Tag: statistics

Ann Clin Psychiatry. 2023 May;35(2):110-117. doi: 10.12788/acp.0110.

ABSTRACT

BACKGROUND: Transcranial magnetic stimulation (TMS) is a neuro-modulation technique for treatment-resistant major depressive disorder (MDD). Standard TMS protocols for MDD involve once-daily treatment for 6 to 9 weeks. We report a case series of an accelerated TMS protocol for outpatient MDD treatment.

METHODS: From July 2020 through January 2021, patients deemed appropriate candidates for TMS treatment were offered an accelerated TMS protocol consisting of intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex, localized by the Beam F3 method, and consisting of 5 treatments daily for 5 days. Assessment scales were obtained as part of standard clinical care.

RESULTS: A total of 19 veterans received the accelerated protocol and 17 completed treatment. Statistically significant mean reductions from baseline to end of treatment were observed across all assessment scales. Remission and response rates, as defined by changes in Montgomery-Åsberg Depression Rating Scale scores, were 47.1% and 64.7%, respectively. Treatments were well tolerated without unexpected or serious adverse events.

CONCLUSIONS: This case series details the safety and efficacy of an accelerated iTBS TMS protocol consisting of 25 treatments over 5 days. Improved depressive symptoms were observed, with remission and response rates similar to standard TMS protocols of daily TMS for ≥6 weeks.

PMID:37074971 | DOI:10.12788/acp.0110

Ann Clin Psychiatry. 2023 May;35(2):103-108. doi: 10.12788/acp.0107.

ABSTRACT

BACKGROUND: Although major depressive disorder (MDD) and bipolar depression can present with similar symptoms, biological differences exist. One difference is the possible variance in adverse effects associated with treatment. This study examined the association of cognitive impairment and delirium in patients treated with electroconvulsive therapy (ECT) plus lithium for MDD or bipolar depression.

METHODS: The Nationwide Inpatient Sample included 210 adults receiving ECT plus lithium. Descriptive statistics and a Chi-square test were used to evaluate the differences between mild cognitive impairment and drug-induced delirium for those with MDD or bipolar depression. We calculated the odds ratio (OR) for drug-induced delirium in inpatients with MDD (compared to inpatients with bipolar depression) using a binomial logistic regression model.

RESULTS: Mild cognitive impairment was observed in 9.1% of patients with MDD (n = 110), compared to 0 in bipolar depression (n = 100) (P = .002). Drug-induced delirium was more prevalent in MDD (OR 1.19; 95% CI, 1.11 to 1.30).

CONCLUSIONS: ECT plus lithium is associated with less cognitive impairment and drug-induced delirium in bipolar depression compared to MDD. This study may also support biological differences between the 2 types of depression.

PMID:37074968 | DOI:10.12788/acp.0107

Plast Reconstr Surg. 2023 Apr 20. doi: 10.1097/PRS.0000000000010567. Online ahead of print.

ABSTRACT

INTRODUCTION: The traditional design for truncal perforator flaps are ipsilateral without midline decussation. The presumed rational is to minimize the risk of distal flap necrosis. In this paper we present our experience and results contralateral truncal perforator flaps designed and raised crossing the midline.

METHODS: This retrospective analysis included 43 patients (25 men and 18 women) who underwent reconstructive surgery from 1984 to 2021 using a contralateral flap design crossing the midline in the anterior trunk and upper back. Considerations included: pathology, location, as well as the dimensions of the defect and flap. An arithmetic and weighted mean with their 95% CI was estimated to compare ipsilateral and contralateral techniques.

RESULTS: Contralateral flaps utilized included the internal mammary perforator flap (n=28) superficial superior epigastric artery (n=8), superior epigastric perforator (n=2), and the 2 nd or 9 th dorsal intercostal artery perforator flaps (n=5). All of these flaps excluding the superficial superior epigastric artery demonstrated length and coverage surface averages that were significantly greater than those traditional ipsilateral flaps. However, with the contralateral superficial superior epigastric artery, both measures were statistically similar to those traditional ipsilateral flaps.

CONCLUSIONS: The anatomic variation design suggests that trunk midline is not a barrier and that perforator flaps in these two regions may be raised on different longitudinal axes without compromising vitality.

