Nevin Manimala

Genes Genomics. 2024 Nov 6. doi: 10.1007/s13258-024-01584-w. Online ahead of print.

ABSTRACT

BACKGROUND: The permutation test has been widely used to provide the p-values of statistical tests when the standard test statistics do not follow parametric null distributions. However, the permutation test may require huge numbers of iterations, especially when the detection of very small p-values is required for multiple testing adjustments in the analysis of datasets with a large number of features.

OBJECTIVE: To overcome this computational burden, we suggest a novel enhanced adaptive permutation test that estimates p-values using the negative binomial (NB) distribution. By the method, the number of permutations are differently determined for individual features according to their potential significance.

METHODS: In detail, the permutation procedure stops, when test statistics from the permuted dataset exceed the observed statistics from the original dataset by a predefined number of times. We showed that this procedure reduced the number of permutations especially when there were many insignificant features. For significant features, we enhanced the reduction with Stouffer’s method after splitting datasets.

RESULTS: From the simulation study, we found that the enhanced adaptive permutation test dramatically reduced the number of permutations while keeping the precision of the permutation p-value within a small range, when compared to the ordinary permutation test. In real data analysis, we applied the enhanced adaptive permutation test to a genome-wide single nucleotide polymorphism (SNP) dataset of 327,872 features.

CONCLUSION: We found the analysis with the enhanced adaptive permutation took a feasible time for genome-wide omics datasets, and successfully identified features of highly significant p-values with reasonable confidence intervals.

PMID:39503929 | DOI:10.1007/s13258-024-01584-w

Cancer Med. 2024 Nov;13(21):e70358. doi: 10.1002/cam4.70358.

ABSTRACT

BACKGROUND: Rising metastatic prostate cancer incidence has renewed debate regarding benefits of prostate-specific antigen (PSA) screening. Identifying barriers to accessing screening for individuals at high risk of lethal prostate cancer may slow this rise. We examined associations of access barriers with receipt of PSA testing, stratified by sociodemographic factors.

METHODS: We pooled data from male respondents to Behavior Risk Factor Surveillance Systems (BRFSS) surveys from 2006 to 2020. Questions related to affordability (insurance, cost of visits) and accommodation (regular primary care provider (PCP), physician recommending a PSA test) were considered as individual-level barriers. For availability, we linked provider density from the 2012 Area Health Resource File and estimated driving times to closest health facility within Micropolitan and Metropolitan Statistical Area (MMSA) using Google Earth Engine. These measures were used to compute a spatial accessibility index. We fit survey-weighted, covariate-adjusted logistic regression models to estimate associations of barriers with receipt of PSA within the past 2 years and examined effect modification by sociodemographic factors.

RESULTS: There were 185,643 participants, of whom 73% were White, 11% were Black, 4% were Asian, and 11% were Hispanic. Physician recommendation was the strongest predictor of having a PSA test (aOR: 14.5, 95% CI: 13.6, 15.6). Not having a regular PCP (aOR: 0.29, 95% CI: 0.27, 0.31), insurance (aOR: 0.64, 95% CI: 0.58, 0.71), and prohibitive cost of care (aOR: 0.82, 95% CI: 0.75, 0.90) were associated with lower PSA testing. Access barriers were stronger predictors of PSA testing for Asian and White participants compared to other groups (P_het < 0.004 for insurance and regular PCP) and for those with college education compared to those without (P_het < 0.05 for insurance, perceived unaffordability).

DISCUSSION: Physician recommendation was the strongest predictor of receipt of PSA testing, regardless of sociodemographic grouping. Future studies should consider access barriers jointly and across sociodemographic strata.

PMID:39503193 | DOI:10.1002/cam4.70358

Diabetes Obes Metab. 2024 Nov 6. doi: 10.1111/dom.16041. Online ahead of print.

ABSTRACT

AIMS: Type 2 diabetes (T2D) patients with a clinical phenotype characterized by a high degree of insulin resistance are at increased risk of chronic kidney disease (CKD). We previously demonstrated that the endothelin receptor antagonist (ERA) atrasentan reduced insulin resistance in T2D. In this study, we compared the effect of atrasentan on insulin resistance across different phenotypic clusters of patients with T2D.

