Subsequent Doses Research Articles

Evaluating hepatitis B screening, prevalence, vaccination coverage, and linkage to care in Abuja, Nigeria: insights from a cross-sectional study

BackgroundHepatitis B virus (HBV) is a major global health threat, especially in Sub-Saharan Africa, where Nigeria has a prevalence exceeding 8%. Despite the availability of effective vaccines, inadequate coverage and lack of awareness have resulted in high rates of chronic infections and HBV-attributable liver disease. The study aimed to raise awareness of HBV, enroll participants for HBV screening, determine HBV prevalence across various communities, vaccinate negative cases and link positive cases to care.MethodsA cross-sectional study was conducted in 16 districts of Abuja from April 2022 to March 2023. Participants aged 18 and over were screened for hepatitis B, and those testing negative were offered on-site vaccination. Blood samples were collected and tested using HBV immunochromatographic tests and real-time polymerase chain reaction (RT-PCR) for HBV DNA quantification. Data were collected through interviews and analyzed using R software, with descriptive statistics calculated for continuous and categorical variables. Associations between socio-demographic factors and hepatitis B/vaccine status were assessed using the Chi-square test of independence.ResultsOut of 3,245 individuals screened, 141 (4.3%) tested positive for HBV. The highest prevalence was observed in the 20–39 age group (5.9%), with males showing a higher infection rate (5.4%) compared to females (3.7%) [p = 0.02]. The mean age of HBV-positive individuals was significantly lower (30.8 years) than those negative for HBV (36.2 years) [p = < 0.001]. Among 2,506 participants who consented to vaccination, 2,488 received the first dose (99.3%), 1,834 the second dose (73.2%), and 1,100 the third dose (43.9%). Vaccination uptake declined with each subsequent dose, but more older participants completed the third dose. A similar pattern of HBV prevalence was observed across gender and age groups.ConclusionThe study reveals a 4.3% prevalence of hepatitis B, with the highest infection rate among individuals aged 20–39 years, and males showing a higher prevalence than females. Although vaccination uptake was high for the first dose, adherence declined for subsequent doses. These findings highlight the need for targeted public health interventions, particularly among younger adults and males, to improve awareness and vaccination completion. Enhanced community engagement and sustained vaccination efforts are crucial for reducing HBV transmission and achieving better coverage.

Protective Effect of Silver Nanoparticles Against Cytosine Arabinoside Genotoxicity: An In Vivo Micronucleus Assay

Cancer treatments have harmful side effects, including genotoxic ones. Our previous research discovered that a specific silver nanoparticle (AgNPs) formulation could reduce the genotoxic effects of an alkylating agent, cyclophosphamide. This study aims to evaluate if this protective effect is observed against an antimetabolite anticancer agent, cytosine arabinoside (Ara-C). An erythrocyte micronucleus assay was conducted on BALB/c mice. A most significant effect was observed after the application scheme, including three doses of Ara-C and three subsequent doses of AgNPs, resulting in a 3.7 and 2.0-fold decrease in the frequency of micronucleated reticulocytes and accumulated erythrocytes, respectively. Current and previous studies reveal that AgNPs could be used as a genoprotector against the genotoxic damage produced by the currently used antineoplastic antimetabolites and alkylating agents. It was revealed that AgNPs could be considered a new class of promising synthetic antineoplastic genoprotectants along with the known class of derivatives from natural sources.

Analysis of existent catalytic filter materials for removal of iron and manganese

Decentralized water supply in war and post-war times is one of the main sources of water for the population and enterprises. As a source of water supply, as a rule, water from wells is used for this type of water supply. The main problems of drill-fish water are the increased content of iron, manganese, hydrogen sulfide, hardness salts, nitrates, sulfates, chlorides in some regions, high dry residue. The rapid development of technologies based on membrane technologies such as reverse osmosis or nanofiltration allow us to adjust the salt composition of water, remove nitrates and make water suitable for drinking needs and production cycles. But before membrane technologies, compounds of iron, manganese, and hydrogen sulfide, which can form inorganic impurities on the surface of membrane elements and cause their premature failure, must be removed. One of the best methods of pre-treatment of water before membrane systems is complex ion-exchange materials, which are simultaneously capable of removing hardness salts, iron, and manganese. But the main disadvantage of such pre-filtration methods is the use of tableted salt, which makes this method expensive and not environmentally friendly. Purification of water from iron and manganese on pressure filters by catalytic loading with subsequent dosing of antiscalant before membrane installations is a modern trend in local water treatment. Catalytic loadings have been used for quite a long time, but most manufacturers do not provide clear and practical recommendations for their use. The use of such materials, as a rule, largely depends on many factors and is based on the experience of the specialist's qualifications. Analysis of the technical parameters of filter materials, analysis of parameters of the source water quality are the main components of the selection and organization of the correct technological scheme of water purification.

