Risk Of Severe Side Effects Research Articles

Highly sensitive MXene-based voltammetric sensor for nanomolar clozapine detection

Clozapine is vital for managing schizophrenia and other psychiatric disorders. As a potent medication with risks of severe side effects, accurate detection ensures effective treatment monitoring, patient safety, and optimization of therapeutic outcomes. Herein, niobium carbide two-dimensional transition metal carbides (Nb2CTx MXene) was prepared by etching niobium aluminum carbide (Nb2AlC), which was next partially oxidized by a hydrothermal method to niobium oxide (Nb2O5)/Nb2CTx and ultrasonically bound to carboxylated multi-walled carbon nanotubes (MWCNTs-COOH). It was modified onto a glassy carbon electrode for the detection of the antipsychotic drug clozapine ingested by humans. The morphology and electrochemical properties of MXene-based nanocomposite electrode were verified by scanning electron microscopy, X-ray diffractometry, Raman, cyclic voltammetry and electrochemical impedance characterization methods. The results showed that electrode responded well to clozapine solutions, with good linearity (R2 = 0.9979 and 0.9995) of the peak currents with clozapine concentrations (0.01–1.0 μM and 1.0–10.0 μM) and that this sensor had good immunity, repeatability, reproducibility and stability. The limit of detection was 8.38 nM and the recovery was 92.5 % ~ 106.5 % in real serum and urine samples. The MXene-based sensors offer excellent analytical performance and hold promise for cost-effective generalisation to the detection of nanomolar clozapine in a variety of clinical applications.

Understanding the experience, treatment preferences and goals of people living with chronic lymphocytic leukemia (CLL) in Australia

BackgroundListening to patient voices is critical, in terms of how people experience their condition as well as their treatment preferences. This research explored the patient journey, therapy attributes and goals among treatment experienced adults with chronic lymphocytic leukemia (CLL). We sought to understand patient experiences, needs and expectations to identify areas for improvement of treatment and care delivery.MethodsTwo online surveys were developed for completion by CLL patients. In Stage 1, participants completed a best-worst scaling (BWS) task to evaluate eleven previously validated healthcare journey moments that matter (MTM). Responses were used to generate the patient experience index (PEI) score. In Stage 2, participants completed a survey that included both a discrete choice experiment (DCE) to assess drivers of treatment preferences by evaluating the relative attribute importance (RAI) of seven features and a BWS exercise which explored long-term treatment goals.ResultsTwenty-five patients completed Stage 1 and thirty patients Stage 2. Treatment experience was balanced between oral and intravenous medication. The most important/least satisfied MTM were treatment effectiveness, access to support and other treatments as well as monitoring progress. The median PEI score was 66.2 (out of 100). DCE results demonstrated that patients most value treatments for CLL that are associated with prolonged progression free survival (PFS; RAI: 24.6%), followed by treatments that have a lower risk of severe side effects and lower out-of-pocket costs (RAI: 19.5%, 17.4%, respectively). The remainder of the weight in decision making (38.5%) was split between the remaining attributes, namely ‘mild to moderate side effects’ (13.4%), ‘long-term risks’ (12.2%), type of treatment (i.e., oral, IV or a combination of oral and IV; 8.7%) and treatment duration (i.e., ongoing versus fixed; 4.2%). Patients preferred oral to intravenous therapy. The most valued long-term treatment goal was to be physically healthy, followed by living a long life, spending time with family/friends, and avoiding hospitalization.ConclusionTreatment experienced patients with CLL are focused on receiving effective, safe therapies and value long PFS. Consideration and discussion of other attributes, such as once daily dosing, oral only medication, out-of-pocket costs and access to support services may affect patient treatment choices and ultimately enhance their healthcare experience and outcomes.

