Risk Of Serious Side Effects Research Articles

The Role of Dihydroresveratrol in Enhancing the Synergistic Effect of Ligilactobacillus salivarius Li01 and Resveratrol in Ameliorating Colitis in Mice.

Currently approved therapeutical strategies for inflammatory bowel diseases (IBD) suffer from variable efficacy and association with risk of serious side effects. Therefore, efforts have been made in searching for alternative therapeutics strategies utilizing gut microbiota manipulation. In this study, we show that the probiotic strain Ligilactobacillus salivarius Li01 (Li01) and the phytochemical prebiotic resveratrol (RSV) have synergistic effect in ameliorating colitis in mice. Oral coadministration of Li01 (109 CFU/d) and RSV (1.5 g/kg/d) promoted restoration of various inflammatory injuries and gut microbiota composition, exhibiting a favorable anti-inflammatory effect in DSS-induced colitis mice. The combination treatment was associated with reductions in the levels of proinflammatory cytokines IL-1β and IL-6 and increases in the levels of the anti-inflammatory cytokine IL-17A in mouse serum. Moreover, the combination treatment was found to alter the composition and metabolism of the gut microbiota, especially influencing the production of short chain fatty acids and anti-inflammatory related molecules. The mechanism underlying the improved anti-inflammatory effect from the RSV and Li01 combination treatment was found to be associated with the environmental sensor mammalian aryl hydrocarbon receptor (AHR) and tryptophan metabolism pathway. Administration of RSV in combination with Li01 in different mouse model led to enhanced conversion of RSV into metabolites, including dihydroresveratrol (DHR), resveratrol-sulfate, and resveratrol-glucuronide. DHR was found to be the dominant metabolite of RSV in conventional and colitis mice. An increased DHR/RSV ratio was confirmed to activate AHR and contribute to an enhanced anti-inflammatory effect. DHR is considered as a potential AHR ligand. The DHR/RSV ratio also affected the serotonin pathway by controlling the expression of Tph1, SERT, and 5-HT7R leading to amelioration of colitis in mice. Our data suggest that treatment with a combination of Li01 and RSV has potential as a therapeutic strategy for IBD; further investigation of this combination in clinical settings is warranted.

A Review of Acute and Long-Term Neurological Complications Following Haematopoietic Stem Cell Transplant for Paediatric Acute Lymphoblastic Leukaemia.

Despite advances in haematopoietic stem cell transplant (HSCT) techniques, the risk of serious side effects and complications still exists. Neurological complications, both acute and long term, are common following HSCT and contribute to significant morbidity and mortality. The aetiology of neurotoxicity includes infections and a wide variety of non-infectious causes such as drug toxicities, metabolic abnormalities, irradiation, vascular and immunologic events and the leukaemia itself. The majority of the literature on this subject is focussed on adults. The impact of the combination of neurotoxic drugs given before and during HSCT, radiotherapy and neurological complications on the developing and vulnerable paediatric and adolescent brain remains unclear. Moreover, the age-related sensitivity of the nervous system to toxic insults is still being investigated. In this article, we review current evidence regarding neurotoxicity following HSCT for acute lymphoblastic leukaemia in childhood. We focus on acute and long-term impacts. Understanding the aetiology and long-term sequelae of neurological complications in children is particularly important in the current era of immunotherapy for acute lymphoblastic leukaemia (such as chimeric antigen receptor T cells and bi-specific T-cell engager antibodies), which have well-known and common neurological side effects and may represent a future treatment modality for at least a fraction of HSCT-recipients.

In vivo treatment with M8, a highly diluted tinctures complex, reduced the malignancy of a mouse melanoma model

Background: Cancer is a class of disease responsible for 13% of death cause worldwide. Among all types of cancers, one of the most aggressive and with the highest death rate is melanoma. It is highly metastatic and current treatments with chemotherapeutic drugs do not yield satisfactory results. Therefore, the interest on new therapeutics for cancer treatment has been increasing on research. Highly diluted tinctures (HDT) are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Previous results have demonstrated in vitro inhibition of invasion ability and in vivo anti-metastatic potential of B16F10 lung metastasis model after mice treatment with M8 inhalation.
 
 Aims: Now we have evaluated M8 effects on hyaluronic acid and its specific melanoma cell surface receptor (CD44) expression on lungs after inhalation by mice.
 