Safety and Efficacy of Loading Doses of Vitamin D: Recommendations for Effective Repletion

Background/Objectives: Epidemiological data on vitamin D status revealed that, despite various dosage and durations of supplementation, the effectiveness often fails to achieve optimal outcomes. The need for higher doses than previously recommended was suggested, but several modifying factors should be considered, including the level of deficiency, and BMI. The objectives of this post hoc evaluation are to characterize treatment effectiveness based on the applied dose, duration and BMI; and to assess the safety aspects associated with rapid repletion of vitamin D. Methods: Vitamin D deficient subjects selected in the post-hoc analysis: seventy patients included from a combined loading-maintenance supplementation (300,000 IU followed by 60,000 IU) protocol and 62 deficient subjects received a low-dose maintenance (1000 IU/day) therapy. The risk of overload and the incidence of hypercalciuria and hypercalcemia resulting from loading or post-loading maintenance were investigated. Results: The moderate–fast-loading schedule of 60,000 IU per week for 5 weeks, effectively achieves the target in 25(OH)D levels over 30 ng/mL for all deficient subjects, regardless of their BMI. Slower loading with lower weekly doses confirms the safety of supplementation, but the effectiveness is dependent on the subjects’ BMI; overweight and obese patients require higher doses to reach the same vitamin D levels. No difference in safety parameters observed compared to low-dose therapies. Conclusions: The loading treatment involving a total dose of 300,000 IU administered over 5 or 10 weeks is effective for repletion, does not lead to 25(OH)D overload, and poses no additional risks of hypercalcemia or hypercalciuria. Furthermore, there are no safety concerns regarding changes in bone resorption markers. A combination of the loading treatment with a subsequent maintenance dose of 2000 IU daily is adequate to achieve the target vitamin D levels.

Sex and common germline variants impact the toxicity profile and pharmacokinetics of alectinib: a nation-wide cohort study in patients with ALK-positive non-small cell lung cancer

IntroductionAlectinib, a small-molecule kinase inhibitor, is used as first-line treatment for anaplastic lymphoma kinase–positive (ALK+) non-small cell lung cancer (NSCLC). Albeit generally well-tolerated, a considerable subset of patients requires dose adjustments due to drug-related toxicity. Single-nucleotide polymorphisms (SNPs) in genes related to the metabolism of alectinib may upfront identify patients at risk for toxicity. MethodsIn this multicenter observational cohort study in patients with advanced ALK+ NSCLC receiving alectinib treatment, we investigated the association between toxicity, pharmacokinetics, and key genetic variants in ABCB1, CYP3A4, PPAR-α, POR, and CYP3A5. Data on demographics, adverse events, and alectinib trough levels were collected from five hospitals. ResultsAmong 215 patients, 47% experienced severe toxicity. Women experienced more severe toxicity (female versus male: 56% versus 34%; p=0.001) and also had +35% higher alectinib trough levels (p<0.001). Homozygous carriers of the PPAR-α 209G>A variant exhibited a higher incidence of grade ≥ 3 toxicity (38%) compared to patients who carried at least one wild-type allele (11%) (p=0.004). This remained significant after Bonferroni correction. Patients who experienced severe toxicity had +18.5% (95%CI: 2.9–36.6%; p=0.019) higher trough levels. ConclusionsFemale patients encounter more severe toxicity due to higher alectinib exposure, which warrants further exploration. PPAR-α 209G>A significantly increased relevant alectinib-induced toxicity, most likely due to an increase in alectinib exposure. Pre-treatment testing for genetic variants with a subsequent dose reduction could provide a viable approach to reduce alectinib-related toxicity.

Sintilimab plus HPV vaccine for recurrent or metastatic cervical cancer

PurposeRecurrent or metastatic cervical cancer (r/m CC) presents limited treatment options for patients failed or progressed quickly following first-line therapy. This study investigated the potential of sintilimab with a prophylactic...

