Expected Side Effect Research Articles

Functional Role of Novel Anthranilic Acid Derivatives as Anti-inflammatory Agents

Abstract: Background: The discovery of new cyclooxygenase (COX) inhibitors with high efficacy and safety would be a great achievement in developing anti-inflammatory drugs. This study evaluated the anti-inflammatory activity and the expected side effect of two synthesized anthranilic acid derivatives (JS-3 and JS-4). Materials and Methods: The COX selectivity of compounds was assessed in a whole blood assay. The results were confirmed by molecular docking studies. In vivo anti-inflammatory activity was tested in complete Freund’s adjuvant (CFA)-induced rheumatoid arthritis (RA) in rats. The safety profile was determined by administering a dose three times the therapeutic dose. Results: In vitro COX-2 selectivity of JS-4 was higher than JS-3 (13.70 vs. 5.56). Docking studies supported the higher selectivity of both derivatives against COX-2 than mefenamic acid. Treatment of CFA-arthritic rats with both compounds showed significant (P < 0.01) decreases in paw volume, paw thickness, arthritic index, and inflammatory parameters such as rheumatoid factor, interleukin (IL)-1β, IL-6, prostaglandin (PG) E2, PGI2, and TXB2 compared to untreated RA animals. JS-3 and JS-4 improved synovial joint histopathology and protected against RA-induced pathological changes: splenomegaly, thymomegaly, and cardiomyopathy. Both derivatives produced minimal effects on liver and renal functions, without any ulcerogenic effects. Conclusion: These results suggest that JS-4 is a potential and safe candidate for managing RA without renal, liver, gastrointestinal, or cardiovascular toxicity. Keywords: Cyclooxygenase inhibitors, Anthranilic acid derivatives, Mefenamic acid, Rheumatoid arthritis, Anti-inflammatory, Safety evaluation, Molecular docking.

Changes in perception of immunotherapy over time among patients with advanced genitourinary cancers.

328 Background: Previous studies have shown that a significant proportion of patients with metastatic genitourinary cancers harbor inaccurate expectations of cure prior to starting treatment with immunotherapy. This study sought to compare changes in perceptions of immunotherapy reported before, and three months after, the start of therapy, as well as treatment side-effects and quality of life. Methods: This longitudinal study enrolled patients diagnosed with advanced genitourinary cancers (bladder, renal, and prostate cancers) prior to commencing immunotherapy. Patients’ perceptions were assessed prior to starting treatment (T0) and three months later (T1). Patients responded to the same survey at both time points assessing expectations of side effects, clinical outcomes (expectation of cure) and quality of life (Functional Assessment of Chronic Illness Therapy-General). Results: Among the 30 patients enrolled, the median age was 67 years old (range, 44-91); most were male (70%), married (80%), and well-educated (70%). Renal cell carcinoma (70%) was the most common form of cancer. Before starting immunotherapy (T0), patients expected (1) fewer side effects (83%) compared with other types of cancer treatment, (2) great efficacy in preventing tumor progression (90%). and (3) increased survival (90%). Notably, the expectation of cure with immunotherapy treatment had changed over time (T0 = 24% vs T1 = 7%; P = 0.001) and overall quality of life had increased (median at T0 = 90 vs T1 = 98; P = 0.01). Three months into treatment (T1), patients perceived themselves as less active (T0 = 70% vs T1 = 63%; P = 0.02), however just 16% reported severe side effects, including fatigue (10%) and diarrhea (10%). In general, patients were satisfied with the management of these side effects (60%). The majority of patients perceived improvement in their condition (50%) and were satisfied with their treatment (60%). Conclusions: This longitudinal study suggests that inaccurate perceptions of cure with immunotherapy may recede over time, with an increased proportion of patients estimating a more accurate (and lower) chance of cure after 3 months of treatment. Patients also reported improved quality of life despite these adjusted expectations of cure.