Successful Management of Opioid-refractory Pelvic Cancer Pain Using Continuous Local Anesthetic Infusion via a Tunneled Epidural

Opioid refractory pelvic cancer pain is common and difficult to manage, which often results in analgesic polypharmacy and escalating opioid doses, alongside the use of interventional techniques. However, up-titration of opioids often results in systemic side effects, and interventional procedures have limitations in their duration of action, efficacy, and risk of nerve damage. Therefore, intrathecal pumps have been utilized as a more permanent option for pain management. Their ability to deliver localized therapy using a variety of pharmacological agents makes it an attractive option for cancer pain management. However, they are limited by a need for careful titration, pump volume constraints, and risks of severe side effects. These limitations can be mitigated by targeting the epidural space instead, and we propose the use of a tunneled epidural catheter technique for continuous local anesthetic infusion in opioid-refractory pelvic and abdominal cancer pain. In this case report, we describe a patient with pelvic and abdominal cancer pain due to stage IV sigmoid adenocarcinoma with widespread metastases, who received adequate pain management from a continuous local anesthetic infusion through a tunneled lumbar epidural catheter. Throughout this patient’s hospital admission, their opioid requirements remained the same, and their pain remained well controlled on review in the community one month after discharge. This case demonstrated that epidural catheters with local anesthetic as the sole neuraxial analgesic agent over a short duration could potentially provide preventive analgesia. This case highlights that a local anesthetic tunneled epidural, without addition of neuraxial opioids, is an effective alternative to intrathecal pumps in managing complex cancer pain and has potential for preventive analgesia.

Understanding Lithium intoxication in Bipolar Disorder: a comparative analysis and clinical implications

IntroductionLithium treatment is a proven method for bipolar disorder management, but its narrow therapeutic range and the risk of severe side effects, including lithium intoxication, pose significant clinical hurdles. Lithium intoxication, a potentially life-threatening complication, can occur during treatment, raising ongoing questions about its clinical factors, risk elements, and best practices for management.ObjectivesOur objective is a comparative analysis between patients who have experienced lithium intoxication and those who have not, aiming to identify influencing factors and enhance clinical care.MethodsWe collected demographic data, age at lithium treatment initiation, treatment duration, therapeutic adherence, Mental Health consultations, and lithium level monitoring from 14 individuals requiring clinical attention due to lithium intoxication and 14 patients with similar gender, age, and diagnosis with lithium treatment but without intoxication during four years of follow-up.ResultsRegarding the results, the age of onset of lithium treatment in patients with lithium intoxication was 30.2 years (SD=8), and the duration of lithium treatment averaged 11.1 years (SD=8.8), which did not significantly differ from the control group with ages of onset at 38.1 years (SD=15.1) and treatment duration of 9.27 years (SD=8.8), respectively. Lithium intoxication patients developed severe complications, including hospitalizations in medical-surgical units, the necessity for dialysis, and death, one fatal case. Although therapeutic adherence to lithium, measured through pharmaceutical dispensation, exceeded 90% and was comparable in both groups, patients affected by lithium intoxication exhibited a significantly higher treatment discontinuation rate (OR 32.5; 95% CI, 3.1 to 337.8) during the follow-up period. Patients who experienced lithium intoxication had an average of psychiatric consultations every 11.2 months (SD=13.4), with 35.7% not attending at least once a year, while the control group had an appointment every 5.31 months (SD=2.7) (p > 0.05). Lastly, despite both groups having a similar frequency of plasma lithium level monitoring, occurring approximately every 5.5 months (SD=2.6) and 7.8 months (SD=4.8), respectively, in 28.5% of those who suffered from lithium intoxication did not undergo any monitoring for periods exceeding 18 months (p < 0.05).ConclusionsOur research highlights the significance of delivering thorough clinical care and continuous monitoring to patients receiving lithium treatment for bipolar disorder. Ensuring effectiveness therapeutic adherence and maintaining strict monitoring of lithium levels are critical factors that significantly enhance treatment safety. Appropriate management has the potential to improve the quality and safety of care for people with bipolar disorder who are dependent on lithium therapy.Disclosure of InterestNone Declared

Paresis Following Type A Botulinum Toxin (Dysport) Injection: A Case Report

: Primary hyperhidrosis (PH) is a condition characterized by excessive sweating. Primary treatment options include antiperspirants or anticholinergics for symptomatic relief, while axillary and palmar hyperhidrosis can be addressed with surgery. Botulinum toxin type A (BTX-A) is a significant treatment option for these patients. This toxin inhibits the release of acetylcholine, preventing overactive eccrine sweat glands from causing excessive sweating. Despite its effectiveness in treating various neurological and cosmetic conditions, Botox may pose the risk of severe side effects resulting from local or systemic drug release. We report the case of a 21-year-old woman who developed weakness in all four limbs, dyspnea, dysphagia, and blurred vision two weeks after botulinum toxin injection for hyperhidrosis treatment.

