Nevin Manimala

Circulation. 2022 Jul 26:101161CIRCULATIONAHA121058426. doi: 10.1161/CIRCULATIONAHA.121.058426. Online ahead of print.

ABSTRACT

BACKGROUND: Understanding the predictive utility of previously derived polygenic risk scores (PRSs) for long-term risk of coronary heart disease (CHD) and its additive value beyond traditional risk factors can inform prevention strategies.

METHODS: Data from adults 20 to 59 years of age who were free of CHD from the FOS (Framingham Offspring Study) and the ARIC (Atherosclerosis Risk in Communities) study were analyzed. Because the PRS was derived from samples of predominantly European ancestry, individuals who self-reported White race were included. The sample was stratified by age and cohort: young (FOS, 20-39 years [median, 30 years] of age), early midlife (FOS, 40-59 years [median, 43] years of age), and late midlife (ARIC, 45-59 years [median, 52 years] of age). Two previously derived and validated prediction tools were applied: (1) a 30-year traditional risk factor score and (2) a genome-wide PRS comprising >6 million genetic variants. Hazard ratios for the association between each risk estimate and incident CHD were calculated. Predicted and observed rates of CHD were compared with assess discrimination for each model individually and together with the optimism-corrected C index (95% CI).

RESULTS: Among 9757 participants, both the traditional risk factor score (hazard ratio per 1 SD, 2.60 [95% CI, 2.08-3.27], 2.09 [95% CI, 1.83-2.40], and 2.11 [95% CI, 1.96-2.28]) and the PRS (hazard ratio, 1.98 [95% CI, 1.70-2.30], 1.64 [95% CI, 1.47-1.84], and 1.22 [95% CI, 1.15-1.30]) were significantly associated with incident CHD in young, early midlife, and late midlife, respectively. Discrimination was similar or better for the traditional risk factor score (C index, 0.74 [95% CI, 0.70-0.78], 0.70 [95% CI, 0.67-0.72], and 0.72 [95% CI, 0.70-0.73]) compared with an age- and sex-adjusted PRS (0.73 [95% CI, 0.69-0.78], 0.66 [95% CI, 0.62-0.69], and 0.66 [95% CI, 0.64-0.67]) in young, early-midlife, and late-midlife participants, respectively. The ΔC index when PRS was added to the traditional risk factor score was 0.03 (95% CI, 0.001-0.05), 0.02 (95% CI, -0.002 to 0.037), and 0.002 (95% CI, -0.002 to 0.006) in young, early-midlife, and late-midlife participants, respectively.

CONCLUSIONS: Despite a statistically significant association between PRS and 30-year risk of CHD, the C statistic improved only marginally with the addition of PRS to the traditional risk factor model among young adults and did not improve among midlife adults. PRS, an immutable factor that cannot be directly intervened on, has minimal clinical utility for long-term CHD prediction when added to a traditional risk factor model.

PMID:35880530 | DOI:10.1161/CIRCULATIONAHA.121.058426

Stroke. 2022 Jul 26:101161STROKEAHA122038491. doi: 10.1161/STROKEAHA.122.038491. Online ahead of print.

ABSTRACT

BACKGROUND: In 2015, endovascular therapy (EVT) for large vessel occlusions became standard of care for acute ischemic stroke. Lower utilization of IV alteplase has been reported in women, but whether sex differences in EVT use in the United States exists has not been established.

METHODS: We identified all acute ischemic stroke discharges from Get With The Guidelines-Stroke hospitals between 2012 and 2019 who were potentially eligible for EVT, based on National Institutes of Health Stroke Scale score ≥6 and arrival <6 hours, according to 2018 American Heart Association/ASA guidelines. Multivariable regression analyses were used to determine the association between sex and EVT utilization, and outcomes (including mortality, discharge home, functional status) after EVT. Separate analyses were conducted for the 2 time periods: 2012 to 2014, and 2015 to 2019.

RESULTS: Of 302 965 patients potentially eligible for EVT, 42 422 (14%) received EVT. Before 2015, EVT treatment rates were 5.3% in women and 6.6% in men. From 2015 to 2019, treatment rates increased in both sexes to 16.7% in women and 18.5% in men. The adjusted odds ratio for EVT in women compared with men was 0.93 (95% CI, 0.87-0.99) before 2015, and 0.98 (95% CI, 0.96-1.01) after 2015. There were no significant sex differences in outcomes except that after 2015, women were less able to ambulate at discharge (adjusted odds ratio, 0.95 [95% CI, 0.95-0.99]) and had lower in-hospital mortality (adjusted odds ratio, 0.93 [95% CI, 0.88-0.99]).