Side-effect expectations from COVID-19 vaccination: Findings from a nationally representative cross-sectional survey (CoVAccS – wave 2)

ObjectivesConcern about side effects is one of the most common reasons for refusing vaccination. Side-effect expectations are known to predict perception of side effects. We aimed to investigate the percentage of people who thought side effects from COVID-19 vaccination were likely and investigate factors associated with side-effect expectation. MethodsOnline cross-sectional survey of 1470 UK adults who had not been vaccinated for COVID-19 (conducted 13 to 15 January 2021). We asked participants how likely they thought side effects from COVID-19 vaccination were. Linear regression analyses were used to investigate associations with side-effect expectations. ResultsMost participants were uncertain whether they would experience side effects from a COVID-19 vaccine; only a minority reported that side effects were very likely (9.4%, 95% CI 7.9% to 10.9%, n = 138/1470). Personal and clinical characteristics, general, and COVID-19 vaccination beliefs and attitudes explained 29.7% of the variance in side-effect expectation, with COVID-19 vaccination beliefs alone accounting for 17.2%. Side-effect expectations were associated with: older age, being clinically extremely vulnerable to COVID-19, being afraid of needles, lower perceived social norms for COVID-19 vaccination, lower perceived necessity and safety of COVID-19 vaccination, and perceived lack of information about COVID-19 and vaccination. ConclusionsSide-effect expectation was associated with believing that COVID-19 vaccination was unsafe, ineffective and that others would be less likely to approve of you having a COVID-19 vaccination. Communications should emphasise the safety, effectiveness, and widespread uptake of vaccination, while promoting accurate perceptions of the incidence of vaccination side effects.

A bio-what? Medical companions' perceptions towards biosimilars and information needs in rheumatology.

Patient perceptions influence biosimilar uptake in non-mandatory transitions. Companions (support people) are often actively involved in the patient's medical journey and are likely to have unique perceptions of biosimilars, which may shape patient attitudes. This study explores the congruence between patient and companion perceptions towards biosimilars and their information needs. Patients taking bio-originators for rheumatic diseases (59% forrheumatoid arthritis) and their companions received an explanation about biosimilars. Participants (N = 78) completed questionnaires assessing their familiarity with biosimilars, perceptions, concerns, and benefits of being accompanied. Contingency tables and paired sample t-tests were used to explore differences in familiarity, confidence in knowledge,and perceptions. Intra-class correlation coefficients were calculated to assess the degree of congruence for perceptions towards biosimilars. Companions were significantly less familiar with biosimilars (p = 0.014, Cramer's V = 0.28) and reported lower confidence in their knowledge (p = 0.006, Cohen's d = 0.47) than patients. Companions and patients had moderate to good congruency for perceptions toward confidence in biosimilar use and safety, efficacy, and side-effect expectations (intra-class correlation coefficients ranging from 0.75 to 0.81). Companions and patients were most concerned about safety and effectiveness. Companions also reported concerns about cost savings driving the transition, while patients had concerns about uncertainty and testing. Patients reported the ability for discussion, improved understanding, and validation as benefits of being accompanied. Companions and patients have similar levels of perceptions and expectations towards biosimilars but report some unique information needs. Future educational interventions should involve companions and address their concerns to help improve biosimilar acceptance.

Metabolic and Endocrine Toxicities of Mitotane: A Systematic Review.

Simple SummaryThis is, to our knowledge, the first systematic review conducted on the endocrine effects of mitotane, which aims to collect all available evidence in the literature and provide complete and useful information regarding the management of the endocrine and metabolic side effects of mitotane in clinical practice.Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this systematic review is to collect the available evidence on the side effects of mitotane on the endocrine and metabolic systems in both children and adults affected by adrenal carcinoma. Sixteen articles on 493 patients were included. Among the adrenal insufficiency, which is an expected side effect of mitotane, 24.5% of patients increased glucocorticoid replacement therapy. Mineralocorticoid insufficiency usually occurred late in treatment in 36.8% of patients. Thyroid dysfunction is characterized by a decrease in FT4, which occurs within 3–6 months of treatment in 45.4% of patients, while TSH seems to not be a reliable marker. Dyslipidemia is characterized by an increase in both LDL-c and HDL-c (54.2%). Few studies have found evidence of hypertriglyceridemia. In males, gynecomastia and hypogonadism can occur after 3–6 months of treatment (38.4% and 35.6%, respectively), while in pre-menopausal women, mitotane can cause ovarian cysts and, less frequently, menstrual disorders. Most of these side effects appear to be reversible after mitotane discontinuation. We finally suggest an algorithm that could guide metabolic and endocrine safety assessments in patients treated with mitotane for ACC.

