SETTING
Secondary care elective settings.
PARTICIPANTS
Adults with symptomatic uncomplicated gallstone disease referred to a secondary care setting were considered for inclusion.
INTERVENTIONS
Participants were randomised 1: 1 at clinic to receive either laparoscopic cholecystectomy or observation/conservative management.
MAIN OUTCOME MEASURES
The primary outcome was quality of life measured by area under the curve over 18 months using the Short Form-36 bodily pain domain. Secondary outcomes included the Otago gallstones' condition-specific questionnaire, Short Form-36 domains (excluding bodily pain), area under the curve over 24 months for Short Form-36 bodily pain domain, persistent symptoms, complications and need for further treatment. No outcomes were blinded to allocation.
RESULTS
Between August 2016 and November 2019, 434 participants were randomised (217 in each group) from 20 United Kingdom centres. By 24 months, 64 (29.5%) in the observation/conservative management group and 153 (70.5%) in the laparoscopic cholecystectomy group had received surgery, median time to surgery of 9.0 months (interquartile range, 5.6-15.0) and 4.7 months (interquartile range 2.6-7.9), respectively. At 18 months, the mean Short Form-36 norm-based bodily pain score was 49.4 (standard deviation 11.7) in the observation/conservative management group and 50.4 (standard deviation 11.6) in the laparoscopic cholecystectomy group. The mean area under the curve over 18 months was 46.8 for both groups with no difference: mean difference -0.0, 95% confidence interval (-1.7 to 1.7); -value 0.996; = 203 observation/conservative, = 205 cholecystectomy. There was no evidence of differences in quality of life, complications or need for further treatment at up to 24 months follow-up. Condition-specific quality of life at 24 months favoured cholecystectomy: mean difference 9.0, 95% confidence interval (4.1 to 14.0), < 0.001 with a similar pattern for the persistent symptoms score. Within-trial cost-utility analysis found observation/conservative management over 24 months was less costly than cholecystectomy (mean difference -£1033). A non-significant quality-adjusted life-year difference of -0.019 favouring cholecystectomy resulted in an incremental cost-effectiveness ratio of £55,235. The Markov model continued to favour observation/conservative management, but some scenarios reversed the findings due to uncertainties in longer-term quality of life. The core outcome set included 11 critically important outcomes from both patients and healthcare professionals.
CONCLUSIONS
The results suggested that in the short term (up to 24 months) observation/conservative management may be a cost-effective use of National Health Service resources in selected patients, but subsequent surgeries in the randomised groups and differences in quality of life beyond 24 months could reverse this finding. Future research should focus on longer-term follow-up data and identification of the cohort of patients that should be routinely offered surgery.
TRIAL REGISTRATION
This trial is registered as ISRCTN55215960.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/71) and is published in full in ; Vol. 28, No. 26. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Gallstones; Cholecystectomy, Laparoscopic; Cost-Benefit Analysis; Male; Female; Middle Aged; Quality of Life; Quality-Adjusted Life Years; Conservative Treatment; Adult; Technology Assessment, Biomedical; Aged; United Kingdom; Markov Chains
PubMed: 38943314
DOI: 10.3310/MNBY3104 -
Trials Jun 2024Most patients starting chronic in-center hemodialysis (HD) receive conventional hemodialysis (CHD) with three sessions per week targeting specific biochemical clearance....
Comparative effectiveness of an individualized model of hemodialysis vs conventional hemodialysis: a study protocol for a multicenter randomized controlled trial (the TwoPlus trial).
BACKGROUND
Most patients starting chronic in-center hemodialysis (HD) receive conventional hemodialysis (CHD) with three sessions per week targeting specific biochemical clearance. Observational studies suggest that patients with residual kidney function can safely be treated with incremental prescriptions of HD, starting with less frequent sessions and later adjusting to thrice-weekly HD. This trial aims to show objectively that clinically matched incremental HD (CMIHD) is non-inferior to CHD in eligible patients.
METHODS
An unblinded, parallel-group, randomized controlled trial will be conducted across diverse healthcare systems and dialysis organizations in the USA. Adult patients initiating chronic hemodialysis (HD) at participating centers will be screened. Eligibility criteria include receipt of fewer than 18 treatments of HD and residual kidney function defined as kidney urea clearance ≥3.5 mL/min/1.73 m and urine output ≥500 mL/24 h. The 1:1 randomization, stratified by site and dialysis vascular access type, assigns patients to either CMIHD (intervention group) or CHD (control group). The CMIHD group will be treated with twice-weekly HD and adjuvant pharmacologic therapy (i.e., oral loop diuretics, sodium bicarbonate, and potassium binders). The CHD group will receive thrice-weekly HD according to usual care. Throughout the study, patients undergo timed urine collection and fill out questionnaires. CMIHD will progress to thrice-weekly HD based on clinical manifestations or changes in residual kidney function. Caregivers of enrolled patients are invited to complete semi-annual questionnaires. The primary outcome is a composite of patients' all-cause death, hospitalizations, or emergency department visits at 2 years. Secondary outcomes include patient- and caregiver-reported outcomes. We aim to enroll 350 patients, which provides ≥85% power to detect an incidence rate ratio (IRR) of 0.9 between CMIHD and CHD with an IRR non-inferiority of 1.20 (α = 0.025, one-tailed test, 20% dropout rate, average of 2.06 years of HD per patient participant), and 150 caregiver participants (of enrolled patients).