MATERIALS AND METHODS: We performed a post hoc analysis of the SONAR trial, a randomized, placebo-controlled trial of the ERA atrasentan in patients with T2D and CKD. Patients were stratified into four previously identified phenotypic clusters: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD). Changes in insulin resistance, assessed by HOMA-IR, were compared between the phenotypic clusters using a mixed effects model.

RESULTS: In total, 931 patients were included in the analysis. In the overall population, atrasentan compared to placebo reduced HOMA-IR by 12.9% [95%CI 3.5,21.4]. This effect of atrasentan was more pronounced in clusters characterized by insulin resistance or deficiency: (SIRD cluster 26.2% [95% CI 3.8,43.3] and SIDD cluster 18.5% [95%CI -3.8,35.9]), although the latter did not reach statistical significance. The effect of atrasentan compared to placebo was less pronounced in the other two clusters (MARD 12.2% [95% CI -1.7,24.12] and MOD -5.3% [95% CI -28.9,13.9]).

CONCLUSIONS: Atrasentan significantly improved insulin sensitivity in patients with T2D and CKD, especially in those characterized by high insulin resistance (SIRD cluster). Further studies are warranted to investigate the long-term clinical outcomes of atrasentan treatment in these distinct phenotypic clusters.

PMID:39503150 | DOI:10.1111/dom.16041

Anesth Prog. 2024 Sep 9;71(3):115-122. doi: 10.2344/201833.

ABSTRACT

OBJECTIVE: More than 1 in 8 New Zealand (NZ) adults are dentally anxious, which can lead to avoiding dental care and a higher risk of poor oral health. However, little is known about how dentally anxious patients are identified and managed by NZ general dentists. This survey aimed to investigate how NZ dentists identify and manage dentally anxious patients.

METHODS: We conducted an email survey of NZ dentists in 2022, obtaining 212 responses. Along with demographic information, respondents were queried about whether they ask patients about past/current dental fears and their likely origin, how they assessed those fears, their usual management of dentally anxious patients, and how the management of dentally anxious patients could be improved.

RESULTS: Almost three-quarters reported personally asking patients about past and/or current dental fears, and half enquired about bad life experiences that had led to those fears. Only 6 respondents (2.8%) reported using a formal dental anxiety/phobia assessment tool prior to treatment. For managing severely anxious adult dental patients, all dentists used at least 1 pharmacologic or psychological technique or referral to a colleague.

CONCLUSION: The study identified several weaknesses among NZ dentists in identifying and managing dental anxiety patients. The use of formal dental anxiety/phobia assessment tools prior to treatment needs improvement. Addressing dental anxiety is a complex issue that requires a multipronged approach involving improved education, the development and implementation of better assessment tools, and a greater understanding of how dentists’ current assessment and management of dental anxiety can be improved.

PMID:39503143 | DOI:10.2344/201833

Anesth Prog. 2024 May 3;71(1):15-18. doi: 10.2344/22-00037.

ABSTRACT

OBJECTIVE: The goal of this study was to compare the efficacy of midazolam/meperidine (M/M) vs midazolam/hydromorphone (M/H) for enteral moderate sedation along with inhalational sedation in pediatric dental patients.

METHODS: This retrospective chart review analyzed the charts of pediatric patients who received dental treatment under enteral moderate sedation with either M/M or M/H in combination with inhalational sedation (nitrous oxide/oxygen) at El Rio Community Health Centers (affiliated with NYU Langone) in Tucson, Arizona, from July 2014 to December 2020. Included subjects were between 2 and 5 years of age, less than 20 kg, and otherwise healthy. In addition to demographic and drug-dosing data, treatment completion, sedation level, behavioral score, overall effectiveness, and sedation duration data were collected and analyzed from each patient’s chart.

RESULTS: No statistically significant differences were observed when comparing the 2 drug regimens in treatment completion (P = .89), sedation level (P = .74), and overall effectiveness (P = .70). There was a statistically significant difference in behavior scoring, with the M/H group demonstrating higher scores (P = .04) than the M/M group.

CONCLUSION: The combination of midazolam and hydromorphone may provide an effective alternative to midazolam and meperidine when used with inhalational sedation (nitrous oxide/oxygen) for the moderate sedation of pediatric dental patients.

PMID:39503125 | DOI:10.2344/22-00037

Anesth Prog. 2024 May 3;71(1):8-14. doi: 10.2344/23-00023.