Evaluating the Effects of Gastric By-Pass Surgery and Sleeve Gastrectomy, as New GDV Treatment Modalities, on Vitamin B12 Values in Dogs

The purpose of this study is to evaluate the effects of gastric bypass surgery and sleeve gastrectomy on vitamin B12 values in dogs. Gastric dilation and volvulus (GDV) is an acute disease with a high mortality rate in dogs. Either gastric bypass surgery or sleeve gastrectomy can be utilized as surgical treatments for GDV. These techniques can provide increased success and fewer complications, however, one undesirable outcome can be vitamin B12 insufficiency. Three groups of dogs received gastric surgeries, one group underwent gastric rotation and derotation with no tissue gastric incisions, the two other groups had gastric bypass surgery and sleeve gastrectomy. Vitamin B12 level was evaluated two weeks prior to surgery, at the time of surgery, two, four, and six weeks after surgery. The results demonstrated no inter-group differences two weeks prior to surgery until four weeks after surgery. However, six weeks post-operation, significant differences between the sleeve gastrectomy group, and the other two groups were shown in vitamin B12 levels. Gastric bypass surgery and sleeve gastrectomy can both be utilized as new surgical managements of GDV. However, as we have demonstrated in this article, an important expected side effect is vitamin B12 insufficiency, in dogs that receive sleeve gastrectomy for GDV treatment. This necessary element must be substituted artificially for all dogs which had received these surgical managements.

Predicting Expectations of Side-Effects for Those Which Are Warned Versus Not Warned About in Patient Information Leaflets.

Research investigating predictors of side-effect expectations is disparate and largely based on hypothetical vignettes. To carry out a secondary analysis of a randomized controlled trial and investigate the predictors of side-effect expectations for side-effects that were, or were not, warned about. Two hundred and three healthy adults completed measures concerning demographics, psychological factors, baseline symptoms, and medication-related beliefs before reading one of two types of patient information leaflet (PIL) (standard or positively framed PIL) for a sham medication and asking them about their side-effect expectations. Associations between these measures and side-effect expectations whilst controlling for the PIL received were assessed using regression analyses. 82.8% of participants expected side-effects that were warned about in the PIL, and 29.1% expected side-effects that were not warned about. Participants who were younger, from White backgrounds, less optimistic, experienced increased anxiety and received the standard PIL were more likely to expect side-effects that were warned about. Those with higher beliefs about medicine overuse and lower trust in medicine development were more likely to expect side-effects that were not warned about. Higher somatization, baseline symptoms, modern health worries scores, and lower trust in pharmaceutical companies were associated with increased expectations for all side-effects. The results suggest we can not only rely on altering side-effect risk communication to reduce side-effect expectations and therefore nocebo effects. We must also consider patients' beliefs about trust in medicines. More work is needed to investigate this in a patientsample in which the medication is known to them.

Pediatric subcutaneous treprostinil site maintenance and pain control strategies from the Pediatric Pulmonary Hypertension Network.

Pulmonary arterial hypertension is a chronic, progressive, and life-threatening disease in children with diverse causes of pulmonary arterial hypertension. The most severe cases of pulmonary arterial hypertension require aggressive treatments with systemic administration of continuous prostacyclin therapy, including treprostinil and epoprostenol. The successful use of continuous subcutaneous treprostinil therapy eliminates the need for an indwelling central venous catheter and its associated risks. However, pain at the subcutaneous infusion site, an expected side effect of this therapy, is often a deterrent to its widespread use. Effective subcutaneous treprostinil site maintenance and pain management is essential to achieve success with this therapy, but strategies surrounding site maintenance and pain control vary significantly between pediatric pulmonary hypertension treatment centers. In an attempt to standardize practice, a survey on the use of subcutaneous treprostinil and site maintenance and pain management strategies, as well as its perceived effectiveness, was disseminated to 13 pediatric pulmonary hypertension centers of the Pediatric Pulmonary Hypertension Network. Responses to the survey were collected and analyzed and were developed into a set of formalized strategies to facilitate knowledge sharing and standardization of practice.

