Protocol for the Wessex AsThma CoHort of difficult asthma (WATCH): a pragmatic real-life longitudinal study of difficult asthma in the clinic.

BACKGROUND: Asthma is now widely recognised to be a heterogeneous disease. The last two decades have seen the identification of a number of biological targets and development of various novel therapies. Despite this, asthma still represents a significant health and economic burden worldwide. Why some individuals should continue to suffer remains unclear. METHODS: The Wessex Asthma Cohort of Difficult Asthma (WATCH) is an ongoing 'real-life', prospective study of patients in the University Hospital Southampton Foundation Trust (UHSFT) Difficult Asthma service. Research data capture is aligned with the extensive clinical characterisation required of a commissioned National Health Service (NHS) Specialist Centre for Severe Asthma. Data acquisition includes detailed clinical, health and disease-related questionnaires, anthropometry, allergy and lung function testing, radiological imaging (in a small subset) and collection of biological samples (blood, urine and sputum). Prospective data are captured in parallel to clinical follow up appointments, with data entered into a bespoke database. DISCUSSION: The pragmatic ongoing nature of the WATCH study allows comprehensive assessment of the real world clinical spectrum seen in a Specialist Asthma Centre and allows a longitudinal perspective of deeply phenotyped patients. It is anticipated that the WATCH cohort would act as a vehicle for potential collaborative asthma studies and will build upon our understanding of mechanisms underlying difficult asthma.

Antenatal consultation for parents whose child may require admission to neonatal intensive care: a focus group study for media design.

BACKGROUND: For parents whose child may require admission to a neonatal intensive care unit (NICU), the antenatal consultation is often their first point of contact with the child's medical team. Consultation challenges health professionals, as parents may be anxious, overwhelmed, or even exhausted by what is and what might occur. Despite consultation being a common practice, there is a paucity of research on how to support practitioners and parents. The purpose of this study was to gain insights into important relational aspects of antenatal consultation that may be used to spur the development of media to support consultation. METHODS: Focus group, as a data collection method, was employed to gather insights about antenatal consultation from a total of 50 hospital staff and 17 NICU parents from a large urban NICU program in western Canada. Qualitative content analysis was applied to the obtained materials to explicate themes that may serve as necessary understandings for media design. RESULTS: Participating hospital staff and parents expressed their desire for a good antenatal consultation with comments grouped under the following themes: supporting the building of a caring relation; sharing information in conversation; and, preparing for what is to come. CONCLUSIONS: To support the emerging relations of baby, parent, and hospital staff, a good antenatal consultation needs to convey care, understanding, and empathy; create possibilities for open and genuine conversations; and, foster the buildings of respect, confidence, and trust.

Evaluation of target and cardiac position during visually monitored deep inspiration breath-hold for breast radiotherapy.

A low-resource visually monitored deep inspiration breath-hold (VM-DIBH) technique was successfully implemented in our clinic to reduce cardiac dose in left-sided breast radiotherapy. In this study, we retrospectively characterized the chest wall and heart positioning accuracy of VM-DIBH using cine portal images from 42 patients. Central chest wall position from field edge and in-field maximum heart distance (MHD) were manually measured on cine images and compared to the planned positions based on the digitally reconstructed radiographs (DRRs). An in-house program was designed to measure left anterior descending artery (LAD) and chest wall separation on the planning DIBH CT scan with respect to breath-hold level (BHL) during simulation to determine a minimum BHL for VM-DIBH eligibility. Systematic and random setup uncertainties of 3.0 mm and 2.6 mm, respectively, were found for VM-DIBH treatment from the chest wall measurements. Intrabeam breath-hold stability was found to be good, with over 96% of delivered fields within 3 mm. Average treatment MHD was significantly larger for those patients where some of the heart was planned in the field compared to patients whose heart was completely shielded in the plan (p < 0.001). No evidence for a minimum BHL was found, suggesting that all patients who can tolerate DIBH may yield a benefit from it.

