Management of chemotherapy hypersensitivity reactions and desensitization: An SGO clinical practice statement.

OBJECTIVE: The goal of this practice statement is to help members and their multidisciplinary teams recognize infusion reactions and hypersensitivity reactions in the clinical setting. It will provide recommendations to help guide response to reactions and desensitization when appropriate, to promote safe use of chemotherapeutic agents among all providers in the delivery process. METHODS: A multi-disciplinary team of healthcare professionals from the Society of Gynecologic Oncology Education Committee collaborated to review peer reviewed literature and guidelines to develop a practice statement on the management of chemotherapy hypersensitivity reactions and desensitization regimens. RESULTS: There is always potential for a patient to have a reaction to any medication, with both infusion reactions and hypersensitivity reactions potentially occurring in the treatment of gynecologic cancers. Premedication to prevent reactions should be given at least prior to infusion for regimens that include the most common agents associated with reactions. At the time when reaction is occurring it might be difficult to distinguish between an infusion reaction versus true hypersensitivity given the similarities in signs and symptoms, therefore it is important that orders to manage reactions be included in every chemotherapy order set so the infusion nurse can provide immediate interventions while waiting for the provider to arrive to assess the patient. Desensitization is a potential option to allow the patient to continue to receive the offending agent. While a variety of desensitization regimens have been presented in the literature, the goal is to minimize steps and variability to decrease opportunity for errors during chemotherapy preparation or administration. CONCLUSION: Incorporating a review of the literature and clinical experience from the SGO Education Committee, this paper provides an overview of current approaches for prevention and management of reactions to commonly used chemotherapy agents for gynecologic cancers.

Global health context for the military in Defence Engagement (Health).

Global health practice is becoming a key enabler within UK Defence and foreign policy. The definition of global health remains debated, though some important themes have been identified including: the multidisciplinary nature of global health, its ethical foundation and the political nature of global health. This paper contributes to the ongoing rational discourse that this important discipline deserves and recommends a framework and principles to apply to military health and care system strengthening in the Defence Engagement (Health) (DE(H)) practitioner role. DE(H) involves complex multiorganisational relationships and processes, and while practitioners should be mindful of the political nature of their role, the broad aims of preventing conflict and building stability mean DE(H) should contribute positively to global health.This paper forms part of a special issue of BMJ Military Health dedicated to Defence Engagement.

Medics as influencers: a historical analysis of British Army military medical exercises in Kenya over two decades.

INTRODUCTION: Annual British Army medical training exercises have run in Kenya since the early 1990s, initially with a dual purpose-to deliver the Kenyan Extended Programme of Immunisation (in remote locations) and to undertake austere training. This provided a specific response to a capability gap request from the partner nation, but as this gap closed, the exercise changed in various ways. This study aimed to qualitatively explore the impact of these exercises on the Kenyan healthcare system and the influence and relationships between the nations. METHODS: Semistructured interviews were conducted for 10 former senior commanders and medical officers who had deployed in key command and clinical positions from 1993 to 2019. Three researchers conducted thematic content analysis on the key-informant interviews. RESULTS: Five domains with 18 subdomains formed the study's analysis framework. 16 recurring themes were identified and placed into four categories that denote if they were of benefit to the engagement, enabled success, had the potential to cause harm or were a barrier to successful engagement. Three distinct phases of the exercise were identified: supporting Kenyan vaccinations, direct clinical care, training and education. CONCLUSIONS: This is the first qualitative analysis of the impact of a British Defence Engagement (Health) on the partner nation and UK influence gained through it. It has identified factors which may improve outcomes, namely, ensuring sustainability and continuity between iterations; maintaining enduring stakeholder relationships; responding to a capability gap request; intelligence-led planning with incorporated assessment, monitoring and evaluation; adapting to changes in needs or contextual settings; while ensuring mutual benefit in objective setting. These may be used as the basis for a conceptual framework supporting the planning and execution of high-quality, mutually beneficial Defence Engagement (Health) activities in future. This framework and future research would also benefit from gaining perspectives from the partner nation.

The Patient's perspective: A review of the results from a radiotherapy patient experience survey in the North-West of England.