 Methodology: M8 compounds include Aconitum napellus 20dH, Arsenicum album 18dH, Asa foetida 20dH, Calcarea carbonica 16dH, Conium maculatum 17dH, Ipecacuanha 13dH, Phosphorus 20dH, Rhus toxicodendron 17H, Silicea 20dH, Sulphur 24dH, and Thuja occidentalis 19dH. B16F10 Melanoma cells were inoculated into C57B/L6 mouse lateral tail vein. Treatment started 24 hours after inoculation, and was repeated after each 12 hours during 14 days on an inhalation chamber that is adapted to little rodents. Mice were subjected to euthanasia by intraperitoneal injection of thiopental followed by decapitation. Lungs were surgically removed and analyzed under a stereomicroscope for the presence of metastatic foci. They were formaldehyde fixed, dehydrated and paraffin embedded. Histological sections were processed for hematoxilin/eosin (HE), Fontana-Masson and immunohistochemistry staining methods. Images were captured and blindly analysed by ImageJ (NIH) software.
 
 Results: HE and Fontana-Masson showed a reduction in number and size of metastatic nodules, as previously demonstrated. We have detected a reduction on hyaluronic acid as well as CD44 expression on mice lungs after M8 treatment. The high metastatic potential of melanoma is proportional to hyaluronic acid expression level, together with its specific cell surface receptor, the CD44. These results suggest that M8 treatment reduces malignancy of mouse melanoma through modulation of hyaluronic acid and CD44 expression, which play crucial roles in tumor invasion and growth.
 
 Conclusion: Even though further investigation are necessary to elucidate the mechanisms of action of M8 treatment there is an indication that these highly diluted tinctures could be a promising therapy to treat metastatic melanoma.

Clinical outcomes in adults' subjects with aphthous stomatitis treated with an oral hyaluronic acid-based medical device.

Oral mucosal ulcers are quite common in an otherwise healthy population and can determine a real worsening of the quality of life. Conventional therapy is not appropriate since ulcers often recur and, even if not needed, therapy lasting not less than 2-3 weeks carries a high risk of serious side effects. The use of hyaluronic acid applied as an adhesive gel over the lesions seems to have potential in terms of efficacy and the avoidance of side effects. Of course, hyaluronic acid-based formulations show different effects and tolerability. In our study, we retrospectively reported the results obtained using a medical device, Bloxaphte® (Bausch & Lomb, Macherio, Monza-Brianza, Italy), applied for 14 days to counteract ulcers in adults. Treatment with the HA-based oral gel determined better results both in terms of the number of oral lesions and in terms of lesion sizes. Regarding the number of lesions, the results are significant even after 6 days of treatment, while 3 days are enough to differentiate the two groups with respect to lesion sizes. Our data clearly demonstrate the healing capability and safety profile of the product in reducing the number and size of the ulcers within the first week of daily application.

Association between body composition and chemotherapy‐related toxicity in children with lymphoma and rhabdomyosarcoma

Body composition is associated with chemotherapy toxicity (chemotoxicity) in adults with cancer; this association remains unexplored in children with cancer. Using baseline computed tomography scans of 107 children with Hodgkin lymphoma (n = 45), non-Hodgkin lymphoma (n = 42), or rhabdomyosarcoma (n = 20), this study examined body composition (skeletal muscle index [SMI], skeletal muscle density [SMD], and height-adjusted total adipose tissue [hTAT]) to determine its association with chemotoxicity. Clinical characteristics and chemotoxicities were abstracted from medical records. Primary outcomes included grade 4 or higher hematologic toxicities and grade 3 or higher nonhematologic toxicities within 6 months of the diagnosis. Logistic regression models accounting for repeated measures were constructed to examine the association between body composition indices and chemotoxicities; adjustments were made for age at diagnosis, sex, race/ethnicity, cancer type, risk group, body mass index (measured as a percentile), or body surface area. The median SMI was 41.0 cm2 /m2 (range, 25.8-68.6 cm2 /m2 ), the median SMD was 54.1 HU (range, 35-69.4 HU), and the median hTAT was 19.5 cm2 /m2 (range, 0-226.7 cm2 /m2 ). Grade 4 or higher hematologic toxicities and grade 3 or higher nonhematologic toxicities were observed in 74.7% and 66.3% of the chemotherapy cycles, respectively. A higher SMD at diagnosis was associated with lower odds of grade 4 or higher hematologic toxicity (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.85-0.97; P = .004). SMI (OR, 0.99; 95% CI, 0.95-1.04; P = .7) and hTAT (OR, 1.00; 95% CI, 0.99-1.01; P = .9) were not associated with hematologic toxicities. Nonhematologic toxicities did not show any association with body composition. The association between low SMD and hematologic toxicities in children with lymphoma or rhabdomyosarcoma could be due to body composition-based biodistribution of chemotherapeutic agents and needs further investigation. Body composition at cancer diagnosis in children with lymphoma and rhabdomyosarcoma may provide information that could identify those at risk for serious side effects from chemotherapy. Routinely used measures such as body mass index and body surface area show poor correlations with body composition assessed via computed tomography scans.