PMID:37075277 | DOI:10.1097/PRS.0000000000010567

Inflamm Bowel Dis. 2023 Apr 19:izad059. doi: 10.1093/ibd/izad059. Online ahead of print.

ABSTRACT

BACKGROUND: Pregnancy-onset inflammatory bowel disease (PO-IBD) may pose a clinical challenge. We investigated the clinical course of PO-IBD, including time to diagnosis, medical treatment, and the impact on birth outcomes.

METHODS: All pregnancies in women with IBD at a tertiary IBD center in Denmark were identified from 2008 to 2021. Maternal and offspring outcome data, retrieved from medical records of women with new onset IBD during pregnancy, were compared with the outcomes of women with IBD diagnosed prior to pregnancy (controls). Outcomes included subtype of IBD, disease location, medical treatment, birth weight, intrauterine growth retardation (IUGR), gestational age at birth, caesarean section, stillbirth, congenital malformations, and time elapsed from onset of symptoms to diagnosis.

RESULTS: In total, 378 women contributed with 583 pregnancies. Pregnancy-onset IBD affected 34 (9.0%) women. Ulcerative colitis (UC; n = 32) was more prevalent than Chron’s disease (CD; n = 2). Birth outcomes in pregnancies affected by PO-IBD were comparable to that of the 549 controls. Women with PO-IBD received more corticosteroids and biologics following their diagnosis than did the controls (5 [14.7%] vs 2 [2.9%]; P = .07; and 14 [41.2%] vs 9 [13.2%]; P = .003, respectively). Concerning time to IBD diagnosis, there was no statistically significant difference between the 2 groups (PO-IBD, 2.5 months, interquartile range [2-6] vs controls 2 months [1-4.5]; P = .27).

CONCLUSION: Although we observed a trend towards a diagnostic delay, PO-IBD was not associated with a significantly increased time to diagnosis. Birth outcomes in women with PO-IBD were comparable to those diagnosed with IBD prior to pregnancy.

PMID:37075485 | DOI:10.1093/ibd/izad059

Inflamm Bowel Dis. 2023 Apr 19:izad063. doi: 10.1093/ibd/izad063. Online ahead of print.

ABSTRACT

BACKGROUND: Histological response to treatment is an important outcome in patients with ulcerative colitis (UC). The accuracy of biopsy-based measurements of inflammation may be limited by error imposed by natural microscopic heterogeneity on the scale of individual biopsies. We determined the magnitude of this error, its histological correlates, and the density of biopsy sampling within mucosal regions of interest required to meet specified benchmarks for accuracy.

METHODS: A total of 994 sequential 1-mm digital microscopic images (virtual biopsies) from consecutive colectomies from patients with clinically severe UC were scored by 2 pathologists. Agreement statistics for Geboes subscores and Nancy (NHI) and Robarts Histological Indices (RHI) between random samples from 1 to 10 biopsies and a reference mean score across a 2-cm region of mucosa were calculated using bootstrapping with 2500 iterations.

RESULTS: The agreement statistics improved across all indices as the biopsy density increased, with the largest proportional gains occurring with addition of the second and third biopsies. One biopsy achieved moderate to good agreement with 95% confidence for NHI and RHI corresponding to scale-specific errors of 0.40 (0.25-0.66) and 3.02 (2.08-5.36), respectively; and 3 biopsies achieved good agreement with 95% confidence corresponding to scale-specific errors of 0.22 (0.14-0.39) and 1.87 (1.19-3.25), respectively. Of the individual histological features, erosions and ulcers had the greatest impact on the agreement statistics.

CONCLUSIONS: In the setting of active colitis, up to 3 biopsy samples per region of interest may be required to overcome microscopic heterogeneity and ensure accurate histological grading.

PMID:37075483 | DOI:10.1093/ibd/izad063

Nicotine Tob Res. 2023 Apr 19:ntad057. doi: 10.1093/ntr/ntad057. Online ahead of print.