Factors associated with COVID-19 vaccine uptake and hesitancy among healthcare workers in the Democratic Republic of the Congo.

Vaccination is a critical intervention to reduce morbidity and mortality and limit strain on health systems caused by COVID-19. The slow pace of COVID-19 vaccination uptake observed in some settings raises concerns about COVID-19 vaccine hesitancy. The Democratic Republic of the Congo experienced logistical challenges and low uptake at the start of vaccine distribution, leading to one of the lowest overall COVID-19 vaccine coverage rates in the world in 2021. This study assessed the magnitude and associated factors of COVID-19 vaccine uptake among healthcare workers (HCWs) in seven provinces in DRC. We implemented a cross-sectional Knowledge, Attitudes, and Practices (KAP) questionnaire targeting HCWs, administered by trained data collectors in Haut-Katanga, Kasaï Orientale, Kinshasa, Kongo Centrale, Lualaba, North Kivu, and South Kivu provinces. Data were summarized and statistical tests were performed to assess factors associated with vaccine uptake. HCWs across the seven provinces completed the questionnaire (N = 5,102), of whom 46.3% had received at least one dose of COVID-19 vaccine. Older age, being married, being a medical doctor, being a rural resident, and having access to or having previously worked in a COVID-19 vaccination site were all strongly associated with vaccination uptake. Vaccinated individuals most frequently cited protection of themselves, their families, and their communities as motivations for being vaccinated, whereas unvaccinated individuals were most concerned about safety, effectiveness, and risk of severe side effects. The findings suggest an opinion divide between vaccine-willing and vaccine-hesitant HCWs. A multidimensional approach may be needed to increase the acceptability of the COVID-19 vaccine for HCWs. Future vaccine campaign messaging could center around the positive impact of vaccination on protecting friends, family, and the community, and also emphasize the safety and very low risk of adverse effects. These types of messages may further be useful when planning future immunization campaigns with new vaccines.

Patients' Preferences for Systemic Lupus Erythematosus Treatments-A Discrete Choice Experiment.

Symptoms of systemic lupus erythematosus (SLE) vary between patients, but those of increased disease activity typically include musculoskeletal and mucocutaneous manifestations such as joint pain, swelling, and rashes. Several treatment options are available to patients with SLE with variable efficacy. Many treatments, especially corticosteroids, cause unwanted side effects, although little is currently known about patients' preferences for treatments of SLE. We aimed to identify which attributes of SLE treatment are valued by patients and to quantify their relative importance. Adult participants with moderate-to-severe SLE were asked to make a series of choices between two hypothetical treatments in an online discrete choice experiment (DCE). A latent class model (LCL) was estimated to analyze choice data. Relative attribute importance (RAI) was calculated to determine the importance of each attribute to participants. A total of 342 participants from the USA completed the survey. A three-class LCL model was found to have the best fit. Class 1 (non-attenders) had non-significant preferences across all attributes. To achieve a better fit, a constrained LCL (cLCL) model was run with the two remaining classes. The most important attributes for participants in class 2 (benefit-seekers) were joint pain (RAI = 32.0%), non-joint pain (RAI = 21.8%), fatigue (RAI = 20.1%), and skin rashes and itching (RAI = 19.1%). The most important attributes for participants in class 3 (risk-avoiders) were risk of non-severe side effects from corticosteroids (RAI = 28.4%), risk of severe side effects from corticosteroids (RAI = 21.4%), and the risk of infections (RAI = 19.2%). Risk-avoiders were more likely to have been diagnosed with SLE for a longer period (>1 year) and were more likely to have experience with oral corticosteroids. SLE patients fall into two groups with distinct preferences: benefit-seekers, who prioritize reducing the impact of disease symptoms, and risk-avoiders, who prioritize avoiding treatment risks. The implication of this finding will depend on the reasons for these differences, which warrant further research. Our study suggests that these differences arise due to the impact of disease and treatment experience on preferences. If so, well-informed patients may not be willing to tolerate the risks associated with oral corticosteroids in exchange for their benefits.