Permanent hair loss associated with taxane chemotherapy use in breast cancer: A retrospective survey at two tertiary UK cancer centres.

Taxane chemotherapy is commonly used in the management of breast cancer. Hair loss (alopecia) is an expected side effect which may have a significant effect on quality of life. Alopecia is normally temporary but permanent chemotherapy-induced alopecia (pCIA) is increasingly recognised especially following docetaxel chemotherapy. However, the prevalence following docetaxel is not well understood and there is no published literature for paclitaxel chemotherapy. The aim of this study is to investigate the prevalence and patterns of pCIA resulting from both docetaxel and paclitaxel chemotherapy at two tertiary UK cancer centres. In collaboration between Clatterbridge Cancer Centre and The Christie NHS Foundation Trusts, a retrospective survey was conducted for breast cancer patients who had received taxane chemotherapy in the neoadjuvant and adjuvant settings. Patients who had concluded chemotherapy at least a year previously were contacted by post and invited to participate by completing a questionnaire and returning it to their treatment centre. Data collected included the incidence and pattern of pCIA using the Savin pictorial hair loss scale, and the methods used by patients to manage it. Fisher's exact test was used to compare pCIA between the docetaxel and paclitaxel cohorts. 383 patients responded to the survey (a 63.3% overall response rate). These comprised 245 patients receiving docetaxel and 138 patients treated with paclitaxel. pCIA was reported by 23.3% of patients receiving docetaxel and 10.1% paclitaxel (p<0.01). Overall 16.7% of patients in both groups reported the ongoing use of products or appliances such as wigs to camouflage their pCIA. In the docetaxel group, pCIA appeared to be more frequent in post-menopausal women than peri- or pre-menopausal women (37.8%, 12.3% and 19.6% respectively [Chi-square test p<0.01]). Also in the docetaxel group, there appeared to be a trend for more severe scalp alopecia when the patient also received an aromatase inhibitor (AI) or tamoxifen and this difference was most marked in those who had received both an AI and tamoxifen as components of their treatment regime (p=0.04). The use of scalp cooling was only recorded in the Christie paclitaxel group (n=12). Of these 12 patients, 83.3% reported no hair loss. While overall rates of permanent eyebrow, eyelash and nostril hair loss were low, this pattern of hair loss appeared more frequent in the paclitaxel than the docetaxel group 4.3% vs. 1.8% (p=0.29). Both docetaxel and paclitaxel may cause permanent scalp hair loss, but it is significantly more prevalent with docetaxel compared with paclitaxel. Clinicians should counsel patients regarding the risk of permanent alopecia prior to embarking upon taxane chemotherapy and routinely offer scalp cooling if available. More research is required to understand the pathobiology of this important and previously under recognised long-term side effect to enable more active preventive and management approaches.