Accelerated Partial Breast Irradiation Using 5 Daily Fractions: A Prospective, Phase 2, Multicenter Trial of Cosmetic Outcomes and Toxicity-ACCEL Final Results.

PURPOSE: This study investigated the cosmetic degradation and toxicity for an accelerated partial breast irradiation (APBI) prescription delivered in 5 fractions over 1 week and compared the outcomes with those of whole breast irradiation (WBI). METHODS AND MATERIALS: The trial was a multicenter, single-arm, phase 2 prospective cohort study. Eligible women 50 years of age or older with estrogen receptor-positive and human epidermal growth factor receptor 2-negative invasive ductal carcinoma or ductal carcinoma in situ after breast-conserving surgery received 27 Gy in 5 daily fractions of APBI. The primary endpoint was noninferiority of 2-year cosmesis using the RAPID trial's WBI arm as the control arm. A global consensus cosmetic score using a European Organisation for Research and Treatment of Cancer rating scale score of excellent, good, fair, or poor for each patient at baseline and 2 years was generated by a panel of 5 radiation oncologists using photographs of treated and untreated breasts. RESULTS: From 2016 to 2019, 298 eligible women were enrolled. By the 2-year follow-up, 76 patients had been lost or withdrawn and 3 had died, resulting in 219 patients available for complete, 2-year photographic cosmetic evaluation. The median follow-up for all participants was 4.7 years (IQR, 3.8-5.5 years). No patient had a fair or poor cosmetic score at the 2-year evaluation. Cosmesis was better or unchanged for 97% of patients and worse for 3% (excellent to good), and no cosmetic failures occurred. The confidence intervals were 0.88 (0.86-0.90) and 1.00 (0.99-1.00) for the RAPID and ACCEL trials, respectively. CONCLUSIONS: Cosmetic degradation with 5 daily treatments of the ACCEL trial's APBI intervention is noninferior to the WBI arm of the RAPID trial.

Cannabidiol exposures in the United States, National Poison Data System, July 2014-June 2021.

INTRODUCTION: There has been an increase in the interest and availability of products asserting to contain cannabidiol (CBD). OBJECTIVE: To describe demographic and clinical patterns in cases involving CBD exposures documented by the America's Poison Centers (AAPCC). METHODS: We extracted human exposure cases involving CBD from the U.S. National Poison Data System between July 2014 and June 2021. We described monthly case counts and data on demographics, exposure reason, clinical effects, medical outcomes, and co-exposures, overall and by U.S. Food and Drug Administration (FDA) approval status. RESULTS: We identified 6,496 cases, of these, 85.2% involved exposures to non-FDA approved CBD. The monthly number of cases peaked at 336 in March 2021. Cases often occurred in children ages 2-12 years (36.2%). Although in this age group unintentional exposures represented most cases (94.1%), we identified therapeutic errors (3.9%), intentional use (3.0%), and adverse reactions (1.6%) in cases involving exposures to non-FDA approved CBD. Among the 5,248 (80.8%) cases involving exposure to a single product, we identified 44 major medical outcomes, all related to exposures to non-FDA approved CBD. The most frequent clinical effects included neurological, cardiac, and gastrointestinal effects. Among the 1,248 (19.2%) involving exposure to more than one product, the most frequent co-exposures included stimulants and street drugs, sedatives-hypnotics, antipsychotics, and analgesics. CONCLUSIONS: This case series identified an increasing trend in CBD exposure cases managed by AAPCC. It showed serious medical outcomes in temporal association with exposure to non-FDA approved CBD products. Our findings also suggest both unintentional and intentional use of non-FDA approved CBD in children. Consumers should keep these products out of reach of children and exercise caution when purchasing and using non-FDA approved CBD products.

The transition in practice to reduce bolus use in post-mastectomy radiotherapy: A dosimetric study of skin and subcutaneous tissue.

