Holm-Bonferroni Correction Research Articles

P214 Cine MRI assessment of colonic motility in patients with ulcerative colitis associated constipation.

Abstract Background Constipation may be a feature of ulcerative colitis (uc) especially in left sided or distal disease. UC associated constipation (UCAC) can cause significant morbidity; treatment is typically with dietary fibre changes and laxatives. Diagnosis may be challenging but adequate treatment may improve clinical outcomes. The cause is incompletely understood with few studies of motility and transit. Study populations often having heterogenous groups, with limited assessment of right sided colonic motility. Cine MRI is a novel technique that can assess pan-colonic motility. Using this technique, We aim to investigate regional colonic motility in patients with active disease and UCAC symptoms. Methods The study was performed prospectively with 30 participants at a single-centre. Disease extent was confirmed to be distal to the splenic flexure. Active disease was defined as a faecal calprotectin >250, partial Mayo score ≥ 4 (rectal bleeding score ≥ 1) or an endoscopic mayo score >1. The 3 groups comprised 10 healthy controls with no symptoms of IBS/ constipation, 11 patients with active uc with symptoms of UCAC, and 9 patients with active uc without symptoms of UCAC. UCAC subjects met American Gastroenterology Association constipation criteria. Exclusion criteria comprised the use of drugs affecting motility, concomitant GI conditions, and recent laxative use. Subjects underwent two constipation questionnaires. Subjects were fasted > 8 hours and subjects consumed 1.4 litres of 2% mannitol over 90 minutes prior to a morning MRI scan. Post drink cine MRI was not acquired until the mannitol had reached the ascending colon (AC). Images were acquired over the entire abdomen for 10 minutes and using GI Quant software®(Motilent) regional colonic motility was assessed (Figure A), generating a motility index (MI) score (range 0-1000). Kruskal-Wallis and Mann-Whitney U (with Holm-Bonferroni correction) statistics were used. Results Baseline characteristics and questionnaire scores are outlined in Figure B and MI scores in Figure C. There was no clear trend for differences in motility in the caecum or AC. In the transverse colon (TC) there was a trend to reduced MI in patients with UCAC compared to controls which was nearly significant (p=0.06). Conclusion We present a new technique for assessing regional colonic motility in patients with uc with a 10-minute scan, and offers a method to study the dysmotility that underpins UCAC. Motility appears to be reduced in the TC in patients with left sided uc and symptoms of UCAC compared to controls. Although not statistically significant this suggests hypomotility may be a contributing factor to UCAC. It suggests that stimulants/prokinetic may be more effective than change to dietary fibre in its treatment.

The Analysis of the Context of Digital Access to Healthcare in Russia

Digital accessibility is one of the key principles of modern healthcare. The Internet has become a main tool to both communicate and engage patients. This study aims to analyze adults’ preferences on health information resources and the utilization of digital healthcare tools in Russia. The data were collected from the online survey conducted in August-September 2020. The association of factors with individual preferences was analyzed using Pearson’s χ2 with Holm–Bonferroni correction. The sample included 1319 respondents’ submissions. The most prioritized activity on the Internet among all the respondents was social media 64.1% (95% CI 61.4–66.6%). Females, those who are more educated, and more active Internet users were more likely to use all available sources to gather health information. Almost one-half of the respondents (48.0%; 95% CI 45.3–50.7%) reported that they did not use any digital tools to manage their medical appointments. Smartphones were more likely to be used by younger and more active Internet users, while personal computers were prioritized as the preferable device to access the Internet by males and older adults. The study revealed that both public health authorities and health providers must provide a wider range of information and digital interaction experiences appropriate to the needs and preferences of patients.

RF26 | PMON327 Patient and Parent Characteristics Related to Quality of Life and Self-esteem in Healthy Youth Undergoing Provocative GH Testing