Intrinsic immunomodulatory hydrogels for chronic inflammation.

The immune system plays a pivotal role in maintaining physiological homeostasis and influencing disease processes. Dysregulated immune responses drive chronic inflammation, which in turn results in a range of diseases that are among the leading causes of death globally. Traditional immune interventions, which aim to regulate either insufficient or excessive inflammation, frequently entail lifelong comorbidities and the risk of severe side effects. In this context, intrinsic immunomodulatory hydrogels, designed to precisely control the local immune microenvironment, have recently attracted increasing attention. In particular, these advanced hydrogels not only function as delivery mechanisms but also actively engage in immune modulation, optimizing interactions with the immune system for enhanced tissue repair, thereby providing a sophisticated strategy for managing chronic inflammation. In this tutorial review, we outline key elements of chronic inflammation and subsequently explore the strategic design principles of intrinsic immunomodulatory hydrogels based on these elements. Finally, we examine the challenges and prospects of such immunomodulatory hydrogels, which are expected to inspire further preclinical research and clinical translation in addressing chronic inflammation.

Patients accept therapy using embryonic stem cells for Parkinson’s disease: a discrete choice experiment

BackgroundNew disease-modifying ways to treat Parkinson’s disease (PD) may soon become a reality with intracerebral transplantation of cell products produced from human embryonic stem cells (hESCs). The aim of this study was to assess what factors influence preferences of patients with PD regarding stem-cell based therapies to treat PD in the future.MethodsPatients with PD were invited to complete a web-based discrete choice experiment to assess the importance of the following attributes: (i) type of treatment, (ii) aim of treatment, (iii) available knowledge of the different types of treatments, (iv) effect on symptoms, and (v) risk for severe side effects. Latent class conditional logistic regression models were used to determine preference estimates and heterogeneity in respondents’ preferences.ResultsA substantial difference in respondents’ preferences was observed in three latent preference patterns (classes). “Effect on symptoms” was the most important attribute in class 1, closely followed by “type of treatment,” with medications as preferred to other treatment alternatives. Effect on symptoms was also the most important attribute in class 2, with treatment with hESCs preferred over other treatment alternatives. Likewise for class 3, that mainly focused on “type of treatment” in the decision-making. Respondents’ class membership was influenced by their experience in treatment, side effects, and advanced treatment therapy as well as religious beliefs.ConclusionsMost of the respondents would accept a treatment with products emanating from hESCs, regardless of views on the moral status of embryos. Preferences of patients with PD may provide guidance in clinical decision-making regarding treatments deriving from stem cells.

Initial Report of Boswellia Serrata for Management of Cerebral Radiation Necrosis after Stereotactic Radiosurgery for Brain Metastases