Vaccination against Cancer or Infectious Agents during Checkpoint Inhibitor Therapy.

The use of immune checkpoint inhibitors (ICI) has substantially increased the overall survival of cancer patients and has revolutionized the therapeutic situation in oncology. However, not all patients and cancer types respond to ICI, or become resistant over time. Combining ICIs with therapeutic cancer vaccines is a promising option as vaccination may help to overcome resistance to immunotherapies while immunotherapies may increase immune responses to the particular cancer vaccine by reinvigorating exhausted T cells. Thus, it would be possible to reprogram a response with appropriate vaccines, using a particular cancer antigen and a corresponding ICI. Target populations include currently untreatable cancer patients or those who receive treatment regimens with high risk of serious side effects. In addition, with the increased use of ICI in clinical practice, questions arise regarding safety and efficacy of administration of conventional vaccines, such as influenza or COVID-19 vaccines, during active ICI treatment. This review discusses the main principles of prophylactic and therapeutic cancer vaccines, the potential impact on combining therapeutic cancer vaccines with ICI, and briefly summarizes the current knowledge of safety and effectiveness of influenza and COVID-19 vaccines in ICI-treated patients.

Evaluating patient and physician knowledge of risks and safe use of rivaroxaban: a survey across four countries

ABSTRACT Background At the request of the European Medicines Agency, a Prescriber Guide and Patient Alert Card were developed to increase awareness and understanding about the initiation of rivaroxaban and potential bleeding risk associated with its use. This study evaluated physician and patient awareness and understanding of key safety messages in these educational materials in three waves. Research design and methods Three cross-sectional surveys were administered to physicians and one survey was administered to patients (wave 1 only) with recent rivaroxaban experience in France, Germany, Spain, and the United Kingdom. Results Patient and physician knowledge of key safety information in the educational materials was generally high. Patients’ knowledge was high for questions related to bleeding risk (80% responded correctly), indication (96%), consulting their doctor (86%-91%), and informing other physicians they are taking rivaroxaban (95%). Physicians’ knowledge was particularly high for questions related to bleeding risk (92%-94% across waves), populations at increased risk of serious side effects (76%-94%), contraindications (70%-92%), and invasive procedures (76%-82%). Conclusions Among patients and physicians, the highest levels of knowledge were on the most important risks, as expected. The Prescriber Guide and Patient Alert Card were found to be useful sources of information.

Benefits of Vaccination

Vaccines in routine use around the world have been shown to be clinically well-tolerated and in double-blind randomized prospective controlled field trials – to be efficacious. Furthermore, they have been proven to be effective in routine vaccination programmes worldwide. They have had an excellent safety profile. Vaccinated individuals will face a greatly reduced danger of contracting the targeted disease with a minimal risk of serious side-effects. Should the vaccine fail to give complete protection, the severity of the "breakthrough" disease and its accompanying complications will, in most cases, be less than among the unvaccinated. Mortality, if a possible outcome, will also be greatly reduced. Mass vaccination of children in developed nations have brought many vaccine-preventable diseases under control or even eliminated them. Vaccines have made erstwhile lethal infectious diseases so rare that they have become "victims of their own success" to the point that uninformed people query the necessity of continuing to use them. Unless a disease is eradicated on a global scale – as has been achieved for smallpox and will soon be for poliomyelitis – vaccination cannot cease since the pathogen will quickly reappear and spread with dire consequences. Elimination of disease has many socio-economic, educational, and geo-political advantages. Healthy children grow to become well-educated and productive citizens that live longer. Increased life-expectancy brings prosperity and wealth buys health. Reduced infant mortality will put a brake on population growth in less developed countries and ease pressure on land and food – a determinant of belligerence. Vaccines are a powerful tool to foster equity and peace in the world.

