Duration Of Episodes Research Articles

Prevalence of insulin resistance and its associated factors in drug-naïve patients with bipolar disorder among Han Chinese population

BackgroundMetabolic syndrome (Mets) is commonly seen in bipolar disorder (BD). As the key component and early biological index of Mets, insulin resistance (IR) among BD has received more and more attention. However, little is known about the prevalence of IR and its associated factors in drug-naïve patients with (BD), especially among Han Chinese population.MethodsA cross-sectional study was conducted on 125 drug-naïve patients with bipolar disorder (BD) and 85 healthy controls (HC). The Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated, and IR was defined as HOMA-IR greater than the 75th percentile value for health controls (2.35). Clinical characteristics of BD were collected through semi-structural interview performed by a trained interviewer with background of psychiatric education.ResultsAmong the measured anthropocentric variables including BMI, waist circumference, abdomen circumference, hipline, and hip-waist ratio, waist circumference was found to be the most closely related to IR (0R = 1.070, 95%CI = 1.031–1.110, P < 0.001). Male was another factor that was associated with IR (OR = 2.281, 95%CI = 1.107–4.702, P = 0.025). After adjusted for gender and waist circumference, the risk of IR was significantly higher in bipolar disorder than in healthy controls (OR = 2.66, 95%CI = 1.364–5.214, P = 0.004). No significant association was found between IR and any of the observed physical and mental comorbidities, any characteristic of illness course including age onset, number of mixed episodes, types of current state, duration of current episode, duration of illness course, rapid cycling, number of mood episodes, and subgroup of BD. Hypersomnia was the only symptomatic feature that was significantly associated with IR (OR = 0.316, 95%CI = 0.124–0.803, P = 0.016).ConclusionsBipolar disorder increases two-to-three-fold risk of IR, both circumference and male are the risk factors of IR but hypersomnia act as a protective factor.

Sympathetic toggled paroxysmal atrial fibrillation and recurrent premature atrial contractions in ambulatory patients

BackgroundAutonomic nerve activity is important in the mechanisms of paroxysmal atrial fibrillation (PAF). ObjectiveThe purpose of this study was to test the hypothesis that a single burst of skin sympathetic nerve activity (SKNA) can toggle on and off PAF or premature atrial contraction (PAC) clusters. MethodsSimultaneous recording of SKNA and electrocardiogram (neuECG) recording was performed over 7 days in patients with PAF. ResultsIn study 1, 8 patients (7 men and 1 woman; age 62 ± 8 years) had 124 episodes of PAF. An SKNA burst toggled both on and off PAF in 8 episodes (6.5%) (type 1), toggled on but not off in 12 episodes (9.7%) (type 2), and toggled on a PAC cluster followed by PAF in 4 episodes (3.2%) (type 3). The duration of these PAF episodes was <10 minutes. The remaining 100 episodes (80.6%) were associated with active SKNA bursts throughout PAF (type 4) and lasted longer than type 1 (P = .0185) and type 2 (P = .0027) PAF. There were 47 PAC clusters. Among them, 24 (51.1%) were toggled on and off, and 23 (48.9%) were toggled on but not off by an SKNA burst. In study 2, 17 patients (9 men and 8 women; age 58 ± 12 years) had <10 minutes of PAF (4, 8, 0, and 31 of types 1, 2, 3, and 4, respectively). There were significant circadian variations of all types of PAF. ConclusionA single SKNA burst can toggle short-duration PAF and PAC cluster episodes on and off. The absence of continued SKNA after the onset might have affected the maintenance of these arrhythmias.

Relationship between sense of coherence and depression, a network analysis

The “sense of coherence” incorporates the notion that when life seems comprehensive, manageable, and meaningful for an individual, even under tremendous adversity, this accounts for stamina and confidence. Its absence is associated with mental health problems, including depression. The current analysis aimed to explore the relationship between the sense of coherence and depression through a network analysis approach in a sample of 181 people with depression. The mean age of the individuals in the sample was 35.59 (11.50) years, and 76.8% were females (n = 139). All participants had at least one previous depressive episode; the duration of the current episode was 30.30 (77.30) days. Sense of coherence was assessed using the 13-item Sense of Coherence Scale (SOC-13). The severity of depression was quantified with the Beck Depression Inventory (BDI-I). The correlations between the two scales, three networks (i.e., SOC-13; BDI-I and joint SOC-13/BDI-I), and their centrality indices were calculated. The mean SOC-13 was 40.56 ± 9.99, and the mean BDI-I was 49.90 ± 9.26. There was a strong correlation-concordance (− 0.65; 95% CI: − 0.72 to − 0.55) index between the two scales. We identified detailed relationship dynamics between symptoms, clusters, and domains through the novel network analysis approach. The analysis of SOC-13 nodes revealed the pivotal role of social relationships in the network. However, in the depression network, we found a role for affection (in contrast to neglect) and joy (as opposed to boredom). In conclusion, solid and sustainable personal relationships in distress and adversity stand against the burden of depression.