ABSTRACT

INTRODUCTION: As smoking prevalence has decreased, there has been debate about “hardening” (smokers are more resistant to established tobacco control measures) or “softening” (smokers are more responsive to interventions) of the remaining smoking population. Despite growing evidence to reject the “hardening” hypothesis, there is lack of long-term population-based studies to test this hypothesis by educational level.

AIMS AND METHODS: Repeated cross-sectional population-based surveys during 1978-2014 and in 2018 were utilized. The target population consisted of ~5000 25-64-year-old Finns annually. The data included 109 257 respondents of which 53 351 ever-smoking individuals were included in the analyses. Response rates varied between 84% and 43%. Five hardening indicators considering smoking frequency, intensity and smoking cessation were used as the dependent variables. The main independent variable was study year (time). Statistical analyses were based on regression models using restricted cubic splines by educational level.

RESULTS: Contrary to the hardening hypothesis, hardening indicators showed softening over time among all educational groups. However, educational groups differed from each other. Compared with the highly educated, the quit ratio was lower, number of cigarettes per day (CPD) was higher, the proportions of daily smokers among current smokers and heavy smokers among daily smokers were higher among the less educated.

CONCLUSIONS: In accordance with growing evidence, also the Finnish smoking population has “softened” over time. Although the change has been predominantly in the same direction for all educational groups, the rate of change has been stronger among the highly educated, highlighting the continued burden of smoking among the less educated.

IMPLICATIONS: Even though “softening” of smoking has occurred, lighter smoking also poses health risks. Therefore, tobacco control policies and cessation services should be developed and targeted to a greater extent also for people who smoke less than daily and for those who smoke fewer CPD. Furthermore, interventions should focus on special requirements of the lower educational groups to promote health equity.

PMID:37075474 | DOI:10.1093/ntr/ntad057

Hum Reprod. 2023 Apr 19:dead069. doi: 10.1093/humrep/dead069. Online ahead of print.

ABSTRACT

STUDY QUESTION: How does an altered maternal hormonal environment, such as that seen during superovulation with gonadotropins in ART, impact human uterine immune cell distribution and function during the window of implantation?

SUMMARY ANSWER: Hormonal stimulation with gonadotropins alters abundance of maternal immune cells including uterine natural killer (uNK) cells and reduces uNK cell ability to promote extravillous trophoblast (EVT) invasion.

WHAT IS KNOWN ALREADY: An altered maternal hormonal environment, seen following ART, can lead to increased risk for adverse perinatal outcomes associated with disordered placentation. Maternal immune cells play an essential role in invasion of EVTs, a process required for proper establishment of the placenta, and adverse perinatal outcomes have been associated with altered immune cell populations. How ART impacts maternal immune cells and whether this can in turn affect implantation and placentation in humans remain unknown.

STUDY DESIGN, SIZE, DURATION: A prospective cohort study was carried out between 2018 and 2021 on 51 subjects: 20 from natural cycles 8 days after LH surge; and 31 from stimulated IVF cycles 7 days after egg retrieval.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial biopsies and peripheral blood samples were collected during the window of implantation in subjects with regular menstrual cycles or undergoing superovulation. Serum estradiol and progesterone levels were measured by chemiluminescent competitive immunoassay. Immune cell populations in blood and endometrium were analyzed using flow cytometry. uNK cells were purified using fluorescence-activated cell sorting and were subjected to RNA sequencing (RNA-seq). Functional changes in uNK cells due to hormonal stimulation were evaluated using the implantation-on-a-chip (IOC) device, a novel bioengineered platform using human primary cells that mimics early processes that occur during pregnancy in a physiologically relevant manner. Unpaired t-tests, one-way ANOVA, and pairwise multiple comparison tests were used to statistically evaluate differences.

MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics were comparable for both groups. As expected, serum estradiol levels on the day of biopsy were significantly higher in stimulated (superovulated) patients (P = 0.0005). In the setting of superovulation, we found an endometrium-specific reduction in the density of bulk CD56+ uNK cells (P < 0.05), as well as in the uNK3 subpopulation (P = 0.025) specifically (CD103+ NK cells). In stimulated samples, we also found that the proportion of endometrial B cells was increased (P < 0.0001). Our findings were specific to the endometrium and not seen in peripheral blood. On the IOC device, uNK cells from naturally cycling secretory endometrium promote EVT invasion (P = 0.03). However, uNK cells from hormonally stimulated endometrium were unable to significantly promote EVT invasion, as measured by area of invasion, depth of invasion, and number of invaded EVTs by area. Bulk RNA-seq of sorted uNK cells from stimulated and unstimulated endometrium revealed changes in signaling pathways associated with immune cell trafficking/movement and inflammation.