SAFETY OF GENERAL ANESTHESIA DURING INTERVENTIONAL BRONCHOSCOPY PROCEDURE

SESSION TITLE: Procedures Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Technologic advancements in Interventional Pulmonary have increased the technical complexity and consequently duration of many bronchoscopic procedures, increasing the need for both deeper and longer sedation. In fact, at our institution, the vast majority of bronchoscopies are performed under general anesthesia. While bronchoscopy is generally considered a safe procedure with relatively few intra-procedural complications, the safety of general anesthesia during bronchoscopy has not yet been fully described. METHODS: This study is a retrospective chart review analyzing data from 295 patients who underwent bronchoscopy between August 2017 -October 2018. These procedures are performed in our Endoscopy Unit, where standard cardiopulmonary monitoring and anesthesia equipment is available. ASA Physical Status Classification is assigned by the Anesthesia team pre-procedurally. If the procedure was terminated as a consequence of an intra-procedural event, it was considered a complication. Patients who were free of complications for two hours post-procedure were considered to have not had a procedural complication.Transient intra-procedural hypotension resolving by the end of the procedure is considered an expected side effect of anesthesia and not reported as a complication; RESULTS: Of the 295 bronchoscopies, 98.3% (290) were performed under general anesthesia. The patient cohort was 44% female; 60% White, 38% African-American and 1% Hispanic . The median age was 63 years-old and average BMI is 26.8 . Patients had multiple medical comorbidities with 19% ASA-2, 68% ASA-3, and 13% ASA-4. Respiratory complications: Acute respiratory failure occurred in eight patients of whom four required ICU admissions on mechanical ventilation, two patients admitted to medicine floor, and two discharged on the same day after oxygen and nebulizer treatments. Cardiovascular complications: No patients experienced acute coronary syndrome, but two patients had heart failure exacerbation, who were appropriately treated and released. Only one patient had a hypotensive episode requiring early termination of the procedure. CONCLUSIONS: In our experience, general anesthesia for bronchoscopy was only rarely associated with significant complication, despite ASA scores that are typically associated with significant risk, and taking into consideration the patient's underlying respiratory pathologies. Overall, bronchoscopy is a safe procedure to be done under general anesthesia even in patients with multiple comorbidities. CLINICAL IMPLICATIONS: As technological advancements in the field of Interventional Pulmonology are occurring at a rapid rate, the need for general anesthesia to facilitate longer and more complex procedures may be increasing. We have provided data to support that even in patient's with serious comorbid conditions, general anesthesia for bronchoscopy is a safe procedure. DISCLOSURES: No relevant relationships by Ammar Alqaid, source=Web Response No relevant relationships by Rishi Arora, source=Web Response No relevant relationships by David Chambers, source=Web Response No relevant relationships by Allen Elster, source=Web Response No relevant relationships by Paul Fisher, source=Web Response No relevant relationships by UZAIR GHORI, source=Web Response Site investigator for EMPROVE relationship with olympus Please note: $1001 - $5000 Added 06/15/2020 by Robert Holladay, source=Web Response, value=Grant/Research Support No relevant relationships by Aditya Sithamraju, source=Web Response

Educating Our Colleagues: Radiation Basics for Obstetrics and Gynecology Residents

Exposure to Radiation Oncology is minimal among medical students, except for those who intend to pursue a career in Radiation Oncology. Consequently, fundamental knowledge of radiation treatment in gynecologic malignancies may vary among Obstetrics and Gynecology residents depending upon their experiences and level of training. To develop a curriculum to educate Obstetrics and Gynecology residents about basic concepts in Radiation Oncology to improve coordination and management of patients with gynecologic malignancies. Radiation oncology residents met with Obstetrics and Gynecology residents to identify gaps in their knowledge related to radiation oncology topics of interest. A lecture was developed to cover these topics with the help of Radiation Oncology and Gynecologic Oncology attending physicians. The target audience of the lecture were the members of the Department of Gynecology and Obstetrics, including residents, attending physicians, nurse practitioners, and patient care coordinators. The session was divided into an orientation lecture, followed by hands-on training. The orientation lecture covered the following topics: • Common gynecologic malignancies and standard of care treatments • Indications for radiation treatments including emergent radiation treatment • Description of different radiation modalities including external beam radiation and brachytherapy and how they are used • EBRT: CT simulation, radiation planning software, and treatment machines • Brachytherapy: Basic physics background, placement of Smit sleeve for cervical cancer brachytherapy, CT simulation, and treatment planning and delivery • Expected treatment side effects • Radiation safety and protection • Radiation and pregnancy A demonstration/ hands-on-training session was conducted with patient mannequins to familiarize attendees with treatment planning, brachytherapy equipment, and placement of devices. Attendees also toured the department to learn more about the following: • Tandem and ovoids, tandem and ring, cylinders, and interstitial needles/catheters • Treatment planning software • Treatment machines – LINAC, brachytherapy after-loaders. This training session resulted in a better understanding of the rationale and logistics of radiation treatments and improved coordination of patient care for gynecologic oncologic patients. Future research opportunities and avenues for collaboration were identified as well. A Radiation Oncology education program targeted at Obstetrics and Gynecology residents led to greater knowledge about radiation treatments and enhanced patient care and coordination.

Aripiprazole-induced oculogyric crisis (acute dystonia) in 11 years old girl: a case report

Acute dystonic reaction which is described as involuntary muscle spasms and contractions including neck, chin, eye and mouth muscles is an extrapyramidal adverse effect. Acute dystonic reactions are rarely seen with atypical antipsychotics. In this study, we present a case of an aripiprazole-induced oculogyric crisis in an 11 years old girl who diagnosed with mild intellectual disability attention deficit and hyperactivity disorder, and conduct disorder. This case is important as aripiprazole-induced oculogyric crisis caused is not an expected side effect in the child and adolescent population.

