Fentanyl

• Vaccines with higher effectiveness and longer protection were preferred • Risk of side effects significantly reduced vaccine acceptance likelihood • Vaccines from the US, UK, and EU were preferred over Chinese and Russian ones • Two latent classes identified: pro-vaccine and vaccine-resistant groups • Trust, attitudes, and prior experience derived class membership The objective of this study was to quantify public preferences for alternative vaccination programme strategies, combining vaccine attributes and policy measures, that could be deployed in future outbreaks similar to COVID-19 in South Africa. A discrete choice experiment (DCE) was conducted among 3,002 South African respondents. Attributes included vaccine effectiveness, duration of protection, side-effect risk, vaccine origin, approval time, and social restrictions including stringency of restrictions and vaccine mandate. Multinomial Logit (MNL) and Latent Class (LC) models were estimated to explore preferences. Vaccines with higher effectiveness were consistently preferred by South African respondents. Similarly, vaccines offering longer immunity durations and those approved after longer evaluation periods were preferred. Vaccines originating from the EU, UK, and US were preferred over those from China. In contrast, vaccines associated with higher risks of severe side effects were significantly less preferred. A latent class model identified two distinct groups: a majority (68.3%) classified as “provaccine,” who demonstrated strong preference for vaccination, often driven by trust in institutions and positive vaccine attitudes; and a minority (31.7%) categorised as “vaccine-resistant” who exhibited reluctance towards vaccination, likely driven by lower institutional trust, negative vaccine attitudes, and reduced health risk aversion. COVID19 vaccine preferences in South Africa were strongly influenced by perceived effectiveness, approval time, origin of the vaccine, duration of protection, risks of side effects, social restrictions and vaccine mandates. Respondents exhibited diverse preference patterns, and public health strategies should be designed to reflect these differences. Understanding how people make decisions about vaccines can help improve public health communication and planning. This research used a method that asked South Africans to imagine different vaccine scenarios and choose which ones they would prefer. People preferred vaccines that were highly effective, lasted longer, and had fewer side effects. Vaccines made in Western countries like the US, UK, and EU were preferred over those from China or Russia. Importantly, not everyone thinks about vaccines the same way. We found two main groups: one willing to vaccinate, trusting institutions and prioritising community health, and another prioritising individual rights, and not willing to vaccinate. By recognizing and addressing the diverse values that influence decision-making, public health initiatives can better support informed choices and strengthen community engagement during future outbreaks.

The impact of vaccination and patient characteristics on influenza vaccination uptake of elderly people: A discrete choice experiment

OBJECTIVE: This study aimed to compare the efficacy of oral prednisolone prescribed to admitted patients in two ways: full-dose prednisolone (continuous maximum tolerable doses of prednisolone) and tapering doses of prednisolone (steadily reduced doses of prednisolone). MATERIALS and METHODS: Fifty-four sudden sensorineural hearing loss (SSNHL) patients, admitted to our hospital between January 2012 and April 2013, were enrolled as the study subjects. Based on the specialists’ clinical experience, 27 patients received full-dose prednisolone (Group I). The other 27 received a tapering dose of prednisolone (Group II). We analyzed the efficacy of the two management groups by assessing the patients’ hearing recovery after 6 months of treatment. RESULTS: After 6 months, the average absolute hearing gain and recovery rate in Group I were 23.94 dB and 74% respectively, which was better than the 19.83 dB and 63% in Group II. However, there was no statistically significant difference in the efficacy of treatment between the groups. One patient in Group I developed the side effect of acute closed-angle glaucoma. The other 53 patients were free from severe side effects. CONCLUSION: Prescription of a tapering dose of prednisolone is highly recommended as routine management for patients with sudden sensorineural hearing loss. Compared with full-dose treatment, it has equivalent efficacy while reducing the risk of severe side effects.