CONCLUSIONS: EVT utilization has increased dramatically in both women and men since EVT approval in 2015. Following statistical adjustment, women were less likely to receive EVT initially, but after 2015, women were as likely as men to receive EVT. After EVT, women were more likely to be disabled at discharge but less likely to experience in-hospital death compared with men.

PMID:35880521 | DOI:10.1161/STROKEAHA.122.038491

J Korean Med Sci. 2022 Jul 25;37(29):e231. doi: 10.3346/jkms.2022.37.e231.

ABSTRACT

BACKGROUND: Although depression and motion sickness are prevalent in military personnel and seafarers, the association between depression and seasickness has been not yet elucidated. We aimed to evaluate the relationship of depression with initial susceptibility and adaptation to seasickness amongst military seafarers.

METHODS: This retrospective cohort enrolled Navy seafarers who started seafaring between 2017 and 2019. Three groups were established according to the Beck Depression Inventory (BDI) score: no depression (BDI score of 0), minimal depression (BDI score 1-9), and mild-to-moderate depression (BDI score 10-29). The occurrence of seasickness requiring treatment was observed as the prescription of medication for the first 30 distant seafaring days. Considering adjustment period, the two different outcomes were defined. The susceptibility to seasickness was evaluated via at least one day suffered from seasickness requiring treatment during the early period (the first 5 seafaring days), and adaptation ability to seasickness was defined by more than 10% of the ratio, calculated days suffered from seasickness requiring treatment/days of seafaring during the late period (the 6-30th seafaring days). Binary logistic regression was further evaluated to estimate the odds of BDI groups and BDI score adjusted for age and workplace whether outside visual perception was possible.

RESULTS: Among the 185 recruits, 179 participants (97%) sailed for more than 5 days were included in the study. Of the participants, 36% was susceptible to seasickness in the early and 17% was poorly adapted to seasickness in the late period. Multivariable model revealed that mild-to-moderate depression had elevated risk of poor adaptation (odds ratio [OR], 4.63; 95% confidence interval [CI], 1.31-16.98) whereas the results were not statistically significant for susceptibility to seasickness in the early period BDI score was independently associated with increased odds of poor adaptation (OR, 1.10; 95% CI, 1.04-1.18).

CONCLUSION: The present study suggests that depression is associated with poor adaptation to seasickness in Navy seafarers. Depression screening tool might be helpful for providing preventable strategies for population at risk.

PMID:35880507 | DOI:10.3346/jkms.2022.37.e231

J Korean Med Sci. 2022 Jul 25;37(29):e230. doi: 10.3346/jkms.2022.37.e230.

ABSTRACT

BACKGROUND: This study was performed to evaluate etiologies and secular trends in primary amenorrhea in South Korea.

METHODS: This retrospective multi-center study analyzed 856 women who were diagnosed with primary amenorrhea between 2000 and 2016. Clinical characteristics were compared according to categories of amenorrhea (hypergonadotropic/hypogonadotropic hypogonadism, eugonadism, disorders of sex development) or specific causes of primary amenorrhea. In addition, we assessed secular trends of etiology and developmental status based on the year of diagnosis.

RESULTS: The most frequent etiology was eugonadism (39.8%). Among specific causes, Müllerian agenesis was most common (26.2%), followed by gonadal dysgenesis (22.4%). Women with hypergonadotropic hypogonadism were more likely to have lower height and weight, compared to other categories. In addition, the proportion of cases with iatrogenic or unknown causes increased significantly in hypergonadotropic hypogonadism category, but overall, no significant secular trends were detected according to etiology. The proportion of anovulation including polycystic ovarian syndrome increased with time, but the change did not reach statistical significance.

CONCLUSION: The results of this study provide useful clinical insight on the etiology and secular trends of primary amenorrhea. Further large-scale, prospective studies are necessary.

PMID:35880506 | DOI:10.3346/jkms.2022.37.e230

J Prim Care Community Health. 2022 Jan-Dec;13:21501319221114850. doi: 10.1177/21501319221114850.

ABSTRACT

BACKGROUND: Non-communicable diseases and psychiatric pathologies are the health problems that most affect the population in the United States.