To inform clinical practice for women receiving post-mastectomy radiotherapy (PMRT), this study demonstrates the dosimetric impact of removing daily bolus on skin and subcutaneous tissue. Two planning strategies were used: clinical field-based (n = 30) and volume-based planning (n = 10). The clinical field-based plans were created with bolus and recalculated without bolus for comparison. The volume-based plans were created with bolus to ensure a minimum target coverage of the chest wall PTV and recalculated without bolus. In each scenario, the dose to superficial structures, including skin (3 mm and 5 mm) and subcutaneous tissue (a 2 mm layer, 3 mm deep from surface) were reported. Additionally, the difference in the clinically evaluated dosimetry to skin and subcutaneous tissue in volume-based plans were recalculated using Acuros (AXB) and compared to the Anisotropic Analytical Algorithm (AAA) algorithm. For all treatment planning strategies, chest wall coverage (V90%) was maintained. As expected, superficial structures demonstrate significant loss in coverage. The largest difference observed in the most superficial 3 mm where V90% coverage is reduced from a mean (± standard deviation) of 95.1% (± 2.8) to 18.9% (± 5.6) for clinical field-based treatments with and without bolus, respectively. For volume-based planning, the subcutaneous tissue maintains a V90% of 90.5% (± 7.0) compared to the clinical field-based planning coverage of 84.4% (± 8.0). In all skin and subcutaneous tissue, the AAA algorithm underestimates the volume of the 90% isodose. Removing bolus results in minimal dosimetric differences in the chest wall and significantly lower skin dose while dose to the subcutaneous tissue is maintained. Unless the skin has disease involvement, the most superficial 3 mm is not considered part of the target volume. The continued use of the AAA algorithm is supported for the PMRT setting.

Immune responses against SARS-CoV-2 variants after two and three doses of vaccine in B-cell malignancies: UK PROSECO study.

Patients with hematological malignancies are at increased risk of severe COVID-19 outcomes due to compromised immune responses, but the insights of these studies have been compromised due to intrinsic limitations in study design. Here we present the PROSECO prospective observational study ( NCT04858568 ) on 457 patients with lymphoma that received two or three COVID-19 vaccine doses. We show undetectable humoral responses following two vaccine doses in 52% of patients undergoing active anticancer treatment. Moreover, 60% of patients on anti-CD20 therapy had undetectable antibodies following full vaccination within 12 months of receiving their anticancer therapy. However, 70% of individuals with indolent B-cell lymphoma displayed improved antibody responses following booster vaccination. Notably, 63% of all patients displayed antigen-specific T-cell responses, which increased after a third dose irrespective of their cancer treatment status. Our results emphasize the urgency of careful monitoring of COVID-19-specific immune responses to guide vaccination schemes in these vulnerable populations.

Experiences of transition from children's to adult's healthcare services for young people with a neurodevelopmental condition.

Previous research has highlighted a lack of continuity of care when young people with a neurodevelopmental condition make the transition from children's to adult specialist healthcare services. A lack of planning, consistency, and availability of adult services has been found to lead to; increased anxiety, poor health outcomes, reduced support and some young people not receiving healthcare. The majority of transition research has focused on what health professionals consider important in the transition process, rather than focusing on the experiences of the young people and those closest to them. Our objective was to gather evidence from young people (and their families) who had experienced transition from children's to adult specialist healthcare services through semi-structured interviews. Volunteers were recruited from two London boroughs. All young people were aged between 18 and 25 years with a neurodevelopmental condition (Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder and/or an Intellectual Disability). Overall, we interviewed six young people with support from a family member. Five further family members were interviewed on behalf of the young person. In total, ten semi-structured interviews were transcribed verbatim and analysed using Interpretative Phenomenological Analysis. Four themes emerged from the analysis: (a) Parents as advocates, (b) Availability of adult's specialist health and social care services, (c) Lack of information sharing and (d) Transition as a binary, abrupt change. Our findings suggest the transition experience could be improved by changing service specifications to incorporate assessment and handover across the age range of 16-20 years. Additionally, statutory services should understand and provide the coordination role now offered by parents in transition. We suggest future research could evaluate the feasibility of a patient-owned online information sharing tool with information about relevant services for young people and their families.

