The impact of COVID-19 on PRO development, collection and implementation: views of UK and Ireland professionals.

BACKGROUND: PROs are valuable tools in clinical care to capture patients' perspectives of their health, symptoms and quality of life. However the COVID-19 pandemic has had profound impacts on all aspects of life, in particular healthcare and research. This study explores the views of UK and Irish health professionals, third sector and pharmaceutical industry representatives and academic researchers on the impact of COVID-19 on PRO collection, use and development in clinical practice. METHODS: A volunteer sample took part in a 10 question cross sectional qualitative survey, on the impact of COVID-19, administered online via Qualtrics. Demographic data was descriptively analysed, and the qualitative free text response data was subject to thematic analysis and summarised within the Strengths, Weaknesses, Opportunities and Threats (SWOT) framework. RESULTS: Forty nine participants took part located in a range of UK settings and professions. Participants highlighted staff strengths during the pandemic including colleagues' flexibility and ability to work collaboratively and the adoption of novel communication tools. Weaknesses were a lack of staff capacity to continue or start PRO projects and insufficient digital infrastructure to continue studies online. Opportunities included the added interest in PROs as useful outcomes, the value of electronic PROs for staff and patients particularly in relation to integration into systems and the electronic patient records. However, these opportunities came with an understanding that digital exclusion may be an issue for patient groups. Threats identified included that the majority of PRO research was stopped or delayed and funding streams were cut. CONCLUSIONS: Although most PRO research was on hold during the pandemic, the consensus from participants was that PROs as meaningful outcomes were valued more than ever. From the opportunities afforded by the pandemic the development of electronic PROs and their integration into electronic patient record systems and clinical practice could be a lasting legacy from the COVID-19 pandemic.

Laser induced breakdown spectroscopy for the rapid detection of SARS-CoV-2 immune response in plasma.

As the SARS-CoV-2 pandemic persists, methods that can quickly and reliably confirm infection and immune status is extremely urgently and critically needed. In this contribution we show that combining laser induced breakdown spectroscopy (LIBS) with machine learning can distinguish plasma of donors who previously tested positive for SARS-CoV-2 by RT-PCR from those who did not, with up to 95% accuracy. The samples were also analyzed by LIBS-ICP-MS in tandem mode, implicating a depletion of Zn and Ba in samples of SARS-CoV-2 positive subjects that inversely correlate with CN lines in the LIBS spectra.

Treatment of MOG antibody associated disorders: results of an international survey.

INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD. METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

Use of the Skin Cancer Quality of Life Impact Tool (SCQOLIT) - a feasibility study in non-melanoma skin cancer.

BACKGROUND: Incidence of non-melanoma skin cancers (NMSCs) is increasing and can significantly impact on quality of life (QOL), yet there are few studies evaluating patient-reported outcome measures (PROMs) in NMSC populations. We undertook a prospective feasibility study to evaluate a skin cancer-specific PROM, the Skin Cancer Quality of Life Impact Tool (SCQOLIT), in patients with a new diagnosis of NMSC. OBJECTIVES: (i) To establish acceptability of SCQOLIT in dermatology clinics, (ii) a descriptive analysis of SCQOLIT scores in NMSC. METHODS: Patients with histologically confirmed NMSC completed SCQOLIT, EQ-5D and a transition item. Questionnaires were completed at baseline and 3 months for group 1 ('low-risk' NMSC) and group 2 ('high-risk' NMSC) with additional questionnaires at 6-9 months for group 2. Patients participated in structured interviews. Clinician experience was captured through staff evaluation forms and a focus group. Acceptability and psychometric properties of SCQOLIT were assessed. RESULTS: Overall, 318 patients consented to participate. Mean SCQOLIT score at baseline was 5.33, with 2.6% of patients scoring ≥20. No ceiling effects were observed, whilst 13.9% scored 0. Validity was demonstrated against EQ-5D. Cronbach's alpha 0.84 demonstrated internal consistency. Thirteen patients were interviewed and thought SCQOLIT was comprehensive, captured impact on health-related QOL and helped express their needs to clinicians. Most clinicians found SCQOLIT 'very useful' or 'useful to some extent' in facilitating discussions. CONCLUSIONS: This feasibility study demonstrates that SCQOLIT is acceptable to patients and staff in dermatology skin cancer clinics. The psychometric properties of SCQOLIT confirm its utility in NMSC populations.

A structured review of patient-reported outcome measures for patients with skin cancer, 2013.