Clinical Outcomes in Patients With Benign Paroxysmal Positional Vertigo and Vitamin D Deficiency: A Singaporean Perspective.

Benign paroxysmal positional vertigo (BPPV) is the primary vestibular disorder causing peripheral vertigo. Given the role of vitamin D in maintaining otoconia homeostasis, its deficiency may elevate the risk of BPPV. Our study seeks to evaluate the correlation between vitamin D deficiency and clinical outcomes of patients with BPPV in the local Asian population. We performed a retrospective analysis of 149 consecutive adult patients referred to a tertiary center's Otolaryngology dizziness clinic between 2018 and 2021. All of these patients had both BPPV and vitamin D deficiency. The mean serum vitamin D level was 19.4 ± 5.5 ng/mol. Approximately 51.7% (77/149) of patients experienced recurrent episodes of BPPV. Univariate Chi-square analyses demonstrated vitamin D levels (P < 0.001) and history of migraine (P= 0.04) were related to BPPV recurrence. On multivariate analyses, patients with higher serum vitamin D levels were 16.7% less likely to develop recurrent BPPV (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.76-0.90, P< 0.001). However, migraine history was not significantly related to BPPV recurrence (OR 0.38, 95% CI 0.14-1.00, P= 0.050). There was no statistically significant difference in the duration of BPPV episodes based on vitamin D levels (P = 0.327). Patients with vitamin D deficiency are at higher risk of recurrent BPPV. Future research directions that would be beneficial include conducting a randomized controlled trial to evaluate both the effectiveness of vitamin D supplementation and its optimal dosage.

Contingency management for substance use disorders in the U.S. Veterans Health Administration: 2018–2022

Introduction: Contingency management (CM) is one of the most effective interventions for substance use disorders (SUDs), including stimulant use disorder. In the United States, the Veterans Health Administration (VHA) led the largest-scale rollout of CM in the US to date, but little is known about characteristics of patients treated and CM clinical practices.Methods: In this retrospective cohort study, we used VHA electronic health records data to descriptively examine CM treatment course (e.g., number of visits, time between visits, duration of treatment episode) and characteristics of patients receiving CM for SUDs from 2018 to 2022.Results: From January 2018 to September 2022, 2844 patients received CM at 90 VA Health Systems (including 98 VA Medical Center, 7 community-based outpatient clinics, and 15 other sites). The median number of CM visits was 8 (mean = 10.17, SD = 8.12) visits over the course of 1.5 months (median = 45 days, mean = 57.46 days, SD = 62.65). The target substance was stimulants in 86.42 % of visits. Average age of patients was 52.29 years (SD = 12.10), with 55.06 % of patients experiencing homelessness or housing instability, and 97.50 % of patients diagnosed with more than one SUD. Compared to the year prior to the COVID-19 pandemic (03/2019–02/2020; mean = 957.33, SD = 157.71 visits/month), CM visits declined by 83.20 % in the year following the pandemic (03/2020–02/2021; mean = 160.83, SD = 164.14), and have yet to return to pre-pandemic levels.Conclusions: The CM rollout has been markedly successful in the VHA, with adoption across multiple VHA sites within a complex patient population, indicating the potential for effective, more widespread CM implementation. At the same time, there was a considerable reduction in CM care during the COVID-19 pandemic and CM has not yet returned to pre-pandemic levels. Moreover, only a small minority of VA patients with stimulant use disorder have received CM. Given increasing rates of overdose, including stimulant-involved overdose, it is important to increase CM provision in VHA and non-VHA settings.

Socio-Demographic and Clinical Profile of Infantile Masturbation Syndrome

Background: Masturbation is not uncommon in younger children. Due to variable presentation in early childhood often leads to misdiagnosis and may result in unnecessary investigation and treatment. Materials &amp; Method: This retrospective case study was conducted at outpatient department of Rehabilitation and Neurology unit of Dr.M R Khan Shishu Hospital and Institute of Child Health between 2013-2019. Result: Among 40 patients, majority (90%) had age of onset within 36 months of age. Mean and median age were 27.45 months and 25.5 months respectively, the range was between 4 months to 84 months. Male: female was 1:1.2. Most of the children came from urban area (85%) and from single family (77.5%). All 40 children shared common features like stereotype movement with variable duration, no alteration of consciousness, cessation with distraction when attempted, remained responsive during the events, their neurological examination was normal and no abnormalities were detected in laboratory studies. Thirty- three (82.5%) children did this behaviour on prone position. Thirty-one (77.5%) children had vocalization. Duration of episode was 5-10 min in 19(47.5%) children. Frequency of masturbation was up to 5 times per day in 30(75%) children. Twenty-two (55%) children did this behaviour when remained unnoticed. Antiepileptic drug was given to 14(35%) children but had no clinical improvement. Home video recordings were available in 18(43.9%) children. Conclusion: Early diagnosis from the knowledge of clinical manifestations helps to minimize unnecessary laboratory investigations and use of drugs. BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 71-75

Prospective evaluation of aura during anti-calcitonin gene-related peptide monoclonal antibody therapy after 52 weeks of treatment