Oral corticosteroids stewardship for asthma in adults and adolescents: A position paper from the Thoracic Society of Australia and New Zealand.

Oral corticosteroids (OCS) are frequently used for asthma treatment. This medication is highly effective for both acute and chronic diseases, but evidence indicates that indiscriminate OCS use is common, posing a risk of serious side effects and irreversible harm. There is now an urgent need to introduce OCS stewardship approaches, akin to successful initiatives that optimized appropriate antibiotic usage. The aim of this TSANZ (Thoracic Society of Australia and New Zealand) position paper is to review current knowledge pertaining to OCS use in asthma and then delineate principles of OCS stewardship. Recent evidence indicates overuse and over‐reliance on OCS for asthma and that doses >1000 mg prednisolone‐equivalent cumulatively are likely to have serious side effects and adverse outcomes. Patient perspectives emphasize the detrimental impacts of OCS‐related side effects such as weight gain, insomnia, mood disturbances and skin changes. Improvements in asthma control and prevention of exacerbations can be achieved by improved inhaler technique, adherence to therapy, asthma education, smoking cessation, multidisciplinary review, optimized medications and other strategies. Recently, add‐on therapies including novel biological agents and macrolide antibiotics have demonstrated reductions in OCS requirements. Harm reduction may also be achieved through identification and mitigation of predictable adverse effects. OCS stewardship should entail greater awareness of appropriate indications for OCS prescription, risk–benefits of OCS medications, side effects, effective add‐on therapies and multidisciplinary review. If implemented, OCS stewardship can ensure that clinicians and patients with asthma are aware that OCS should not be used lightly, while providing reassurance that asthma can be controlled in most people without frequent use of OCS.

Drug Targeting of Inflammatory Bowel Diseases by Biomolecules.

Inflammatory bowel disease (IBD) is a group of disabling, destructive and incurable immune-mediated inflammatory diseases comprising Crohn’s disease (CD) and ulcerative colitis (UC), disorders that are highly prevalent worldwide and demand a large investment in healthcare. A persistent inflammatory state enables the dysfunction and destruction of healthy tissue, hindering the initiation and endurance of wound healing. Current treatments are ineffective at counteracting disease progression. Further, increased risk of serious side effects, other comorbidities and/or opportunistic infections highlight the need for effective treatment options. Gut microbiota, the key to preserving a healthy state, may, alternatively, increase a patient’s susceptibility to IBD onset and development given a relevant bacterial dysbiosis. Hence, the main goal of this review is to showcase the main conventional and emerging therapies for IBD, including microbiota-inspired untargeted and targeted approaches (such as phage therapy) to infection control. Special recognition is given to existing targeted strategies with biologics (via monoclonal antibodies, small molecules and nucleic acids) and stimuli-responsive (pH-, enzyme- and reactive oxygen species-triggered release), polymer-based nanomedicine that is specifically directed towards the regulation of inflammation overload (with some nanosystems additionally functionalized with carbohydrates or peptides directed towards M1-macrophages). The overall goal is to restore gut balance and decrease IBD’s societal impact.

Topical Delivery of Fenugreek Seed Extract Loaded Solid Lipid Nanoparticles Based Hydrogels for Alopecia