BACKGROUND: The collection of patient-reported outcome measures (PROMs) within the national PROMs programme for elective procedures is now established mandatory practice in the NHS with high response rates and completion. OBJECTIVES: This review examines the evidence of PROMs for people with skin cancer. METHODS: Comprehensive searches were conducted using several sources and databases, using a detailed search strategy developed by the University of Oxford's PROM Group. Articles were assessed for eligibility. Data were extracted per PROM for each measurement property and appraised using an appraisal framework. RESULTS: A total of 3517 articles were identified in the searches, and 28 were included in the final review after assessment by two independent reviewers. Two generic instruments (SF-36 and Sickness Impact Profile) and nine condition-specific PROMs were identified. CONCLUSIONS: Overall, there is a limited volume of published evidence for the application of generic PROMs for people with skin cancer. Evaluation of the EQ-5D may be particularly important given its widespread use in many other healthcare contexts in the U.K. The Skin Cancer Index could be considered for piloting in the NHS. For patients with nonmelanoma skin cancers, the Skindex measures may also be considered. The SCQOLIT has some evidence of applicability across both skin cancer types but more evaluations are needed. The FACT-M does have more promising characteristics for patients with malignant melanomas although no evidence of testing in the U.K. was found. The forthcoming EORTC-M may prove a useful measure given the expertise and track record of this European collaboration in cancer and quality of life.

Comparison between real-time intra-operative ultrasound-based dosimetry and CT-based dosimetry for prostate brachytherapy using cesium-131.

The purpose of this study was to evaluate the correlation between real-time intra-operative ultrasound-based dosimetry (USD) and day 0 post-implant CT dosimetry (CTD) (131)Cs permanent prostate brachytherapy. Fifty-two consecutive patients who underwent prostate brachytherapy with (131)Cs were evaluated. Real time operating room planning was performed using VariSeed 7.1 software. Post-needle placement prostate volume was used for real-time planning. Targets for dosimetry were D(90) >110%, V(100) >90%, V(150) <50%, and V(200) <20%. The CT scan for post-operative dosimetry was obtained on day 0. The mean values for USD, CTD, and the linear correlation, respectively, were, for D(90): 114.0%, 105.61%, and 0.15; for V(100): 95.1%, 91.6%, and 0.22; for V(150): 51.5%, 46.4%, and 0.40; and for V(200): 15.8%, 17.9%, and 0.42. The differences between the mean values for USD and CTD for D(90) (p<0.01), V(100) (p<0.01), and V(150) (p<0.05) were statistically significant. For D(90), 30.8% of patients had a >15% difference between USD and CTD and 51.9% of patients had a >10% difference between these values. In contrast, the USD and CTD for V(100) were within 5% in 55.8% of patients and within 10% in 86.5% of patients. This study demonstrates a correlation between the mean intra-operative USD and post-implant day 0 CTD values only for V(200). Significant variation in D(90), V(150), and V(200) values existed for individual patients between USD and CTD. These results suggest that real-time intra-operative USD does not serve as a surrogate for post-operative CTD, and that post-operative CTD is still necessary.

Validation of the Fournier's gangrene severity index in a large contemporary series.

PURPOSE: In this study we identified prognostic factors for survival and validated the accuracy of the Fournier's gangrene severity index in patients with Fournier's gangrene. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients diagnosed with Fournier's gangrene between 1996 and 2006. Fournier's gangrene severity index scores were assessed using a receiver operating characteristic curve. Using an outcome variable of inpatient mortality, univariate analyses were performed using the Mann-Whitney U, chi-square and Fisher exact tests. RESULTS: A total of 68 patients (79.4% male, mean age 55.8 +/- 15.2 years) diagnosed with Fournier's gangrene met the criteria for review. The inpatient mortality rate was 10% (7 patients). The mean Fournier's gangrene severity index score for survivors was 5.4 +/- 3.5 vs 10.9 +/- 4.7 for nonsurvivors (p = 0.006). Isolated Fournier's gangrene severity index and individual laboratory parameters associated with mortality included heart rate (p = 0.05), respiratory rate (p = 0.02), serum creatinine (p = 0.03), serum bicarbonate (p = 0.001), serum lactate (p = 0.001) and serum calcium (p = 0.03). Although mean total body surface area was only suggestive of an association (p = 0.169), abdominal wall (p = 0.004) or lower extremity (p = 0.005) involvement was associated with increased mortality. Using a Fournier's gangrene severity index score threshold of 9 (sensitivity 71.4%, specificity 90%) there was a 96% survival rate in patients with a Fournier's gangrene severity index of less than 9 and a 46% mortality rate in those with a Fournier's gangrene severity index of 9 or greater (p = 0.001, OR 22, 95% CI 3.5-139.7). CONCLUSIONS: The Fournier's gangrene severity index remains an objective and simple method to quantify the extent of metabolic aberration at presentation in patients with Fournier's gangrene. A Fournier's gangrene severity index threshold value of 9 is sensitive and specific for predicting mortality in this patient population.