A retrospective analysis to demonstrate achievable dosimetry for the left anterior descending artery in left-sided breast cancer patients treated with radiotherapy.

PURPOSE: To demonstrate achievable dose for the left anterior descending artery (LAD) for left-sided breast cancer patients. METHODS: A retrospective analysis was conducted on all left-sided breast cancer patients receiving whole breast or post-mastectomy chest wall irradiation between 2013 and 2018. All patients in this study were treated with tangent-based techniques with the LAD prospectively contoured as routine clinical care. This large patient cohort was used to benchmark achievable mean doses to the LAD in the context of heart dose. The primary cohort of study were patients undergoing treatment with deep-inspiration breath-hold (DIBH), stratified by internal mammary nodes (IMN) inclusion. In all cases, the median (25th-75th percentile) is reported. RESULTS: A total of 1221 left-sided breast cancer patients were included in this study with 1045 in the DIBH cohort. The median heart mean dose for this cohort is 1.0 Gy (0.8-1.1). For patients treated in DIBH with IMNs included (n = 422), the median of the mean LAD dose is 3.6 Gy (2.9-4.4) and, for patients treated in DIBH with IMNs excluded (n = 623), the median of the mean LAD dose is 3.2 Gy (2.5-3.8). CONCLUSIONS: Appropriate respiratory management can be utilized to achieve low dose to the LAD for the majority of patients without compromising target coverage.

Systemic Lupus Erythematosus is Not Necessarily a Contraindication to Adjuvant Breast Radiation Therapy.

A 41-year-old woman presented with pT4dN1aM0, right-sided, inflammatory breast cancer. She had a co-morbid diagnosis of systemic lupus erythematosus (SLE) at the age of 20 and was found to have significant kidney involvement (lupus-associated nephritis) at the age of 28. She went on to receive six cycles of neoadjuvant chemotherapy consisting of fluorouracil, epirubicin, cyclophosphamide, and docetaxcel (FEC-D) after which she had radiographically stable disease. She then had definitive treatment with bilateral mastectomy. Pathology showed a 4-cm residual invasive ductal carcinoma in the right breast and three residual metastatic lymph nodes in the right axilla. After extensive discussions with the patient, which included counseling on the potential increased risk of radiation-induced side effects, she received 50.4 Gy in 28 fractions of adjuvant radiotherapy (RT) to the chest wall and regional lymphatics including the internal mammary chains (IMCs). To minimize the risk of pulmonary toxicity, RT field arrangement consisted of a field-in-field modulated supraclavicular anterior/posterior parallel pair matched to shallow, photon tangent pair with 0.5 cm bolus to the lateral aspect of the chest wall and two matched direct anterior electron fields of 9 MeV with 1 cm bolus and 12 MeV with 0.5 cm bolus medially to cover the remaining residual chest wall and IMCs. This was immediately followed by a boost of 7.5 Gy in three fractions delivered via a photon tangent pair with 1 cm bolus to an area 6 cm superior and inferior to the surgical scar. Total treatment time was 50 days. The patient tolerated the therapy well but she developed grade three acute dermatitis. There were no pulmonary, shoulder joint movement, or brachial plexus side effects. This case is unusual in that SLE is generally considered a contraindication for elective RT. However, given her high risk for breast cancer recurrence, RT was offered with additional caution to minimize lung dose. Having completed the treatment, the side effects experienced were no greater than what would be expected in someone who did not have a diagnosis of SLE.

Unexpected Symptomatic Pneumonitis Following Breast Tangent Radiation: A Case Report.