Deep learning-based multiple-CT optimization: An adaptive treatment planning approach to account for anatomical changes in intensity-modulated proton therapy for head and neck cancers

BackgroundsIntensity-modulated proton therapy (IMPT) is particularly susceptible to range and setup uncertainties, as well as anatomical changes. PurposeWe present a framework for IMPT planning that employs a deep learning method for dose prediction based on multiple-CT (MCT). The extra CTs are created from cone-beam CT (CBCT) using deformable registration with the primary planning CT (PCT). Our method also includes a dose mimicking algorithm. MethodsThe MCT IMPT planning pipeline involves prediction of robust dose from input images using a deep learning model with a U-net architecture. Deliverable plans may then be created by solving a dose mimicking problem with the predictions as reference dose. Model training, dose prediction and plan generation are performed using a dataset of 55 patients with head and neck cancer in this retrospective study. Among them, 38 patients were used as training set, 7 patients were used as validation set, and 10 patients were reserved as test set for final evaluation. ResultsWe demonstrated that the deliverable plans generated through subsequent MCT dose mimicking exhibited greater robustness than the robust plans produced by the PCT, as well as enhanced dose sparing for organs at risk. MCT plans had lower D2% (76.1 Gy vs. 82.4 Gy), better homogeneity index (7.7% vs. 16.4%) of CTV1 and better conformity index (70.5% vs. 61.5%) of CTV2 than the robust plans produced by the primary planning CT for all test patients. ConclusionsWe demonstrated the feasibility and advantages of incorporating daily CBCT images into MCT optimization. This approach improves plan robustness against anatomical changes and may reduce the need for plan adaptations in head and neck cancer treatments.

Adaptive dosing of high-dose busulfan in real-world adult patients undergoing haematopoietic cell transplant conditioning.

To evaluate the effectiveness of a Bayesian adaptive dosing strategy in achieving target busulfan exposure in adult patients undergoing haematopoietic cell transplantation (HCT). This study included 71 adult patients scheduled to receive high-dose busulfan. Busulfan was administered to achieve a cumulative area under the curve (AUC) of 66.0mg/L/h (16 000 μM/min), 82.60 mg/L/h (20 000 μM/min) or 87.6mg/L/h (21 200 μM/min) depending on the regimen. Individual pharmacokinetic (PK) parameters of busulfan were estimated from three blood samples using a one-compartment model and Bayesian estimation after the first standard dose. Individual PK parameters were used to adjust subsequent doses to achieve the target exposure. All patients had their dose adjusted after the first dose administration. The final deviation from the target AUC was significantly improved compared to the initial deviation after standard mg/kg dosing (mean absolute deviation 19.5% vs 11.7%, P< .01). In addition, the proportion of patients with marked deviation from target exposure (ie, >25%) decreased significantly from 31% after standard dosing to 10% after PK-guided dosing (P< .01). Canonical busulfan-related toxicity, specifically veno-occlusive disease, was observed in 5% of patients who achieved successful PK-guided dosing. In contrast, one-third of patients with off-target exposure with poor dosing experienced toxicity. The Bayesian adaptive dosing strategy significantly improves the accuracy of achieving the target busulfan AUC in patients undergoing HCT. This approach not only reduces marked deviations from target exposure, but also reduces the incidence of busulfan-related toxicity, thereby maintaining a favourable toxicity/efficacy ratio.

Nurses' Characteristics Associated with Good Knowledge, Attitude, and Practices (KAP) of the Malaria Vaccine in Bungoma County, Kenya.