External cost internalisation of urban transport: a case study of Dublin.

Transport users do not currently pay all costs associated with their transport activities and in particular do not pay the costs they impose on the environment. Case studies on Dublin, Amsterdam, Brussels and London have been conducted to evaluate how best to meet the requirement of the European Commission in its fair and efficient pricing aims in the transport sector, i.e. where transport users are made to pay all costs they impose. The paper presents the results of Do Nothing (DN) and Do Something (DS) scenarios for 2005 where in the latter case each transport user pays for all costs they impose including pollution, noise, accidents etc. The Dublin results, from an economics model used in the study, are examined in detail; the findings are compared with those of parallel studies conducted in the other cities to demonstrate the international relevance of this work. The comparison between the DN and DS scenarios indicates that taxes on all transport modes should be increased substantially, particularly in the morning and evening peak periods. As a result of the price increases, travel demand is reduced. A practical example where transport users could be made to pay for all their costs is road use pricing, i.e. charging individuals for the use of road space. The taxation levels suggested in the DS scenario have been used in a road use pricing trial in Dublin, the results of which were published in O'Mahony, Geraghty and Humphreys (Transportation 27, 269-283, 2000), to see if the reductions in the travel requirements of individuals proposed by the economics model are in fact true. The principles of the work presented in this paper are not only relevant to environmental impact management in the transport sector but can also be applied to other sectors.

Degradation of dehydroascorbic acid in parenteral nutrition mixtures.

The degradation of ascorbic acid (AA) stored in parenteral nutrition (PN) regimens is initially by oxidation, catalysed by trace elements, in particular copper. After prolonged storage the concentration of AA remains relatively constant, with little variation, due to the lack of available oxygen. The initial degradation product is dehydroascorbic acid (DHAA). This is generated in an anaerobic environment, and is hypothesised to degrade by hydrolysis. It is the purpose of this investigation to ascertain the effect of temperature and trace elements on the anaerobic degradation of DHAA, and to identify the kinetics of the reaction. A stability-indicating reversed-phase HPLC assay was used. The column contained C(18) reverse-phase packing (Luna), mean diameter 5 microm. The column dimensions were 15 cm long with an internal diameter of 0.4 cm. The mobile phase consisted of methanol: phosphate buffer (pH 7.8: 0.067 mol dm(-3)) at a ratio of 40: 60 (v/v) and also included Cetrimide (mixed alkyltrimethylammonium bromide) (0.05 mol dm(-3)) as an ion pair reagent. The flow rate was 0.7 ml min(-1) and detection was by ultra-violet light absorption at 278 nm. This assay was used to monitor the degradation rate of DHAA in PN mixtures with and without trace elements over a range of temperatures (5-35 degrees C). Results indicated a first order reaction that was temperature-dependent but trace elements independent.

Plasma catecholamine and cardiovascular reactivity during an acute high ropes course event.

The primary purpose of this study was to describe physiological responses to an acute high ropes course stress. The selected dependent variables were epinephrine (E), norepinephrine (NE), heart rate (HR), systolic/diastolic blood pressure (BPs and BPd) and self-reported anxiety. A secondary purpose was to explore possible relationships between the observed physiological responses and physical fitness. College-age males were recruited for preliminary V(O(2)) max testing to identify a high-fit and low-fit subject pool. Eleven were identified as eligible participants and gave informed consent. Six participants were in the high-fit category (V(O(2)) max>60 ml/kg) and five in the low-fit category (V(O(2)) max<42 ml/kg). The Power Pole, a common high ropes course event, was selected as the acute field-based challenge activity. During participation in the challenge, a series of five (T1-T5) 10-ml blood samples were taken (via intravenous catheter) to be analyzed for E and NE. Subjective anxiety, HR, BPs and BPd were also measured at T1-T5. When the data were analyzed in a 2 (fitness group) x 5 (time) factorial ANOVA, there was a significant main effect for time with each dependent variable. However, the only difference between fitness levels was found with HR. These results indicate that the Power Pole is an acute field-based stressor for individuals of both high and low fitness levels. Due to the lack of difference between fitness groups for all variables other than HR, we conclude that participating in the Power Pole event elicits more stress of a psychosocial nature than stress of physical exertion.