Symptomatic radiation pneumonitis (RP) following radiation therapy (RT) to the breast alone is very uncommon. We report a case of an 80-year-old female who presented with fatigue, exertional dyspnea, fever, and cough 11.5 weeks following adjuvant breast RT with tangent fields alone. Imaging was consistent with RP, and she responded to a tapering course of steroids.

Dosimetric variations in permanent breast seed implant due to patient arm position.

PURPOSE: Planning and delivery for permanent breast seed implant (PBSI) are performed with the ipsilateral arm raised; however, changes in implant geometry can be expected because of healing and anatomical motion as the patient resumes her daily activities. The purpose of this study is to quantify the effect of ipsilateral arm position on postplan dosimetry. METHODS AND MATERIALS: Twelve patients treated at the Tom Baker Cancer Centre were included in this study. Patients underwent two postimplant CT scans on the day of implant (Day 0) and two scans approximately 8 weeks later (Day 60). One scan at each time was taken with the ipsilateral arm raised, recreating the planning scan position, and the other with both arms down in a relaxed position beside the body, recreating a more realistic postimplant arm position. Postplans were completed on all four scans using deformable image registration (MIM Maestro). RESULTS: On the Day 0 scan, the V200 for the evaluation planning target volume was significantly increased in the arm-down position compared with the arm-up position. Lung, rib, and chest wall dose were significantly reduced at both time points. Left anterior descending coronary artery, heart, and skin dose showed no significant differences at either time point. CONCLUSIONS: Although some dosimetric indices show significant differences between the arm-up and arm-down positions, the magnitude of these differences is small and the values remain indicative of implant quality. Despite the delivery of the majority of dose with the arm down, it is reasonable to use CT scans taken in the arm-up position for postplanning.

Cardiac dose reduction with deep inspiration breath hold for left-sided breast cancer radiotherapy patients with and without regional nodal irradiation.

BACKGROUND: Deep inspiration breath hold (DIBH) reduces heart and left anterior descending artery (LAD) dose during left-sided breast radiation therapy (RT); however there is limited information about which patients derive the most benefit from DIBH. The primary objective of this study was to determine which patients benefit the most from DIBH by comparing percent reduction in mean cardiac dose conferred by DIBH for patients treated with whole breast RT ± boost (WBRT) versus those receiving breast/chest wall plus regional nodal irradiation, including internal mammary chain (IMC) nodes (B/CWRT + RNI) using a modified wide tangent technique. A secondary objective was to determine if DIBH was required to meet a proposed heart dose constraint of Dmean < 4 Gy in these two cohorts. METHODS: Twenty consecutive patients underwent CT simulation both free breathing (FB) and DIBH. Patients were grouped into two cohorts: WBRT (n = 11) and B/CWRT + RNI (n = 9). 3D-conformal plans were developed and FB was compared to DIBH for each cohort using Wilcoxon signed-rank tests for continuous variables and McNemar's test for discrete variables. The percent relative reduction conferred by DIBH in mean heart and LAD dose, as well as lung V20 were compared between the two cohorts using Wilcox rank-sum testing. The significance level was set at 0.05 with Bonferroni correction for multiple testing. RESULTS: All patients had comparable target coverage on DIBH and FB. DIBH statistically significantly reduced mean heart and LAD dose for both cohorts. Percent reduction in mean heart and LAD dose with DIBH was significantly larger in the B/CWRT + RNI cohort compared to WBRT group (relative reduction in mean heart and LAD dose: 55.9 % and 72.1 % versus 29.2 % and 43.5 %, p < 0.02). All patients in the WBRT group and five patients (56 %) in the B/CWBRT + RNI group met heart Dmean <4 Gy with FB. All patients met this constraint with DIBH. CONCLUSIONS: All patients receiving WBRT met Dmean Heart < 4 Gy on FB, while only slightly over half of patients receiving B/CWRT + RNI were able to meet this constraint in FB. DIBH allowed a greater reduction in mean heart and LAD dose in patients receiving B/CWRT + RNI, including IMC nodes than patients receiving WBRT. These findings suggest greatest benefit from DIBH treatment for patients receiving regional nodal irradiation.