ABSTRACT

OBJECTIVE: Although there are conflicting data, several authors have proposed that articaine’s molecular properties suggest improved perfusion capabilities over other amide anesthetics. The purpose of this prospective, randomized, crossover study was to evaluate the anesthetic efficacy of palatal soft-tissue anesthesia following a buccal infiltration of 1.8 and 3.6 mL of 4% articaine with 1:100,000 epinephrine.

METHODS: One hundred eighteen adults received 1.8 or 3.6 mL of 4% articaine with 1:100,000 epinephrine as a buccal infiltration of the maxillary first molar at 2 separate appointments. Palatal soft-tissue anesthesia was evaluated with a dental explorer. Anesthetic success was defined as the absence of pain with an explorer stick. For the subjects who achieved palatal anesthesia, mapping was conducted over 70 minutes, and the overall area of palatal anesthesia was calculated. The data were analyzed using chi-square tests.

RESULTS: The highest percentage of palatal anesthetic success was 20% for the 1.8-mL volume and 32% for the 3.6-mL volume both at 30 minutes. A statistically significant difference between the 1.8- and 3.6-mL volumes was seen at 40 minutes. There was high variability in area measurements for subjects who achieved palatal anesthesia. The highest area measurements were 92 mm2 for the 1.8-mL volume at 20 minutes and 113 mm2 for the 3.6-mL volume at 10 minutes.

CONCLUSION: Because of the low success rates (20%-32%) and the high variability of the area anesthetized for the subjects who achieved palatal anesthesia, the clinical efficacy of 1.8 or 3.6 mL of articaine via buccal infiltration for palatal anesthesia is of questionable value.

PMID:39503116 | DOI:10.2344/23-00023

Acta Psychol (Amst). 2024 Oct 26;250:104553. doi: 10.1016/j.actpsy.2024.104553. Online ahead of print.

ABSTRACT

Traumatic brain injury (TBI) often causes persistent deficits in cognitive flexibility and information updating. Cognitive flexibility refers to the brain’s ability to adjust its thinking and behavior in response to changing circumstances, whereas information updating is the process of incorporating new facts into current knowledge. Both cognitive flexibility and information updating are critical components of executive function, and their impairment can have a major influence on a person’s capacity to operate independently and adjust to life’s problems following a TBI. Understanding and addressing these specific cognitive processes is therefore critical in designing successful therapies for TBI patients. Previous studies have examined the effects of non-invasive brain stimulation and cognitive training separately. This study investigated the effects of combining transcranial direct current stimulation (tDCS) with computer-based cognitive training, comparing this combined intervention against a control group with no treatment, to assess improvements in two executive functions in TBI patients: cognitive flexibility and information updating. Thirty TBI patients, 2-12 weeks post-injury with impaired executive dysfunction, were randomized to an experimental or control group. The experimental group received ten 30-minute sessions over 2 weeks of anodal (A-tDCS), 2.0 mA to the prefrontal cortex while performing cognitive training tasks from the RehaCom software. The control group received no intervention during this period. Cognitive flexibility and information updating were assessed before and after the intervention period using the n-back working memory task, Wisconsin Sorting Card Test, and quantitative electroencephalography (qEEG) during eyes-closed state. Statistically significant differences in theta, alpha, beta, and gamma band power were observed between groups (p < .05, 4 < f < 6). Secondary outcomes indicated significant improvements in cognitive flexibility within Wisconsin Card Sorting Test and information updating performance within n-back task (p < .05, 7 < f < 20). The combination of tDCS and cognitive training may improve cognitive flexibility and information updating in TBI patients by enhancing plasticity and connectivity in prefrontal regions involved in these complex cognitive processes.

PMID:39503106 | DOI:10.1016/j.actpsy.2024.104553

Acta Psychol (Amst). 2024 Oct 26;250:104536. doi: 10.1016/j.actpsy.2024.104536. Online ahead of print.