Abstract Background Families often seek medical care for a child's short stature due to concerns about how short stature affects psychosocial function in childhood and projected into adulthood. However, height is a poor predictor of psychosocial adjustment, and there is a critical gap in our understanding of how patient and parent characteristics alter the potential impact of being short. Hypothesis We hypothesized that among healthy youth undergoing medical evaluation for short stature, youth quality of life (QoL) and self-esteem would be associated with youth and parental characteristics rather than height. Methods Healthy youth aged 8-14 years who underwent provocative GH testing in our Growth Center and a parent participant each completed surveys at or around the time of testing. Surveys collected demographic data; youth and parent report of youth health-related QoL (PedsQL and Quality of Life in Short Stature Youth [QoLISSY]); youth reports of self-esteem (Self-Perception Profile for Children [SPP]), coping skills (Coping Strategies Inventory), and social support (Social Support Scale for Children); and parent reports of perceived environmental threats (World Out There), goals for their child (Achievement Goals), and autonomy support (Parents As Social Context Questionnaire). Clinical data were extracted from the patients’ electronic health records. Continuous variables were summarized as mean ± SD. Univariate models with Holm-Bonferroni correction of significance level 0.05 assessed the marginal effect of each factor on QoL and self-esteem outcomes. Multivariable linear regression models with stepwise selection approaches were used to identify significant predictors of QoL and self-esteem. Results Participants included 60 youth (15 female/45 male; age 11.77 ± 1.93 years; 50% prepubertal, 37% Tanner 2, 13% Tanner 3; height Z-score -2.18 ± 0.61) and their parents (55 female/5 male; age 45.65 ± 7.25 years). In multivariable regression, the youth PedsQL physical domain was associated positively with grade in school and perceived friend support. The youth PedsQL psychosocial domain was associated positively with perceived support from classmates and friends, but negatively with disengaged coping. The youth QoLISSY total score was associated positively with perceived support from classmates. Youth's global self-esteem (SPP) was associated positively with perceived classmate support and mid-parental height Z-score. Parent report of youth psychosocial QoL (PedsQL) was associated positively with perceived classmate support. None of the other analogous parent assessment outcomes were associated with the QoL or self-esteem outcomes. Neither youth height nor height Z-score was associated with any of the QoL or self-esteem outcomes. Conclusions Perceived social support and coping skills were associated with QoL and self-esteem in healthy short youth, whereas youth height was not, and constitute an important potential area of clinical intervention. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.

Hepatitis C viral load and mother-to-child transmission: A systematic review and meta-analysis.

We aim to assess the association between maternal hepatitis C virus (HCV) viral load and human immunodeficiency virus (HIV) coinfection and the risk for mother-to-child transmission (MTCT) among pregnant women infected with HCV. A literature search of the Medline, Embase, Central, Science Citation Index Expanded (SCIE), Conference Proceedings Citation Index-Science (CPCIS), Scopus, Literature Latino-Americana e do Caribe em Ciências da Saúde (LILACS), and WHO Global Index Medicus databases, from inception to June 21, 2022, was performed. Studies that reported the incidence HCV-MTCT were included. Pooled effect estimates were calculated using the random-effects model, and Holm-Bonferroni correction was performed for multiple pooled associations. The present meta-analysis included 26 studies involving 4934 newborns with maternal HCV infection. Pregnant women with HCV viremia exhibited increased risk for MTCT (odds ratio [OR] 8.25 [95% confidence interval (CI) 4.65-14.63]) compared with those negative for HCV-RNA. Multiple subgroup analysis revealed that the HCV viremia/HIV-positive group demonstrated the highest risk for HCV MTCT, followed by the HCV viremia mono-infected group, while HCV-RNA-negative women demonstrated the lowest risk for HCV MTCT. Among females with HCV viremia, elevated risk for MTCT was found among subjects with a viral load ≥6 log10 copies/mL compared with those with viral load <6 log10 copies/mL (OR 4.58 [95% CI: 2.52-8.34]). The incidence of HCV MTCT was increased among pregnant women with detectable HCV viremia and was even higher in those with a viral load ≥6 log10 copies/mL. HIV coinfection further increased the risk for HCV MTCT.

Comparison between clear aligners and 2 × 4 mechanics in the mixed dentition: a randomized clinical trial.

To compare the efficacy and efficiency between clear aligners and 2 × 4 fixed appliances for correcting maxillary incisor position irregularities in the mixed dentition. The sample comprised 32 patients from 7 to 11 years of age randomly allocated into two parallel treatment groups: the clear aligners group, 14 patients (6 girls, 8 boys) with a mean initial age of 9.33 years (standard deviation [SD] = 1.01) treated with clear aligners; and the fixed appliances group, 13 patients (9 girls, 4 boys) with a mean initial age of 9.65 years (SD = 0.80) treated with partial (2 × 4) fixed appliances. Digital models were acquired before treatment and after appliance removal. Primary outcomes were incisor irregularity index and treatment time. Secondary outcomes were arch width, perimeter, length, size and shape, incisor leveling, incisor mesiodistal angulation, plaque index, and white spot lesion formation (International Caries Detection and Assessment System index). Intergroup comparisons were evaluated using t-tests or Mann-Whitney U-tests with Holm-Bonferroni correction (P < .05). Treatment time was approximately 8 months in both groups. No intergroup differences were observed for changes in any of the variables. Similar posttreatment arch shapes were observed in both groups. Clear aligners and 2 × 4 mechanics displayed similar efficacy and efficiency for maxillary incisor position corrections in the mixed dentition. The choice of appliance should be guided by clinician and family preference.

Prosthesis accuracy of fit on 3D-printed casts versus stone casts: A comparative study in the anterior maxilla.