The study examined nurse characteristics associated with Knowledge, Attitudes, and Practices (KAP) regarding malaria vaccination in Bungoma County, Kenya. Malaria remains a major health burden in Kenya, with 3.4 million cases and 12,000 deaths in 2021. Bungoma County, a malaria-endemic area, implemented the RTS S1 malaria vaccine, but dropout rates for subsequent doses are high. The fourth dose dropout, particularly in Bungoma and Siaya, poses a significant challenge to vaccine adherence. A cross-sectional descriptive study comprising mixed research methods; comprising key informant interviews was conducted among nurses in Bungoma County. A stratified random sampling was used to select 63 health facilities providing malaria vaccine. Data collection involved structured questionnaires, observation checklist, and key informant interview guide. Hawthorne effect was minimized by rapport building or familiarizing the participants by spending a whole morning at the facility CWC and assuring sampled participants of anonymity, this made the participants calm and can provide immunization services without fear of being judged. Data was analyzed through descriptive and inferential statistics to determine associations between nurse demographics and KAP scores. The study found good KAP was significantly associated with characteristics such as age, years of experience, education level, and prior malaria vaccine training. Nurses aged over 35, with higher education, and those trained in malaria vaccine administration had a higher likelihood of exhibiting good knowledge and positive attitudes. The study concludes that implementing targeted training programs and mentorship initiatives for less experienced and younger nursing staff is essential for strengthening vaccine implementation effectiveness. Enhanced continuous education programs in Bungoma County would likely improve malaria vaccine practices and outcomes. Additionally, the findings indicate that structured support systems and ongoing professional development are crucial elements in maintaining high standards of vaccine delivery. The study recommends that mandatory comprehensive training programs should be established, incorporating both theoretical knowledge and hands-on practical skills development. These programs should be regularly updated to reflect current best practices and emerging challenges in vaccine delivery. Furthermore, the implementation of structured on-site mentorship programs, combined with continuous supervision, should be prioritized to ensure consistent application of proper vaccination protocols. Regular refresher courses should be offered to maintain and update healthcare workers' knowledge and skills, while a peer support system should be established to facilitate knowledge sharing and professional development.

CTIM-24. PHASE II TRIAL OF RHIL-7-HYFC IN PATIENTS WITH HIGH-GRADE GLIOMA DEMONSTRATED ACCEPTABLE SAFETY PROFILE AND REDUCED LYMPHOPENIA

Abstract BACKGROUND Lymphopenia, a common finding in patients with high-grade gliomas (HGGs), is associated with poor outcomes including worse survival, fatigue, and in some cases, increased opportunistic infections. Interleukin-7 (IL-7) is a cytokine crucial for lymphocyte survival and proliferation. We previously demonstrated long-acting IL-7 (rhIL-7-hyFc, efineptakin alfa, NT-I7) increases absolute lymphocyte counts (ALCs) and extends survival in preclinical murine models of HGG. Here, we report results using rhIL-7-hyFc to effectively reduce lymphopenia in patients with HGG. METHODS We performed a phase II randomized, placebo-controlled, double-blind study of rhIL-7-hyFc in patients with newly diagnosed HGGs (82% IDH-wildtype glioblastoma in both groups). Patients received rhIL-7-hyFc (720mcg/kg) or placebo one-week post-radiation and temozolomide, with subsequent doses at weeks 13, 25, and 37. The primary endpoint was ALC four weeks post-initial administration; exploratory endpoints included CD4 count, progression-free survival (PFS), and overall survival (OS). RESULTS We enrolled 22 patients (median age 59.5 years, range 33-74; 40.9% female) with HGG. Both groups exhibited comparable demographics, including MGMT methylation status, and received a median of 2 doses of rhIL-7-hyFc or placebo. At 4 weeks, the pre-specified primary endpoint, ALC significantly increased relative to baseline in the treatment group, compared to placebo (median percent change=148% vs. 16.7%, p=0.007), as did CD4 count (121% vs. 10.5%, p=0.011). There were no treatment-related grade 4/5 adverse events. Exploratory endpoints of PFS and OS will be reported at time of conference. CONCLUSIONS rhIL-7-hyFc is safe and effective in improving ALC and CD4 count in patients with newly diagnosed HGG undergoing temozolomide and concurrent radiation therapy. This study was powered to meet the primary endpoint; larger trials will likely be required to demonstrate clinical efficacy. Nevertheless, these data support the continued exploration of rhIL-7-hyFc as an adjunct to standard therapy to mitigate lymphopenia and potentially extend survival for patients with HGG.