Background: Clinical studies have shown the efficacy and safety of monoclonal antibodies (mAbs) against calcitonin gene-related peptide (anti- CGRP) in migraine patients with and without aura. Early evidence from post hoc and small subgroup analyses suggests that anti-CGRP mAbs reduce the frequency and intensity of aura. Herein, we prospectively assessed the changes in aura after 12 months of anti-CGRP mAb treatment and performed a literature review.Methods: All outpatients treated with anti-CGRP mAbs for one year in two tertiary Headache Centers and who experienced ≥1 episode of aura/month were enrolled. The study reports data from one month before (baseline) and the last three months (months 10, 11, 12) of treatment.Results: Data from 13 patients with a diagnosis of migraine with and without aura were collected. The mean duration from aura onset was 17.8±7.9 years. At baseline nine patients (69.2%) reported visual aura, and four (30.8%) visual and sensory aura. Mean duration of aura episodes was of 34.2±15.7 minutes. At baseline, the mean number of monthly migraine days (MMDs) was 22.3±7.5, and the mean number of MMDs preceded by aura was 9.15±9.0. At month 12 of treatment, there was a significant reduction of MMDs (6.2±9.0, p=0.002) and MMDs with aura (2.6±2.7, p=0.015). Three patients reported episodes of aura without subsequent headache, a phenomenon that was absent prior to treatment. We identified 14 studies that reported changes in aura during anti-CGRP mAbs treatment.Conclusions: This prospective study shows that anti-CGRP mAbs reduce the number of migraine attacks with aura consistently with the reduction of MMDs. Randomized studies with anti-CGRP mAbs specifically assessing migraine aura are required.

Influence of mesenchymal stromal cells of different origins on behavioural reactions of rats with cerebral ischemia-reperfusion

A new direction in cell therapy for ischemic stroke has been the use of mesenchymal stromal cells, which have shown a positive impact on functional changes in the central nervous system due to their neuroprotective effects, reduction of ischemia-reperfusion-induced injury, inhibition of ischemia-reperfusion-induced apoptosis, and restoration of motor function. This study aimed to investigate the effect of mesenchymal stromal cells of different origins, their lysate, and citicoline on the functional state of the central nervous system in rats with experimental brain ischemia-reperfusion. The study considered the effect of mesenchymal stromal cells derived from human umbilical cord Wharton’s jelly, human and rat adipose tissue, rat embryonic fibroblasts, as well as mesenchymal stromal cell lysate and citicoline on the emotional and behavioural responses of sexually mature Wistar rats (3-4 months) weighing 160-190 g. The behavioural responses of rats were studied using the open field test on the 7th and 14th days of the experiment; the following behavioural acts were recorded: ambulation (locomotion), climbing, rearing, and grooming. The significance of differences was determined using the non-parametric Mann-Whitney U test. It was established that after ischemia-reperfusion, animals with control pathology showed a significant decrease in the duration of episodes of ambulation in peripheral and central squares, vertical locomotor activity, and exploratory activity compared to the sham-operated group. In rats that received citicoline and transplanted human umbilical cord Wharton’s jelly mesenchymal stromal cells, a significant increase in the duration of episodes of horizontal locomotor activity was observed compared to other types of stem cells and the control. Intravenous administration of rat embryonic fibroblasts increased the emotional activity of the experimental animals. The least impact on locomotor and adaptive exploratory activity in rats with ischemia-reperfusion was registered in groups of animals that received mesenchymal stromal cells from human and rat adipose tissue, as well as mesenchymal stromal cell lysate. The practical significance of the study lies in the search for the most effective class of stem cells with neuroprotective properties for the creation of an injectable drug for intravenous transplantation in the treatment of patients with acute ischemic stroke

Abstract PS14-05: Safety evaluation from the KEYNOTE-522 study of neoadjuvant pembrolizumab (or placebo) plus chemotherapy followed by adjuvant pembrolizumab (or placebo) in patients with early triple-negative breast cancer (TNBC)