Laminin expression in adult and developing retinae: evidence of two novel CNS laminins.

Components of the extracellular matrix exert myriad effects on tissues throughout the body. In particular, the laminins, a family of heterotrimeric extracellular glycoproteins, have been shown to affect tissue development and integrity in such diverse organs as the kidney, lung, skin, and nervous system. Of these, we have focused on the roles that laminins play in the differentiation and maintenance of the nervous system. Here, we examine the expression of all known laminin chains within one component of the CNS, the retina. We find seven laminin chains-alpha3, alpha4, alpha5, beta2, beta3, gamma2, and gamma3-outside the retinal basement membranes. Anatomically, these chains are coexpressed in one or both of two locations: the matrix surrounding photoreceptors and the first synaptic layer where photoreceptors synapse with retinal interneurons. Biochemically, four of these chains are coisolated from retinal extracts in two independent complexes, confirming that two novel heterotrimers-alpha4beta2gamma3 and alpha5beta2gamma3-are present in the retinal matrix. During development, all four of these chains, along with components of laminin 5 (the alpha3, beta3, and gamma2 chains) are also expressed at sites at which they could exert important effects on photoreceptor development. Together, these data suggest the existence of two novel laminin heterotrimers in the CNS, which we term here laminin 14 (composed of the alpha4, beta2, and gamma3 chains) and laminin 15 (composed of the alpha5, beta2, and gamma3 chains), and lead us to hypothesize that these laminins, along with laminin 5, may play roles in photoreceptor production, stability, and synaptic organization.

The longitudinal course of bipolar disorder.

Course of illness is central to our focus on bipolar disorder due to the lifelong nature of this illness in the majority of patients. In this overview, we highlight areas of consensus and debate on factors that impact course of illness. Findings on age at onset, psychiatric comorbidity, frequency of episodes, cycle pattern, rapid cycling, mixed symptoms, and precipitants of episodes including use of substances and antidepressants and lithium discontinuation are discussed. The diversity and range of presentation and even course of illness become quickly apparent in this review. Highlighting these factors rather than seeking a unifying theory should be a productive way to refine our ability to identify additive factors contributing to course of illness for patients with bipolar disorder.

Effects of sex composition by class and instructor's sex on physical self-efficacy of college men.

The relationship of sex composition of class and instructor's sex to Physical Self-efficacy has yielded conflicting results in several studies. This study examined the relationship of sex composition of class and instructor's sex to scores on Physical Self-efficacy, Perceived Physical Ability, and Physical Self-presentation Confidence of 80 male students enrolled in one of four sections of a strength training class. Analysis indicated no significant difference on Physical Self-efficacy between male students who were enrolled in all male classes or in coeducational classes; improvements in scores on Physical Self-efficacy were not specific to the sex composition of the class or sex of the instructor and no significant difference on Perceived Physical Ability and Physical Self-presentation Confidence between male students who joined an all male class or a coeducational class. Perceived Physical Ability improved from the pretest to the posttest in all classes; and no improvement in scores for Physical Self-presentation Confidence was found in all classes. In conclusion, the analysis showed sex composition of the class and sex of the instructor were not significantly related to scores for self-efficacy.

The impact of economic sanctions on health and human rights in Haiti, 1991-1994.

OBJECTIVES: This report examines the impact of an economic embargo from 1991 to 1994 on health, well-being, and human rights in Haiti. METHODS: Data from surveillance systems for nutrition, reportable diseases, and hospital diagnoses were combined with survey data and interviews with affected women, governmental representatives, diplomats, and staff of nongovernmental organizations. RESULTS: Changes included declining income, rising unemployment, poorer nutrition, declining infant mortality, rising mortality among 1- to 4-year-olds, decreased attention to children's well-being and education, and family breakdown. Survival strategies among poor Haitians included changed dietary habits, informal-sector economic activity, moving in with relatives, selling domestic goods, increased informal unions among couples, decreased school attendance, and indentured servitude among children. CONCLUSIONS: The implementation of economic sanctions in Haiti resulted in extensive violations of rights; the impact was greatest on the most disadvantaged Haitians. Many Haitian and international supporters of democracy were unaware of the extensive negative impact that sanctions could have. The impact continues now, 5 years after sanctions ended. Modified policies reduced some of the burden of sanctions, and international assistance prevented what otherwise might have become a humanitarian disaster during sanctions.

Can aromatherapy replace pre-medication?