OBJECTIVE: This study aimed to examine the mediating role of patient-centered communication (PCC) in the relationship between satisfaction with medical care, physical health, and emotional well-being in American men.

METHODS: A cross-sectional – predictive study was carried out. The variables analyzed were satisfaction with medical care, physical health, and emotional well-being. Information from the Health Information National Trends Survey Data (HINTS) was used; HINTS 5, cycle 3 (collected between January and June 2019) and 4 (2020). Data from 3338 men were considered (mean age: M = 55.40, SD = 19.53). Data analyses were carried out using structural equation modeling (SEM) to represent the statistical mediation model with latent and observable variables.

RESULTS: Analyses showed that the variables were significantly related (P < .01). In the mediation model, there is evidence that satisfaction predicts communication (β = .764, P < .001) and this, in turn, is related to physical health (β = .079, P = .007) and emotional well-being (β = .145, P < .001). In addition, the standardized estimates of the structural multiple mediation model presented acceptable goodness-of-fit indices: χ²/gl = 2.24, CFI = 0.999, TLI = 0.999, RMSEA = 0.019 [90% CI: 0.013-0.022], SRMR = 0.018.

CONCLUSION: Patient-centered communication plays a significant dual mediating role in the relationship between satisfaction with medical care, physical health, and emotional well-being, respectively. Therefore, PCC is essential in healthcare for American men.

PMID:35880499 | DOI:10.1177/21501319221114850

Curr Med Res Opin. 2022 Jul 26:1-26. doi: 10.1080/03007995.2022.2105072. Online ahead of print.

ABSTRACT

OBJECTIVE: Factor VIII (FVIII) replacement and emicizumab have demonstrated efficacy for prevention of bleeds among patients with hemophilia A (PwHA) compared to on-demand use. Evidence investigating clinical outcomes and healthcare costs of non-inhibitor PwHA switching from prophylaxis with FVIII concentrates to emicizumab has not been well-established within large real-world datasets. This study aimed to investigate billed annualized bleed rates (ABR_b) and total cost of care (TCC) among non-inhibitor PwHA switching from FVIII-prophylaxis to emicizumab-prophylaxis.

METHODS: This retrospective, observational study was conducted using IQVIA PharMetrics® Plus, a US administrative claims database. The date of first claim for emicizumab was defined as the index date. On-demand patients and inhibitor patients were excluded. Bleeds were identified using a list of 535 diagnosis codes. Bayesian models were developed to estimate the probability ABR_b worsens and TCC increases after switching to emicizumab. Wilcoxon rank-sum tests were used to test statistical significance of changes in ABR_b and TCC after switch.

RESULTS: Among the 121 identified patients, the difference in mean ABR_b between FVIII-prophylaxis (0.68 [SD =1.28]) and emicizumab (0.55 [SD =1.48]) was insignificant (p = 0.142). The mean annual TCC significantly increased for patients switching from FVIII-prophylaxis ($518,151 [SD=$289,934]) to emicizumab ($652,679 [SD=$340,126]; p< 0.0001). The Bayesian models estimated a 21.0% probability of the ABR_b worsening and a 99.9% probability of increasing TCC after switch.

CONCLUSION: This study found that in male non-inhibitor PwHA, switching from FVIII prophylaxis to emicizumab incurs substantial cost increase with no significant benefit in ABR_b. This evidence may help guide providers, payers, and patients in shared decision-making conversations around best treatment options.

PMID:35880468 | DOI:10.1080/03007995.2022.2105072

J Gerontol Soc Work. 2022 Jul 26:1-13. doi: 10.1080/01634372.2022.2103762. Online ahead of print.

ABSTRACT

Caregiving has become an increasingly important medical and social issue in recent decades. We performed a cross-sectional study on pulmonary patients and accompanying informal caregivers who were hospitalized in the chest disease ward of a tertiary center in Turkey between January 2020 and April 2021. Informal caregivers were asked to complete the Zarit Caregiver Burden Interview. A total of 141 inpatients (39% female, mean age: 76.8 ± 10.2 years) and their informal caregivers (77% female, mean age: 54 ± 11.9 years) were evaluated. The caregivers were classified as light to medium burden (group 1, burden score ≤40) and medium to heavy burden (group 2, burden score >40). The mean burden score was 35.7 ± 13.3 points. The number of female caregivers was higher in group 2 (p = 0.025). There was a positive correlation between the burden score and female gender (p = 0.002) and the number of chronic diseases of caregivers (p = 0.020). Statistical analysis revealed a negative correlation between the burden score and the level of education (r = > -0.174, p = 0.040). Caregiver burden is related to the characteristics of the caregiver rather than those of the patient being cared for. Female caregivers with lower education and more than one chronic disease perceive a higher caregiver burden.

