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Intensive Care Medicine Jan 2024We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo.
METHODS
We conducted pre-planned analyses of 1-year outcomes in the Agents Intervening against Delirium in the ICU (AID-ICU) trial, including mortality and health-related quality of life (HRQoL) assessed by Euroqol (EQ) 5-dimension 5-level questionnaire (EQ-5D-5L) index values and EQ visual analogue scale (EQ VAS) (deceased patients were assigned the numeric value zero). Outcomes were analysed using logistic and linear regressions with bootstrapping and G-computation, all with adjustment for the stratification variables (site and delirium motor subtype) and multiple imputations for missing HRQoL values.
RESULTS
At 1-year follow-up, we obtained vital status for 96.2% and HRQoL data for 83.3% of the 1000 randomised patients. One-year mortality was 224/501 (44.7%) in the haloperidol group versus 251/486 (51.6%) in the placebo group, with an adjusted absolute risk difference of - 6.4%-points (95% confidence interval [CI] - 12.8%-points to - 0.2%-points; P = 0.045). These results were largely consistent across the secondary analyses. For HRQoL, the adjusted mean differences were 0.04 (95% CI - 0.03 to 0.11; P = 0.091) for EQ-5D-5L-5L index values, and 3.3 (95% CI - 9.3 to 17.5; P = 0.142) for EQ VAS.
CONCLUSIONS
In acutely admitted adult ICU patients with delirium, haloperidol treatment reduced mortality at 1-year follow-up, but did not statistically significantly improve HRQoL.
Topics: Adult; Humans; Delirium; Haloperidol; Hospitalization; Intensive Care Units; Quality of Life
PubMed: 38170227
DOI: 10.1007/s00134-023-07282-7 -
European Journal of Internal Medicine Dec 2023Individuals with lower levels of education are at a higher risk of developing various health conditions due to limited access to healthcare and unhealthy lifestyle...
INTRODUCTION
Individuals with lower levels of education are at a higher risk of developing various health conditions due to limited access to healthcare and unhealthy lifestyle choices. However, the association between non-alcoholic fatty liver disease (NAFLD) and educational level remains unclear. Therefore, the aim of this study was to investigate whether there is an independent relationship between NAFLD and educational level as a surrogate marker for socioeconomic status (SES).
METHODS
This cross-sectional study included 8,727 participants from the Paracelsus 10,000 study. The association between NAFLD and educational level was assessed using multivariable logistic regression models and multivariable linear regression. The primary endpoints were NAFLD (FLI score > 60) and liver fibrosis (FIB-4 score > 1.29). Further subgroup analysis with liver stiffness measurement was done.
RESULTS
In the study, NAFLD prevalence was 23% among participants with high education, 33% among intermediate, and 40% among those with low education (p<0.01). Importantly, a significantly reduced risk of NAFLD was observed in individuals with higher education, as indicated by an adjusted relative risk of 0.52 (p < 0.01). Furthermore, higher education level was associated with significantly lower odds of NAFLD and fibrosis. Additionally, a subgroup analysis revealed that higher liver stiffness measurements were independently associated with lower levels of education.
CONCLUSION
The study's findings indicate that a lower education level increases the risk of NAFLD independent of confounding factors. Therefore, these findings highlight the potential impact of educational attainment on NAFLD risk and emphasize the need for targeted interventions in vulnerable populations.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Risk Factors; Cross-Sectional Studies; Liver Cirrhosis; Educational Status
PubMed: 37541922
DOI: 10.1016/j.ejim.2023.07.039 -
ERJ Open Research May 2024COPD is a major healthcare problem and cause of mortality worldwide. COPD patients at increased mortality risk are those who are more symptomatic, have lower lung... (Review)
Review
COPD is a major healthcare problem and cause of mortality worldwide. COPD patients at increased mortality risk are those who are more symptomatic, have lower lung function and lower diffusing capacity of the lung for carbon monoxide, decreased exercise capacity, belong to the emphysematous phenotype and those who have concomitant bronchiectasis. Mortality risk seems to be greater in patients who experience COPD exacerbations and in those who suffer from concomitant cardiovascular and/or metabolic diseases. To predict the risk of death in COPD patients, several composite scores have been created using different parameters. In previous years, large studies (also called mega-trials) have evaluated the efficacy of different therapies on COPD mortality, but until recently only nonpharmaceutical interventions have proven to be effective. However, recent studies on fixed combinations of triple therapy (long-acting β-agonists, long-acting muscarinic antagonists and inhaled corticosteroids) have provided encouraging results, showing for the first time a reduction in mortality compared to dual therapies. The aim of the present review is to summarise available data regarding mortality risk in COPD patients and to describe pharmacological therapies that have shown effectiveness in reducing mortality.