LIMITATIONS, REASONS FOR CAUTION: Patient numbers utilized for the study were low but were enough to identify significant overall population differences in select immune cell types. With additional power and deeper immune phenotyping, we may detect additional differences in immune cell composition of blood and endometrium in the setting of hormonal stimulation. Flow cytometry was performed on targeted immune cell populations that have shown involvement in early pregnancy. A more unbiased approach might identify changes in novel maternal immune cells not investigated in this study. We performed RNA-seq only on uNK cells, which demonstrated differences in gene expression. Ovarian stimulation may also impact gene expression and function of other subsets of immune cells, as well as other cell types within the endometrium. Finally, the IOC device, while a major improvement over existing in vitro methods to study early pregnancy, does not include all possible maternal cells present during early pregnancy, which could impact functional effects seen. Immune cells other than uNK cells may impact invasion of EVTs in vitro and in vivo, though these remain to be tested.

WIDER IMPLICATIONS OF THE FINDINGS: These findings demonstrate that hormonal stimulation affects the distribution of uNK cells during the implantation window and reduces the proinvasive effects of uNK cells during early pregnancy. Our results provide a potential mechanism by which fresh IVF cycles may increase risk of disorders of placentation, previously linked to adverse perinatal outcomes.

STUDY FUNDING/COMPETING INTEREST(S): Research reported in this publication was supported by the University of Pennsylvania University Research Funding (to M.M.), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD068157 to M.M., S.S., and S.M.), National Center for Advancing Translational Sciences of the National Institutes of Health (TL1TR001880 to J.K.), the Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania, the Children’s Hospital of Philadelphia Research Institute (to S.M.G.), and the National Institute of Allergy and Infectious Diseases (K08AI151265 to S.M.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All authors declare no conflict of interest.

TRIAL REGISTRATION NUMBER: N/A.

PMID:37075311 | DOI:10.1093/humrep/dead069

J Neuroophthalmol. 2023 Apr 19. doi: 10.1097/WNO.0000000000001836. Online ahead of print.

ABSTRACT

BACKGROUND: There is modest literature regarding fellowship applicant factors that may predict future career achievement. We aim to characterize neuro-ophthalmology fellows and identify and analyze characteristics that may predict future career trajectory.

METHODS: Data, including demographic information, academic background, scholarly activities, and practice information, were collected using publicly available sources, on individuals who completed neuro-ophthalmology fellowships from 2015 to 2021. Summary statistics describing the cohort were calculated. Prefellowship characteristics were compared with postfellowship characteristics to evaluate which prefellowship characteristics may predict postfellowship academic productivity and career achievement.

RESULTS: Data were collected on 174 individuals (41.6% men, 58.4% women). Sixty-five percent were residency-trained in ophthalmology, 31% neurology, 1.7% both, and 1.7% pediatric neurology. Fifty-eight percent completed residency in the US, 8% in Canada, 32% internationally, and 2% in multiple locations. Among those practicing in the US/Canada, 63.8% practice at academic centers, 35.3% private practice, and 0.9% at both. Thirty-one percent completed additional subspecialty training and 17.8% additional graduate degrees. Completion of additional fellowship training or graduate degrees, and publication of more papers before fellowship, correlated with later academic productivity. There were no significant correlations between completion of an additional fellowship or graduate degree with current practice environment or attainment of leadership roles. There were no significant correlations between total publishing productivity prefellowship and practice environment or leadership roles postfellowship.

CONCLUSIONS: Additional graduate degrees/subspecialty training, and prefellowship academic productivity, correlated with later academic productivity among neuro-ophthalmologists, suggesting that these metrics may be helpful in predicting future academic performance among fellowship applicants.