ABSTRACT

The integration of virtual reality (VR) and multisensory experiences offers a novel approach to enhancing workspace design, particularly for home office environments. This preliminary study examines the effects of visual and olfactory stimuli in a VR-simulated smart home environment on presence, task performance, heart rate, and mood. Sensory conditions, including visual, olfactory, and combined stimuli, were controlled in an experiment with 60 participants to assess both physiological and psychological responses. Task performance was measured through cognitive tests, while heart rate and mood states were monitored using a heart rate sensor and the Positive and Negative Affect Schedule (PANAS), respectively. Statistical results showed that the sense of presence provided by VR and specific conditions-such as visual stimuli (e.g., intelligent lighting systems)-effectively enhanced work efficiency, with task performance under visual stimuli significantly outperforming that under olfactory stimuli (e.g., peppermint scent). However, these sensory stimuli did not significantly affect heart rate or emotions. Our findings underscore the potential of sensory design to improve task performance and highlight the importance of the sensory environment in designing home offices, suggesting that sensory stimuli can enhance work efficiency in remote or virtual work settings.

PMID:39503105 | DOI:10.1016/j.actpsy.2024.104536

Trans R Soc Trop Med Hyg. 2024 Nov 6:trae088. doi: 10.1093/trstmh/trae088. Online ahead of print.

ABSTRACT

BACKGROUND: Schistosomiasis is one of the neglected tropical diseases that pose a significant burden in developing countries, particularly in sub-Saharan Africa. Hepatosplenic schistosomiasis (HSS) is a substantial cause of morbidity and mortality. This study aimed to determine clinical patterns, outcomes and factors associated with HSS in the Harari Region of Ethiopia.

METHODS: An institutional-based retrospective cross-sectional study was conducted among 93 adult patients diagnosed with HSS at public hospitals in the Harari Region from December 2018 to November 2022. Data were extracted from medical records using a standardized data extraction tool. EpiData version 4.2 and SPSS version 26.0 were used for data entry and analysis. Fisher’s exact test was used to identify the association between dependent and independent variables, and statistical significance was declared at p<0.05.

RESULTS: In the current study, HSS-related mortality was recorded in 7.5% of patients. Recurrent episodes of upper gastrointestinal (GI) bleeding (p=0.04), hypotension (p=0.02), altered mental status at admission (p=0.009) and antibiotic use for the treatment of spontaneous bacterial peritonitis (p=0.04) were significant factors associated with HSS-related mortality.

CONCLUSIONS: The study found that treatment outcomes of HSS patients were strongly associated with recurrent upper GI bleeding, hypotension, altered mental status and antibiotic use for spontaneous bacterial peritonitis treatment. The use of antibiotics for spontaneous bacterial peritonitis treatment was strongly associated with the treatment outcome of patients with HSS and was unique to our study. Adequate recording of patient data, improving chart keeping, integration of preventive and curative programs, improvement of the diagnostic tools, comprehensive treatment guidelines, early diagnosis and treatment are strongly recommended. Rigorous prospective studies that can fully reflect cause-and-effect relationships are crucial to fill fundamental evidence gaps.

PMID:39503071 | DOI:10.1093/trstmh/trae088

Trans R Soc Trop Med Hyg. 2024 Nov 6:trae091. doi: 10.1093/trstmh/trae091. Online ahead of print.

ABSTRACT

BACKGROUND: Without a cure, antiretroviral therapy (ART) continues to be the primary mode of managing HIV, transforming it from a formerly lethal disease to a less severe one. Adherence to ART can be impacted by several factors, including poor quality of care.

METHODS: A quantitative cross-sectional study design was used to assess the factors that influence adherence to ART among adults receiving care at two health facilities in Accra. A structured interviewer-administered questionnaire was used to collect data on factors associated with medication adherence using a modified four-item Medication Adherence Rating from 255 people living with HIV (PLHIV). Descriptive statistics were used to summarise the data, while multiple binary logistic regression was used to assess the factors influencing adherence to ART.

RESULTS: Adherence to HIV medication was 44.7% among PLHIV. Adherence was positively correlated with high client health service satisfaction (adjusted OR [AOR]: 26.59, 95% CI 7.46 to 94.82, p<0.001), increased privacy at the HIV clinics (AOR: 3.40, 95% CI 1.40 to 8.21, p<0.007) and among PLHIV who had been diagnosed with HIV for ≥5 y (AOR: 7.59, 95% CI 2.76 to 20.85, p<0.001).

CONCLUSIONS: Adherence to ART was significantly low among study participants. The study highlights the importance of maintaining privacy and confidentiality at the facility while ensuring client satisfaction with HIV care to promote adherence to ART.

PMID:39503068 | DOI:10.1093/trstmh/trae091