To compare in vitro the accuracy of fit of a reference prosthesis seated on three-dimensional (3D) printed casts generated from digital implant scans vs stone casts made by conventional implant impressions. A partially edentulous maxillary master cast with two internal connection implants was generated, while a reference implant-supported prosthesis was fabricated. Conventional splinted open-tray impressions were taken to create stone casts (n= 10) (control group). A digital scan was taken of the master cast using a white light intraoral optical scanner (IOS) (TRIOS, 3Shape), and a Standard Tessellation Language (STL) file was obtained. Four 3D printers were used to print the casts (n= 10 from each 3D printer): Straumann® P30+, Varseo S, Form 3b+and M2 Carbon. Accuracy of fit of the reference prosthesis on all control and test casts was assessed using the screw resistance test and radiographic test. Additionally, all casts were digitized using the same IOS, and the STL files were superimposed to the master cast STL file (reference) to evaluate the 3D accuracy with inspection Geomagic Control software using the root-mean-square (RMS) error. The reference prosthesis presented with clinically acceptable fit on all casts. The highest median RMS error was found in the stone cast group (94.6μm) while the lowest median was in the M2 Carbon group (46.9μm). The Kruskal-Wallis test revealed a statistically significant difference between the groups (p< 0.001). For post hoc comparisons, Dunn's test with the Holm-Bonferroni correction resulted in a statistically significant difference in four tests, with M2 Carbon exhibiting lower RMS error than the stone cast (p < 0.001) and P30+ (p < 0.001) groups, Form 3b exhibiting lower RMS error than the stone cast (p < 0.001) group, and Varseo S exhibiting lower RMS error than the stone cast (p=0.006) group. Using the screw-resistance test and radiographic assessment, the reference prosthesis fit presented with clinically acceptable accuracy of fit on all casts. Printed casts from 3 different printers demonstrated statistically significant lower 3D deviations than stone casts generated using a conventional implant impression for the present partially edentulous scenario with two implants, but this did not affect prosthesis fit. Even though there were 3D deviations between the master cast and all control and test casts generated from conventional impressions and digital scans respectively, the reference prosthesis presented with accurate fit on all casts. This indicates that there is a threshold for clinically acceptable accuracy of fit and that 3D-printed casts may be used as definitive master casts to fabricate implant-supported fixed dental prostheses for the partially edentulous anterior maxilla.

Does the Number of Levels of Decompression Have an Impact on the Clinical Outcomes of Patients With Lumbar Degenerative Spondylolisthesis: A Retrospective Study in Single-Level Fused Patients.

IntroductionThe American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) 2014 lumbar fusion guidelines for stenosis with degenerative spondylolisthesis (DS) support surgical decompression and fusion as an effective treatment option for symptomatic stenosis associated with DS. The association between the number of levels decompressed in patients with single-level fusion and clinical outcomes has never been published.MethodsA retrospective analysis of a single-center, prospectively collected database was performed on 77 patients to compare the effect of the number of decompression levels in patients that received single-level fusion surgery. A total of 77 patients met the criteria. Group one had one level decompressed, group two had two levels decompressed, and group three had three or four levels decompressed. All patients received lumbar fusion surgery at a single spinal level. Outcomes at six months included: Substantial Clinical Benefit (SCB) (ΔODI ≥ 10 points); Minimal Clinically Important Difference (MCID) (ΔODI ≥ 5); no MCID (ΔODI <5 points). Student's t-tests, one-way analysis of variance (ANOVA), and post hoc comparison using unpaired two-tailed student's t-test with Holm-Bonferroni correction were performed. p -values were ranked from smallest to largest, and alpha level adjustments were made. ResultsA sub-analysis of each group's clinical outcomes showed that patients with two levels decompressed reached greater clinical outcomes. SCB was obtained by approximately 60% (group one: 12.5% vs. group three: 40%) of the patients. A total of 77.6% (38/49) achieved MCID (group one: 62.5% vs. group three: 55%). Single-level fused patients with two levels of decompression showed an improvement of 48% from baseline ODI, as opposed to group one: 17.85% and group three: 21.1%. Patients belonging to group two showed the lowest rate of no improvement. Baseline ODI scores were similar upon presentation (p=0.46), and the difference was found among groups after six months of follow-up (p=0.009). Post hoc comparison showed statistical significance in the comparison between group two and group three (p=0.009, alpha value: 0.017).ConclusionThe addition of more than two levels of decompression to single-level fused patients might be associated with poor clinical outcomes and spinal instability.