Abstract Background: In KEYNOTE-522 (NCT03036488), neoadjuvant (neoadj) pembrolizumab (pembro) + chemotherapy (chemo) followed by adjuvant (adj) pembro led to statistically significant and clinically meaningful improvements in the primary endpoints, pCR and EFS, vs neoadj placebo (pbo) + chemo followed by adj pbo in patients (pts) with newly diagnosed, high-risk, early TNBC. In the safety population at preplanned interim analysis 4 (IA4), treatment-related AEs in the combined phases (neoadj + adj) occurred in 98.9% of pts with pembro + chemo/pembro and 99.7% of pts with pbo + chemo/pbo; immune-mediated AEs of any grade occurred in 33.5% and 11.3% of pts, respectively. We report additional safety findings, beyond the already reported safety results, on immune-mediated AEs and management in the combined phases from IA4 of KEYNOTE-522. Methods: Eligible pts were randomized 2:1 to receive neoadj pembro 200 mg or pbo Q3W + paclitaxel-carboplatin for 4 cycles and then doxorubicin or epirubicin + cyclophosphamide for 4 cycles. After definitive surgery, pts received radiation therapy as indicated + adj pembro 200 mg or pbo Q3W for up to 9 cycles. Safety was assessed in all randomized pts who received ≥1 dose, underwent surgery, or both. AEs were monitored throughout the study and for 30 d post-treatment (90 d for serious AEs). Results: At IA4 (data cut-off: March 23, 2021), median treatment duration was 13.3 (range, 0-21.9) mo with pembro + chemo/pembro (n = 783) and 13.6 (range, 0-19.8) mo with pbo + chemo/pbo (n = 389). Of 341 pts with immune-mediated AEs and infusion reactions in the pembro + chemo/pembro arm (most events occurred in neoadj phase), 224 had grade 1-2 events and 117 had grade 3–5 events. The most common immune-mediated AEs with pembro + chemo/pembro were hypothyroidism (15.1%) and severe skin reactions (5.7%); infusion reactions occurred in 18.0% of pts (table). Of 118 pts with hypothyroidism, median time to onset was 105 d (range, 7–510 d) and 106 were treated with thyroid replacement, suggesting an endocrine abnormality and need for continued thyroid replacement. Of 45 pts with severe skin reactions, median time to onset was 64 d (range, 4–479 d) and 28 were treated with corticosteroids. Of 141 pts with infusion reactions, median time to onset was 16 d (range, 1–458 d) and 85 were treated with corticosteroids. Other immune-mediated AEs of interest with pembro + chemo/pembro were adrenal insufficiency (2.6%), pneumonitis (2.2%), and hypophysitis (1.9%); most of these events were grade 2–3. All 20 pts with adrenal insufficiency were treated with hormone replacement. Of 17 pts with pneumonitis, median time to onset was 167 d (range, 22-537 d) and 12 were treated with corticosteroids; median episode duration was 92 d. Of 15 pts with hypophysitis, 14 were treated with corticosteroids. Conclusion: In pts with newly diagnosed, high-risk, early TNBC, neoadj pembro + chemo followed by adj pembro had a manageable safety profile that was generally consistent with the known safety profiles of pembro and the chemo regimens. Most immune-mediated AEs and infusion reactions were grade 1-2, manageable with treatment interruption, corticosteroids, and/or hormone replacement therapy, and did not result in treatment discontinuation. Together with the efficacy findings, our results support neoadj pembro + chemo followed by adj pembro as a standard of care regimen for these pts. Table Citation Format: Javier Cortés, Rebecca Dent, Lajos Pusztai, Heather McArthur, Sherko Kuemmel, Carsten Denkert, Yeon Hee Park, Rina Hui, Masato Takahashi, Carlos Barrios, Yalin Zhu, Xiaoli Zhang, Wilbur Pan, Vassiliki Karantza, Joyce O'Shaughnessy, Peter Schmid. Safety evaluation from the KEYNOTE-522 study of neoadjuvant pembrolizumab (or placebo) plus chemotherapy followed by adjuvant pembrolizumab (or placebo) in patients with early triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS14-05.

Abstract PS14-08: Safety evaluation from the KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy in patients with previously untreated, locally recurrent inoperable or metastatic triple-negative breast cancer

Abstract Background: In KEYNOTE-355 (NCT02819518), pembrolizumab (pembro) + chemotherapy (chemo) led to statistically significant and clinically meaningful improvements in PFS and OS (primary endpoints) vs placebo (pbo) + chemo in patients (pts) with previously untreated PD-L1 positive advanced TNBC (combined positive score ≥10). In the overall safety population at final analysis, treatment-related AEs occurred in 96.3% of pts in the pembro + chemo arm and 95.0% of pts in the pbo + chemo arm; immune-mediated AEs occurred in 26.5% and 6.4% of pts, respectively. We report additional safety information, beyond the already reported safety results, on immune-mediated AEs and management from the final analysis of KEYNOTE-355. Methods: Eligible pts were randomized 2:1 to receive pembro 200 mg or pbo Q3W for up to 35 cycles + investigator’s choice of nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin. Safety was assessed in all randomized pts who received ≥1 dose of study treatment. AEs were monitored throughout the study and for 30 d post-treatment (90 d for serious AEs). Results: At final analysis (data cut-off: June 15, 2021), median treatment duration was 6.1 (range, 0.0–48.8) mo in the pembro + chemo arm (n = 562) and 5.3 (range, 0.0–51.5) mo in the pbo + chemo arm (n = 281). Of 157 pts with immune-mediated AEs and infusion reactions in the pembro + chemo arm, 125 had grade 1-2 events and 32 had grade 3-4 events; none were grade 5. The most common immune-mediated AEs with pembro + chemo were hypothyroidism (15.8%) and hyperthyroidism (4.3%); infusion reactions occurred in 3.7% of pts (table). Of 89 pts with hypothyroidism, median time to onset was 105 d (range, 19–707 d) and 70 were treated with thyroid replacement, suggesting an endocrine abnormality and need for continued thyroid replacement. Of 24 pts with hyperthyroidism, median time to onset was 53.5 d (range, 20–209 d) and 2 were treated with corticosteroids. Of 21 pts with infusion reactions, median time to onset was 147 d (range, 1–729 d) and 10 were treated with corticosteroids. Other immune-mediated AEs of interest in the pembro + chemo arm were pneumonitis (2.5%) and adrenal insufficiency (1.4%); most of these events were grade 2–3. Of 14 pts with pneumonitis, median time to onset was 99.5 d (range, 29–288 d) and 11 were treated with corticosteroids; median episode duration was 56 d. All 8 pts with adrenal insufficiency were treated with hormone replacement. There were no reports of hypophysitis. Conclusion: In pts with previously untreated advanced TNBC, pembro + chemo had a manageable safety profile that was generally consistent with the known safety profiles of pembro and the chemo regimens. Most immune-mediated AEs and infusion reactions were grade 1-2, manageable with treatment interruption, corticosteroids, and/or hormone replacement therapy, and did not result in discontinuation of study treatment. Together with the efficacy findings, our results support pembro + chemo as a standard of care regimen for these pts. Table. Citation Format: Hope Rugo, Peter Schmid, Zbigniew Nowecki, David Cescon, Seock-Ah Im, Mastura Yusof, Carlos Gallardo, Hiroji Iwata, Carlos Barrios, Sherene Loi, Xuan Zhou, Xiaoli Zhang, Wilbur Pan, Vassiliki Karantza, Javier Cortés. Safety evaluation from the KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy in patients with previously untreated, locally recurrent inoperable or metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS14-08.