INTRODUCTION: A patient experience survey was undertaken for patients completing radiotherapy at the three Northwest of England Radiotherapy Providers. METHODS: A previously reported National Radiotherapy Patient Experience Survey was adapted and undertaken in the Northwest of England. Quantitative data was analysed to establish trends. Frequency distribution was applied to appraise the number of participants selecting each of the pre-determined responses. Thematic analysis of free text responses was conducted. RESULTS: The questionnaire received 653 responses from the 3 providers across seven departments. Thematic analysis revealed 3 themes; logistics, information and operational. CONCLUSION: The results indicate that the majority of patients are satisfied with their treatment and care. Patients' responses indicate areas for improvements. Expectancy theory states that an individual's satisfaction is related to the difference between expected service and the service received. Consequently, when reviewing services and developing improvement it is important to understand patients' expectations. This regional survey starts to capture what people receiving radiotherapy expect from the service and the professionals delivering their treatment. IMPLICATIONS FOR PRACTICE: This survey responses make a case for reviewing the information provision pre and post radiotherapy. This includes clarifying the understanding of consent for treatment including the intended benefits and potential late effects. There is an argument to offer information sessions prior to radiotherapy to achieve more relaxed and informed patients. A recommendation from this work is for the radiotherapy community undertake a national radiotherapy patient experience survey, facilitated via the 11 Radiotherapy ODNs. A national radiotherapy survey has multiple benefits to inform improvements in practice. This includes benchmarking services against national averages. This approach is aligned with the principles of the service specification in terms of reducing variation and increasing quality.

Amplifying the Patient Voice: A Survey of Practitioners' Use of Patient-reported Outcome Measures Across Radiotherapy Providers in England.

AIMS: The NHS England Radiotherapy Service Specification calls for routine use of patient-reported outcome measures (PROMs). However, barriers exist at patient, healthcare professional and service levels. The aim of the present study was to determine the current use of PROMs within radiotherapy services in England. The current attitudes, barriers and enablers to the implementation of PROMs in radiotherapy practice were evaluated and practical recommendations to inform future implementation were developed. MATERIALS AND METHODS: A mixed-methods approach was adopted to obtain quantitative and qualitative data. An online questionnaire was developed and disseminated to all radiotherapy operational delivery network managers across England. The questionnaire consisted of 12 open and closed questions relating to PROMs use, with the option to provide free-text responses. Inductive thematic analysis was conducted on free-text comments, whereas descriptive statistics were used to analyse quantitative data. RESULTS: In total, 182 responses were received from 40 of the 50 radiotherapy providers, resulting in a response rate of 84%. The current use of PROMs was analysed, including rationale for use, tools used, format of PROMs collection and timing within the radiotherapy pathway. Most respondents indicated that PROMs were used in the context of clinical trials only. Through thematic analysis, four identical key themes were identified relating to both barriers and enablers to PROMs use; these included IT infrastructure, time, human/financial resources and training/education. A fifth theme, standardisation, was identified as a key enabler to PROMs use. CONCLUSIONS: Our findings show that outside of clinical trials, PROMs are not routinely used in radiotherapy services due to barriers identified at professional and service levels. Here we provide recommendations to mitigate the barriers identified and implement PROMs in radiotherapy, including training for healthcare professionals and standardisation of PROMs tools and storage. This study provides a key first step in driving PROMs implementation within radiotherapy services across England.

Effect of neuromuscular reversal with neostigmine/glycopyrrolate versus sugammadex on postoperative ileus following colorectal surgery.