832-P: Five-Year Weight and Glycemic Outcomes following a Very-Low-Carbohydrate Intervention Including Nutritional Ketosis in Patients with Type 2 Diabetes

Objective: We previously reported long term effectiveness of a very low carbohydrate intervention including nutritional ketosis (VLCI) delivered via continuous remote care (CRC) for improving weight and glycemia at 2 years in people with type 2 diabetes (T2D) . We assessed 5-year changes to determine if the intervention is sustainable, durable, and effective over a longer period of time. Research Design and Methods: Patients with T2D who were initially enrolled in a 2 year non-randomized, controlled clinical trial received a CRC emphasizing a VLCI. These patients were offered to continue for an additional 3 years of prospective follow-up. Of the 200 patients completing 2 years, 169 (84.5%) patients consented to the extension and 122 (72.2%) were retained at 5 years. Among those who extended, baseline versus 5 year differences in weight and glycemic outcomes were assessed using linear mixed effects models in an intent-to-treat analysis. P-values were adjusted using Holm-Bonferroni correction. Results: At five years, there were persistent improvements in weight from 116.4 to 107.6 kg (-8.8 kg, 95%CI [-11.0, -6.6]) , fasting insulin from 25.8 to 24.5 mIU/L (-7.9 mIU/L, 95%CI [-10.0, -5.8]) , and HOMA-IR from 9.1 to 6.6 (-2.5, 95%CI [-3.5, -1.5]) (all adjusted p-values &amp;lt;0.05) . Total diabetes medications were reduced 46.6%, and 59.9% excluding metformin were deprescribed. The percent of patients prescribed diabetes medications significantly decreased at 5 years (from 85.2% to 71.3%; p&amp;lt;0.01) , including patients taking sulfonylureas (from 27.0% to 4.9%) , insulin (from 26.2% to 13.1%) , and SGLT2i (from 10.7% to 2.5%) . Despite less medication use, HbA1c improved from 7.5 to 7.2% (-0.3%, 95%CI [-0.6, 0.0], unadjusted p-value&amp;lt;0.05) . Conclusions: Over 5 years follow-up, the VLCI with CRC showed excellent retention, sustained clinically significant weight loss, and stable glycemic control with reduced dependency on antidiabetes medications. Disclosure S.J.Athinarayanan: Employee; Virta Health Corp. S.Phinney: Employee; Virta Health Corp. M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.Hallberg: Advisory Panel; Atkins Nutritionals Inc., Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. C.G.P.Roberts: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. B.M.Volk: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.N.Adams: Employee; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp. J.Volek: Advisory Panel; Abbott Diagnostics, Simply Good Foods, Stock/Shareholder; Virta Health Corp.

29-OR: Impact of Carbohydrate-Restricted Nutrition Therapy Delivered via Continuous Remote Care on Metabolic Markers in Veterans with Type 2 Diabetes: A Nationwide, Real-World Study

Type 2 Diabetes (T2D) affects one in four Veterans and often occurs with dyslipidemia, chronic kidney disease, and nonalcoholic fatty liver disease (NAFLD) . In a pilot program, the Veterans Health Administration partnered with Virta Health to provide carbohydrate restricted nutrition therapy via continuous remote care to Veterans to reverse T2D by reducing glucose and dependence on medication, as demonstrated in prior research. This retrospective analysis assessed the 1- and 2-year effects on lipids and renal and hepatic markers in a real-world sample of Veterans with T2D using medical record data. Changes in metabolic markers from enrollment to 1- and 2-years (E, 1y, 2y) were assessed with paired t-tests with Holm-Bonferroni correction for multiple comparisons. Veterans retained at least two years at time of analysis were included (n=254, 58.5% of 434 eligible enrolled, 60±8 years, 12% female) . HDL-C (E: 42±16, 1y: 46±12, 2y: 44±11 mg/dl; ps&amp;lt;0.001) and triglycerides (E: 205±168, 1y: 186±184, 2y: 160±119 mg/dl; 2y p&amp;lt;0.05) improved. Total cholesterol (E: 165±46 mg/dl) and nonHDL-C (E: 124±46 mg/dl) were unchanged. Serum creatinine (E: 1.0±0.3 mg/dl) and eGFR (E: 85±18 ml/min/1.73m2) were stable; BUN increased (E: 17.3±6.1; 1y: 19.6±8.4, 2y: 18.9±7.6 mg/dl, ps&amp;lt;0.05) but remained within normal limits. Liver enzymes (ALP at E: 77.8±24.6 U/L; ALT at E: 32.3±17.1 U/L) were within normal limits and unchanged except AST decreased (E: 26.6±14.1, 1y: 21.7±8.7, 2y: 21.8±9.3 U/L, 2y p&amp;lt;0.05) . Veterans with T2D who underwent two years of diabetes reversal treatment improved atherogenic dyslipidemia and AST with no adverse effects on other markers of NAFLD and renal function, suggesting long term broad metabolic health benefit of this care model in the real world. Disclosure M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp.

Differences in Blood Flow Patterns and Endothelial Shear Stress at the Carotid Artery Using Different Exercise Modalities and Intensities.

