Towards co-design of rehabilitation technologies: a collaborative approach to prioritize usability issues.

Introduction: Early stakeholder engagement is critical to the successful development and translation of rehabilitation technologies, a pivotal step of which is usability testing with intended end-users. To this end, several methods employ end-user feedback to identify usability and implementation issues. However, the process of prioritizing identified issues seldom leverages the knowledge and expertise of the range of stakeholders who will ultimately affect the demand and supply of a device. This paper describes a novel method to prioritize end-user feedback using transdisciplinary stakeholder consultation and address it in subsequent product development. The proposed approach was demonstrated using a case study relating to the development of a novel technology for neural recovery after spinal cord injury. Method: Feedback from five individuals with chronic spinal cord injury was collected during two-hour usability evaluation sessions with a fully functional high-fidelity system prototype. A think-aloud and semi-structured interview protocol was used with each participant to identify usability and acceptability issues relating to the system in a 3-phase approach. Phase 1 involved extracting usability issues from think-aloud and semi-structured interview data. Phase 2 involved rating the usability issues based on their significance, technical feasibility, and implementation priority by relevant internal and external stakeholders. Finally, Phase 3 involved aggregating the usability issues according to design and implementation elements to facilitate solution generation, and these solutions were then raised as action tasks for future design iterations. Results: Sixty usability issues representing nine facets of usability were rated. Eighty percent of issues were rated to be of moderate to high significance, 83% were rated as being feasible to address, and 75% were rated as addressable using existing project resources. Fifty percent of the issues were rated to be a high priority for implementation. Evaluation of the grouped issues identified 21 tasks which were mapped to the product roadmap for integration into future design iterations. Discussion: This paper presents a method for meaningful transdisciplinary stakeholder engagement in rehabilitation technology development that can extended to other projects. Alongside a worked example, we offer practical considerations for others seeking to co-develop rehabilitation technologies.

Kynanthropic and vampirism delusions: a case report and review of the literature.

Zooanthropy (delusional beliefs of turning into an animal) is a rare but well recognised psychiatric phenomenon. This case describes the presence of kynanthropic delusions (delusional beliefs of turning into a dog). Multiple other psychotic symptoms were also evident including unusually the additional presence of delusions of vampirism. Delusional beliefs in this case were associated with behavioural changes including growling and barking, and less commonly an expressed craving for biting people's necks to suck human blood. Symptom intensity was associated with increased psychosocial stressors for this patient, with some benefit noted from very high doses of anti-psychotic medications. Brief admissions to the acute psychiatric inpatient unit and thus removal from environmental stressors has been associated with an amelioration in symptomatology.

A 2-year longitudinal evaluation of the impact of the COVID-19 pandemic on individuals with pre-existing anxiety disorders.

OBJECTIVES: To examine if the COVID-19 pandemic is associated with a differential effect over a 2-year time period in relation to its psychological and social impact on patients with established anxiety disorders. METHODS: Semi-structured interviews were conducted with 21 individuals attending the Galway-Roscommon Mental Health Services in Ireland with an ICD-10 diagnosis of an anxiety disorder. Interviews occurred at three time-points over a 2-year period to determine the impact of the COVID-19 pandemic and associated restrictions on anxiety and depressive symptoms, social and occupational functioning, and quality of life. RESULTS: No statistical difference in symptomatology was noted between the three time-points in relation to anxiety symptoms as measured utilising psychometric rating scales (Beck Anxiety Inventory (BAI), Hamilton Anxiety Rating Scale (HARS) or Likert Scale measures). The greatest impact of COVID-19 at all time-points related to social functioning and quality of life. Significant variability was noted for individual participants. Qualitative analysis noted a tentative optimism for the future in the setting of vaccination and societal re-opening. Fear of re-emerging anxiety symptoms with the removal of societal restrictions was noted. CONCLUSIONS: No significant overall change in symptomatology or functioning over time was noted for individuals with pre-existing anxiety disorders, however variability was demonstrated, with some individuals describing ongoing anxiety, social isolation and concern for their future. A strong theme of hope for the future and less concern regarding the COVID-19 pandemic was evident; however tailored supports including the utilisation of tele-psychiatry is suggested, particularly for those experiencing increased anxiety with the removal of societal restrictions.

Childhood pneumonia and crowding, bed-sharing and nutrition: a case-control study from The Gambia.

SETTING: Greater Banjul and Upper River Regions, The Gambia. OBJECTIVE: To investigate tractable social, environmental and nutritional risk factors for childhood pneumonia. DESIGN: A case-control study examining the association of crowding, household air pollution (HAP) and nutritional factors with pneumonia was undertaken in children aged 2-59 months: 458 children with severe pneumonia, defined according to the modified WHO criteria, were compared with 322 children with non-severe pneumonia, and these groups were compared to 801 neighbourhood controls. Controls were matched by age, sex, area and season. RESULTS: Strong evidence was found of an association between bed-sharing with someone with a cough and severe pneumonia (adjusted OR [aOR] 5.1, 95%CI 3.2-8.2, P < 0.001) and non-severe pneumonia (aOR 7.3, 95%CI 4.1-13.1, P < 0.001), with 18% of severe cases estimated to be attributable to this risk factor. Malnutrition and pneumonia had clear evidence of association, which was strongest between severe malnutrition and severe pneumonia (aOR 8.7, 95%CI 4.2-17.8, P < 0.001). No association was found between pneumonia and individual carbon monoxide exposure as a measure of HAP. CONCLUSION: Bed-sharing with someone with a cough is an important risk factor for severe pneumonia, and potentially tractable to intervention, while malnutrition remains an important tractable determinant.