Radiation necrosis (RN) is a concerning late toxicity after radiation therapy (RT) for brain metastases. Oral corticosteroids are the mainstay of management; however, they are not optimal for long-term use given multiple side effects and drug interactions, particularly with the emergence of immunotherapy for several cancers. Boswellia serrata (BS) is an over-the-counter supplement used for its anti-inflammatory properties and has been recently shown to reduce cerebral edema after brain RT. We evaluated the response rates with BS in a series of patients with brain metastases treated with stereotactic radiosurgery (SRS) who developed RN. We included patients who developed RN after SRS for brain metastases at our institution from 2020-2022 and were treated with BS. Patients were prescribed over the counter BS 4.2-4.5g daily in divided doses. Follow-up MRI imaging was obtained every 2-3 months after starting BS. Response was assessed using Response Assessment in Neuro-Oncology (RANO) criteria. Primary endpoint was ≥25% decrease in edema volume on T2-FLAIR MRI from baseline. Patients were censored if they had tumor progression or repeat RT to necrotic area, or death. Kaplan-Meier curves were used for survival estimates. A total of 50 patients received BS for Grade 1-3 CTCAE v5.0 RN (G1 = 11, G2 = 36, and G3 = 3). Median age was 62.8 years (range 36.9 - 50) and median RT dose was 24 Gy in 3 fractions. Median time to RN after SRS was 10 months(m). Median follow-up after starting BS was 6m and 40 patients had at least 1 follow up MRI available to evaluate response. The best response was complete response (CR) in 15% patients and partial response (PR) in 40% while 35% had stable disease (SD) and 10% had progressive disease. Median time to CR was 9m (6-12m) and PR was 6m (3-12m). Percentage of patients who had any response (CR or PR) at 3, 6, 9 and 12 months was 25%, 60%, 43% and 50%, respectively. 56% patients had symptomatic RN, of which 35.7% had improvement in symptoms with BS alone, while 64% required steroid use. Overall, median duration of response in patients with CR, PR or SD was 7.5m(range 2-31m). Salvage treatment for RN was steroids (33), surgery (4), Bevacizumab (5) or hyperbaric oxygen therapy (1). No patients had any CTCAE grade 3 or higher toxicities. 3 patients (6%) had any side-effects all of whom had Grade 1-2 gastrointestinal intolerance or diarrhea. 2 patients stopped treatment due to enrolment on an immunotherapy clinical trial. Overall, 39 patients remained on BS at last follow-up or death. We observed >50% response rates with use of BS in our cohort of patients with Grade 1-3 RN after SRS. More than 1/3rd patients with symptomatic RN were able to avoid long-term steroid use. BS is an easily available over-the-counter drug that appears to be a safe and promising treatment option for RN, and can potentially decrease steroid dependence in these patients, reducing the risk of several side-effects. Further prospective studies to compare Boswellia with placebo is warranted.

Potential analgesic effects of psychedelics on select chronic pain conditions: A survey study.

Chronic pain is a major cause of suffering and disability and is often associated with psychiatric complications. Current treatments carry the risk of severe side effects and may lead to limited or no relief at all in a relevant portion of this patient population. Preliminary evidence suggests that classical psychedelics (e.g. LSD and psilocybin) may have analgesic effects in healthy volunteers, and in certain chronic pain conditions and observational studies reveal that they are used in naturalistic settings as a means to manage pain. In order to gain insight on the effectiveness of such compounds in chronic pain conditions, we set up a survey addressed to chronic pain patients inquiring about psychedelic use and the relief levels achieved with both conventional treatments, full psychedelic doses and microdoses. We analysed data related to five conditions selected based on diagnostic homogeneity within each of them: fibromyalgia, arthritis, migraine, tension-type headache and sciatica. Except for sciatica, volunteers reported that psychedelics led to better pain relief compared to conventional medication in all examined conditions. More specifically, full doses performed better than conventional medication. Microdoses led to significantly better relief compared to conventional medication in migraines and achieved comparable relief in the remaining three categories. Implications for future research are discussed. Full doses and microdoses may hold value in the treatment of some specific chronic pain conditions. Psychedelic substances are receiving increasing attention from the scientific literature because of evidence showing beneficial effects on several measures related to mental health in clinical samples and healthy volunteers samples. Previous evidence suggests that people suffering from chronic pain are using psychedelics to seek relief and the present paper presents the results of a survey study investigating their use and analgesic effects among individuals suffering from fibromyalgia, arthritis, migraine, tension-type headache and sciatica.

Investigating preferences of the covid-19 vaccine among individuals in Iran: Discrete choice experiment analysis.

This study aimed to estimate the preferences for COVID-19 vaccines among a sample of Iranian adults and to understand the sources of preference heterogeneity. A web-based survey was conducted from April to July 2021; out of 1747 participants, 678 completed the survey. Seven key attributes were selected, namely effectiveness, risk of severe side effects, risk of mild side effects, number of doses, duration of protection, location of manufacture, and price. Additionally, conditional logit and mixed logit models were used to analyze the data. The results of this study indicate that vaccine effectiveness, protective duration, the risk of side effects, and price are the most important factors that influence vaccine preferences. Furthermore, we identified heterogeneity in preferences, indicating that not all individuals respond in the same way to vaccine attributes. The majority of Iranians prefer to get the Covid-19 vaccine. Policymakers should consider these findings when implementing successful programs. This study contributes to the literature by estimating Iranian respondents' preferences for the Covid-19 vaccine and identifying the heterogeneity in their preferences for vaccine attributes. The findings may also inform future research and policies related to Covid-19 vaccination programs in Iran.