An examination of the use of the therapy within the theatre environment would be a useful extension of the care we already give our patients. It would be interesting to explore the cost effectiveness of oils versus conventional medication, and even though there may be a negative result the desire to provide holistic care may overshadow the cost. If this care can be achieved through therapeutic touch such as massage, and enhanced by the addition of aromatic oils, then perhaps theatre nurses should be training to meet the needs of the patient. It may be appropriate therefore for studies to be undertaken into the suggested benefits of aromatherapy. If, as it has been implied, this therapy is beneficial in reducing the levels of anxiety, it would seem sensible to introduce it to preoperative patients who suffer varying degrees of anxiety.

Maternal immunization of pregnant cattle with recombinant VP8* protein of bovine rotavirus elicits neutralizing antibodies to multiple serotypes. Colostral neutralizing antibody by rotavirus VP8*.

Neonatal calf diarrhoea caused by bovine rotavirus is one of the most common diseases in cattle. VP8 portion of the rotavirus VP4 protein is known to contain neutralizing epitopes and hemagglutination activity. We expressed the VP8* portion of bovine rotavirus strain C486 (G6P1 serotype) in E. coli, and examined potential of the recombinant VP8* protein for induction of neutralizing antibody responses in host animals. One hundred twenty pregnant beef cows were selected and immunized eight weeks prior to parturition with the recombinant VP8* protein. Colostral and milk samples were collected 12 hours and 10 days post-calving, respectively, and the virus neutralizing titers elicited by the recombinant subunit antigen were determined by plaque reduction assay. Colostral antibody titres of the vaccinated group were significantly higher than those of the unvaccinated control group, and these titers were equivalent to the titers elicited by a commercial vaccine. While titers of the control group rapidly decreased to 220 after 10 days of calving, neutralizing titers in the milk of the vaccinees remained 510. Rabbit and bovine antibodies induced by the recombinant VP8* protein were also able to neutralize bovine rotavirus P5 serotype (B641) at significant level and P11 serotype (B223) moderately. Our results suggest that the E. coli-produced recombinant VP8* protein can be an useful subunit vaccine candidate to prevent rotavirus infection in new-born calves.

Antiviral screening of British Columbian medicinal plants.

One hundred methanolic plant extracts were screened for antiviral activity against seven viruses. Twelve extracts were found to have antiviral activity at the non-cytotoxic concentrations tested. The extracts of Rosa nutkana and Amelanchier alnifolia, both members of the Rosaceae, were very active against an enteric coronavirus. A root extract of another member of the Rosaceae, Potentilla arguta, completely inhibited respiratory syncytial virus. A Sambucus racemosa branch tip extract was also very active against respiratory syncytial virus while the inner bark extract of Oplopanax horridus partially inhibited this virus. An extract of Ipomopsis aggregata demonstrated very good activity against parainfluenza virus type 3. A Lomatium dissectum root extract completely inhibited the cytopathic effects of rotavirus. In addition to these, extracts prepared from the following plants exhibited antiviral activity against herpesvirus type 1: Cardamine angulata, Conocephalum conicum, Lysichiton americanum, Polypodium glycyrrhiza and Verbascum thapsus.

Immunological response to recombinant VP8* subunit protein of bovine roravirus in pregnant cattle.

Bovine rotavirus VP8*, N-terminal trypsin cleavage product of VP4, was produced in Escherichia coli. To examine if this antigen could induce neutralizing antibody responses, different species of animals were immunized with the recombinant VP8* protein. The VP8* antigen was found to stimulate a neutralizing immune response in rabbits. When VP8*-immunized mice were exposed to bovine rotavirus strain C486, significantly higher antibody responses were observed than if they were only exposed to C486. To stimulate a current vaccination protocol in the field with livestock, mice were exposed to live C486 virus first and then to VP8*. These mice had the elevated immune responses indicating that VP8* could boost immunity in primed mice. The immune response to VP8* was also tested in pregnant cows. The efficacy of VP8* in stimulating milk antibody was compared with a commercial inactivated vaccine. Differences in colostral antibody titres between VP8*-vaccinated and unvaccinated cows were statistically significant (P < 0.05) and equivalent to the commercial vaccine (P = 0.0569). The milk antibody titres on day 10 were comparable between VP8*- and commercial vaccine-vaccinated animals and were significantly higher (P < 0.05) than in unvaccinated controls. Furthermore, rabbit and bovine antibodies induced by VP8* were able to neutralize different P types of bovine rotaviruses to varying degrees, suggesting that serotype-specific and cross-reactive epitope(s) are present on the VP8* protein of rotavirus. Taken together, E. coli-expressed VP8* may be useful as a subunit vaccine candidate for bovine rotavirus.