BackgroundThe main characteristics present in patients with psychomotor agitation include restlessness, excessive motor activity, irritability, and heightened responsiveness to internal and external stimuli. This umbrella review evaluates the efficacy and safety of pharmacological interventions for patients with psychiatric disorders presenting psychomotor agitation, aged 18 years or older. A comprehensive literature search was conducted to identify umbrella reviews that met our study's inclusion criteria. However, no reviews were found that specifically investigated the efficacy and safety of pharmacological interventions for agitated psychiatric patients presenting with both behavioral and psychological symptoms, such as emotional lability, decreased attention span, and cognitive and behavioral alterations. The primary objective is to assess the effectiveness of pharmacological interventions in controlling patients within a short time frame, measured in hours rather than days. The focus was placed on studies addressing treatment in emergency settings, whether in general hospitals or psychiatric facilities, with an emphasis on managing acute psychomotor agitation rather than long-term maintenance treatment.MethodA comprehensive literature search for meta-analyses and systematic reviews assessing the efficacy and safety of pharmacological treatment for psychomotor agitation in psychiatric inpatients and emergency department patients was conducted across various databases such as PubMed, Scopus, EMBASE, Web of Science and COCHRANE Central database. Included reviews comprised those that incorporated randomized controlled trials (RCTs) or non-randomized controlled trials (NRCTs) comparing the efficacy and safety of pharmacological interventions for agitated psychiatric patients (with both psychological and behavioral symptoms).ResultsLoxapine (10 mg) demonstrated superior efficacy over 5 mg in reducing agitation within 120 min, with inhaled formulations providing rapid relief in patients with acute psychosis. Aripiprazole was effective and caused less sedation compared to Olanzapine, although Haloperidol required fewer additional doses but was less effective at 60 min. Ziprasidone, administered intramuscularly, offered a faster onset and was better tolerated than Haloperidol. Lorazepam proved effective with fewer side effects than antipsychotics and showed enhanced efficacy when combined with them. Midazolam provided rapid sedation but posed risks of severe side effects, especially in older adults. Droperidol was as effective as Olanzapine but provided faster sedation. Combination therapy, such as Haloperidol with Promethazine, effectively reduced aggression with a lower incidence of adverse effects.ConclusionThis umbrella review offers a comprehensive overview of the pharmacological management of psychomotor agitation in patients with psychiatric disorders. Among the most frequently used medications in the reviewed studies were haloperidol, olanzapine, and lorazepam. The findings underscore the importance of tailored treatment approaches and the need for further research to refine the management of psychomotor agitation in psychiatric settings.

Should health authorities exclude vaccines with a small risk of severe side effects during a deadly pandemic, even if this is expected to lead to more harm due to delayed vaccination and prolonged social distancing measures? This question was at the centre of controversy amid the COVID-19 pandemic, where countries excluded vaccines with harmful side effects for some or all groups. Through this case study, I test the normative force and empirical applicability of principles for vaccine allocation and argue for the superiority of a Principle of Sufficient Benefit, according to which health authorities should only offer vaccines that sufficiently improve the recipient’s prospects. I present multiple challenges to the principle: that it is self-defeating, leads to unfair and societally worse outcomes, and prevents people from doing their duties. Given the force of these objections, I conclude that the most satisfactory justification for excluding riskier vaccines fails. In the final section, I argue that compensating people for receiving vaccines with higher risks is a way of retaining the force of the Principle of Sufficient Benefit while accounting for the possibly unfair and harmful consequences that result from putting the recipients first.

Among the more than 90 identified genetic risk loci for late-onset Alzheimer's disease (AD) and related dementias, the apolipoprotein E gene ( APOE ) ɛ2/ɛ3/ɛ4 polymorphism remains the longstanding benchmark for genetic disease risk with a consistently large effect across studies 1-10 . Despite this massive signal, the exact mechanisms for how ɛ4 increases and for how ɛ2 decreases dementia risk is not well-understood. Importantly, recent trials of anti-amyloid therapies suggest less efficacy and higher risks of severe side effects in ε4 carriers 11-13 , hampering the treatment of those with the highest unmet need. To improve our understanding of the genetic architecture of AD in the context of its main genetic driver, we performed genome-wide association studies (GWASs) stratified by ε4 and ε2 carrier status. Such insights may help to understand and overcome side effects, to impact clinical trial enrolment strategies, and to create the scientific basis for targeted mechanism-driven therapies in neurodegenerative diseases.