The Effect of Positively Framing Side-Effect Risk in Two Different Formats on Side-Effect Expectations, Informed Consent and Credibility: A Randomised Trial of 16- to 75-Year-Olds in England.

Reframing side-effect information in patient information leaflets (PILs) in terms of those who remain side-effect-free may reduce negative expectations and side-effects, although there are concerns this may impact informed consent. This study compared two versions of positively framed PILs with current practice to see which reduces side-effect expectations whilst maintaining informed consent and credibility. We commissioned Ipsos MORI to conduct an online survey of 16- to 75-year-olds in England. 1067 people completed the study and were randomised to receive a PIL for a hypothetical new antibiotic that either communicated side-effects following current practice (n = 356), used positive framing with natural frequencies (n = 356), or positive framing with percentages (n = 355). After reading the leaflet, participants completed measures of their side-effect expectations, absolute risk perceptions, and satisfaction and credibility of the leaflet. Both positively framed PILs resulted in significantly lower side-effect expectations compared with the current PIL for all side-effects (ps < 0.001), apart from seizure. Pairwise comparisons showed no difference in side-effect expectations between the two positively framed PILs (ps > 0.626). The positively framed PIL using natural frequencies produced more accurate risk perceptions than the same leaflet using percentages; but performed equally to the current PIL. There was no difference between the leaflets in terms of satisfaction with or credibility of the PILs. Positively framed PILs using natural frequencies significantly reduced side-effect expectations and provided the most accurate risk perceptions without impacting satisfaction or credibility. Replication is needed with patients prescribed new medication and those with lower educational status.

A systematic review of factors associated with side-effect expectations from medical interventions.

BackgroundFear of side‐effects can result in non‐adherence to medical interventions, such as medication and chemotherapy. Side‐effect expectations have been identified as strong predictors of later perception of side‐effects. However, research investigating predictors of side‐effect expectations is disparate.ObjectiveTo identify factors associated with side‐effect expectations.Search strategyWe systematically searched Embase, Ovid MEDLINE, Global Health, PsycARTICLES, PsycINFO, Web of Science and Scopus.Inclusion criteriaStudies were included if they investigated associations between any predictive factor and expectations of side‐effects from any medical intervention.Data extraction and synthesisWe extracted information about participant characteristics, medication, rates of side‐effects expected and predictors of side‐effect expectations. Data were narratively synthesized.Main resultsWe identified sixty‐four citations, reporting on seventy‐two studies. Predictors fell into five categories: personal characteristics, clinical characteristics, psychological traits and state, presentation format of information, and information sources used. Using verbal risk descriptors (eg ‘common’) compared to numerical descriptors (eg percentages), having lower quality of life or well‐being, and currently experiencing symptoms were associated with increased side‐effect expectations.Discussion and conclusionsDecreasing unrealistic side‐effect expectations may lead to decreased experience of side‐effects and increased adherence to medical interventions. Widespread communications about medical interventions should describe the incidence of side‐effects numerically. Evidence suggests that clinicians should take particular care with patients with lower quality of life, who are currently experiencing symptoms and who have previously experienced symptoms from treatment. Further research should investigate different clinical populations and aim to quantify the impact of the media and social media on side‐effect expectations.

Instruments to Evaluate Self-Management of Radiation Dermatitis in Patients With Breast Cancer.

Radiation dermatitis (RD) is an expected side effect of radiation to the breast and chest wall. Healthcare providers routinely grade the severity of RD without assessing its impact on quality of life for patients with breast cancer. Instruments are needed to identify a patient's ability and confidence to self-manage RD. A search was conducted of published literature from 2001 to 2018 that included patients who had received radiation therapy for breast cancer. A validated instrument was used to assess RD. Eleven instruments were identified and evaluated for assessing self-management. One instrument was identified that measured a patient's ability to self-manage symptoms. The Patient-Reported Outcomes Measurement Information System Self-Efficacy for Managing Chronic Conditions-Manage Symptoms should be considered for clinical integration. Using a validated instrument to assess patients' needs and ability to self-manage RD will promote personalized care plans tailored to each patient. Findings can be used to implement a patient-reported outcome measure into clinical practice, develop educational programs for RD management, and create personalized care plans.

