Nevin Manimala

PLoS One. 2022 Jun 16;17(6):e0269369. doi: 10.1371/journal.pone.0269369. eCollection 2022.

ABSTRACT

Recently there have been tremendous efforts to develop statistical procedures which allow to determine subgroups of patients for which certain treatments are effective. This article focuses on the selection of prognostic and predictive genetic biomarkers based on a relatively large number of candidate Single Nucleotide Polymorphisms (SNPs). We consider models which include prognostic markers as main effects and predictive markers as interaction effects with treatment. We compare different high-dimensional selection approaches including adaptive lasso, a Bayesian adaptive version of the Sorted L-One Penalized Estimator (SLOBE) and a modified version of the Bayesian Information Criterion (mBIC2). These are compared with classical multiple testing procedures for individual markers. Having identified predictive markers we consider several different approaches how to specify subgroups susceptible to treatment. Our main conclusion is that selection based on mBIC2 and SLOBE has similar predictive performance as the adaptive lasso while including substantially fewer biomarkers.

PMID:35709188 | DOI:10.1371/journal.pone.0269369

PLoS One. 2022 Jun 16;17(6):e0269995. doi: 10.1371/journal.pone.0269995. eCollection 2022.

ABSTRACT

OBJECTIVE: To assess association between Hashimoto thyroiditis (HT) and clinical outcomes of papillary thyroid carcinoma (PTC).

METHODS: Databases including Pubmed, Embase, Cochrane Library, and Web of Science were searched. Weighed mean differences (WMDs) and odds ratios (ORs) were used to evaluate association between HT and clinical outcomes of PTC, and the effect size was represented by 95% confidence intervals (CIs). Heterogeneity test was performed for each indicator. If the heterogeneity statistic I2≥50%, random-effects model analysis was carried out, otherwise, fixed-effect model analysis was performed. Sensitivity analysis was performed for all outcomes, and publication bias was tested by Begg’s test.

RESULTS: Totally 47,237 patients in 65 articles were enrolled in this study, of which 12909 patients with HT and 34328 patients without HT. Our result indicated that PTC patients with HT tended to have lower risks of lymph node metastasis (OR: 0.787, 95%CI: 0.686-0.903, P = 0.001), distant metastasis (OR: 0.435, 95%CI: 0.279-0.676, P<0.001), extrathyroidal extension (OR: 0.745, 95%CI: 0.657-0.845, P<0.001), recurrence (OR: 0.627, 95%CI: 0.483-0.813, P<0.001), vascular invasion (OR: 0.718, 95%CI: 0.572-0.901, P = 0.004), and a better 20-year survival rate (OR: 1.396, 95%CI: 1.109-1.758, P = 0.005) while had higher risks of multifocality (OR: 1.245, 95%CI: 1.132-1.368, P<0.001), perineural infiltration (OR: 1.922, 95%CI: 1.195-3.093, P = 0.007), and bilaterality (OR: 1.394, 95%CI: 1.118-1.739, P = 0.003).

CONCLUSIONS: PTC patients with HT may have favorable clinicopathologic characteristics, compared to PTCs without HT. More prospective studies are needed to further elucidate this relationship.

PMID:35709179 | DOI:10.1371/journal.pone.0269995

PLoS One. 2022 Jun 16;17(6):e0269911. doi: 10.1371/journal.pone.0269911. eCollection 2022.

ABSTRACT

BACKGROUND: Dementia is a big medical and socioeconomic problem on aging society, and cardiac diseases have already shown a significant contribution to developing dementia. However, the risk of dementia related to hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has never been evaluated.

METHODS: In a large-scale longitudinal cohort using National Health Insurance database, 4,645 subjects with HCM aged ≥50 years between 2010 and 2016 were collected and matched with 13,935 controls, based on propensity scores (1:3). We investigated the incidence and risk of dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) between groups.

RESULTS: During follow-up (median 3.9 years after 1-year lag), incident dementia occurred in 739 subjects (4.0%): 78.2% for AD and 13.0% for VaD. The incidence of dementia, AD, and VaD were 23.0, 18.0, and 2.9/1,000 person-years, respectively, and was generally more prevalent in HCM. HCM group had a 50% increased risk of dementia, particularly AD, whereas there was no difference in the risk of VaD. The impact of HCM on AD (HR 1.52, 95% CI 1.26-1.84, p<0.001) was comparable with that of diabetes mellitus and smoking. Increased risk of AD in relation to HCM was consistent in various subgroups including younger healthier population.