PubMed: 38887682
DOI: 10.1183/23120541.00850-2023 -
JCI Insight Apr 2024BACKGROUNDAs Omicron is prompted to replicate in the upper airway, neutralizing antibodies (NAbs) delivered through inhalation might inhibit early-stage infection in the...
BACKGROUNDAs Omicron is prompted to replicate in the upper airway, neutralizing antibodies (NAbs) delivered through inhalation might inhibit early-stage infection in the respiratory tract. Thus, elucidating the prophylactic efficacy of NAbs via nasal spray addresses an important clinical need.METHODSThe applicable potential of a nasal spray cocktail containing 2 NAbs was characterized by testing its neutralizing potency, synergetic neutralizing mechanism, emergency protective and therapeutic efficacy in a hamster model, and pharmacokinetics/pharmacodynamic (PK/PD) in human nasal cavity.RESULTSThe 2 NAbs displayed broad neutralizing efficacy against Omicron, and they could structurally compensate each other in blocking the Spike-ACE2 interaction. When administrated through the intranasal mucosal route, this cocktail demonstrated profound efficacy in the emergency prevention in hamsters challenged with authentic Omicron BA.1. The investigator-initiated trial in healthy volunteers confirmed the safety and the PK/PD of the NAb cocktail delivered via nasal spray. Nasal samples from the participants receiving 4 administrations over a course of 16 hours demonstrated potent neutralization against Omicron BA.5 in an ex vivo pseudovirus neutralization assay.CONCLUSIONThese results demonstrate that the NAb cocktail nasal spray provides a good basis for clinical prophylactic efficacy against Omicron infections.TRIAL REGISTRATIONwww.chictr.org.cn, ChiCTR2200066525.FUNDINGThe National Science and Technology Major Project (2017ZX10202203), the National Key Research and Development Program of China (2018YFA0507100), Guangzhou National Laboratory (SRPG22-015), Lingang Laboratory (LG202101-01-07), Science and Technology Commission of Shanghai Municipality (YDZX20213100001556), and the Emergency Project from the Science & Technology Commission of Chongqing (cstc2021jscx-fyzxX0001).
Topics: Animals; Cricetinae; Humans; Nasal Sprays; China; Antibodies, Neutralizing; Trachea; Healthy Volunteers
PubMed: 38587080
DOI: 10.1172/jci.insight.171034 -
Science China. Life Sciences Oct 2023Coronaviruses (CoVs) have brought serious threats to humans, particularly severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which continually evolves into...
Coronaviruses (CoVs) have brought serious threats to humans, particularly severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which continually evolves into multiple variants. These variants, especially Omicron, reportedly escape therapeutic antibodies and vaccines, indicating an urgent need for new antivirals with pan-SARS-CoV-2 inhibitory activity. We previously reported that a peptide fusion inhibitor, P3, targeting heptad repeated-1 (HR1) of SARS-CoV-2 spike (S) protein, could inhibit viral infections. Here, we further designed multiple derivatives of the P3 based on structural analysis and found that one derivative, the P315V3, showed the most efficient antiviral activity against SARS-CoV-2 variants and several other sarbecoviruses, as well as other human-CoVs (HCoVs). P315V3 also exhibited effective prophylactic efficacy against the SARS-CoV-2 Delta and Omicron variants in mice via intranasal administration. These results suggest that P315V3, which is in Phase II clinical trial, is promising for further development as a nasal pan-SARS-CoV-2 or pan-CoVs inhibitor to prevent or treat CoV diseases.
Topics: Humans; Animals; Mice; COVID-19; SARS-CoV-2; Administration, Intranasal; Amino Acid Sequence; Peptides
PubMed: 37574525
DOI: 10.1007/s11427-023-2410-5 -
Heliyon Nov 2023Increasing production requires the development of high yielding cultivars adapted to various environments. Multi-environment trials (MET) remains the best approach to...