Prévention par insectifuge chez l’enfant

Peanut (Arachis hypogaea) allergy is a major cause of food-induced anaphylaxis, with increasing prevalence worldwide. To date, there is no cure for peanut allergy, and, unlike many other food allergies, it usually persists through to adulthood. Prevention of exposure to peanuts is managed through strict avoidance, which can be compromised by the frequent use of peanuts and peanut products in food preparations. Conventional subcutaneous-injection allergen immunotherapy using crude peanut extract is not a recommended treatment because of the risk of severe side effects, largely as a result of specific IgE antibodies. Consequently, there is an urgent need to develop a suitable peanut allergen preparation that can induce specific clinical and immunological tolerance to peanuts in allergic individuals without adverse side effects. This requires detailed molecular and immunological characterisation of the allergenic components of peanut. This article reviews current knowledge on clinically relevant peanut allergens, in particular Ara h 1, Ara h 2 and Ara h 3, together with options for T-cell-reactive but non-IgE-binding allergen variants for specific immunotherapeutic strategies. These include T-cell-epitope peptide and hypoallergenic mutant vaccines. Alternative routes of administration such as sublingual are also considered, and appropriate adjuvants for delivering effective treatments at these sites examined.

An abnormal increase in blood glucose level leads to diabetes, which is characterized as major metabolic disorder. Risk of various serious complications like diabetic retinopathy, diabetic neuropathy, diabetic non-healing foot ulcers and muti-organ failure increases in patients present with uncontrolled diabetes. Diabetes can be managed in patients by using various marketed conventional anti-diabetic drugs which are expensive and lead to multiple severe side-effects in patients. Considering this, various cost-effective herbal medicines are developed that can be used for the effective management of diabetes with a lower risk of severe side effects. Investigation of various herbal plants has been conducted in past few years to evaluate their efficacy in the treatment of Type 1 and Type 2 diabetes. Findings of experimental studies provide evidence that presence of natural antioxidants, flavonoids, and tannins as secondary active metabolites is responsible for the significant anti-hyperglycemic activity of various herbal plants which are associated with considerable potential to regenerate beta-cells activity and reduce blood glucose levels. Providing detailed information about the herbal plant’s utility as anti-diabetics in various conventional medicines is the major objective of this review article. These include Coriandar Sativum, Aloe Vera, Zingiber Officinale, Tinospora Cardiofolia, Ferula Asafoetida, and Andrographis Paniculata.

BackgroundAdapter chimeric antigen receptor (CAR) approaches have emerged has promising strategies to increase clinical safety of CAR T-cell therapy. In the UniCAR system, the safety switch is controlled via a target module (TM) which is characterized by a small-size and short half-life. The rapid clearance of these TMs from the blood allows a quick steering and self-limiting safety switch of UniCAR T-cells by TM dosing. This is mainly important during onset of therapy when tumor burden and the risk for severe side effects are high. For long-term UniCAR therapy, the continuous infusion of TMs may not be an optimal setting for the patients. Thus, in later stages of treatment, single infusions of TMs with an increased half-life might play an important role in long-term surveillance and eradication of residual tumor cells. Given this, we aimed to develop and characterize a novel TM with extended half-life targeting the tumor-associated carbohydrate sialyl-Tn (STn).MethodsThe extended half-life TM is composed of the STn-specific single-chain variable fragment (scFv) and the UniCAR epitope, fused to the hinge region and Fc domain of a human immunoglobulin 4 (IgG4) antibody. Specific binding and functionality of the αSTn-IgG4 TM as well as pharmacokinetic features were assessed using in vitro and in vivo assays and compared to the already established small-sized αSTn TM.ResultsThe novel αSTn-IgG4 TM efficiently activates and redirects UniCAR T-cells to STn-expressing tumors in a target-specific and TM-dependent manner, thereby promoting the secretion of proinflammatory cytokines and tumor cell lysis in vitro and in experimental mice. Moreover, PET-imaging results demonstrate the specific enrichment of the αSTn-IgG4 TM at the tumor site, while presenting a prolonged serum half-life compared to the short-lived αSTn TM.ConclusionIn a clinical setting, the combination of TMs with different formats and pharmacokinetics may represent a promising strategy for retargeting of UniCAR T-cells in a flexible, individualized and safe manner at particular stages of therapy. Furthermore, as these molecules can be used for in vivo imaging, they pose as attractive candidates for theranostic approaches.