Endothelial dysfunction is the first pathophysiological step of atherosclerosis, which is responsible for 90% of strokes. Exercise programs aim to reduce the risk of developing stroke; however, the majority of the beneficial factors of exercise are still unknown. Endothelial shear stress (ESS) is associated with endothelial homeostasis. Unfortunately, ESS has not been characterized during different exercise modalities and intensities in the carotid artery. Therefore, the purpose of this study was to determine exercise-induced blood flow patterns in the carotid artery. Fourteen apparently healthy young adults (males = 7, females = 7) were recruited for this repeated measures study design. Participants completed maximal oxygen consumption (VO2max) tests on a Treadmill, Cycle-ergometer, and Arm-ergometer, and 1-repetition maximum (1RM) tests of the Squat, Bench Press (Bench), and Biceps Curl (Biceps) on separate days. Thereafter, participants performed each exercise at 3 different exercise intensities (low, moderate, high) while a real-time ultrasound image and blood flow of the carotid artery was obtained. Blood flow patterns were assessed by estimating ESS via Womersley’s estimation and turbulence via Reynold’s number (Re). Data were analyzed using a linear mixed-effects model. Pairwise comparisons with Holm-Bonferroni correction were conducted with Hedge’s g effect size to determine the magnitude of the difference. There was a main effect of intensity, exercise modality, and intensity * exercise modality interaction on both ESS (p < 0.001). Treadmill at a high intensity yielded the greatest ESS when compared to the other exercise modalities and intensities, while Bench Press and Biceps curls yielded the least ESS. All exercise intensities across all modalities resulted in turbulent blood flow. Clinicians must take into consideration how different exercise modalities and intensities affect ESS and Re of the carotid artery.

School-age outcomes in patients with unilateral coronal synostosis: comparison of fronto-orbital advancement and endoscopic strip craniectomy.

Outcomes research on unilateral coronal synostosis is mostly limited to the early postoperative period. This study examines facial asymmetry, desire for revision, and patient-reported outcomes at school age in children who received either endoscopic strip craniectomy with helmet therapy or fronto-orbital advancement (open repair). Patients with repaired unilateral coronal synostosis born between 2000 and 2017, with 3D photographs taken when they were between 3.5 and 8 years of age, were eligible for study inclusion. Three pairs of bilateral linear measurements and two angular measurements were taken. Parent- and physician-reported desire for revision and patient-reported outcomes (Patient-Reported Outcomes Measurement Information System cognitive function and Quality of Life in Neurological Disorders stigma scores) were collected from patient charts. Thirty-five patients qualified, including 25 with open repair and 10 with endoscopic repair. The median patient ages at repair were 3 months and 8 months in the endoscopic and open groups, respectively. The average ages at final 3D photography were 5.8 years and 5.5 years in the endoscopic and open groups, respectively. Digital anthropometry revealed no significant differences in measures of facial asymmetry between the repair groups (p ≥ 0.211). Midface depth (tragion to subnasale) was significantly less symmetric at school age than other linear measures (F(2,102) = 9.14, p < 0.001). Forehead asymmetry was significantly associated with parent- and physician-reported desire for revision (p ≤ 0.006). No significant associations were found between physical asymmetry and patient-reported stigma or cognitive function (p > 0.046, Holm-Bonferroni correction). Children who underwent open or endoscopic repair for unilateral coronal synostosis have comparable facial symmetry at school age, but midface depth remains highly asymmetrical in both groups. Forehead asymmetry at school age correlates with parent- and physician-reported desire for revision.

Rapid Adjustments to Autonomic Control of Cardiac Rhythm at the Onset of Exercise in Healthy Young Adults

Changes in sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) influences on cardiac rhythm during exercise can be reflected in time‐ and frequency‐based heart rate variability (HRV) analysis and differ depending on exercise intensity. However, the SNS and PNS contributions to cardiac rhythm at the onset of exercise has not been investigated due to the complexity of applying HRV analysis during short durations of exercise. Continuous wavelet transform (CWT) combines time‐ and frequency‐based analyses to allow autonomic influences on beat‐to‐beat fluctuations in R‐R intervals (RRI) to be captured in rapidly changing signals, such as at the onset of exercise. Therefore, the objective of this study was to characterize the rapid autonomic adjustments influencing cardiac rhythm at the onset of exercise in healthy young adults. This study was a secondary analysis of data previously collected from 14 healthy young adults (26 ± 2 years, 6 male/8 female) during two trials: a 5‐minute baseline followed by performance of isometric, right‐calf exercise at 70% maximal voluntary contraction (MVC) for 30 seconds (70% MVC) or continued rest (0% trial). Heart rate was continuously measured using a three‐lead electrocardiogram from which RRIs were derived. Analysis involved applying CWT to the RRI data using low‐frequency (LF; 0.04‐0.15 Hz) and high‐frequency (HF; 0.15‐0.4 Hz) bands for HRV analysis. Log‐transformed absolute (aLF, aHF) and normalized (nLF, nHF) LF and HF time‐frequency bands and their ratio (LF/HF) were calculated for each time period (one baseline time period – 0‐30 seconds, and six rest/exercise time periods – 300‐305, 305‐310, 310‐315, 315‐320, 320‐325, and 325‐330 seconds) in each trial (0% and 70% MVC). Group means and standard deviations for all five variables were calculated for each time period in each trial. Statistical analysis involved two‐way repeated measures analysis of variance with post hoc analysis involving paired t tests and a Holm‐Bonferroni correction with statistical significance set at P &lt; 0.05. It was hypothesized that the SNS influence on cardiac rhythm, measured by LF and LF/HF, would increase while the PNS influence on cardiac rhythm, measured by HF, would decrease at the onset of exercise in healthy young adults. There was a significant trial‐time interaction for aHF, aLF, and LF/HF (P &lt; 0.001, P = 0.003, and P = 0.027, respectively). aHF was lower during 5‐30 seconds (all P ≤ 0.025), aLF was lower during 20‐30 seconds (all P ≤ 0.011), and LF/HF was higher during 5‐20 seconds (all P ≤ 0.045) following the start of exercise in the 70% MVC trial compared to the 0% trial. There were significant effects of trial for aHF, nLF, nHF, and LF/HF (all P ≤ 0.014) and time for aHF and LF/HF (all P ≤ 0.011). These results indicate that the reduction of the PNS influence on cardiac rhythm begins sooner than the augmentation of the SNS influence on cardiac rhythm at the onset of exercise in healthy young adults.