BACKGROUND: Postoperative ileus (POI) is a common complication following colorectal surgery and is mediated in part by the cholinergic anti-inflammatory pathway (CAIP). Neostigmine (acetylcholinesterase inhibitor), co-administered with glycopyrrolate, is frequently given for neuromuscular reversal before tracheal extubation and modulates the CAIP. An alternative reversal agent, sugammadex (selective rocuronium or vecuronium binder), acts independently from the CAIP. The aim of our study was to assess the impact of neuromuscular reversal agents used during anaesthesia on gastrointestinal recovery. METHODS: Three hundred thirty-five patients undergoing elective colorectal surgery at the Royal Adelaide Hospital between January 2019 and December 2021 were retrospectively included. The primary outcome was GI-2, a validated composite measure of time to diet tolerance and passage of stool. Demographics, 30-day complications and length of stay were collected. Univariate and multivariate analyses were performed. RESULTS: Two hundred twenty-four (66.9%) patients (129 [57.6%] males and 95 [42.4%] females, median age 64 [19-90] years) received neostigmine/glycopyrrolate and 111 (33.1%) received sugammadex (62 [55.9%] males and 49 [44.1%] females, median age 67 [18-94] years). Sugammadex patients achieved GI-2 sooner after surgery (median 3 (0-10) vs. 3 (0-12) days, p = 0.036), and reduced time to first stool (median 2 (0-10) vs. 3 (0-12) days, p = 0.035). Rates of POI, complications and length of stay were similar. On univariate analysis, POI was associated with smoking history, previous abdominal surgery, colostomy formation, increased opioid use and postoperative hypokalaemia (p < 0.05). POI was associated with increased complications, including anastomotic leak and prolonged hospital stay (p < 0.001). On multivariate analysis, neostigmine, bowel anastomoses and increased postoperative opioid use (p < 0.05) remained predictive of time to GI-2. CONCLUSIONS: Patients who received sugammadex had a reduced time to achieving first stool and GI-2. Neostigmine use, bowel anastomoses and postoperative opioid use were associated with delayed time to achieving GI-2.

Group B Streptococcus (GBS) colonization is dynamic over time, whilst GBS capsular polysaccharides-specific antibody remains stable.

Group B Streptococcus (GBS) is a leading cause of adverse pregnancy outcomes due to invasive infection. This study investigated longitudinal variation in GBS rectovaginal colonization, serum and vaginal GBS capsular polysaccharide (CPS)-specific antibody levels. Non-pregnant women were recruited in the UK and were sampled every 2 weeks over a 12-week period. GBS isolates were taken from recto-vaginal swabs and serotyped by polymerase chain reaction. Serum and vaginal immunoglobulin G (IgG) and nasal immunoglobulin A (IgA) specific to CPS were measured by Luminex, and total IgG/A by ELISA. Seventy women were enrolled, of median age 26. Out of the 66 participants who completed at least three visits: 14/47 (29.8%) women that were GBS negative at screening became positive in follow-up visits and 16/19 (84.2%) women who were GBS positive at screening became negative. There was 50% probability of becoming negative 36 days after the first positive swab. The rate of detectable GBS carriage fluctuated over time, although serum, vaginal, and nasal CPS-specific antibody levels remained constant. Levels of CPS-specific antibodies were higher in the serum of individuals colonized with GBS than in non-colonized, but similar in the vaginal and nasal mucosa. We found correlations between antibody levels in serum and the vaginal and nasal mucosa. Our study demonstrates the feasibility of elution methods to retrieve vaginal and nasal antibodies, and the optimization of immunoassays to measure GBS-CPS-specific antibodies. The difference between the dynamics of colonization and antibody response is interesting and further investigation is required for vaccine development.

The use of oxygen hoods in patients failing on conventional high-flow oxygen delivery systems, the effects on oxygenation, mechanical ventilation and mortality rates in hypoxic patients with COVID-19. A Prospective Controlled Cohort Study.