Concizumab prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial

Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody in development as a once-daily, subcutaneous prophylaxis for patients with haemophilia A or haemophilia B with or without inhibitors. We aimed to assess the efficacy and safety of concizumab in patients with haemophilia A or B without inhibitors. Here we report the results from the confirmatory analysis cutoff. This prospective, multicentre, open-label, randomised, phase 3a trial (explorer8) was conducted at 69 investigational sites in 31 countries. Eligible patients were male, aged 12 years or older, and had congenital severe haemophilia A or moderate or severe haemophilia B without inhibitors and with documented treatment with clotting factor concentrate in the 24 weeks before screening. The trial was paused because of non-fatal thromboembolic events in three patients (two from this trial [explorer8] and one from a related trial in haemophilia with inhibitors [explorer7; NCT04083781]) and restarted with mitigation measures, including a revised dosing regimen of subcutaneous concizumab at 1·0 mg/kg loading dose on day 1 and subsequent daily doses of 0·20 mg/kg from day 2, with options to decrease to 0·15 mg/kg, stay on 0·20 mg/kg, or increase to 0·25 mg/kg on the basis of concizumab plasma concentration measured after 4 weeks on concizumab. Patients recruited after treatment restart were randomly assigned 1:2 using an interactive web response system to receive no prophylaxis and continue on-demand clotting factor (group 1) or concizumab prophylaxis (group 2). The primary endpoints were the number of treated spontaneous and traumatic bleeding episodes for patients with haemophilia A and haemophilia B separately, assessed at the confirmatory analysis cutoff in randomly assigned patients. Analyses were by intention-to-treat. There were two additional groups containing non-randomly-assigned patients: group 3 contained patients who entered the trial before the trial pause and were receiving concizumab in the phase 2 trial (explorer5; NCT03196297), and group 4 contained patients who received previous clotting factor concentrate prophylaxis or on-demand treatment in the non-interventional trial (explorer6; NCT03741881), patients randomly assigned to groups 1 or 2 before the treatment pause, and patients from explorer5 enrolled after the treatment pause. The safety analysis set contained all patients who received concizumab. Superiority of concizumab over no prophylaxis was established if the two-sided 95% CI of the treatment ratio was less than 1 for haemophilia A and for haemophilia B. This trial is registered with ClinicalTrials.gov, NCT04082429, and its extension part is ongoing. Patients were recruited between Nov 13, 2019 and Nov 30, 2021; the cutoff date for the analyses presented was July 12, 2022. 173 patients were screened, of whom 148 (86%) were randomly assigned or allocated to the four groups in the study after trial restart on Sept 30, 2020 (nine with haemophilia A and 12 with haemophilia B in group 1; 18 with haemophilia A and 24 with haemophilia B in group 2; nine with haemophilia A in group 3; and 46 with haemophilia A and 30 with haemophilia B in group 4). The estimated mean annualised bleeding rate ratio for treated spontaneous and traumatic bleeding episodes during concizumab prophylaxis versus no prophylaxis was 0·14 (95% CI 0·07-0·29; p<0·0001) for patients with haemophilia A and 0·21 (0·10-0·45; p<0·0001) for patients with haemophilia B. The most frequent adverse events in patients who received concizumab were SARS-CoV-2 infection (19 [13%] of 151 patients), an increase in fibrin D-dimers (12 [8%] patients), and upper respiratory tract infection (ten [7%] patients). There was one fatal adverse event possibly related to treatment (intra-abdominal haemorrhage in a patient from group 4 with haemophilia A with a long-standing history of hypertension). No thromboembolic events were reported between the trial restart and confirmatory analysis cutoff. Concizumab was effective in reducing the bleeding rate compared with no prophylaxis and was considered safe in patients with haemophilia A or B without inhibitors. The results of this trial suggest that concizumab has the potential to be one of the first subcutaneous treatment options for patients with haemophilia B without inhibitors. Novo Nordisk.

Obstetric Penicillin Allergy Evaluations

BackgroundPenicillin allergy is reported in 5-15% of the world population, with 3-10% of pregnant women reporting the same. However, more than 90% of these patients can tolerate penicillin after appropriate evaluation. Penicillin is indicated for various issues that arise in pregnancy, and a history of allergy can have negative individual and public health consequences. ObjectiveTo prospectively evaluate the feasibility, safety, and select obstetric outcomes of obstetric penicillin allergy evaluations arranged through a direct referral phone line from obstetric practices to an employed allergy/immunology practice. MethodsPatients were referred via direct phone line for evaluation during their antenatal visits between May 2019 and May 2022. Patients skin prick testing, and those with negative PST were given an amoxicillin challenge. In select cases, direct oral challenge was performed with a low-risk history. Data were analyzed using descriptive statistics. For detailed Methods, please see the Methods section in this article's Online Repository at www.jacionline.org ResultsOf the 324 patients referred between May 2019 to May 2022, 251 (77.5%) presented for in-office evaluations. 239/251 (95.2%) patients underwent penicillin skin testing followed by oral challenge if negative, 12 (4.8%) patients underwent direct challenge without skin testing, and all of them passed the challenge. Of the patients undergoing penicillin skin testing, 230 (97.2%) had negative skin testing and 229 tolerated subsequent oral amoxicillin doses, with 1 patient experiencing a delayed reaction to the amoxicillin. The patients who presented for evaluation had more people who lived in Zip codes that have been attributed to have high socioeconomic status, compared to the no-show group (73.7% vs 63.3%). ConclusionWe are the largest study to date to demonstrate the safety and feasibility of a phone line for obstetric penicillin allergy referrals. We demonstrate a better show rate than previous analyses, with most of these patients successfully de-labeled.