Background: Alopecia, a chronic dermatological inflammatory condition affecting the hair follicles. Conventional treatments are associated with the risk of serious side effects. The stratum corneum limits the percutaneous absorption of drugs. Hence, the development of novel herbal formulations for topical delivery has been the target, with the enhancement of their therapeutic efficacy and safety of use.
 Aims: To formulate and characterize Fenugreek seed extract loaded solid lipid nanoparticles carrier for the management of Alopecia to reduce the systemic side effects.
 Methodology: Fenugreek seed extract loaded solid lipid nanoparticles (SLN) were prepared by melt emulsification accompanied by probe sonication. The formulation was prepared using GMS, Tween 80, and Soya lecithin as Lipid, Surfactant, and Co-Surfactant. The SLN was incorporated into carbapol 934 dispersion to convert it into a gel. The SLN formulation was evaluated for size, Polydispersity Index, Zeta Potential, Entrapment efficiency, Transmission Electron Microscopy. After that, the SLN gel was examined for Spreadability, Extrudabilty, Viscosity, In vitro drug release, Ex vivo permeation, and Skin deposition studies.
 Results: The formulated Fenugreek seed extract loaded showed a particle size of 223.36 nm with a narrow PDI of 0.313. Entrapment efficiency revealed that 74.56±0.12% of the drug was entrapped. Transmission electron microscopy images confirmed the spherical nature of the SLN. The extended-release pattern of the formulated SLN for 24h was observed in the in vitro release studies and followed Higuchi model(R2=0.9964). Ex vivo permeability showed a 72.05±0.15% deposition of Fenugreek seed extract loaded SLN. The formulation was stable for three months without significant changes.
 Conclusion: Fenugreek seed extract loaded NLC demonstrated enhanced permeation, improved skin retention, and extended release compared to conventional gel. The developed formulation would be further used for in vivo studies and by seeing above results it can be an alternative for Alopecia in the future.

Tapering of prescribed opioids in patients with long-term non-malignant pain (TOPIO)\u2014efficacy and effects on pain, pain cognitions, and quality of life: a study protocol for a randomized controlled clinical trial with a 12-month follow-up

BackgroundOpioids are still widely prescribed to long-term pain patients although they are no longer recommended for long-term treatments due to poor evidence for long-term efficacy, risks of serious side effects, and the possibility of inducing opioid hyperalgesia. In a Cochrane study from 2017, the authors identified an urgent need for more randomized controlled trials investigating the efficiency and effects of opioid tapering.The study aimed to assess (1) the efficiency of a structured intervention in causing stable reductions of opioid consumption in a population with long-term non-malignant pain and (2) effects on pain, pain cognitions, physical and mental health, quality of life, and functioning in response to opioid tapering.MethodsThe study is a randomized controlled trial. The sample size was set to a total of 140 individuals after estimation of power and dropout. Participants will be recruited from a population with long-term non-malignant pain who will be randomly allocated to (1) the start of tapering immediately or (2) the control group who return to usual care and will commence tapering of opioids 4 months later. A 12-month follow-up is included.When all follow-ups are closed, data from the Swedish drug register of the National Board of Health and Welfare will be collected and individual mean daily opioid dose in morphine equivalents will be calculated at three time points: baseline, 4 months, and 12 months after the start of the intervention. At the same time points, participants fill out the following questionnaires: Numeric Pain Rating Scale (NPRS), Tampa Scale of Kinesiophobia (TSK), Pain Catastrophizing Scale (PCS), Chronic Pain Acceptance Questionnaire (CPAQ-8), Hospital Anxiety and Depression Scale (HADS), and RAND-36. At baseline and follow-up, a clinical assessment of opioid use disorder is performed.DiscussionA better understanding of the efficiency and effects of opioid tapering could possibly facilitate attempts to taper opioid treatments, which might prove beneficial for both the individual and society.Trial registrationClinicalTrials.gov NCT03485430. Retrospectively registered on 26 March 2018, first release date. “Tapering of Long-term Opioid Therapy in Chronic Pain Population. RCT with 12 Months Follow up (TOPIO).” First patient in trial 22 March 2018.

Management of behavioral and psychological symptoms of dementia

IntroductionBehavioral and psychological symptoms of dementia (BPSD) are a heterogeneous group of clinical manifestations related to dementia, including apathy, depression, anxiety, delusions, hallucinations, disinhibition, sleep-wake cycle disturbances, aggression and agitation. BPSD have a negative impact on cognitive decline and increase complications.ObjectivesReview treatment management of BPSD including non-pharmacological and pharmacological options, but mainly interventional approaches, such as electroconvulsive therapy (ECT).MethodsWe conducted a search in PubMed and ClinicalKey with the terms: “Behavioral and psychological symptoms of dementia”; “Electroconvulsive therapy”.ResultsThe vast majority of patients with dementia will develop one or more BPSD. The etiopathogenesis of BPSD is complex and multifactorial, with multiple direct and indirect factors, namely biological, psychological and social aspects and related to changes in cholinergic, dopaminergic, noradrenergic and serotoninergic circuits. Current guidelines recommend non-pharmacological interventions as the first-line approach for BPSD. Pharmacotherapy is often applied, but it carries out the risk of serious side-effects and pharmacologic interactions. There is now growing evidence that interventional approaches, such as ECT, could be safe and efficient when previous treatment options have been exhausted or ineffective, with few contraindications and transient/limited adverse effects.ConclusionsBPSD represent a heterogeneous group of non-cognitive symptoms and behavior that affects most of dementia patients. Combination of non-pharmacological and pharmacological interventions is the recommended therapeutic for BPSD. However, there is usually limited clinical improvement and issues related to tolerability and effectiveness. Currently, ECT is considered a safe and effective option.