Increasing production requires the development of high yielding cultivars adapted to various environments. Multi-environment trials (MET) remains the best approach to assess the performance of accessions across environments. The objective of this study was to select the best performing and stable accessions of sesame across different environments in Benin Republic. Nineteen sesame accessions were evaluated across eight environments using a randomized complete block design with four replicates. The accessions were evaluated for three traits: days to 50% flowering (D50F), thousand-seed weight (TSW), and seed yield (SY) during 2020 growing season. The stable and top-performing accessions across environments were determined using AMMI (Additive main effects and multiplicative interaction), GGE (Genotype main effect and genotype × environment interaction), and MTSI (Multi-trait stability index). AMMI analysis of variance showed a significant difference across environments for the three traits. The accessions were affected by environmental conditions for the three traits. The broad-sense heritability estimates were high (>0.60) for all the traits, indicating the improvement is achievable through selection. AMMI1 and AMMI2 biplots identified G10 and G13 as high seed yielding accessions adapted to environments E1, E2. The GGE biplot showed two mega-environments for TSW and three mega-environments for D50F and SY. For SY, G11 and G13 were the best accessions in the first mega-environment, G10 the best accession in the second mega-environment; G3 and G8 were the best accessions in the third mega-environment. AMMI and GGE analyses identified G10, G5, G12 as high seed yielding and stable accessions across environments. GGE biplot revealed that E1 and E2 were the most suitable environments for multi-location trials based on their discriminating ability and representativeness. MTSI indicated G10, G13, G19 as promising germplasm to be recommended for breeding program.
PubMed: 38034689
DOI: 10.1016/j.heliyon.2023.e21656 -
Cerebral Cortex (New York, N.Y. : 1991) May 2024Anhedonia is a transdiagnostic symptom and associated with a spectrum of reward deficits among which the motivational dysfunction is poorly understood. Previous studies...
Anhedonia is a transdiagnostic symptom and associated with a spectrum of reward deficits among which the motivational dysfunction is poorly understood. Previous studies have established the abnormal cost-benefit trade-off as a contributor to motivational deficits in anhedonia and its relevant psychiatric diseases. However, it remains elusive how the anhedonic neural dynamics underlying reward processing are modulated by effort expenditure. Using an effort-based monetary incentive delay task, the current event-related potential study examined the neural dynamics underlying the effort-reward interplay in anhedonia using a nonclinical sample who scored high or low on an anhedonia questionnaire. We found that effort prospectively decreased reward effect on the contingent variation negativity and the target-P3 but retrospectively enhanced outcome effect on the feedback-P3 following effort expenditure. Compared to the low-anhedonia group, the high-anhedonia group displayed a diminished effort effect on the target-P3 during effort expenditure and an increased effort-enhancement effect for neutral trials during the feedback-P3 period following effort expenditure. Our findings suggest that anhedonia is associated with an inefficient control and motivation allocation along the efforted-based reward dynamics from effort preparation to effort production.
Topics: Anhedonia; Humans; Reward; Male; Female; Young Adult; Motivation; Electroencephalography; Adult; Evoked Potentials; Brain; Adolescent
PubMed: 38741268
DOI: 10.1093/cercor/bhae193 -
The Lancet Regional Health. Europe Sep 2023We investigated ophthalmological outcomes at 2.5 years of corrected age in children born extremely preterm (EPT) to evaluate the effects of postnatal enteral...
BACKGROUND
We investigated ophthalmological outcomes at 2.5 years of corrected age in children born extremely preterm (EPT) to evaluate the effects of postnatal enteral supplementation with ω-3 and ω-6 long-chain polyunsaturated fatty acids.
METHODS
In the Mega Donna Mega clinical trial, EPT infants born at less than 28 weeks of gestation were randomized to receive an enteral supplementation of docosahexaenoic acid (DHA) and arachidonic acid (AA) from birth to 40 weeks postmenstrual age. In this exploratory follow-up at 2.5 years of corrected age, we assessed visual acuity (VA), refraction, manifest strabismus, and nystagmus. Satisfactory VA was defined as ≥20/63. Multiple imputation (MI) was used to address the issue of missing data.