PMID:35880439 | DOI:10.1080/01634372.2022.2103762

Per Med. 2022 Jul 26. doi: 10.2217/pme-2022-0014. Online ahead of print.

ABSTRACT

The application of artificial intelligence (AI) to healthcare has garnered significant enthusiasm in recent years. Despite the adoption of new analytic approaches, medical education on AI is lacking. We aim to create a usable AI primer for medical education. We discuss how to generate a clinical question involving AI, what data are suitable for AI research, how to prepare a dataset for training and how to determine if the output has clinical utility. To illustrate this process, we focused on an example of how medical imaging is employed in designing a machine learning model. Our proposed medical education curriculum addresses AI’s potential and limitations for enhancing clinicians’ skills in research, applied statistics and care delivery.

PMID:35880428 | DOI:10.2217/pme-2022-0014

Brief Bioinform. 2022 Jul 25:bbac286. doi: 10.1093/bib/bbac286. Online ahead of print.

ABSTRACT

Single-cell RNA-sequencing (scRNA-seq) enables researchers to quantify transcriptomes of thousands of cells simultaneously and study transcriptomic changes between cells. scRNA-seq datasets increasingly include multisubject, multicondition experiments to investigate cell-type-specific differential states (DS) between conditions. This can be performed by first identifying the cell types in all the subjects and then by performing a DS analysis between the conditions within each cell type. Naïve single-cell DS analysis methods that treat cells statistically independent are subject to false positives in the presence of variation between biological replicates, an issue known as the pseudoreplicate bias. While several methods have already been introduced to carry out the statistical testing in multisubject scRNA-seq analysis, comparisons that include all these methods are currently lacking. Here, we performed a comprehensive comparison of 18 methods for the identification of DS changes between conditions from multisubject scRNA-seq data. Our results suggest that the pseudobulk methods performed generally best. Both pseudobulks and mixed models that model the subjects as a random effect were superior compared with the naïve single-cell methods that do not model the subjects in any way. While the naïve models achieved higher sensitivity than the pseudobulk methods and the mixed models, they were subject to a high number of false positives. In addition, accounting for subjects through latent variable modeling did not improve the performance of the naïve methods.

PMID:35880426 | DOI:10.1093/bib/bbac286

Bosn J Basic Med Sci. 2022 Jul 25. doi: 10.17305/bjbms.2022.7440. Online ahead of print.

ABSTRACT

The aim of this in vitro study was to evaluate the effect of three final irrigants, namely QMix, MTAD and EDTA, combined with three irrigation techniques, namely conventional needle irrigation (CNI), passive ultrasonic irrigation (PUI) and photon-induced photoacoustic streaming (PIPS), on smear layer removal, dentin mineral content and microhardness in oval-shaped canals. 130 decoronated premolars with single, oval root canals were equally divided into1 blank control group and 12 treatment groups (n=10) according to the final irrigation protocols. Roots in treatment groups were instrumented with ProTaper Gold to size F4 and subjected to final irrigation. Smear layer removal was assessed by using a four-level scoring system under an environmental scanning electron microscope. Energy dispersive X-ray spectroscopy was performed to measure the dentin mineral content. Dentin microhardness was measured by Knoop microhardness testing. Statistical analysis of the data was performed by using Kruskal-Wallis test, followed by Dunn’s post hoc test with Bonferroni correction. PUI- and PIPS-activated QMix and EDTA removed smear layer more effectively than MTAD groups (p<0.05). Regarding the dentin mineral content and microhardness, QMix groups yielded the least calcium (Ca), phosphorus (P) and Ca/P ratio, followed by EDTA groups and MTAD groups (p<0.05). QMix groups produced significantly lower dentin microhardness values and higher hardness reduction percentages than MTAD groups (p<0.05). Within the limitations of the present study, it was concluded that QMix and EDTA were superior to MTAD in smear layer removal, especially when activated by PUI and PIPS, but these agents produced more pronounced effect on dentin mineral content and microhardness than MTAD.

PMID:35880401 | DOI:10.17305/bjbms.2022.7440