RTS, S malaria vaccination among children aged 24–59 months in the Sunyani Municipality, Ghana; 2023

BackgroundFollowing the successful pilot of RTS,S malaria vaccine, it has been recommended by the WHO for prevention of Plasmodium falciparum malaria in children living in endemic areas. Despite the proven benefits of the malaria vaccine, uptake especially of the fourth dose, remains relatively low. We assessed complete uptake of RTS,S malaria vaccine among children 24–59 months and associated factors in the Sunyani Municipality of Ghana. MethodsA cross-sectional study was conducted among 361 caregivers of children aged 24–59 months in the Sunyani Municipality, who had received at least one dose of RTS,S malaria vaccine. Structured questionnaires were administered to caregivers and relevant vaccination information was extracted from the maternal and child health record books. Binary logistic regression analysis was used to determine factors associated with complete uptake of the vaccine at 95 % confidence interval (CI). ResultsApproximately 45 % (164/361) of the children had completed the RTS,S malaria vaccination schedule. Children aged 48–59 months (AOR:0.26, 95 %CI:0.09–0.76), those with caregivers who believed that children were being used for experiment (AOR:0.29, 95 %CI:0.16–0.54) or doubted the safety of the vaccine (AOR:0.27, 95 %CI:0.14–0.52) were less likely to complete the four doses. On the other hand, children of caregivers who reported vaccine shortages and travelled long distances to access immunization services (AOR:3.15, 95 %CI:1.17–8.47), and those with adequate knowledge on the malaria vaccine (AOR:1.89, 95 %CI:1.08–3.29) were more likely to complete the vaccination schedule. ConclusionLess than half of the children who started RTS,S malaria vaccination completed the full schedule. Age of child, caregiver knowledge and perception of the malaria vaccine, and access to immunization service were associated with complete uptake of the RTS,S malaria vaccine. Strengthening caregiver education and access to immunization services could improve uptake of the subsequent doses and coverage of the fourth dose.

Short-Acting Oral Nifedipine versus Intravenous Labetalol for the Control of Severe Hypertension in the Postpartum Period: A Retrospective Cohort Study.

This study aimed to compare the effectiveness of oral short-acting (SA) nifedipine with intravenous (IV) labetalol for the treatment of postpartum (PP) severe hypertension. We conducted a retrospective cohort study of women who delivered at a tertiary care facility between January and December 2018, had not previously received antihypertensive medication, and required treatment for PP severe hypertension defined as systolic blood pressure (SBP) ≥ 160 mm Hg and/or diastolic blood pressure (DBP) ≥110 mm Hg. Exposure groups were defined by the receipt of either oral SA nifedipine or IV labetalol. The primary outcome was time (minutes) to BP control (SBP < 160 mm Hg and DBP <110 mm Hg). Secondary outcomes included number of doses required to achieve BP control, crossover to the alternative medication, and recurrence of severe range BP after the achievement of BP control. t-Tests and Wilcoxon-Mann-Whitney tests were used to analyze continuous variables and chi-square tests or Fisher's exact tests were used to analyze categorical variables. Multivariable linear regression models were conducted for the primary outcome, controlling for potential confounders in a sequential fashion across three models. A Kaplan-Meier plot was also created. Of the 99 women included, 74 received oral SA nifedipine and 25 received IV labetalol. There was no significant difference in minutes to initial BP control between groups (30.5 minutes [interquartile range, IQR: 20.0-45.0] vs. 25.0 minutes [IQR: 14.0-50.0]; p = 0.82) or in the rate of recurrent severe BP. However, patients who received nifedipine required fewer doses to achieve control (p < 0.01) and did not require crossover (0 vs. 12%, p = 0.01). Both oral SA nifedipine and IV labetalol are effective options for treating PP severe hypertension. An initial choice of nifedipine was associated with a lower requirement for subsequent doses of medication and no need for crossover to an alternative antihypertensive medication. · Nifedipine and labetalol effectively treat PP severe HTN.. · Nifedipine requires fewer doses to treat PP severe HTN.. · Both have low recurrence rates of severe HTN..