Sarcoma Patients Admitted to the Intensive Care Unit (ICU): Predictive Relevance of Common Sepsis and Performance Parameters.

Prognosis of sarcoma patients is improving, with a better understanding of sarcomagenesis revealing novel therapeutic targets. However, aggressive chemotherapy remains an essential part of treatment, bearing the risk of severe side effects that require intensive medical treatment. Available data on the characteristics and clinical outcome of sarcoma patients admitted to intensive care units (ICU) are sparse. We performed a retrospective analysis of sarcoma patients admitted to the ICU from 2005 to 2022. Patients ≥18 years with histologically proven sarcoma were included in our study. Sixty-six patients were eligible for analysis. The following characteristics had significant impact on overall survival: sex (p=0.046), tumour localization (p=0.02), therapeutic intention (p=0.02), line of chemotherapy (p<0.001), SAPS II score (p=0.03) and SOFA score (p=0.02). Our study confirms the predictive relevance of established sepsis and performance scores in sarcoma patients. For overall survival, common clinical characteristics are also of significant value. Further investigation is needed to optimize ICU treatment of sarcoma patients.

Combination therapy with immune check point inhibitors and acute kidney injury

Background Immune checkpoint inhibitors have revolutionized the treatment of metastatic renal cell carcinoma and malignant melanoma but are also associated with a risk of severe side effects. Nephrotoxicity is an immune checkpoint inhibitor-related adverse effect, but acute kidney injury (AKI) can also be caused by other more common conditions. This study aimed to describe the incidence and causes of AKI in patients treated with combination therapy of immune checkpoint inhibitors. Material and methods This retrospective cohort study included 200 patients receiving ipilimumab and nivolumab for either metastatic renal cell carcinoma or malignant melanoma at the Department of Oncology at Copenhagen University Hospital, Herlev between 1 January 2019 and 31 December 2020. The incidence and cause of AKI within 6 months after treatment was determined. Results In the 96 patients treated for malignant melanoma 15 patients (16%) had an episode of AKI. Two of these patients had potential immune checkpoint inhibitor-related AKI both of which received treatment with a proton pump inhibitor (PPI). Of the 104 included patients with metastatic renal cell carcinoma 26 patients (25%) developed AKI. Five of these patients had potential immune checkpoint inhibitor-related AKI. Treatment with PPI before the development of AKI occurred in 4 out of these 5 patients. Conclusion Patients receiving combination therapy with checkpoint inhibitors are at high risk of AKI, but different causes of AKI should always be considered. Use of PPI concurrently with ICIs is likely to increase the risk of AKI.

Malaria prevention using antibodies: A promising approach to passive protection.

Madam, malaria is a parasitic infection that is one of the leading causes of death in developing countries like Pakistan. According to WHO, an estimated 241 million malaria cases were reported in 2020 (1). Vaccines have been developed to prevent malaria but with limited efficacy. Using next-generation antibodies can be a possible option to reduce malarial infection. Recently, a phase 1 trial conducted by NIAID at the National Institute of Health (NIH), USA, clinical centre has reported promising results with using intravenous and subcutaneous antibodies for malaria prophylaxis in healthy adults(2). Chemoprophylaxis drugs like chloroquine, mefloquine, and atovaquone/proguanil has been used for malaria in Pakistan, but it has led to the generation of drug-resistant strains(3). WHO approved a subunit vaccine for children in 2021 but it has limited efficacy and risk of severe side effects(4). Considering these aspects, the using monoclonal antibodies may be a practical step toward decreasing the number of malaria cases. The trial demonstrated that using antibodies in adults who had not had malaria or vaccinated previously was associated with substantial passive immunity. The immunity was tested after exposing the participants to controlled human malaria infection. Parasitemia, as determined by PCR, developed in all 6 participants from the control group, while only two out of 17 participants from the intervention group showed parasitemia (2). Pakistan reports malaria cases throughout the year, with most cases occurring in the summer (5). Using malaria antibodies can help advance protection in countries like Pakistan with seasonal transmission. Although, the economic cost of using this intervention must be considered especially for developing countries.