CONCLUSIONS: This is the first to demonstrate the increased risk of dementia, mainly AD rather than VaD, in subjects with HCM. Early surveillance and active prevention for cognitive impairment could help for a better quality of life in an era that HCM is considered a chronic manageable disease with low mortality.

PMID:35709174 | DOI:10.1371/journal.pone.0269911

PLoS One. 2022 Jun 16;17(6):e0269921. doi: 10.1371/journal.pone.0269921. eCollection 2022.

ABSTRACT

INTRODUCTION: Consumer escalation systems allow patients and families to escalate concerns about acute clinical deterioration. Hospital staff can impact upon the success of this process. As part of evaluation processes within a Local Health Network, where a consumer escalation system was introduced in accordance with National requirements, we sought to explore clinicians’ understanding and perceptions of consumer escalation.

METHODS: Voluntary and anonymous staff surveys pre, and post, system introduction. Quantitative data was analysed using descriptive statistics, chi-square independence, and non-parametric independent samples median tests. Qualitative data was evaluated using content analysis and cross-referenced with quantitative responses.

RESULTS: Respondent’s (pre: 215; post: 89) area of work varied significantly between survey periods. Most agreed that patients/families have a sound knowledge of a patient’s typical health status (pre: 192/215 (89.3%); post 82/88 (93.2%)) and that patients/families should be encouraged to escalate concerns of deterioration to ward staff (pre: 209/212 (98.6%); post: 85/89 (95.5%)). Respondent perceptions of patient/family ability to recognise clinical deterioration varied. Staff agreement towards local response expectations decreased as the degree of clinical requirement increased. Staff concerns of increased workloads (pre: 90/214 (42.1%); post 12/72 (16.7%), p<0.001) and conflict generation (pre: 71/213 (33.3%); post: 7/71 (9.9%), p = 0.001) decreased significantly following system introduction. However, clinician perceptions of positive system effects also decreased (patient-staff rapport pre: 163/213 (76.5%); post: 38/72 (52.8%), p = 0.001; patient centred care pre: 188/214 (87.9%); post: 53/72 (73.6%), p = 0.012; patient safety pre: 173/214 (80.8%); post: 49/72 (68.1%), p = 0.077). Only 53% of respondents (pre: 112/213 (52.6%); post: 48/88 (54.5%)) perceived that patient/family have sufficient confidence to escalate concerns.

CONCLUSION: Consumer escalation systems require staff support. Staff perceptions may indicate, and act as, barriers to the operation of consumer escalation processes. Further exploration in identifying and managing staff barriers is crucial to the success of consumer escalation.

PMID:35709173 | DOI:10.1371/journal.pone.0269921

PLoS One. 2022 Jun 16;17(6):e0267560. doi: 10.1371/journal.pone.0267560. eCollection 2022.

ABSTRACT

AlphaFold2 and RoseTTAfold are able to predict, based solely on their sequence whether GFP-like proteins will post-translationally form a chromophore (the part of the protein responsible for fluorescence) or not. Their training has not only taught them protein structure and folding, but also chemistry. The structures of 21 sequences of GFP-like fluorescent proteins that will post-translationally form a chromophore and of 23 GFP-like non-fluorescent proteins that do not have the residues required to form a chromophore were determined by AlphaFold2 and RoseTTAfold. The resultant structures were mined for a series of geometric measurements that are crucial to chromophore formation. Statistical analysis of these measurements showed that both programs conclusively distinguished between chromophore forming and non-chromophore forming proteins. A clear distinction between sequences capable of forming a chromophore and those that do not have the residues required for chromophore formation can be obtained by examining a single measurement-the RMSD of the overlap of the central alpha helices of the crystal structure of S65T GFP and the AlphaFold2 determined structure. Only 10 of the 578 GFP-like proteins in the pdb have no chromophore, yet when AlphaFold2 and RoseTTAFold are presented with the sequences of 44 GFP-like proteins that are not in the pdb they fold the proteins in such a way that one can unequivocally distinguish between those that can and cannot form a chromophore.

PMID:35709156 | DOI:10.1371/journal.pone.0267560

Endocrine. 2022 Jun 16. doi: 10.1007/s12020-022-03102-y. Online ahead of print.