Safety and Efficacy of Repeat Stereotactic Body Radiotherapy (SBRT) for Local Recurrence of Head and Neck Cancer after Initial SBRT

Stereotactic Body Radiation Therapy (SBRT) has been established as an option for treatment of recurrent cancers of the head and neck (H&N) in previously irradiated patients. There has been limited data published on effective means of salvaging patients who fail SBRT. Here we report on the safety and efficacy of repeat SBRT (R-SBRT). From October 2012 to May 2018, 9 patients with local relapse of primary H&N cancer who failed the first course of SBRT (F-SBRT) were retreated with R-SBRT. Median age at time of R-SBRT was 67 years (range, 51-90). 7 patients were men and 2 were women. Median F-SBRT dose was 40 Gy delivered in five biweekly fractions. 5 patients received concurrent systemic therapy with F-SBRT. Local recurrences were diagnosed by CT and/or PET scans showing increasing size and/or avidity and confirmed pathologically via biopsy. Median interval between F-SBRT and R-SBRT was 9 months (range, 5-27). Median R-SBRT dose was 40 Gy in 5 biweekly fractions. Median PTV volume of R-SBRT was 34.7 cubic centimeters (range, 8.6-90.2). The median percentage volume of overlap between the two SBRT courses was 64% (range, 26-100). All patients received concurrent systemic therapy with R-SBRT. Control and survival outcomes were captured for all patients. Toxicity was scored using CTCAE version 5.0. After a median follow-up of 12 months (range, 6-36), rates of local control and overall survival were both 56%. Median time to recurrence was 4 months (range, 2-13). 2 patients experienced grade 3 toxicities, which included fatigue in one patient and hearing loss in another, an expected side effect given that the cochlea fell within the PTV for both courses of SBRT. There were no grade 4 or 5 toxicities. Repeat SBRT was well-tolerated, with rates of grade 3+ toxicity similar to those previously reported on SBRT for head and neck cancer. Repeat SBRT is a viable option for those who fail initial SBRT.

Minimizing Drug Adverse Events by Informing About the Nocebo Effect-An Experimental Study.

Relevance: Informing patients about potential adverse events as part of the informed consent may facilitate the development of nocebo-driven drug adverse events (nocebo side effects). Objective: To investigate whether informing about the nocebo effect using a short information sheet can reduce nocebo side effects. Methods: A total of N = 44 participants with weekly headaches for at least 6 months were recruited using the cover story of a clinical trial for a headache medicine. In reality, all participants took a placebo pill and were randomized to the nocebo information group or the standard leaflet group. Participants were instructed to read the bogus medication leaflet entailing side effects information shortly before pill intake. The nocebo group additionally received an explanation about the nocebo effect as part of the leaflet. Questionnaires were completed at baseline, 2 min, and 4 days after the pill intake. We conducted general linear models with bootstrap sampling. Baseline symptoms were included as a covariate. Results: Most participants (70.5%) reported nocebo side effects at 2 min. Participants who received the nocebo information (n = 24) reported less nocebo symptoms than the control group (n = 20) (estimated difference: 3.3, BCa 95% CI [1.14; 5.15], p = 0.01, Cohen’s d = 0.59). Baseline symptoms, perceived sensitivity to medicine, and side effect expectations each moderated the group effect (estimated difference in slope: 0.47, BCa 95% CI [0.19; 0.73], p = 0.001, d = 0.75; 1.07 [0.27; 1.61], p = 0.006, d = 0.73; 1.57 [0.38; 2.76], p = 0.02, d = 0.58). No group differences were found at 4-day follow-up. After revealing the actual aim of the study, 86% of the participants evaluated the nocebo information to be helpful in general. Conclusions: Results provide the first evidence that informing about the nocebo effect can reduce nocebo side effects.

Owner perceptions of radiotherapy treatment for veterinary patients with cancer.