Assessing the uterine bleeding profile in women using a subcutaneous contraceptive implant containing etonogestrel: Real-life clinical practice

Introduction. Pregnancy planning is one of the leading areas in the population reproductive health care, in particular preventing and reducing the number of abortions.Aim. To evaluate the uterine bleeding profile and other adverse events associated with the use of an etonogestrel subcutaneous contraceptive implant (Implanon NXT®). Materials and methods. We analysed medical records of female patients (n = 153) who used Implanon NXT® in the period from 2013 to 2023, records of adverse events, uterine bleeding, bleeding management techniques and reasons given by women for discontinuing the use of implants.Results. The median duration of uterine bleeding episodes ranged from 7 to 13 days within a three-year period of use of Implanon NXT®. During the first 3 months, the proportion of women with prolonged bleeding was higher as compared to all other observation periods and gradually decreased during the first year of use of the drug from 41.2 to 15.8%. 40 patients with complaints of unsatisfactory uterine bleeding patterns required adjustment of drug dosages; 14 women continued to use Implanon NXT® after adjustment of drug dosages and repeated visits. 17.0% (n = 26) of patients required early removal of the implant. Due to pregnancy planning, the implant was removed early in 13% (n = 20) of patients. The most common adverse events included functional ovarian cysts, mastalgia, increased appetite, decreased libido, dizziness, acne; most of them were transient and did not require any management, and were not considered the reason for implant removal.Conclusion. The number of uterine bleeding episodes in patients using the etonogestrel implant was comparable to the normal menstrual cycle. Some women had changes in the uterine bleeding patterns, such as amenorrhea, frequent and prolonged bleeding, which reduced the duration of use of this contraception method. At the same time, combined oral contraceptives were the most effective as compared to other drugs used in correction regimens.

ПОТЕНЦИАЛ ИСПОЛЬЗОВАНИЯ ДИНАМИКИ ЭЛЕКТРОКАРДИОГРАФИЧЕСКИХ ПОКАЗАТЕЛЕЙ ПРИ ВЫЯВЛЕНИИ КАРДИОТОКСИЧНОСТИ ЧЕРЕЗ 12 МЕСЯЦЕВ ПОСЛЕ ОКОНЧАНИЯ ХИМИОТЕРАПИИ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ ДОКСОРУБИЦИНОМ

Background. Changes in electrocardiographic parameters of the heart, reflecting the processes of depolarization and repolarization of the myocardium, can be signs of early cardiotoxicity (CT). Aim. To study changes in electrocardiographic parameters of the myocardium in patients with verified breast cancer 12 months after the end of chemotherapy with doxorubicin. Material and methods. The study included 100 patients with a confirmed diagnosis of breast cancer who were treated at the health care institution “Grodno University Clinic” (Grodno, Belarus). A number of electrocardiographic parameters of the myocardium were measured in patients before and 12 months after the end of chemotherapy using electrocardiography and 24-hour Holter monitoring. Results. A statistically significant increase in electrocardiographic parameters of depolarization and repolarization was revealed (P, P-Q, Tpeak-Tend, Q-Tc / QRS, Q-Tc - p&lt;0.007; p&lt;0.001; p=0.042; p=0.009; p&lt;0.001, respectively) before and 12 months after the end of chemotherapy. A change in the time and total number of episodes of sinus tachycardia and supraventricular extrasystoles was also noted (p=0.029, p=0.026 and p=0.002). The Tpeak-Tend indicator changed statistically significantly in the CT+ subgroup (p=0.032) after 12 months. The dynamics of the Q-Tc indicator before and 12 months after the end of chemotherapy was observed in almost all patients. However, in the CT+ subgroup, an increase in Q-Tc was recorded statistically significantly more often compared to the CT- subgroup (p &lt;0.005). Conclusion. During chemotherapy with doxorubicin, an increase in Tpeak-Tend and Q-Tc was observed. An especially significant increase in these indicators was noted in the CT+ subgroup. The number and duration of sinus tachycardia episodes as well as the number of supraventricular extrasystoles also increased. This may correlate with the relationship between chemotherapy with doxorubicin and the dynamics of electrocardiographic parameters.