Inhaled antibiotics to improve efficacy and safety in the treatment of upper airway and lung inflammatory diseases

Inhaled antibacterial drugs have been used since the 1940s with greater or lesser effectiveness, due to the possibility of targeted delivery of drugs directly to the infection site at concentrations higher than MICs. High local concentrations of antibacterial agents expand the possibilities of treating infections caused by multiresistant strains and reduces antibiotic resistance in the population. The inhaled delivery method is characterized by a high level of safety due to the absence of systemic toxic effects, which reduces the risk of pseudomembranous colitis and other complications of antibiotic therapy. Thiamphenicol glycinate acetylcysteinate is a combined drug that includes thiamphenicol and N-acetylcysteine, which causes its antibacterial and mucolytic activity. The results of clinical studies have demonstrated the effectiveness of TGA in the treatment of acute and chronic bronchitis, chronic obstructive pulmonary disease, community-acquired pneumonia, laryngotracheitis, rhinosinusitis and other infections of the upper and lower respiratory tract. In pediatrics, the drug is used to treat bronchitis and pneumonia, especially those that cannot be treated with other antibacterial drugs, bronchiolitis, whooping cough, and cystic fibrosis. The article presents data on the effectiveness and safety of containing TGA. A wide spectrum of antibacterial actions, the ability to form high local concentrations of antibacterial and mucolytic components in the focus of infection, a low risk of serious side effects in both adults and children are noted. The topical use of the combination drug has proven to be effective not only in bringing about a pronounced clinical improvement, but also in reducing the frequency of use of systemic antibiotic therapy. The efficacy of thiamphenicol glycinate acetylcysteinate is not inferior to macrolide antibiotics.

Peptide allergen-specific immunotherapy for allergic airway diseases-State of the art.

Allergen-specific immunotherapy (AIT) is the only means of altering the natural immunological course of allergic diseases and achieving long-term remission. Pharmacological measures are able to suppress the immune response and/or ameliorate the symptoms but there is a risk of relapse soon after these measures are withdrawn. Current AIT approaches depend on the administration of intact allergens, often comprising crude extracts of the allergen. We propose that the challenges arising from current approaches, including the risk of serious side-effects, burdensome duration of treatment, poor compliance and high cost, are overcome by application of peptides based on CD4+ T cell epitopes rather than whole allergens. Here we describe evolving approaches, summarize clinical trials involving peptide AIT in allergic rhinitis and asthma, discuss the putative mechanisms involved in their action, address gaps in evidence and propose future directions for research and clinical development.

COVID-19 vaccine hesitancy in a representative working-age population in France: a survey experiment based on vaccine characteristics