PMID:37075283 | DOI:10.1097/WNO.0000000000001836

J Clin Oncol. 2023 Apr 19:JCO2201740. doi: 10.1200/JCO.22.01740. Online ahead of print.

ABSTRACT

PURPOSE: Although the incidence of young-onset digestive tract cancers is increasing worldwide, their risk factors remain largely unknown. We investigated the association between nonalcoholic fatty liver disease (NAFLD) and young-onset digestive tract cancers.

PATIENTS AND METHODS: This nationwide cohort study included 5,265,590 individuals age 20-39 years who underwent national health screening under the Korean National Health Insurance Service between 2009 and 2012. The fatty liver index was used as a diagnostic biomarker for NAFLD. The participants were followed up until December 2018 to determine the incidence of young-onset digestive tract cancers (ie, esophageal, stomach, colorectal, liver, pancreatic, biliary tract, and gallbladder). Multivariable Cox proportional hazards models were conducted to estimate the risk after adjusting for potential confounders.

RESULTS: During the 38.8 million person-years of follow-up, 14,565 patients were newly diagnosed with young-onset digestive tract cancers. The cumulative incidence probability of each cancer type was consistently higher in individuals with NAFLD than in those without NAFLD (all log-rank P < .05). NAFLD was associated with an increased risk of overall digestive tract (adjusted hazard ratio [aHR], 1.16; 95% CI, 1.10 to 1.22), stomach (aHR, 1.14; 95% CI, 1.06 to 1.24), colorectal (aHR, 1.14; 95% CI, 1.06 to 1.22), liver (aHR, 1.13; 95% CI, 1.12 to 1.52), pancreatic (aHR, 1.23; 95% CI, 1.09 to 1.40), biliary tract (aHR, 1.29; 95% CI, 1.00 to 1.66), and gallbladder (aHR, 1.53; 95% CI, 1.01 to 2.31) cancer. These associations remained significant regardless of age, sex, smoking status, alcohol consumption, and obesity status (all P < .05; P for interaction >.05). The aHR for esophageal cancer was 1.67 (95% CI, 0.92 to 3.03).

CONCLUSION: NAFLD may be an independent, modifiable risk factor for young-onset digestive tract cancers. Our findings suggest a crucial opportunity to reduce premature morbidity and mortality associated with young-onset digestive tract cancers in the next generation.

PMID:37075279 | DOI:10.1200/JCO.22.01740

J Chem Theory Comput. 2023 Apr 19. doi: 10.1021/acs.jctc.2c01018. Online ahead of print.

ABSTRACT

Interdependence across time and length scales is common in biology, where atomic interactions can impact larger-scale phenomenon. Such dependence is especially true for a well-known cancer signaling pathway, where the membrane-bound RAS protein binds an effector protein called RAF. To capture the driving forces that bring RAS and RAF (represented as two domains, RBD and CRD) together on the plasma membrane, simulations with the ability to calculate atomic detail while having long time and large length- scales are needed. The Multiscale Machine-Learned Modeling Infrastructure (MuMMI) is able to resolve RAS/RAF protein-membrane interactions that identify specific lipid-protein fingerprints that enhance protein orientations viable for effector binding. MuMMI is a fully automated, ensemble-based multiscale approach connecting three resolution scales: (1) the coarsest scale is a continuum model able to simulate milliseconds of time for a 1 μm² membrane, (2) the middle scale is a coarse-grained (CG) Martini bead model to explore protein-lipid interactions, and (3) the finest scale is an all-atom (AA) model capturing specific interactions between lipids and proteins. MuMMI dynamically couples adjacent scales in a pairwise manner using machine learning (ML). The dynamic coupling allows for better sampling of the refined scale from the adjacent coarse scale (forward) and on-the-fly feedback to improve the fidelity of the coarser scale from the adjacent refined scale (backward). MuMMI operates efficiently at any scale, from a few compute nodes to the largest supercomputers in the world, and is generalizable to simulate different systems. As computing resources continue to increase and multiscale methods continue to advance, fully automated multiscale simulations (like MuMMI) will be commonly used to address complex science questions.

PMID:37075065 | DOI:10.1021/acs.jctc.2c01018