An extended amygdala-midbrain circuit controlling cocaine withdrawal-induced anxiety and reinstatement.

SUMMARYAlthough midbrain dopamine (DA) circuits are central to motivated behaviors, our knowledge of how experience modifies these circuits to facilitate subsequent behavioral adaptations is limited. Here we demonstrate the selective role of a ventral tegmental area DA projection to the amygdala (VTADA→amygdala) for cocaine-induced anxiety but not cocaine reward or sensitization. Our rabies virus-mediated circuit mapping approach reveals a persistent elevation in spontaneous and task-related activity of inhibitory GABAergic cells from the bed nucleus of the stria terminalis (BNST) and downstream VTADA→amygdala cells that can be detected even after a single cocaine exposure. Activity in BNSTGABA→midbrain cells is related to cocaine-induced anxiety but not reward or sensitization, and silencing this projection prevents development of anxiety during protracted withdrawal after cocaine administration. Finally, we observe that VTADA→amygdala cells are strongly activated after a challenge exposure to cocaine and that activity in these cells is necessary and sufficient for reinstatement of cocaine place preference.

Google Trends as a Predictive Tool for COVID-19 Vaccinations in Italy: Retrospective Infodemiological Analysis.

BackgroundGoogle Trends is an infoveillance tool widely used by the scientific community to investigate different user behaviors related to COVID-19. However, several limitations regarding its adoption are reported in the literature.ObjectiveThis paper aims to provide an effective and efficient approach to investigating vaccine adherence against COVID-19 via Google Trends.MethodsThrough the cross-correlational analysis of well-targeted hypotheses, we investigate the predictive capacity of web searches related to COVID-19 toward vaccinations in Italy from November 2020 to November 2021. The keyword “vaccine reservation” query (VRQ) was chosen as it reflects a real intention of being vaccinated (V). Furthermore, the impact of the second most read Italian newspaper (vaccine-related headlines [VRH]) on vaccine-related web searches was investigated to evaluate the role of the mass media as a confounding factor. Fisher r-to-z transformation (z) and percentage difference (δ) were used to compare Spearman coefficients. A regression model V=f(VRH, VRQ) was built to validate the results found. The Holm-Bonferroni correction was adopted (P*). SEs are reported.ResultsSimple and generic keywords are more likely to identify the actual web interest in COVID-19 vaccines than specific and elaborated keywords. Cross-correlations between VRQ and V were very strong and significant (min r²=0.460, P*<.001, lag 0 weeks; max r²=0.903, P*<.001, lag 6 weeks). The remaining cross-correlations have been markedly lower (δ>55.8%; z>5.8; P*<.001). The regression model confirmed the greater significance of VRQ versus VRH (P*<.001 vs P=.03, P*=.29).ConclusionsThis research provides preliminary evidence in favor of using Google Trends as a surveillance and prediction tool for vaccine adherence against COVID-19 in Italy. Further research is needed to establish the appropriate use and limits of Google Trends for vaccination tracking. However, these findings prove that the search for suitable keywords is a fundamental step to reduce confounding factors. Additionally, targeting hypotheses helps diminish the likelihood of spurious correlations. It is recommended that Google Trends be leveraged as a complementary infoveillance tool by government agencies to monitor and predict vaccine adherence in this and future crises by following the methods proposed in this paper.

Structure of Hypomanic Symptoms in Adolescents With Bipolar Disorders: A Network Approach.