INTRODUCTION: Efforts to meet increased oxygen demands in COVID-19 patients are a priority in averting mechanical ventilation (MV), associated with high mortality approaching 76.4-97.2%. Novel methods of oxygen delivery could mitigate that risk. Oxygen hoods/helmets may improve: O2-saturation (SaO2), reduce in-hospital mechanical ventilation and mortality rates, and reduce length of hospitalization in hypoxic Covid-19 patients failing on conventional high-flow oxygen delivery systems. METHODS: DesignProspective Controlled Cohort Study. SettingSingle Center. ParticipantsAll patients admitted with a diagnosis of COVID-19 were reviewed and 136/347 patients met inclusion criteria. Study period3/6/2020 to 5/1/2020. 136 participants completed the study with known status for all outcome measures. Intervention or exposureOxygen hoods/helmets as compared to conventional high-flow oxygen delivery systems. MAIN OUTCOME(S) AND MEASURE(S): 1) Pre and post change in oxygen saturation (SaO2). 2) In-hospital Mechanical Ventilation (MV). 3) In-hospital Mortality. 4) Length of hospitalization. RESULTS: 136 patients including 58-intervention and 78-control patients were studied. Age, gender, and other demographics/prognostic indicators were comparable between cohorts. Oxygen hoods averted imminent or immediate intubation/MV in all 58 COVID-19 patients failing on conventional high-flow oxygen delivery systems with a mean improvement in SaO2 of 8.8%, p < 0.001. MV rates were observed to be higher in the control 37/78 (47.4%) as compared to the intervention cohort 23/58 (39.7%), a difference of 7.7%, a 27% risk reduction, not statistically significant, OR 95%CI 0.73 (0.37-1.5). Mortality rates were observed higher in the control 54/78 (69.2%) as compared to the intervention cohort 36/58 (62.1%), a difference of 7.1%, a 27% risk reduction, not statistically significant OR 95%CI 0.73 (0.36-1.5). CONCLUSION: Oxygen hoods demonstrate improvement in SaO2 for patients failing on conventional high-flow oxygen-delivery systems and prevented imminent mechanical ventilation. In-hospital mechanical ventilation and mortality rates were reduced with the use of oxygen hoods but not found to be statistically significant. The oxygen hood is a safe, effective oxygen-delivery system which may reduce intubation/MV and mortality rates. Their use should be considered in treating hypoxic COVID-19 patients. Further research is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04407260.

Compact, portable, laser induced fluorescence diagnostic for laboratory plasma sources.

As diagnostic groups are increasingly called upon to participate in experimental campaigns at remote facilities, there is a need to develop portable versions of plasma diagnostic systems. One such diagnostic is laser induced fluorescence (LIF). Here, we describe a portable LIF apparatus that eliminates the need for an optical table, beam splitters, and an optical chopper. All of the light exiting the laser system is coupled through optical fibers to the experiment and housekeeping diagnostics. The collected light is coupled through an optical fiber as well. A key feature is modulation of the tapered amplifier current instead of physical modulation of the laser output. Using this portable LIF system, measurements of ion temperature, ion flow, and relative metastable ion density are reported for two different remote experiments.

Correlation length ratio as a parameter for determination of fiber-like structures in soft tissues.

Quantitative ultrasound methods can provide valuable information about the microstructure of a material or tissue. This works well when the common assumptions of homogeneity, isotropy, and diffuse scattering conditions are valid. In biological tissues, however, these assumptions are often violated because the microstructure of biological tissues is often heterogeneous and anisotropic. The microstructure of biological tissues can change with disease, and therefore accurate identification and description of a tissue's microstructure can offer important clinical insight. To address the challenge of evaluating the microstructure of biological tissues, here we introduce a novel parameter called the correlation length ratio (CLR), a ratio of lateral to axial correlation lengths for backscattered echo signals. We developed it to determine the presence of fiber-like structures in soft tissues by comparing this value in tissue to a threshold determined from a reference material that is homogeneous, isotropic, and provides diffuse scattering. We tested this novel parameter in phantoms with spherical scattering sources, in an anisotropic phantom (containing elongated fibers), and in human biceps muscle. We found that the CLR accurately detected the presence of elongated structures in both the anisotropic phantom and muscle. These results encourage further exploration of this novel parameter in microstructurally complex tissues.

The clinical decision making process in the use of mobilisation with movement - A Delphi survey.

BACKGROUND: Mobilisation with movement (MWM) is a method of treating musculoskeletal disorders. Although widely used clinically and with increasing research investigation, little is known about the decision making process for its utilization. OBJECTIVES: To understand the factors experts believe important for utilization of MWM when assessing a patient, predicting responses to its delivery, responsive body areas, and expected outcomes to MWM. DESIGN: A web-based Delphi study of experts in the use of MWM. METHODS: Round one contained five open-ended questions regarding assessment strategies, prediction of successful and unsuccessful outcomes, body areas most responsive, and common outcome measures observed. Rounds 2 and 3 were quantitative and aimed at establishing consensus. RESULTS: Thirty seven experts participated in the study and took part in round 1, thirty two in round 2, and twenty eight in round 3. The exclusion of red flags and impairment in range of motion (ROM), obtained the highest level of consensus for the item assessment strategies. Patient's presenting with a variety of issues on movement, in addition to mild to moderate levels of severity and immediately responsive to a trial MWM, were believed to respond favourably to MWM. Patients with predominant inflammatory pain, with high levels of psychosocial factors, increased central sensitization and not improving after a trial of MWM, were recognized as non-responders. Improvement of different aspects of movement (e.g. ROM, less fear) are the most common outcomes observed. CONCLUSIONS: This study provides factors believed to be important in the decision making process when using MWM clinically.