Background Anticancer treatments near the end of a patient’s life should generally be avoided, as it leaves the patient with no significant anticancer effect but increases the risk of severe side effects. We described the pattern of all end-of-life anticancer treatment in a population of Danish cancer patients. Methods Using the Danish national health registries, we identified all patients deceased due to cancer 2010–2015. Anticancer treatment registered in the last 30 days of life was categorized as end-of-life treatment. Predictors of such treatment were investigated using logistic regression models. Results We identified 42,277 patients (median age 70 years) of whom 16% received end-of-life anticancer treatment. This proportion did not change during the study period (p = .09). Chemotherapy alone was the most frequent treatment, accounting for 78% of all end-of-life treatment in 2010, decreasing to 71% in 2015. In contrast, end-of-life use of immunotherapy, targeted therapy and endocrine therapy increased during the study period. Breast cancer as index cancer was associated with the highest frequency of end-of-life treatment (23%), followed by malignant melanoma (21%), and prostate cancer (18%). Factors associated with lower odds for end-of-life treatment were female sex, older age, high burden of comorbidity, and being diagnosed >6 months prior to death. Conclusions We found a stable overall rate at 16% of patients receiving anticancer treatment within one month prior to death in this nationwide sample of cancer deaths. Further research is needed to assess whether this level of end-of-life treatment is justified or reflects inappropriate use.

19 children with a deeply located cerebral glioma were treated with continuous interstitial irradiation (stereotactically implanted 125-iodine). The accumulated dose at the tumor surface ranged in the low grade glioma group (Group A) from 55 to 100 Gy and in the high grade glioma group (group B) from 50 to 65 Gy. Patients in group B additionally received a fractionated external beam irradiation (15-20 Gy boost dose). Tumor shrinkage as seen on CT-scans 6 months postoperatively could be achieved in 100% of patients with a low grade glioma. The response rate of 6 children with a high grade glioma was 83%. With a mean follow up of 57.0 months (group A) and 56.2 months (group B) respectively the estimated 4.5 year survival probability was 92% for low grade gliomas and 83% for grade III/grade IV lesions. Permanent interstitial irradiation offers the possibility of local tumor control with low risk of severe side effects. The survival rates are promising and comparable with results of other study groups. For gliomas grade I and grade II a dose reduction may be feasible.

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.

The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS) and severe hearing loss is common in NF2 patients. Vascular endothelial growth factor (VEGF) expression level in NF2 correlates with tumour growth rate and bevacizumab, a VEGF-binding antibody, has previously been shown to induce tumour shrinkage and improve hearing. We retrospectively reviewed the effect of bevacizumab on hearing and VS tumour size in 12 consecutive NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every second week for 6 months; hereafter, bevacizumab 15 mg/kg was administered every third week. Patients were evaluated with repeated audiometries, MR scans and clinical evaluations. Radiological response was defined as a 20 % or greater reduction in VS volume. A total of 398 treatments (median 36) were administered and the median duration on therapy was 22 months (range 7-34). We observed a radiological response (≥20 % tumour shrinkage) in seven out of 18 tumours (39 %) in six out of 12 patients (50 %). Sustained radiological responses were maintained in six tumours (33 %) for more than 2 months. Three patients had objectively improved hearing and five patients reported subjective benefit in neurological symptoms, including improved hearing. Toxicity was in general manageable; however, one patient died from cerebral haemorrhage which was possibly related to therapy. In conclusion, bevacizumab improved hearing and reduced the size of VS in some patients with progressive NF2 which corroborates previous findings; however, the risk of severe side effects should be carefully considered and discussed with the patients prior to treatment.

Cebranopadol, a Novel First-in-Class Analgesic Drug Candidate: First Experience With Cancer-Related Pain for up to 26 Weeks