DISCUSSION
Our proposal challenges the status quo of HD care delivery. Our overarching hypothesis posits that CMIHD is non-inferior to CHD. If successful, the results will positively impact one of the highest-burdened patient populations and their caregivers.
TRIAL REGISTRATION
Clinicaltrials.gov NCT05828823. Registered on 25 April 2023.
Topics: Humans; Renal Dialysis; Multicenter Studies as Topic; Treatment Outcome; Time Factors; Comparative Effectiveness Research; Randomized Controlled Trials as Topic; Equivalence Trials as Topic; United States; Kidney Failure, Chronic
PubMed: 38943204
DOI: 10.1186/s13063-024-08281-9 -
Trials Jun 2024Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy...
Biomarker Driven Antifungal Stewardship (BioDriveAFS) in acute leukaemia-a multi-centre randomised controlled trial to assess clinical and cost effectiveness: a study protocol for a randomised controlled trial.
BACKGROUND
Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and β-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing).
METHODS
BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed.
DISCUSSION
The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship.
TRIAL REGISTRATION
ISRCTN11633399. Registered 24/06/2022.
Topics: Humans; Antifungal Agents; Cost-Benefit Analysis; Randomized Controlled Trials as Topic; Invasive Fungal Infections; Multicenter Studies as Topic; Biomarkers; Galactose; Mannans; Treatment Outcome; beta-Glucans; Antimicrobial Stewardship; Leukemia; Time Factors; Cost-Effectiveness Analysis
PubMed: 38943201
DOI: 10.1186/s13063-024-08272-w -
BMC Oral Health Jun 2024Iatrogenic mandibular nerve damage resulting from oral surgeries and dental procedures is painful and a formidable challenge for patients and oral surgeons alike, mainly...
BACKGROUND
Iatrogenic mandibular nerve damage resulting from oral surgeries and dental procedures is painful and a formidable challenge for patients and oral surgeons alike, mainly because the absence of objective and quantitative methods for diagnosing nerve damage renders treatment and compensation ambiguous while often leading to medico-legal disputes. The aim of this study was to examine discriminating factors of traumatic mandibular nerve within a specific magnetic resonance imaging (MRI) protocol and to suggest tangible diagnostic criteria for peripheral trigeminal nerve injury.
METHODS
Twenty-six patients with ipsilateral mandibular nerve trauma underwent T2 Flex water, 3D short tau inversion recovery (STIR), and diffusion-weighted imaging (DWI) acquired by periodically rotating overlapping parallel lines with enhanced reconstruction (PROPELLER) pulse sequences; 26 injured nerves were thus compared with contra-lateral healthy nerves at anatomically corresponding sites. T2 Flex apparent signal to noise ratio (FSNR), T2 Flex apparent nerve-muscle contrast to noise ratio (FNMCNR) 3D STIR apparent signal to noise ratio (SSNR), 3D STIR apparent nerve-muscle contrast to noise ratio (SNMCNR), apparent diffusion coefficient (ADC) and area of cross-sectional nerve (Area) were evaluated.
RESULTS
Mixed model analysis revealed FSNR and FNMCNR to be the dual discriminators for traumatized mandibular nerve (p < 0.05). Diagnostic performance of both parameters was also determined with area under the receiver operating characteristic curve (AUC for FSNR = 0.712; 95% confidence interval [CI]: 0.5660, 0.8571 / AUC for FNMCNR = 0.7056; 95% confidence interval [CI]: 1.011, 1.112).
CONCLUSIONS
An increase in FSNR and FNMCNR within our MRI sequence seems to be accurate indicators of the presence of traumatic nerve. This prospective study may serve as a foundation for sophisticated model diagnosing trigeminal nerve trauma within large patient cohorts.
Topics: Humans; Male; Female; Adult; Middle Aged; Magnetic Resonance Imaging; Mandibular Nerve Injuries; Imaging, Three-Dimensional; Diffusion Magnetic Resonance Imaging; Mandibular Nerve; Aged; Young Adult; Trigeminal Nerve Injuries; Signal-To-Noise Ratio
PubMed: 38943102
DOI: 10.1186/s12903-024-04514-0 -
Evidence-based Dentistry Jun 2024The study was designed as a single-blinded, parallel, randomized controlled trial to compare the effectiveness of the Salvadora persica toothbrush (MTB), Salvadora...
DESIGN
The study was designed as a single-blinded, parallel, randomized controlled trial to compare the effectiveness of the Salvadora persica toothbrush (MTB), Salvadora persica chewing stick (MCS), and a standard toothbrush (STB) in controlling plaque and gingivitis. A total of 78 participants were randomly divided into three groups and instructed to use their assigned oral hygiene tool in a standardized manner for three.