Veterinary clients may have trepidation about treating their pet with radiotherapy because of concerns about radiation side effects or repeated anaesthetics. The purpose of this study is to assess whether owners' attitudes towards veterinary radiotherapy, including concerns over side effects, change during the course of treatment, and whether radiotherapy was perceived to affect pets' quality of life (QOL). A prospective cohort study of clients from 2012 to 2015 was performed. Pets received palliative or definitive radiotherapy for various tumours. Clients completed questionnaires before, during and after radiotherapy. Questions assessed owner preconceptions before treatment, including side effect expectations, actual side effects experienced and overall satisfaction with the process. In addition, at each time point, the owners assessed their pet's QOL using a simple numerical scale. Forty-nine patients were included. After completing treatment, owners were significantly less concerned about potential side effects of radiotherapy (P < 0.001), side effects associated with repeat anaesthetics (P < 0.001), and about radiotherapy in general (P < 0.001). QOL did not show a significant change at any point during or after treatment. Following treatment, 94% reported that the experience was better than expected and 100% supported the use of radiotherapy in pets. This is the first prospective study evaluating client attitudes and satisfaction before and after radiotherapy treatment in pets. The results indicate that radiotherapy is well tolerated, and the anxiety associated with radiotherapy is significantly alleviated after experiencing the process. These results will help veterinarians allay client concerns, and will hopefully lead to an increase in clients pursuing radiotherapy in pets.

The Influence of Side Effect Information Framing on Nocebo Effects.

One contributing factor to the development of nocebo effects is information provided about possible side effects. However, nondisclosure of information can be problematic. We assessed whether positively framed side effect information (highlighting likelihood of not experiencing side effects) can reduce nocebo effects compared to negatively framed information (highlighting likelihood of experiencing side effects). One hundred twelve participants took part in research ostensibly assessing the influence of benzodiazepines (actually sham capsules) on anxiety. Participants were randomized to receive a sham capsule with positively or negatively framed information about four side effects, or a no-treatment control condition. Side effect expectations were assessed after information provision. Framed side effects and other unmentioned symptoms were assessed during the session and 24-hr follow-up. Nocebo effects occurred in symptoms presented as side effects (regardless of framing) during the study session and follow-up (ps < .003). At follow-up, there was also a nocebo effect in other unmentioned symptoms (p = .018). Positive framing reduced side effect symptoms compared with negative framing during the study session (p = .037), but this effect was no longer present at follow-up (p = .53). Side effect expectations did not differ between the framing conditions (p = .14). Positive framing reduced side effects short-term, but not at follow-up. Expectations did not differ between negative and positive framing. Nocebo effects appeared to generalize to other unmentioned symptoms over a 24-hr period. Further research is needed to determine whether the initial impact of positive framing can be maintained over time.

Parental Expectation of Side Effects Following Vaccination Is Self-fulfilling: A Prospective Cohort Study.

One of the major factors contributing to parental refusal of vaccinations is the perception that vaccines cause side effects. Although symptoms are commonly reported following vaccinations, their causes are not always straightforward. Although some may be directly attributable to the vaccine itself, others may reflect pre-existing or coincidental symptoms that are misattributed to the vaccine. To investigate psychological factors associated with parental report of side effects following vaccination with the child influenza vaccine, and parental intention to re-vaccinate one's child the following year. A prospective cohort study was run in primary care practices in London in the 2016-2017 influenza season (ClinicalTrials.gov number NCT02909855). Two hundred seventy parents from 14 practices completed a questionnaire before their child's vaccination. Follow-up questionnaires were completed 3 days after vaccination and one month after vaccination. Parental report of side effects and vaccination intention for the subsequent year were measured. Parental report of side effects was strongly associated with pre-vaccination expectation of side effects. Suggestions received from the media, National Health Service (NHS) vaccination leaflet, and health care workers, as well as uncertainty-related beliefs, perceived sensitivity of the child to medicines, pessimism, and anxiety were also associated with reporting side effects. Side effect report was associated with lower vaccination intention for the following influenza season. Side effect perception following vaccination is influenced by psychological factors, in particular expectations. Perceiving side effects reduces future vaccination intention. Future public health communications should aim to decrease unrealistic expectations of side effects to increase vaccine uptake.