Parental refusal and hesitancy of vaccinating children against COVID-19: Findings from a nationally representative sample of parents in the U.S.

The uptake rate of COVID−19 vaccines among children remains low in the U.S. This study aims to 1) identify sociodemographic and behavioral factors influencing parental refusal of vaccinating children, and 2) quantify the relative importance of vaccine characteristics in parental hesitancy of vaccinating children. An online survey was conducted from October to November 2021 among a probability-based, representative sample of 1456 parents with children under age 18. The survey included a discrete choice experiment asking parents to choose between two hypothetical COVID-19 vaccine alternatives with varying levels of characteristics in 10 hypothetical scenarios. Logistic regressions were used to estimate parental refusal (refused to choose any vaccine alternatives in all hypothetical scenarios) and random parameter logit regressions were used to estimate parental hesitancy (choice of vaccine alternatives depended on vaccine characteristics) of vaccinating children. About 20% parents refused to vaccinate children. The refusal is predicted by parents' sociodemographic characteristics, political orientation, vaccination status, and parents' and children's previous exposure with COVID-19. Among parents who were willing to consider vaccinating children, the most important vaccine characteristics are risk of severe side effects (31.2% relative importance) and effectiveness (30.7%), followed by protection duration (22.6%), local coverage (9.4%), and hospitalization rate of unvaccinated children (6.1%). Our findings imply that policymakers and public health professionals could develop outreach programs at community level to encourage specific subgroups and focus on vaccination depoliticization. Effectively communicating the low risk of severe side effects and high effectiveness of the vaccines may relieve some of the parental hesitancy.

Bile salt deconjugation and in-vitro cholesterol-lowering ability of probiotic bacteria isolated from buttermilk

ABSTRACT Hypercholesterolemia prevalence is increasing in most countries and it increases the risk of microvascular and cardiovascular diseases. Currently available treatments include the use of statins, fibrates, and bile acid sequesters. These treatments carry a risk of severe side effects on the host. Probiotics are well documented for their cholesterol-lowering abilities. The present study has demonstrated the screening of probiotic bacteria from buttermilk samples, their ability to deconjugate bile salts, and cholesterol-lowering ability in the media. Bile salt hydrolysis by the isolates was evaluated by direct plate assay, thin layer chromatography, and cholic acid estimation. The highest amount of cholesterol was removed in the presence of 0.3% bile. Co-precipitation of cholesterol along with cholic acid was also observed. Three isolates considered potent based on their performance through all the tests were identified by 16S- rRNA gene sequencing as PGB01- Lacticaseibacillus paracasei, PGB02- Lactiplantibacillus plantarum, and PGB05- Lacticaseibacillus paracasei subsp. tolerans.

CD9- and CD81-positive extracellular vesicles provide a marker to monitor glioblastoma cell response to photon-based and proton-based radiotherapy.

Glioblastoma multiforme (GBM) is the most aggressive tumor of the central nervous system with a poor prognosis. In the treatment of GBM tumors, radiotherapy plays a major role. Typically, GBM tumors cannot be cured by irradiation because of intrinsic resistance machanisms. An escalation of the irradiation dose in the GBM tumor is difficult due to the high risk of severe side effects in the brain. In the last decade, the development of new irradiation techniques, including proton-based irradiation, promised new chances in the treatment of brain tumors. In contrast to conventional radiotherapy, irradiation with protons allows a dosimetrically more confined dose deposition in the tumor while better sparing the normal tissue surrounding the tumor. A systematic comparison of both irradiation techniques on glioblastoma cells has not been performed so far. Despite the improvements in radiotherapy, it remains challenging to predict the therapeutical response of GBM tumors. Recent publications suggest extracellular vesicles (EVs) as promising markers predicting tumor response. Being part of an ancient intercellular communication system, virtually all cells release specifically composed EVs. The assembly of EVs varies between cell types and depends on environmental parameters. Here, we compared the impact of photon-based with proton-based radiotherapy on cell viability and phenotype of four different glioblastoma cell lines. Furthermore, we characterized EVs released by different glioblastoma cells and correlated released EVs with the cellular response to radiotherapy. Our results demonstrated that glioblastoma cells reacted more sensitive to irradiation with protons than photons, while radiation-induced cell death 72 h after single dose irradiation was independent of the irradiation modality. Moreover, we detected CD9 and CD81-positive EVs in the supernatant of all glioblastoma cells, although at different concentrations. The amount of released CD9 and CD81-positive EVs increased after irradiation when cells became apoptotic. Although secreted EVs of non-irradiated cells were not predictive for radiosensitivity, their increased EV release after irradiation correlated with the cytotoxic response to radiotherapy 72 h after irradiation. Thus, our data suggest a novel application of EVs in the surveillance of anti-cancer therapies.