BackgroundOpinion polls on vaccination intentions suggest that COVID-19 vaccine hesitancy is increasing worldwide; however, the usefulness of opinion polls to prepare mass vaccination campaigns for specific new vaccines and to estimate acceptance in a country's population is limited. We therefore aimed to assess the effects of vaccine characteristics, information on herd immunity, and general practitioner (GP) recommendation on vaccine hesitancy in a representative working-age population in France.MethodsIn this survey experiment, adults aged 18–64 years residing in France, with no history of SARS-CoV-2 infection, were randomly selected from an online survey research panel in July, 2020, stratified by gender, age, education, household size, and region and area of residence to be representative of the French population. Participants completed an online questionnaire on their background and vaccination behaviour-related variables (including past vaccine compliance, risk factors for severe COVID-19, and COVID-19 perceptions and experience), and were then randomly assigned according to a full factorial design to one of three groups to receive differing information on herd immunity (>50% of adults aged 18–64 years must be immunised [either by vaccination or infection]; >50% of adults must be immunised [either by vaccination or infection]; or no information on herd immunity) and to one of two groups regarding GP recommendation of vaccination (GP recommends vaccination or expresses no opinion). Participants then completed a series of eight discrete choice tasks designed to assess vaccine acceptance or refusal based on hypothetical vaccine characteristics (efficacy [50%, 80%, 90%, or 100%], risk of serious side-effects [1 in 10 000 or 1 in 100 000], location of manufacture [EU, USA, or China], and place of administration [GP practice, local pharmacy, or mass vaccination centre]). Responses were analysed with a two-part model to disentangle outright vaccine refusal (irrespective of vaccine characteristics, defined as opting for no vaccination in all eight tasks) from vaccine hesitancy (acceptance depending on vaccine characteristics).FindingsSurvey responses were collected from 1942 working-age adults, of whom 560 (28·8%) opted for no vaccination in all eight tasks (outright vaccine refusal) and 1382 (71·2%) did not. In our model, outright vaccine refusal and vaccine hesitancy were both significantly associated with female gender, age (with an inverted U-shaped relationship), lower educational level, poor compliance with recommended vaccinations in the past, and no report of specified chronic conditions (ie, no hypertension [for vaccine hesitancy] or no chronic conditions other than hypertension [for outright vaccine refusal]). Outright vaccine refusal was also associated with a lower perceived severity of COVID-19, whereas vaccine hesitancy was lower when herd immunity benefits were communicated and in working versus non-working individuals, and those with experience of COVID-19 (had symptoms or knew someone with COVID-19). For a mass vaccination campaign involving mass vaccination centres and communication of herd immunity benefits, our model predicted outright vaccine refusal in 29·4% (95% CI 28·6–30·2) of the French working-age population. Predicted hesitancy was highest for vaccines manufactured in China with 50% efficacy and a 1 in 10 000 risk of serious side-effects (vaccine acceptance 27·4% [26·8–28·0]), and lowest for a vaccine manufactured in the EU with 90% efficacy and a 1 in 100 000 risk of serious side-effects (vaccine acceptance 61·3% [60·5–62·1]).InterpretationCOVID-19 vaccine acceptance depends on the characteristics of new vaccines and the national vaccination strategy, among various other factors, in the working-age population in France.FundingFrench Public Health Agency (Santé Publique France).

Retrospective Observational Study on Predictors of Body Weight and BNP Teduction in Cases of Tolvaptan Induction for Heart Failure

Tolvaptan (TLV) carries the risk of serious side effects, and its introduction requires hospitalization. Therefore, it is important from the viewpoints of safety and medical economics to predict in advance, the patients for whom it will be effective and introduce it. The purpose of this study was to investigate the noninvasive and simple predictors for identifying TLV responders. We conducted a retrospective observational study of patients with heart failure who had TLV introduced at our hospital from January 1, 2017, to December 31, 2018. By using the body weight and BNP reduction as the effect indices, predictors of body weight and BNP reduction were extracted by logistic analysis. The sensitivity and specificity at the cutoff value obtained by ROC analysis were also examined. Among 85 subjects, urine sodium concentration >63 mEq/L [odds ratio (OR): 6.11, 95% confidence interval (CI): 1.36-27.4] was detected as a predictor of body weight reduction. The sensitivity at this cutoff value was 81%, and the specificity was 70%. Serum osmolarity>291 mOsm/L (OR: 3.76, 95% CI: 1.00-14.2), urine potassium concentration<21 mEq/L (OR: 4.45, 95% CI: 1.09-18.2), and urine sodium concentration>71 mEq/L (OR: 7.38, 95% CI: 2.05-26.6) were detected as predictors of BNP reduction. The sensitivities were 62%, 53%, and 73%, and the specificities were 58%, 68%, and 68%, respectively. Therefore, it was suggested that urine sodium concentration may be useful as a predictor of body weight and BNP decrease after TLV induction.