Comparison of 4.54% hypertonic saline and 20% mannitol for brain relaxation during auditory brainstem implantation in pediatric patients: a single-center retrospective observational cohort study

BackgroundMannitol is frequently utilized to achieve intracranial brain relaxation during the retrosigmoid approach for auditory brainstem implantation (ABI). Hypertonic saline (HS) is an alternative for reducing intracranial pressure; however, its application during ABI surgery remains under-investigated. We aimed to compare the efficacy and safety between HS and mannitol for maintaining brain relaxation.MethodsThis single-center retrospective cohort study included pediatric patients undergoing ABI surgery from September 2020 to January 2022 who received only 4.54% HS or 20% mannitol for brain relaxation. The analysis involved initial doses, subsequent doses, and dosing intervals of the two hyperosmolar solutions, as well as the time elapsed from meningeal opening to the first ABI electrode placement attempt. Additionally, the analysis encompassed electrolyte testing, hemodynamic variables, urine output, blood transfusion, second surgeries, adverse events, intensive care unit length of stay, and 30-day mortality.ResultsWe analyzed 68 consecutive pediatric patients; 26 and 42 in the HS and mannitol groups, respectively. The HS group exhibited a reduced rate of supplementary use (7.7% vs. 31%) and lower total urine volume. Perioperative outcomes, mortality, and length of intensive care unit stay did not exhibit significant between-group differences, despite transient increases in blood sodium and chloride observed within 2 h after HS infusion.ConclusionsIn pediatric ABI surgery, as an osmotherapy for cerebral relaxation, 4.54% HS demonstrated a lower likelihood of necessitating additional supplementation than 20% mannitol. Furthermore, the diuretic effect of HS was weak and the increase in electrolyte levels during surgery was temporary and slight.

Dosimetric optimization for dynamic mixed beam arc therapy (DYMBARC).

Non-coplanarity and mixed beam modality could be combined to further enhance dosimetric treatment plan quality. We introduce dynamic mixed beam arc therapy (DYMBARC) as an innovative technique that combines non-coplanar photon and electron arcs, dynamic gantry and collimator rotations, and intensity modulation with photon multileaf collimator (MLC). However, finding favorable beam directions for DYMBARC is challenging due to the large solution space, machine component constraints, and optimization parameters, posing a highly non-convex optimization problem. To establish DYMBARC and solve the pathfinding challenge by employing direct aperture optimization (DAO) to determine the table angles and gantry angle ranges of photon and electron arcs for different clinically motivated cases. The method starts by generating a grid of beam directions based on user-defined resolutions along the gantry and table angle axes for each beam quality considered. Beam directions causing collisions or entering through the end of CT are excluded. For electrons, a fixed source-to-surface distance of 80cm is used to reduce in-air scatter. Electron beam energies with insufficient range to reach the target or beam directions impinging on the table before reaching the patient are excluded. The remaining beam directions form the pathfinding solution space. Promising photon and electron MLC-defined apertures, with associated monitor unit (MU) weights, are iteratively added using a hybrid-DAO algorithm. This algorithm combines column generation to add apertures and simulated annealing to further refine aperture shapes and weights. Apertures are added until the requested number of paths are formed and the user-defined maximum total gantry angle range is reached. Paths are resampled to a finer gantry angle resolution and subject to DAO for simultaneous optimization of beam intensities along the photon/electron arcs. Subsequent final dose calculation and MU weight reoptimization result in a deliverable DYMBARC plan. DYMBARC plans are created for three clinically motivated cases (brain, breast, and pelvis) and compared to DYMBARC variants: colli-DTRT (dynamic collimator trajectory radiotherapy) using non-coplanar photon arcs; and Arc-MBRT (mixed beam radiotherapy) using photons and electrons but restricted to coplanar setup. Additionally, a manually defined volumetric modulated arc therapy (VMAT) setup serves as a reference clinical technique. Dose distributions, dose-volume histograms, and dosimetric endpoints are evaluated. Dosimetric validation with radiochromic film measurements (gamma evaluation, 3% / 2mm (global), 10% dose threshold) is performed on a TrueBeam system in developer mode for one case. While maintaining similar target coverage and homogeneity, DYMBARC reduced mean doses to organs-at-risk compared to VMAT by an average of 3.2, 0.5, and 2.9Gy for the brain, breast, and pelvis cases, respectively. Similar or smaller mean dose reductions were observed for Arc-MBRT or colli-DTRT, compared to VMAT. Electron contributions to the mean planning target volume dose ranged from 2% to 34% for DYMBARC and from 11% to 40% for Arc-MBRT. Measurement validation showed>99.7% gamma passing rate. DYMBARC was successfully established using a dosimetrically optimized pathfinding approach, combining non-coplanarity with mixed beam modality. DYMBARC facilitated the determination of photon and electron contributions on a case-by-case basis, enhancing more personalized treatment modalities.