South African professional Super Rugby players' lived experiences of career-related traumatic injuries: A descriptive phenomenological analysis.

Background: Historically, non-career-ending traumatic rugby injury (TRI) has been viewed from a predominantly biological perspective. However, dimensional perspectives, such as the biopsychosocial model, have highlighted the need to incorporate psychosocial understandings of TRI into treatment plans. Aim: To describe the lived experiences of a cohort of traumatically injured South African Super Rugby players in order to add to the body of literature on the subject of TRI experience. Methods: The employment of a qualitative, descriptive phenomenological method was used to achieve the research outcome. Discussion: Common descriptive themes indicated that TRI seems to exist within three stages: the initial, emotional and subsequent reactions to the traumatic injury. Sub-themes described within each stage included attempts at remaining positive and appraising the severity of the injury during onset, fear responses and concomitant feelings of loss related to foregone career opportunities during the emotional reactions stage, the employment of coping mechanisms, and relying on specific support structures during subsequent reactions. Two novel experiences revealed within this study and not reported in the international literature included the injured players' reliance on compartmentalisation and positive religious belief structures as coping strategies. All themes were reduced to descriptive phenomenological essences that describe a lifeworld or biopsychosocial experience of TRI. Conclusion: Themes drawn from this study can be applied in the future design and implementation of expanded studies and psychological interventions aimed at assisting traumatically injured rugby players during their recovery process. The identified themes affirm aspects from the international literature while highlighting some uniquely South African outcomes.

Addressing negative psychosocial factors linked to severe injury in professional rugby players: An introduction to a group psychotherapy approach.

Background: Negative psychosocial sequelae of severe rugby injury (SRI) in professional rugby players are well documented. Unaddressed, these issues can leave players vulnerable to persistent common mental disorders (CMD) and negatively affect injury recovery processes. Objective: To introduce a psychotherapeutic group intervention aimed at addressing negative psychosocial sequelae linked to SRI in professional rugby player cohorts. Methods: Literature aimed at clarifying the potential efficacy of an integrative group therapy model, the Recovery Mastery Group (RMG), is discussed after which component parts of the intervention are presented. Case illustration: A case illustration is presented comprising examples of how the RMG framework addressed psychosocial recovery issues in a professional South African rugby team during 2019. Conclusion: The proposed Recovery Mastery Group (RMG) is presented as a cost- and time- effective psychotherapeutic intervention that integrates well-researched psychotherapeutic techniques. The RMG appears able to address multiple facets of psychosocial injury recovery, while possibly offering protection from the onset of CMD. This introduction to the RMG can be a forerunner of similar research across larger cohorts, in different team sports, to determine wider therapeutic intervention efficacy.

Cellular rescue in a zebrafish model of congenital muscular dystrophy type 1A.

Laminins comprise structural components of basement membranes, critical in the regulation of differentiation, survival and migration of a diverse range of cell types, including skeletal muscle. Mutations in one muscle enriched Laminin isoform, Laminin alpha2 (Lama2), results in the most common form of congenital muscular dystrophy, congenital muscular dystrophy type 1A (MDC1A). However, the exact cellular mechanism by which Laminin loss results in the pathological spectrum associated with MDC1A remains elusive. Here we show, via live tracking of individual muscle fibres, that dystrophic myofibres in the zebrafish model of MDC1A maintain sarcolemmal integrity and undergo dynamic remodelling behaviours post detachment, including focal sarcolemmal reattachment, cell extension and hyper-fusion with surrounding myoblasts. These observations imply the existence of a window of therapeutic opportunity, where detached cells may be "re-functionalised" prior to their delayed entry into the cell death program, a process we show can be achieved by muscle specific or systemic Laminin delivery. We further reveal that Laminin also acts as a pro-regenerative factor that stimulates muscle stem cell-mediated repair in lama2-deficient animals in vivo. The potential multi-mode of action of Laminin replacement therapy suggests it may provide a potent therapeutic axis for the treatment for MDC1A.