ABSTRACT

PURPOSE: Recent studies claim that immune checkpoint inhibitors are effective in defective mismatch repair (dMMR) cancers. This raises the question of whether similar therapies are effective in PanNETs (pancreatic neuroendocrine tumors); however, in general, assessment of MMR status in PanNETs has been inconsistent in previous studies. MGMT (O6-methylguanine-DNA methyltransferase) is potentially important for guiding temozolomide (TMZ) therapy in glioblastoma. The number of reports on MGMT expression and promoter methylation in PanNETs are limited.

METHODS: In this study we assessed the expression of MGMT and MMR proteins MSH2, MSH6, MLH1 and PMS2 in a series of PanNETs by IHC. The methylation status of MGMT and MMR genes in a subset of PanNETs was further assessed by MS-MLPA analysis. Survival curves were constructed using the Kaplan-Meier method, and differences were assessed using the log-rank test. Multivariate Cox proportional hazards regression models were used to determine the prognostic value of the variables.

RESULTS: According to evaluation criteria for mismatch repair defects, none of PanNETs shown nuclear staining loss for MSH2, MSH6, MLH1, and PMS2. MGMT low-intensity PanNETs were more commonly found in higher grade, higher Ki67 index and non-functional tumors (P < 0.05). In multivariate analysis, stage III-IV and low-intensity MGMT were shown to be independent risk factors for progression of PanNETs in the entire cohort, non-functioning subgroup and G2 subgroup (P < 0.05 for all). MGMT promoter methylation tended to be higher in the group with low expression of MGMT, However, methylation of MGMT did not statistically correlate with low expression of MGMT (P = 0.153).

CONCLUSIONS: In conclusion, our study suggests that decreased expression of MGMT but not MMR is associated with a higher risk of progression of pancreatic neuroendocrine tumors.

PMID:35708896 | DOI:10.1007/s12020-022-03102-y

Eur J Epidemiol. 2022 Jun 16. doi: 10.1007/s10654-022-00886-1. Online ahead of print.

ABSTRACT

Alcohol intake is thought to be a risk factor for breast cancer, but the causal relationship and carcinogenic mechanisms are not clear. We performed an up-to-date meta-analysis of prospective studies to assess observational association, and then conducted MR analysis to make causal inference based on the genetic predisposition to alcohol consumption (“drinks per week”) and pathological drinking behaviours (“alcohol use disorder” and “problematic alcohol use”), as well as genetically predicted DNA methylation at by alcohol-related CpG sites in blood. We found an observational dose-response association between alcohol intake and breast cancer incidence with an additional risk of 4% for per 10 g/day increase in alcohol consumption. Genetic predisposition to alcohol consumption (“drinks per week”) was not causally associated with breast cancer incidence at the OR of 1.01 (95% CI 0.84, 1.23), but problematic alcohol use (PAU) was linked to a higher breast cancer risk at the OR of 1.76 (95% CI 1.04, 2.99) when conditioning on alcohol consumption. Epigenetic MR analysis identified four CpG sites, cg03260624 near CDC7 gene, cg10816169 near ZNF318 gene, cg03345232 near RIN3 gene, and cg26312998 near RP11-867G23.13 gene, where genetically predicted epigenetic modifications were associated with an increased breast cancer incidence risk. Our findings re-affirmed that alcohol consumption is of high risk for breast cancer incidence even at a very low dose, and the pathogenic effect of alcohol on breast cancer could be due to pathological drinking behaviour and epigenetic modification at several CpG sites, which could be potential intervention targets for breast cancer prevention.

PMID:35708873 | DOI:10.1007/s10654-022-00886-1

Eur J Orthop Surg Traumatol. 2022 Jun 16. doi: 10.1007/s00590-022-03301-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Femoral bone fracture is the predominant, lower limb orthopedic surgery that is associated with severe acute and persistent chronic pain that needs better postoperative pain management. Untreated postoperative pain results inability to do physiotherapy resulting in stiffens of joints and immobility. This study aimed to compare the postoperative analgesic efficacy of three-in-one-block versus fascia iliaca block in patients who underwent surgically treated femoral fractured patients under spinal anesthesia.

METHODS: A prospective cohort study was conducted on 110 elective surgically treated femoral fractured orthopedic patients from January to October 2021. Data were entered into epi-data 4.4.2 and imported into a statistical package of social science version 22 for analysis. Shapiro-Wilk normality test was used to check the normality of the data and normally distributed data were analyzed using Student’s independent t-test, whereas non-normally distributed variables were analyzed with Mann-Whitney U-test. The comparisons of categorical parameters were analyzed using the chi-square test and Fisher’s exact test. Finally p-value < 0.05 was declared to be statistically significant.