Development of ionic liquid microemulsion for transdermal delivery of a chemotherapeutic agent

Nowadays skin cancers have become a major area of concern because of the continuous exposure to sun rays (UV rays). Hence, the present work focused on the synthesis of an innovative 5-Fluorouracil (5-FU) microemulsion as a topical delivery system mainly used to treat various forms of skin cancer. The topical administration of most of the active compounds is impaired by limited skin permeability due to the presence of skin barriers. In this sequence, the microemulsion represents a cost-effective and convenient drug carrier system that successfully delivers the drug to and across the skin. Unfortunately, 5-FU reveals high toxicity and low tumor affinity became inefficient for patients with the risk of serious side effects. For decreasing of eluding some of its disadvantages we made it more effective by preparing its microemulsion with tween 80 (surfactant), isopropyl alcohol (co-surfactant), oleic acid (oil) in a four-component system. This study emphasized increasing the drug release by multiple times and a topical gel has been formulated and designs to elongate the drug release. All preparation of 5-FU microemulsion was characterized by physicochemical and drug release studies. The size of the 5-FU microemulsion was 550–600 nm confirmed by transmission electron microscopy (TEM) and Zetasizer. The clear microemulsion was prepared at pH 5–6. It shows viscosity in the limit of 13.52–18.23 Pa s. The outcome of the present work is satisfactory for skin cancer treatment.

Individual preferences for COVID-19 vaccination in China

BackgroundVaccinations are an effective choice to stop disease outbreaks, including COVID-19. There is little research on individuals' COVID-19 vaccination decision-making. ObjectiveWe aimed to determine individual preferences for COVID-19 vaccinations in China, and to assess the factors influencing vaccination decision-making to facilitate vaccination coverage. MethodsA D-efficient discrete choice experiment was conducted across six Chinese provinces selected by the stratified random sampling method. Vaccine choice sets were constructed using seven attributes: vaccine effectiveness, side-effects, accessibility, number of doses, vaccination sites, duration of vaccine protection, and proportion of acquaintances vaccinated. Conditional logit and latent class models were used to identify preferences. ResultsAlthough all seven attributes were proved to significantly influence respondents’ vaccination decision, vaccine effectiveness, side-effects and proportion of acquaintances vaccinated were the most important. We also found a higher probability of vaccinating when the vaccine was more effective; risks of serious side effects were small; vaccinations were free and voluntary; the fewer the number of doses; the longer the protection duration; and the higher the proportion of acquaintances vaccinated. Higher local vaccine coverage created altruistic herd incentives to vaccinate rather than free-rider problems. The predicted vaccination uptake of the optimal vaccination scenario in our study was 84.77%. Preference heterogeneity was substantial. Individuals who were older, had a lower education level, lower income, higher trust in the vaccine and higher perceived risk of infection, displayed a higher probability to vaccinate. ConclusionsPreference heterogeneity among individuals should lead health authorities to address the diversity of expectations about COVID-19 vaccinations. To maximize COVID-19 vaccine uptake, health authorities should promote vaccine effectiveness; pro-actively communicate the absence or presence of vaccine side effects; and ensure rapid and wide media communication about local vaccine coverage.

Characteristics, Preferences and Health Care Utilization in Patients Using a Dietary Supplement for Improving Sleeping Disturbances: Results from an Explorative Online Survey.

PurposeSleeping disturbances are highly prevalent in the general population, and pharmacological drug treatment harbours the risk of serious side effects. Many affected persons use dietary supplements for self-treating their symptoms, but little is known about the specific characteristics and preferences of these patients. Even less evidence exists about the consequences of a specific dietary supplement usage on health care utilization. The aim of this study was to explore characteristics, preferences and the impact on health care utilization in patients using a specific over-the-counter dietary supplement, which is promoted for improving sleeping disturbances.Patients and MethodsWe conducted a structured survey and invited a sample of 297 customers of a specific dietary supplement to participate. The survey was open between June and September 2020. Participants were invited by email. All participants accepted an informed consent.ResultsA total of 127 customers participated in the survey (participation rate: 42.8%). Of them, 87.7% were female and the mean age 50.5 years. Participants reported an overall good improvement of symptoms (7.66 on a ten-point Likert-scale) and showed a strong belief in the effectiveness of supplements in general; 67% of participants reported that the intake led to fever physician encounters, and 48.3% reported that they could stop the intake of other pharmaceutical sleeping drugs.ConclusionA significant proportion of participants reported a substantial reduction in pharmaceutical drug use and health care utilization. While these self-reports lack an adequate control, they are still real consumer experiences, and the large beneficial effects – whether placebo or not – explain the popularity of such supplements and their therapeutic potential in sleeping disorders.