Illuminating the Transition From an Open to a Semi‐Closed Volcanic Vent System Through Episodic Tremor Duration and Shape

Abstract[Volcanic eruptions generate continuous or episodic tremor, which can provide unrivaled information about activity changes during eruption. However, the wealth of information in episodic tremor patterns is often not harvested and transitions between patterns remain obscure. The 2021 Geldingadalir eruption, Iceland, is an exceptional case, where the lava effusion caused continuous tremor, and 8698 tremor episodes spanning two orders of magnitude in duration and repose. Based on seismometer and video camera data, we associate several‐minute‐long, symmetrical episodes with an open vent system, where lava remains in the crater bowl during repose, connected to a shallow magma compartment. Ramp‐shaped episodes, lasting several hours, are associated with a temporary closure of the vent system, where no lava remains in the crater bowl during repose and more time is required to resume effusion. The transition from continuous to episodic effusion is related to the cumulative time spent in effusion and repose, and to external factors like crater wall collapses. The range of observed eruption styles and shifts between them, took place at unchanged magma supply rate. This underpins the importance of processes, geometry and evolution of the shallow conduit with time.]

Ventilatory long-term facilitation following acute intermittent hypoxia in unanesthetized rats: influence of short hypoxic episodes and changes in metabolic rate

Plasticity is a hallmark feature of the neural system controlling breathing. Acute intermittent hypoxia (AIH) elicits plasticity in multiple respiratory motor pools ( e.g., phrenic, intercostal, XII, etc.) and has emerged as a promising therapeutic approach to restore lost respiratory (and non-respiratory) function in people with spinal cord injury and other clinical disorders that compromise movement. In anesthetized rats during the rest phase, AIH-induced phrenic long-term facilitation is enhanced when the AIH consists of short (1-min) versus longer (5-min) moderate hypoxic episodes (PaO2 ~40-50 mmHg), even with the same cumulative duration of hypoxia (15-min). However, since respiratory plasticity is influenced by a variety of behavioral and physiological factors such as sensory feedback, lung/chest wall mechanics and arousal state, the effectiveness of specific AIH protocols may differ when implemented in unanesthetized rats. Since it is unknown how hypoxic episode duration impacts ventilatory long-term facilitation (vLTF) in unanesthetized rats during the rest phase, we initially tested the hypothesis that short (1-min) hypoxic episodes (FIO2 = 0.09) elicit vLTF in young male Sprague-Dawley rats via whole-body plethysmography; metabolic CO2 production was also assessed. Following 15, 1-min hypoxic episodes, significant vLTF was observed, and this effect was more pronounced when ventilation was normalized to metabolic rate ( i.e. VE/VCO2; p &lt; 0.05). AIH-induced vLTF was accompanied by hypometabolism and a post-hypoxic temperature decrease (p &lt; 0.01), consistent with previous work. Additional studies will be performed to compare these results with “traditional” AIH protocols ( i.e., 5-min hypoxic episodes), and across the rats’ rest versus active phase. In perspective, these results set the stage for future investigations concerning the optimization of AIH protocols in unanesthetized rodent models, including rodent models of injury or disease. NIH HL148030 &amp; 147554 (Mitchell). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Clinical variables influencing the severity of diabetes ketoacidosis.

To evaluate clinical indicators in order to examine the intensity of diabetes ketoacidosis (DKA) episodes in children and adolescents diagnosed with type 1 diabetes mellitus (T1DM). Data from 156 T1DM patients aged 6 months to 14 years, who presented with DKA to the emergency room, were retrospectively reviewed from 2018 to 2022. Data on demographic characteristics, economic status, initial clinical presentation, glycemic control, DKA severity, and laboratory evaluations were also collected. Diabetes ketoacidosis episodes were more prevalent among male patients during the middle childhood age group. Notably, these episodes displayed seasonal patterns. The severity was found to be inversely associated with economic status and positively correlated with early adolescence. Newly diagnosed T1DM patients constituted 52.9%, with a statistically significant connection observed between severe DKA and this subgroup. Furthermore, there was a significant escalation in poor glycemic control with episode severity. Prolonged episode duration also exhibited a statistically significant association with more severity. Gastrointestinal symptoms were commonly reported during the presentation. Moreover, several clinical signs and symptoms, including decreased consciousness, reduced activity, drowsiness, Kussmaul breathing, shortness of breath, vomiting, tachycardia, and severe dehydration, were significantly correlated with the severity of DKA (p<0.05). Hypernatremia was more frequent among children with severe DKA. Diabetes ketoacidosis was observed to occur more frequently among males in middle childhood with seasonal variations. Furthermore, the severity of DKA was associated with lower economic status, early adolescence, and the presence of hypernatremia.