CASE SELECTION
Participants were non-dental students and staff of Universiti Kebangsaan Malaysia, Kuala Lumpur Campus, selected through convenience sampling. They met specific inclusion criteria, such as being systemically healthy, having ≥20 teeth, and having a Basic Periodontal Examination score of 0, 1, or 2, with no periodontal pockets greater than 5.5 mm.
DATA ANALYSIS
Clinical outcomes were measured using the Plaque Index (PI) and Periodontal Inflamed Surface Area (PISA) at baseline, one-, and three-weeks post-intervention. Data analysis was performed using mixed-model analysis of variance for continuous variables and Fisher's exact test for categorical variables.
RESULTS
All three groups showed significant improvements in plaque levels and severity of gingivitis from baseline to three weeks post-intervention. The MCS group demonstrated a significant improvement in mean PISA values of the anterior teeth compared to the MTB and STB groups. However, there was no significant difference in plaque level reduction or overall gingivitis severity among the three groups. This indicates that when used correctly, Salvadora persica toothbrushes and chewing sticks are as effective as standard toothbrushes in plaque control and gingival health.
CONCLUSIONS
The study concludes that both Salvadora persica toothbrushes and chewing sticks can serve as effective alternatives to the standard toothbrush for plaque control and gingival health. This showcases the beneficial anti-plaque and anti-gingivitis properties of Salvadora persica. However, the effectiveness of these oral hygiene tools is contingent upon the correct usage techniques.
PubMed: 38942941
DOI: 10.1038/s41432-024-01030-6 -
Trends in Microbiology Jun 2024The study of bacterial immune systems has recently gained momentum, revealing a fascinating trend: many systems form large supramolecular assemblies. Here, we examine...
The study of bacterial immune systems has recently gained momentum, revealing a fascinating trend: many systems form large supramolecular assemblies. Here, we examine the potential mechanisms underpinning the evolutionary success of these structures, draw parallels to eukaryotic immunity, and offer fresh perspectives to stimulate future research into bacterial immunity.
PubMed: 38942717
DOI: 10.1016/j.tim.2024.06.003 -
Trends in Neurosciences Jun 2024Changes in pupil size offer a rich, continuous, and integrated neurophysiological readout of attention and cognition. I here briefly reintroduce examples of a vast,...
Changes in pupil size offer a rich, continuous, and integrated neurophysiological readout of attention and cognition. I here briefly reintroduce examples of a vast, forgotten literature, full of inspiring ideas, which described attentional modulations of pupil size decades earlier than often assumed. I outline parallels between these early studies and recent developments in pupillometry.
PubMed: 38942651
DOI: 10.1016/j.tins.2024.06.002 -
The Science of the Total Environment Jun 2024Hammam Faraun (HF) geothermal site in Egypt shows potential for addressing energy demand and fossil fuel shortages. This study utilizes abandoned oil well logs, seismic...
Hammam Faraun (HF) geothermal site in Egypt shows potential for addressing energy demand and fossil fuel shortages. This study utilizes abandoned oil well logs, seismic data, and surface geology to assess HF geothermal energy resources. Seismic interpretation identified a significant clysmic fault parallel to Hammam Faraun fault (HFF), named CLB fault. The two faults together create a renewable geothermal cycle through circulation of mixed formation-sea waters. Petrophysics revealed two main geothermal reservoirs: the Nubian sandstone reservoir and the Eocene Thebes carbonate reservoir with water saturation values approaching 100 %. Corrected borehole temperatures indicated reservoir temperatures around 120 °C and 140 °C for the Thebes and Nubian reservoirs, respectively. Fracture analysis and stress state provided insights into subsurface fractures. A geomechanical model demonstrated the impact of different stresses and pore pressure on geothermal fluid flow. NE-SW oriented fractures showed a higher dilation tendency due to aquathermal expansion. The integrated conceptual geothermal model suggested a magma chamber beneath HF as the heat source, related to Oligo-Miocene volcanic activity. The breached relay ramp and fault-related open fracture system serve as pathways for geothermal fluids. Evaluation of the geothermal potential utilized volumetric calculations and Monte Carlo simulation. The estimated hot water volumes were 1.72 km, 4.242 km, and 5.332 km for the Nubian reservoir in the onshore part, Thebes reservoir in the offshore part, and Nubian reservoir in the offshore part, respectively. The results indicate a medium enthalpy resource suitable for electricity generation using a Kalina geothermal power plant. The predicted geothermal power output is promising, with an average power output of 9.64 MWe, 21.38 MWe, and 43.76 MWe for the Nubian reservoir in the onshore part, Thebes reservoir in the offshore part, and Nubian reservoir in the offshore part, respectively. These outputs can potentially supply electricity to approximately 12,000, 29,000 and 53,000 households, respectively.
PubMed: 38942302
DOI: 10.1016/j.scitotenv.2024.174283