BackgroundBipolar disorders (BD) are severe mental illnesses that are often misdiagnosed or under-diagnosed. The self-report 33-item Hypomania Checklist (HCL-33) and the 33-item Hypomania Checklist – external assessment (HCL-33-EA) are well-validated scales for BD symptom detection. This study compared the network structure, central symptoms, and network stability of hypomanic symptoms measured by the HCL-33 vs. the HCL-33-EA.MethodsThis cross-sectional study was conducted from January to December 2019. Adolescents (aged between 12 and 18 years) with BD were recruited from the outpatient department of Child Psychiatry, First Affiliated Hospital of Zhengzhou University. All participants were asked to complete the HCL-33, and their caregivers completed the HCL-33-EA. Network analyses were conducted.ResultsA total of 215 adolescents with BD and their family caregivers were recruited. Node HCL17 (“talk more,” node strength = 4.044) was the most central symptom in the HCL-33 network, followed by node HCL2 (“more energetic,” node strength = 3.822), and HCL18 (“think faster,” node strength = 3.801). For the HCL-33-EA network model, node HCL27 (“more optimistic,” node strength = 3.867) was the most central node, followed by node HCL18 (“think faster,” node strength = 3.077), and HCL17 (“talk more,” node strength = 2.998). In the network comparison test, there was no significant difference at the levels of network structure (M = 0.946, P = 0.931), global strength (S: 5.174, P = 0.274), or each specific edge (all P’s > 0.05 after Holm–Bonferroni corrections) between HCL-33 and HCL-33-EA items. Network stabilities for both models were acceptable.ConclusionThe nodes “talk more” and “think faster” acted as central symptoms in BD symptom network models based on the HCL-33 and HCL-33-EA. Although the most prominent central symptom differed between the two models (“talk more” in HCL-33 vs. “more optimistic” in HCL-33-EA model), networks based on each measure were highly similar and underscored similarities in BD symptom relations perceived by adolescents and their caregivers. This research provides foundations for future studies with larger sample sizes toward improving the accuracy and robustness of observed network structures.

Is memory impaired in narcolepsy type 1?

Memory deficits in narcolepsy with cataplexy type 1 (NT1) have been poorly studied, and the results are controversial. Patients with NT1 usually report memory deficits, which are not seen in objective memory assessments. This study aimed to assess attention and memory processes in NT1 patients using standardised neuropsychological tests and to compare the results with a control group. Performance in memory and attention tests was studied in 12 NT1 patients (diagnosed according to ICSD-3 criteria) and the results compared with those of 14 control subjects. All participants completed questionnaires on sleepiness and depression symptoms. Significant differences were found in the depression symptoms questionnaire. Regarding neuropsychological assessment, NT1 patients performed worse in attention than the control group in that they processed fewer stimuli and achieved fewer correct stimuli. However, no significant differences were found in the memory test results, and the performance was similar between both groups. After application of the Holm-Bonferroni correction, the only differences that remained significant were those in the ESS and in BDI-II scores. Our results showed that memory processes are preserved in NT1 patients and that memory complaints may not be associated with an objective memory deficit. In addition, the significant difference observed for patients in the depression questionnaire could explain the subjective memory complaints.

An Exploration of Self-Reported Sleep Inertia Symptoms Using Network Analysis.

PurposeSleep inertia (SI) is the transitional state accompanied by compromised cognitive and physical performance and sleepiness. Network analysis offers a potential new framework to conceptualize a complex network of symptom–symptom interactions, and the network structure is analyzed to reveal the core characteristics. However, no previous study examined the network structure of SI symptoms. Thus, this study aimed to elucidate characteristics and compare sex differences of SI symptom networks in the general population.Materials and MethodsA total of 1491 participants from China were recruited from 30 May to 17 June, 2021. SI symptoms were assessed by using the Sleep Inertia Questionnaire (SIQ). The network structures were estimated and compared using network analytic methods in the R version 4.1.1.ResultsCentrality properties analysis of the expected influence suggested that symptoms of “Feel sleepy”, “Groggy, fuzzy or hazy mind”, and “Dread starting your day” exerted greatest influences. The weighted adjacency matrix revealed that the “Dread starting your day” and “Anxious about the upcoming day” edge showed the strongest connection (edge weight value = 0.70). The network comparison test found no significant difference in network global strength (p=0.928), distribution of edge weights (p=0.194) and individual edge weights (all p values >0.05 after Holm–Bonferroni corrections) between males and females.ConclusionSymptoms of “Feel sleepy”, “Groggy, fuzzy or hazy mind”, and “Dread starting your day” were central in the SI symptom network. Intervention, such as the artificial dawn and change in body temperature, for symptoms of “Feel sleepy”, “Groggy, fuzzy or hazy mind”, and “Dread starting your day” might be crucial to hasten the dissipation of SI in the general population who may need to perform tasks upon waking.

PET/CT imaging of spinal inflammation and microcalcification in patients with low back pain: A pilot study on the quantification by artificial intelligence-based segmentation.