FINDINGS
Of 178 children in the trial, 115 (with median gestational age (GA) of 25 + 4/7 weeks and median birth weights of 790 g) were ophthalmologically assessed at a median corrected age of 2.7 years (range 2.0-3.9 years). VA assessment was missing in 42.1% (75/178), in 41.7% (35/84) of the AA/DHA supplemented infants, and in 42.6% (40/94) of the control infants. After MI and adjustments for GA, study center, plurality, and corrected age at VA exam, no significant effect of AA/DHA supplementation was detected in VA outcome (≥20/63) (odds ratio 2.16, confidence interval 95% 0.99-4.69, p = 0.053).
INTERPRETATION
In this randomized controlled trial follow-up, postnatal supplementation with enteral AA/DHA to EPT children did not significantly alter VA at 2.5 years of corrected age. Due to the high loss to follow-up rate and the limited statistical power, additional studies are needed.
FUNDING
The Swedish Medical Research Council #2020-01092, The Gothenburg Medical Society, Government grants under the ALF agreement ALFGBG-717971 and ALFGBG-971188, De Blindas Vänner, Knut and Alice Wallenberg Foundation - Wallenberg Clinical Scholars, NIHEY017017, EY030904BCHIDDRC (1U54HD090255 Massachusetts Lions Eye Foundation) supported the study.
PubMed: 37671123
DOI: 10.1016/j.lanepe.2023.100696 -
The World Journal of Men's Health Jan 2024The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all...
PURPOSE
The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles.
MATERIALS AND METHODS
The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies).
RESULTS
Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864.
CONCLUSIONS
The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele.
PubMed: 37382284
DOI: 10.5534/wjmh.230034 -
Journal of Refractive Surgery... Aug 2023To compare the visual outcomes of bilateral implantation of two commercially available trifocal intraocular lenses (IOLs) (AcrySof IQ PanOptix IOL; Alcon Laboratories,... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To compare the visual outcomes of bilateral implantation of two commercially available trifocal intraocular lenses (IOLs) (AcrySof IQ PanOptix IOL; Alcon Laboratories, Inc and AcrivaUD Trinova IOL; VSY Biotechnology).
METHODS
This comparative, investigator-initiated, single-center randomized trial was conducted by the Department of Ophthalmology of the Medipol Mega University Hospital in Istanbul, Turkey. Adult patients were randomized in a 1:1 ratio using a block randomization program to undergo cataract surgery and receive the implantation of either the PanOptix or Trinova IOL in both eyes. Outcome measures including binocular uncorrected and corrected visual acuities at distance, intermediate (66 cm), and near (40 cm), defocus curve, refractive outcomes, contrast sensitivity, glare and halos, and patient satisfaction were assessed at a minimum of 3 months following bilateral IOL implantation.
RESULTS
A total of 71 patients (142 eyes) were included, with 35 patients (70 eyes) in the PanOptix IOL group and 36 patients (72 eyes) in the Trinova IOL group. At the 3-month follow-up examination, mean distance-corrected intermediate visual acuity (primary endpoint) was significantly better for the PanOptix IOL group (0.0 ± 0.09 logMAR) compared with the Trinova IOL group (0.01 ± 0.10 logMAR) ( = .0304). Mean logMAR uncorrected intermediate acuity (UIVA) and near (UNVA) visual acuity were also significantly better for the PanOptix IOL group (UIVA = 0.1 ± 0.10 logMAR; UNVA= 0.0 ± 0.09 logMAR) compared with the Trinova IOL group (UIVA = 0.2 ± 0.10 logMAR; UNVA = 0.2 ± 0.11 logMAR) (both < .001). There were no statistically significant differences in all other outcomes between groups. No adverse events were reported in both groups.
CONCLUSIONS
These results suggest that the PanOptix IOL provides better intermediate and near visual outcomes compared to the Trinova IOL and represents a good choice for patients seeking to achieve spectacle independence. .
Topics: Adult; Humans; Lens Implantation, Intraocular; Pseudophakia; Eyeglasses; Refraction, Ocular; Visual Acuity; Patient Satisfaction; Prosthesis Design; Lenses, Intraocular; Phacoemulsification
PubMed: 37578176
DOI: 10.3928/1081597X-20230424-01