RESULT: The median and interquartile range of the postoperative numerical rating scale at rest and on movement was significantly less in three-in-one-block (3IN1B) as compared with fascia-iliaca block (FICB). But at 30 min no significantly different between the two pain management modalities. Moreover, the meantime to seek the first request of analgesia was significantly prolonged in 3IN1B compared with FICB. Regarding the total analgesic consumption, the mean total tramadol consumption was 97. 27 ± 53. 07 and 180 ± 72.96 (p < 0.001) and Diclofenac 53.18 ± 29.28 and 72 ± 43.54 (p < 0. 001) in 3IN1 and FICB, respectively.

CONCLUSION: The present study concludes that three-in-one-block provides more effective analgesia, reduced postoperative analgesic requirements, and prolonged first analgesics requests compared with fascia iliaca block, and Landmark technique fascia-iliaca block (FICB) is an alternative pain management modality in a resource-limited setting.

PMID:35708850 | DOI:10.1007/s00590-022-03301-3

Eur Radiol. 2022 Jun 16. doi: 10.1007/s00330-022-08933-x. Online ahead of print.

ABSTRACT

OBJECTIVE: Evaluation of image characteristics at ultra-low radiation dose levels of a first-generation dual-source photon-counting computed tomography (PCCT) compared to a dual-source dual-energy CT (DECT) scanner.

METHODS: A multi-energy CT phantom was imaged with and without an extension ring on both scanners over a range of radiation dose levels (CTDI_vol 0.4-15.0 mGy). Scans were performed in different modes of acquisition for PCCT with 120 kVp and DECT with 70/Sn150 kVp and 100/Sn150 kVp. Various tissue inserts were used to characterize the precision and repeatability of Hounsfield units (HUs) on virtual mono-energetic images between 40 and 190 keV. Image noise was additionally investigated at an ultra-low radiation dose to illustrate PCCT’s ability to remove electronic background noise.

RESULTS: Our results demonstrate the high precision of HU measurements for a wide range of inserts and radiation exposure levels with PCCT. We report high performance for both scanners across a wide range of radiation exposure levels, with PCCT outperforming at low exposures compared to DECT. PCCT scans at the lowest radiation exposures illustrate significant reduction in electronic background noise, with a mean percent reduction of 74% (p value ~ 10^-8) compared to DECT 70/Sn150 kVp and 60% (p value ~ 10^-6) compared to DECT 100/Sn150 kVp.

CONCLUSIONS: This paper reports the first experiences with a clinical dual-source PCCT. PCCT provides reliable HUs without disruption from electronic background noise for a wide range of dose values. Diagnostic benefits are not only for quantification at an ultra-low dose but also for imaging of obese patients.

KEY POINTS: PCCT scanners provide precise and reliable Hounsfield units at ultra-low dose levels. The influence of electronic background noise can be removed at ultra-low-dose acquisitions with PCCT. Both spectral platforms have high performance along a wide range of radiation exposure levels, with PCCT outperforming at low radiation exposures.

PMID:35708838 | DOI:10.1007/s00330-022-08933-x

Psychiatr Q. 2022 Jun 16. doi: 10.1007/s11126-022-09984-5. Online ahead of print.

ABSTRACT

Peer telemental health recently became Medicaid reimbursable during the COVID-19 crisis, increasing the need for standardized training on digital peer support (DPS) services. DPS has the potential to reduce barriers to services and expand the reach of peer support specialists. The 4-h Digital Peer Support Training program was developed to train peer support specialists for rapid uptake in providing digital peer support during the COVID-19 crisis. The purpose of this study was to examine the impact of the 4-h DPS course for peer support specialists. Surveys were administered to examine pre-post changes in DPS course for participants (N = 75) related to attitudes/ beliefs towards DPS, ability to use/ engage in DPS, and organizational readiness to implement DPS. Data were analyzed by conducting paired samples t-tests. Linear mixed models were used to explore significant results further. Statistically significant (< .05) changes were observed related to readiness to use DPS, attitudes/ beliefs towards DPS, and ability to use/ engage in DPS. The 4-h DPS course may be beneficial in providing diverse groups of peer support specialists with a standardized training framework. Widespread dissemination of the DPS short course may be beneficial in rapidly equipping peer support specialists with the skills and resources needed to expand the reach of peer support services during the COVID-19 crisis and beyond.

PMID:35708827 | DOI:10.1007/s11126-022-09984-5