BackgroundCurrent imaging modalities are often incapable of identifying nociceptive sources of low back pain (LBP). We aimed to characterize these by means of positron emission tomography/computed tomography (PET/CT) of the lumbar spine region applying tracers 18F‐fluorodeoxyglucose (FDG) and 18F‐sodium fluoride (NaF) targeting inflammation and active microcalcification, respectively.MethodsUsing artificial intelligence (AI)‐based quantification, we compared PET findings in two sex‐ and age‐matched groups, a case group of seven males and five females, mean age 45 ± 14 years, with ongoing LBP and a similar control group of 12 pain‐free individuals. PET/CT scans were segmented into three distinct volumes of interest (VOIs): lumbar vertebral bodies, facet joints and intervertebral discs. Maximum, mean and total standardized uptake values (SUVmax, SUVmean and SUVtotal) for FDG and NaF uptake in the 3 VOIs were measured and compared between groups. Holm–Bonferroni correction was applied to adjust for multiple testing.ResultsFDG uptake was slightly higher in most locations of the LBP group including higher SUVmean in the intervertebral discs (0.96 ± 0.34 vs. 0.69 ± 0.15). All NaF uptake values were higher in cases, including higher SUVmax in the intervertebral discs (11.63 ± 3.29 vs. 9.45 ± 1.32) and facet joints (14.98 ± 6.55 vs. 10.60 ± 2.97).ConclusionObserved intergroup differences suggest acute inflammation and microcalcification as possible nociceptive causes of LBP. AI‐based quantification of relevant lumbar VOIs in PET/CT scans of LBP patients and controls appears to be feasible. These promising, early findings warrant further investigation and confirmation.

Measuring timely geographical access to surgical care in India: a geospatial modelling study

BackgroundIn 2015, the Lancet Commission on Global Surgery proposed timely access to surgical care facilities as an indicator of preparedness in surgical systems. Since then, several African and South American countries have mapped the population coverage for their surgical facilities. However, these estimates are missing for India, despite its large population, geographical scope, and sociodemographic diversity. We conducted a nationwide analysis of timely access to surgical care in India and point to rural–urban disparities. MethodsWe extracted a nationwide dataset of 20 802 geolocated surgical care facilities from the IndoHealMap project. We obtained accessibility motorised friction surface raster data cropped for India from the Malaria Atlas Project Explorer. We calculated the travel times from each grid cell (equivalent to 1 km2) in India to its nearest surgical facility under the optimal speed estimation by means of the Djikstra least-cost algorithm. District-level and state-level rural and urban populations were estimated through raster-based analysis via data from WorldPop, Urban-Rural Catchment Areas, and GADM version 3.6. The primary endpoint of the analysis was the proportion of population within 2 h of their nearest surgical care facility at national, state, and district levels. Wilcoxon tests adjusted for multiple comparisons (Holm-Bonferroni correction) were used to investigate rural-urban differences at a 5% significance level. FindingsThe motorised travel-times distribution is highly right-skewed, depicting that a large number of areas in India were within 2 h of their nearest surgical facility. At the national level, 99·2% of the rural population had timely access to surgical care facilities, compared with 99·8% of the urban population. However, less than 80% of the rural population in the northern and northeast regions had timely access to care. The rural regions had a significantly smaller proportion of residents with timely access to surgical care compared with their and urban counterparts at the district level (n=1299, effect size=0·57; p<0·001) and state level (n=71, effect size=0·51; p<0·001) analyses. InterpretationOur findings should be considered upper-bound estimates for geographical access because they assume readily available motorised transport and optimal travel speeds, which might not always be the case. These first-ever estimates can inform India's National Surgical, Obstetric, and Anesthesia Plan and which locations should be focused on for upcoming surgical facilities. FundingNo funding to declare.

Metal artifact reduction in computed tomography: Is it of benefit in evaluating sacroiliac joint fusion?

PurposeThe aim of this study was to compare image quality of computed tomography (CT) images with and without orthopedic metal artifact reduction (O-MAR) in the follow-up of patients after sacroiliac (SI) joint fusion. MethodsThirty-six consecutive patients (31 females and 5 males) undergoing CT within 24 h after SI joint fusion were included. CT images were reconstructed with and without O-MAR and scored by two radiologists with over 20 years of experience using a six-point ordinal scale. Images were scored on overall image quality and five criteria that are important to the clinician for the follow-up of patients after SI joint fusion. In addition, images were scored on how well four bony structures could be delineated. Wilcoxon signed-ranks tests with Holm-Bonferroni correction were used to test for differences between the radiologists’ scores on CT images with and without O-MAR. ResultsBoth radiologists scored overall image quality significantly higher (p < 0.05) on the images without O-MAR than on the images with O-MAR. In addition, two of the follow-up criteria, delineation of the sacrum and delineation of the implanted ilium were scored significantly higher (p < 0.05) on the images without O-MAR. Neither radiologist scored the images with O-MAR significantly higher than the images without O-MAR for any of the criteria. ConclusionCT imaging without O-MAR provided higher image quality and better assessment of SI joint fusion follow-up criteria compared to CT imaging with O-MAR in the follow-up of patients after SI joint fusion.