Social and Emotional Determinants of COVID-19 Vaccination Attitudes among the Elderly at Health Center Manatuto, Timor-Leste

This study aimed to identify the key factors influencing COVID-19 vaccine acceptance among the elderly at Manatuto Villa Health Center, Kota Manatuto, Timor-Leste, with a focus on knowledge, social influence, personal experiences, emotional factors, and access to health information. A cross-sectional design was used, involving 278 respondents aged 60 years and above who completed the structured questionnaires. Data analysis was conducted using univariate, bivariate, and logistic regression to identify the main determinants of vaccine acceptance. The results revealed that 72% of respondents lacked sufficient knowledge about the benefits of COVID-19 vaccination, which was attributed to low education levels and limited access to information (p &lt; 0.05). Additionally, 12% of the respondents reported negative experiences related to vaccine side effects, such as dizziness and nausea, which increased their hesitancy to receive subsequent doses. Social and family influences were also significant, with 71% of respondents following the advice of religious and community leaders in making vaccination decisions. Emotional factors, such as anxiety and fear of declining health due to old age, affected 67% of the respondents, becoming a barrier to vaccine acceptance. This study concludes that improving knowledge through community-based outreach programs, addressing anxiety, and involving trusted local leaders are essential strategies for enhancing vaccine acceptance among the elderly. The practical implications of these findings highlight the need for policies that focus on community education and outreach approaches to increase vaccination coverage in areas with limited access to healthcare.

The effect of a subsequent dose of dexmedetomidine or other sedatives following an initial dose of dexmedetomidine on electrolytes, acid-base, creatinine, and troponin in dogs. Part II

The effect of a subsequent dose of dexmedetomidine or other sedatives following an initial dose of dexmedetomidine on electrolytes, acid-base, creatinine, and troponin in dogs. Part II

The effect of a subsequent dose of dexmedetomidine or other sedatives following an initial dose of dexmedetomidine on sedation and quality of recovery in dogs. Part I

The effect of a subsequent dose of dexmedetomidine or other sedatives following an initial dose of dexmedetomidine on sedation and quality of recovery in dogs. Part I

Anti-ovarian cancer migration and toxicity characteristics of a platinum(IV) pro-drug with axial HDAC inhibitor ligands in zebrafish models

SummaryOvarian cancer is the fifth leading cause of cancer related death in the United States. Cisplatin is a platinum-based anti-cancer drug used against ovarian cancer that enters malignant cells and then damages DNA causing cell death. Typically, ovarian cancer cells become resistant to cisplatin making it necessary to increase subsequent dosage, which usually leads to side-effects including irreversible damage to kidney and auditory system tissue. Ovarian cancer resistance is often associated with upregulation of histone deacetylase (HDAC) enzymes that cause DNA to adopt a closed configuration which reduces the ability of cisplatin to target and damage DNA. Compound B, a platinum(IV) complex with two axial phenylbutyrate (PBA) HDAC inhibitor ligands attached to a cisplatin core, can simultaneously inhibit HDAC activity and damage DNA causing decreased cancer cell viability in cisplatin-sensitive (A2780) and -resistant (A2780cis) ovarian cancer cell lines. However, compound B was not previously evaluated in vivo. As simultaneously inhibiting HDAC-mediated resistance with cisplatin treatment could potentiate the platinum drug’s effect, we first confirmed the anti-cancer effect of compound B in the A2780 and A2780cis cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide spectrophotometric assay. Then, we used zebrafish embryo and transgenic animal models to comparatively analyze the effect of cisplatin, compound B, and controls on general organismal, auditory, and renal system toxicity, and cancer metastasis. We found that lower dosages of compound B (0.3 or 0.6 µM) than of cisplatin (2.0 µM) could cause similar or decreased levels of general, auditory, and renal tissue toxicity, and at 0.6 µM, compound B reduces cancer metastasis more than 2.0 µM cisplatin.