National surveillance using a clinical quality indicator for prolonged antipsychotic use among older Australians with dementia who access aged care services.

Dementia guidelines recommend antipsychotics are only used for behavioral and psychological symptoms when non-drug interventions fail, and to regularly review use. Population-level clinical quality indicators (CQIs) for dementia care in permanent residential aged care (PRAC) typically monitor prevalence of antipsychotic use but not prolonged use. This study aimed to develop a CQI for antipsychotic use >90days and examine trends, associated factors, and variation in CQI incidence; and examine duration of the first episode of use among individuals with dementia accessing home care packages (HCPs) or PRAC. Retrospective cohort study, including older individuals with dementia who accessed HCPs (n=50,257) or PRAC (n=250,196). Trends in annual CQI incidence (2011-12 to 2015-16) and associated factors were determined using Poisson regression. Funnel plots examined geographical and facility variation. Time to antipsychotic discontinuation was estimated among new antipsychotic users accessing HCP (n=2367) and PRAC (n=15,597) using the cumulative incidence function. Between 2011-12 and 2015-16, antipsychotic use for >90days decreased in HCP recipients from 10.7% (95% CI 10.2-11.1) to 10.1% (95% CI 9.6-10.5, adjusted incidence rate ratio (aIRR) 0.97 (95% CI 0.95-0.98)), and in PRAC residents from 24.5% (95% CI 24.2-24.7) to 21.8% (95% CI 21.5-22.0, aIRR 0.97 (95% CI 0.96-0.98)). Prior antipsychotic use (both cohorts) and being male and greater socioeconomic disadvantage (PRAC cohort) were associated with higher CQI incidence. Little geographical/facility variation was observed. Median treatment duration in HCP and PRAC was 334 (interquartile range [IQR] 108-958) and 555 (IQR 197-1239) days, respectively. While small decreases in antipsychotic use >90days were observed between 2011-12 and 2015-16, findings suggest antipsychotic use among aged care recipients with dementia can be further minimized.

Asphyxial Circulatory Arrest with a Complex of Resuscitation Measures in an Experimental Model

The majority of asphyxial circulatory arrest (CA) models have a number of disadvantages, such as the lack of uniform criteria for fixing CA and recovery of spontaneous circulation, short duration of CA episode and limited volume of post-resuscitation intensive care, poor similarity with resuscitation measures in current clinical anesthesiology/intensive care settings.The aim of the study: to improve the experimental model of asphyxicial CA by standardizing experimental procedures and using a complex of resuscitation measures replicating current CA management in clinical anesthesiology-intensive care.Materials and methods. The experiments were conducted on 34 male Wistar rats, distributed into 2 groups: Group I included animals subjected to sham procedure (SP, N=12) and Group II – animals subjected to asphyxial circulatory arrest (CA, N=22) and subsequent resuscitation. Asphyxia in anesthetized rats was induced by rocuronium bromide injection, followed by recording of electrocardiogram (ECG), parameters of invasive blood pressure (BP) measurement and laser Doppler fluxmetry (LDF) to assess skin perfusion. CA episode was maintained for 2 min, followed by a series of resuscitation measures and intensive therapy for 2 h. Circulatory parameters (ECG, BP, LDF), gas composition and arterial blood acid-base state (ABS) dynamics were evaluated.Results. Monitored parameters were comparable in both groups at baseline after stabilization period. After exclusion criteria were applied 11 animals from SP group and 18 — from CA were included in the analysis. Tachycardia (heart rate, beats/min–1, SP vs CA) was documented in the CA group: 218 [205; 236] vs 286 [272; 305], P⩽0.0001), as well as recovery of skin perfusion to subnormal parameters in the first minutes after successful resuscitation. At minute 10 in the post-resuscitation period worsening of skin perfusion (M, perfusion units, SP vs CA): 14.7 [12.1; 16.5] vs 10.1 [7.0; 12.5], P=0.0014), and decompensated mixed acidosis (pH, SP vs CA): 7.42 [7.40; 7.43] vs 7.20 [7.13; 7.23], P⩽0.0001) were documented in the CA group, however BP values were comparable (BP, mmHg, SP vs CA): 60 [58; 72] vs 67 [62; 82], P=0.482). At minute 120 post-resuscitation and at the end of intensive care period, both groups demonstrated similar values of the monitored parameters. Three out of 18 animals in the CA group died after resuscitation.Conclusion. Electromechanical dissociation underlies CA in rats subjected to asphyxia. The use of LDF to assess peripheral blood flow makes it possible to standardize the severity of ischemic reperfusion injuries and improve reproducibility of the model. Series of resuscitation measures in experimental setting is justified from a bioethical point of view, and makes it possible to improve repeatability of preclinical research results in clinical practice.