Stated choice analysis of preferences for COVID-19 vaccines using the Choquet integral

We investigate preferences for COVID-19 vaccines using data from a stated choice survey conducted in the US in March 2021. To analyse the data, we embed the Choquet integral, a flexible aggregation operator for capturing attribute interactions under monotonicity constraints, into a mixed logit model. We find that effectiveness is the most important vaccine attribute, followed by risk of severe side effects and protection period. The attribute interactions reveal that non-pecuniary vaccine attributes are synergistic. Out-of-pocket costs are independent of effectiveness, incubation period, and mild side effects but exhibit moderate synergistic interactions with other attributes. Vaccine adoption is significantly more likely among individuals who identify as male, have obtained a bachelor’s degree or a higher level of education, have a high household income, support the democratic party, had COVID-19, got vaccinated against the flu in winter 2020/21, and have an underlying health condition.

Stereotactic Gamma Knife® Radiosurgery of Intraocular Retinoblastoma: Six-Year Experience.

BackgroundExternal beam radiotherapy for resistant retinoblastoma is now seen as a last resort to saving the eye because of the risk of severe side effects: secondary cancers and cosmetic problems of orbital bone growth retardation. To reduce such complications, treatment modalities have shifted towards new radiation therapy techniques. No information on single fraction Gamma Knife® radiosurgery (GKRS) for intraocular retinoblastoma exists.Materials and methodsEighteen children (19 eyes) with retinoblastoma were treated with GKRS. The mean age at the time of treatment was 35 months (from 12 to 114 months). Before GKRS, all routes of chemotherapy delivery were held in all cases. The eligibility criteria for GKRS were retinoblastomas not amenable either to systemic or local chemotherapy and local ophthalmological treatment, retinoblastomas too large for conventional local methods, and inability to perform intraarterial chemotherapy. Conventional external beam radiotherapy was excluded in the presented cases, given the possible complications mentioned above. In every case, eye removal was suggested to the child's parents, but they flatly refused. GKRS was proposed as the last chance to save the eye (in four cases, it was performed on the only eye). The median prescribed dose was 22 Gy (interquartile range [IQR]: 18-35 Gy), and the median prescribed isodose was 50% (IQR: 36-90%).ResultsLocal control was achieved in 79% of cases (complete tumor regression in 69%, incomplete regression in 10%). Two eyes (10.5%) could not be preserved and had to be enucleated due to the tumor recurrence. Two eyes (10.5%) developed secondary complications (total vitreous hemorrhage, retinal detachment, and iris neovascularization), making adequate tumor control nearly impossible. Overall, 15 eyes (79%) were preserved, and four eyes (21%) were enucleated after GKRS with no signs of tumor recurrence and metastasis in the mean follow-up of 41 months. No acute radiation side effects occurred in any patient after GKRS. Ten children (10 eyes, 53%) were diagnosed with vitreous hemorrhage from mild to severe. Three eyes presented with optic neuropathy one year after GKRS, and four eyes developed retinopathy. Radiation-induced cataract occurred in two eyes. There were no cases of secondary glaucoma or keratopathy in our study. All patients and eyes treated by GKRS were stable within 41 months (from seven to 74 months).ConclusionsSingle fraction Gamma Knife® radiosurgery may be a reasonable salvage treatment for resistant and recurrent retinoblastoma as an alternative approach to enucleation in selected cases. GKRS should be considered in retinoblastoma management.