Computed tomographic and clinical features of pulmonary veno-occlusive disease: raising the radiologist's awareness.

Pulmonary veno-occlusive disease (PVOD) is a rare subtype of pulmonary arterial hypertension (PAH) characterised by preferential remodelling of the pulmonary venules. Differentiation from other subtypes of PAH is essential as the management can differ significantly; for example, initiation of vasodilator therapy may cause fatal pulmonary oedema in a patient with PVOD misdiagnosed with idiopathic PAH. PVOD also carries a substantially worse prognosis. Lung biopsy is required for definitive diagnosis, but this is hazardous, and ideally, should be avoided in pulmonary hypertension. Computed tomography (CT) may suggest the diagnosis, directing the patient towards specialist review. Potential distinguishing CT features between PVOD and other subtypes of PAH include interlobular septal thickening, mediastinal lymphadenopathy, and centrilobular ground-glass opacities. No evidence-based medical therapy exists for PVOD at present and lung transplantation remains the definitive treatment for eligible patients. Therefore, early radiological identification of this challenging diagnosis facilitates timely referral for transplant.

[Erythroderma revealing IPEX syndrome]. / Érythrodermie révélatrice d'un syndrome IPEX.

BACKGROUND: Primary immunodeficiencies are rare and frequently life-threatening conditions in the first year of life. They may present with isolated skin manifestations and the absence of other clinical signs may delay diagnosis and management of the disease. Herein we describe a case of IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome) that illustrates this situation. PATIENTS AND METHODS: A 2.5-month-old boy was seen with a psoriasiform eruption. Despite applications of topical steroids, skin lesions progressed to severe exfoliative ichtyosiform erythroderma. A skin biopsy showed keratinocyte necrosis with a dense, epidermotropic, lymphocytic CD8+ infiltrate. The infant presented increased serum IgE and eosinophilia. He developed an enteropathy with severe and profuse diarrhea, septicemia and hypovolemic shock that led to sudden cardiac arrest. DNA analysis revealed a mutation in the FOXP3 gene, confirming IPEX syndrome. A favorable outcome was achieved following allogeneic bone marrow transplant. DISCUSSION: IPEX syndrome is characterized by early secretory enteropathy with profuse diarrhea, dermatitis and diabetes mellitus. Onset usually occurs within the first weeks or months of life, and the natural course of the disease is often lethal. Cutaneous manifestations appear to be mostly eczematiform, psoriasiform or ichthyosiform. These may be the first sign of the disease and a common inflammatory skin disorder may be wrongly diagnosed. The severity of the lesions and their limited response to topical steroids should alert the clinician. CONCLUSION: The early onset of severe cutaneous manifestations with persistent lesions and poor response to topical steroids should lead to an early skin biopsy. If histopathological changes show a cytotoxic lymphocytic infiltrate with keratinocyte necrosis, a diagnosis of primary immunodeficiency must be considered enabling rapid intitation of specific management.

Full melting of a two-dimensional complex plasma crystal triggered by localized pulsed laser heating.

The full melting of a two-dimensional plasma crystal was induced in a principally stable monolayer by localized laser stimulation. Two distinct behaviors of the crystal after laser stimulation were observed depending on the amount of injected energy: (i) below a well-defined threshold, the laser melted area recrystallized; (ii) above the threshold, it expanded outwards in a similar fashion to mode-coupling instability-induced melting, rapidly destroying the crystalline order of the whole complex plasma monolayer. The reported experimental observations are due to the fluid mode-coupling instability, which can pump energy into the particle monolayer at a rate surpassing the heat transport and damping rates in the energetic localized melted spot, resulting in its further growth. This behavior exhibits remarkable similarities with impulsive spot heating in ordinary reactive matter.