Recurrent ventilator-associated pneumonia in severe Covid-19 ARDS patients requiring ECMO support

ObjectiveTo describe ventilator-associated pneumonia (VAP) recurrence in COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support, and to evaluate the impact of antimicrobial treatment duration of the first VAP episode on VAP recurrence.MethodsAdult patients with COVID-19 severe pneumonia on ECMO admitted between March 2020 and January 2022 were retrospectively included. Primary outcome was incidence of VAP recurrence, and secondary outcome was the impact of duration of antimicrobial treatment on VAP recurrence.ResultsAmong the 252 included patients, 226 (90%) developed a first VAP. Sixteen had lung abscess and were excluded, leaving 210 patients. VAP recurrence occurred in 172 patients (82%), with a median (IQR) time from first VAP to recurrence of 10 (7–13) days. Pseudomonas aeruginosa and Enterobacteriaceae were respectively responsible for 28% and 52% of first VAP, and 51% and 62% of first recurrence episodes. Among the 210 patients with a first VAP, 158 (75%) received a short course of antibiotics [< 8 days, median (IQR) duration 6 (5–7) days] and 52 (25%) received a prolonged course of antibiotics [≥ 8 days, median (IQR) duration 9 (8–10) days]. Estimated cumulative incidence of VAP recurrence, taking into account death and extubation as competing risks, was not different in patients with short– and prolonged–antimicrobial treatment.ConclusionsIn patients with severe Covid-19–ARDS requiring ECMO support, VAP recurrence occurs frequently, with Enterobacteriaceae and Pseudomonas aeruginosa as predominant causative microorganisms. An antimicrobial treatment of ≥ 8 days for the treatment of first VAP episode did not reduce the risk of VAP recurrence, as compared to shorter duration.

Relationship between Neonatal Cerebral Fuels and Neurosensory Outcomes at 3 Years in Well Babies: Follow-Up of the Glucose in Well Babies (GLOW) Study

Plain Language SummaryIn the Glucose in Well babies and their later Neurodevelopment (GLOWiNg) study, we investigated whether the availability of brain fuels in healthy term babies during the first 5 days after birth was associated with their neurodevelopmental progress at 3 years of age. We had measured plasma glucose, lactate, and beta-hydroxybutyrate concentrations when the children were babies, as these are the most common brain fuels. We used the Ages and Stages questionnaire, which is completed by parents, to assess the child’s development in areas including communication, motor skills (fine and gross), and problem solving.We studied 64 families whose babies were part of the Glucose in Well Babies (GLOW) study in New Zealand. Using both structural equation modelling and linear regression, we found that even though many babies experienced episodes of low plasma glucose concentrations, there was no detectable relationship between these episodes and developmental progress at 3 years of age. We explored other factors, including glucose concentrations, total fuels available, and the duration of low glucose episodes, and found no significant associations. Our results suggest that in healthy term babies, episodes of low glucose concentrations in the first days after birth may be part of the normal metabolic transition after birth and may not have long-term implications for neurodevelopment. However, larger studies using different assessment tools are needed to confirm these findings.

Hybrid Closed Loop in Adults With Type 1 Diabetes and Severely Impaired Hypoglycemia Awareness.

Benefits of hybrid closed-loop (HCL) systems in a high-risk group with type 1 diabetes and impaired awareness of hypoglycemia (IAH) have not been well-explored. Adults with Edmonton HYPO scores ≥1047 were randomized to 26-weeks HCL (MiniMed™ 670G) vs standard therapy (multiple daily injections or insulin pump) without continuous glucose monitoring (CGM) (control). Primary outcome was percentage CGM time-in-range (TIR; 70-180 mg/dL) at 23 to 26 weeks post-randomization. Major secondary endpoints included magnitude of change in counter-regulatory hormones and autonomic symptom responses to hypoglycemia at 26-weeks post-randomization. A post hoc analysis evaluated glycemia risk index (GRI) comparing HCL with control groups at 26 weeks post-randomization. Nine participants (median [interquartile range (IQR)] age 51 [41, 59] years; 44% male; enrolment HYPO score 1183 [1058, 1308]; Clarke score 6 [6, 6]; n = 5 [HCL]; n = 4 [control]) completed the study. Time-in-range was higher using HCL vs control (70% [68, 74%] vs 48% [44, 50%], P = .014). Time <70 mg/dL did not differ (HCL 3.8% [2.7, 3.9] vs control 6.5% [4.3, 8.6], P = .14) although hypoglycemia episode duration was shorter (30 vs 50 minutes, P < .001) with HCL. Glycemia risk index was lower with HCL vs control (38.1 [30.0, 39.2] vs 70.8 [58.5, 72.4], P = .014). Following 6 months of HCL use, greater dopamine (24.0 [12.3, 27.6] vs -18.5 [-36.5, -4.8], P = .014), and growth hormone (6.3 [4.6, 16.8] vs 0.5 [-0.8, 3.0], P = .050) responses to hypoglycemia were observed. Six months of HCL use in high-risk adults with severe IAH increased glucose TIR and improved GRI without increased hypoglycemia, and partially restored counter-regulatory responses. ACTRN12617000520336.