The role of self-construal in predicting self-presentational motives for online social network use in the UK and Japan.

Self-presentational motives underlying online social network (OSN) use were explored in samples of British and Japanese users. Self-expression, maintaining privacy, and attention seeking were strong motives in both samples; impression management and modesty were less strongly endorsed. Measures of independent and interdependent self-construal, as well as narcissism and modesty, were investigated as potential predictors of these motivations. Independent self-construal emerged as the most important predictor across both samples, with less independent participants showing more concern with image management and modesty. Participants with more interdependent self-construals were more concerned about maintaining privacy. There were some differences in the patterns of prediction between the samples, but overall self-construal measures contributed to the explanation of the majority of the motivations, whereas narcissistic or modest personality variables did not.

Exploring Identity Motives in Twitter Usage in Saudi Arabia and the UK.

This study explores identity motives for using a microblogging site (Twitter) among Internet users in Saudi Arabia and the UK. The former boasts the world's highest per capita use of Twitter, which provides a forum in which users have more opportunity for self-expression than they do in the offline world, and is not subject to the heavy censorship which the Saudi government imposes on other Internet content [1]. Approximately 5000 tweets from the period April-May 2013 were coded and analyzed, using Motivated Identity Construction Theory as a conceptual framework [2]. This theory proposes six universal identity motives of meaning, belonging, continuity, distinctiveness, efficacy, and self-esteem. We consider these motives in turn, and examine their relative prominence in an online context. Support was found for all six universal motives, but the relative prominence of motives and the ways in which they were pursued appeared to depend on the affordances of both the OSN in question, Twitter and the cultural context in which the user was posting: Saudi users appeared to seek distinctiveness, whereas for British users, belonging was a more salient motive. Themes related to meaning, efficacy, and self-esteem were detected frequently, whereas themes related to continuity were less apparent.

Controlled release of alendronate from polymeric films.

Bisphosphonate drugs alter the balance of bone resorption and formation, leading to a net increase in bone density. Therefore, these drugs are commonly used to treat osteoporosis or as an adjunct to cancer chemotherapy. Local delivery of bisphosphonates, such as alendronate, from polymeric films has the potential to improve efficacy and decrease side-effects common to oral bisphosphonate therapy. Alendronate was effectively encapsulated in film formulations composed of poly(lactic-co-glycolic acid) (PLGA) blended with poly(DL-lactic acid)-block-methoxy poly(ethylene glycol) (diblock co-polymer) and the films were characterized for elasticity, swelling, thermal and drug-release properties. Increasing the proportion of diblock co-polymer in the formulation decreased the glass transition temperature of PLGA, allowing for improved handling via increases in film elasticity. Immersion in aqueous media caused a rapid stiffening and swelling of the films. The inclusion of diblock co-polymer increased the rate of drug release from the films over a 3-week period. Drug-loaded polymeric films containing 0.25% alendronate increased osteoblast viability after 4 days compared to polymer alone. After 5 weeks, there was a significant increase in alkaline phosphatase activity and calcium nodule formation in osteoblasts grown on films containing 1.25% alendronate in 5% diblock co-polymer in PLGA.

Assessment of the efficacy of Viagra (sildenafil citrate) using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS).

Treatment satisfaction is a predictor of long-term compliance in patients with erectile dysfunction (ED). We assessed patient satisfaction with and efficacy of Viagra (sildenafil citrate) using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and 3 global efficacy questions. Twenty-nine men with ED who had completed a prior study of MUSE (alprostadil) versus Caverject (alprostadil) took a 50-mg dose of Viagra 1 h preceding intercourse. Efficacy and patient satisfaction with Viagra were high. Satisfaction as measured by EDITS was highly correlated to patients' final ED treatment choice. This correlation could make EDITS useful in identifying long-term patient satisfaction, and thus of considerable clinical benefit.