Re-Staging Following Long-Course Chemoradiotherapy For Rectal Cancer: Does It Influence Management?

BACKGROUND: In patients with locally advanced or low rectal cancers, long-course chemoradiotherapy (LCCRT) is recommended prior to surgical management.1 The need for restaging afterwards has been questioned as it may be difficult to interpret imaging due to local tissue effects of chemoradiotherapy. The purpose of this study was to determine if restaging affected the management of patients receiving long-course chemoradiotherapy for rectal cancer. METHODS: A retrospective review of patients with rectal cancer discussed at the South Eastern Health and Social Care Trust Lower Gastrointestinal Multi-Disciplinary Team Meeting (LGIMDT) in 2013 who had received long-course chemoradiotherapy was performed. Patients were identified from the Trust Audit Department, LGIMDT notes and patient records. Imaging results and outcomes from meetings were obtained through the Northern Ireland Picture Archiving and Communications System® (NIPACS) and Electronic Care Record® (ECR). Data including patient demographics, initial radiological staging and LGIMDT discussion, restaging modality and result, outcome from post-treatment LGIMDT discussion and recorded changes in management plans were documented using a proforma. RESULTS: Seventy-one patients with rectal cancer were identified as having LCCRT in 2013 (M:F 36:35; age range 31 - 85 years). Fifty-nine patients were restaged following long-course treatment with computed tomography (CT) and magnetic resonance imaging (MRI). Twelve patients did not undergo restaging. Data was not available for 6 patients, one patient underwent emergency surgery, two patients were not fit for treatment, one failed to attend for restaging and two patients died prior to completion of treatment. Of the 59 patients restaged, 19 patients (32%) had their management plan altered from that which had been proposed at the initial LGIMDT discussion. The most common change in plan was not to operate. Ten patients had a complete clinical and radiological response to treatment and have undergone intensive follow-up. Nine patients had disease progression, with 3 requiring palliative surgery and 6 referred for palliative care. CONCLUSION: Of those patients who were restaged, 32% had their management plan altered from that recorded at the initial LGIMDT discussion. Seventeen per cent of patients in this group had a complete clinical and radiological response to treatment. Fifteen percent demonstrated disease progression. We recommend, therefore, that patients with rectal cancer be restaged with CT and MRI following long-course chemoradiotherapy as surgery may be avoided in up to 27% of cases.

Dose-specific efficacy of Haemophilus influenzae type b conjugate vaccines: a systematic review and meta-analysis of controlled clinical trials.

Global coverage of infant Haemophilus influenzae type b (Hib) vaccination has increased considerably during the past decade, partly due to GAVI Alliance donations of the vaccine to low-income countries. In settings where large numbers of children receive only one or two vaccine doses rather than the recommended three doses, dose-specific efficacy estimates are needed to predict impact. The objective of this meta-analysis is to determine Hib vaccine efficacy against different clinical outcomes after receiving one, two or three doses of vaccine. Studies were eligible for inclusion if a prospective, controlled design had been used to evaluate commercially available Hib conjugate vaccines. Eight studies were included. Pooled vaccine efficacies against invasive Hib disease after one, two or three doses of vaccine were 59%, 92% and 93%, respectively. The meta-analysis provides robust estimates for use in decision-analytical models designed to predict the impact of Hib vaccine.

Failure to vaccinate or failure of vaccine? Effectiveness of the 23-valent pneumococcal polysaccharide vaccine program in Indigenous adults in the Northern Territory of Australia.

Over the last decade, there has been no discernible reduction in Invasive Pneumococcal Disease (IPD) amongst Indigenous adults in the Northern Territory (NT) of Australia, despite increasing vaccination coverage. We examined the utility of two common methods, the screening method and the indirect method, to determine the 23-valent pneumococcal polysaccharide vaccine effectiveness (VE) in prevention of IPD amongst Indigenous adults in this setting. VE was calculated for the period 2001-2005 across two distinct geographical areas where the disease burden was known to differ. VE against vaccine-type IPD was 3.4% (95% CI -43, 35) for the NT. However, population vaccination coverage varied widely according to geographical region and where this was within the range appropriate for the use of the screening method, VE was within the expected range (67.2%, 95% CI 47, 80). VE according to the indirect cohort appeared unreliable in this setting due to the analysis being based on a very limited number of non-vaccine-type IPD cases. Surveillance based estimates of VE such as these need to be considered with caution, but the results suggest failure to vaccinate is the most likely reason vaccine-type IPD has not reduced in this setting.

Phase II meningococcal B vesicle vaccine trial in New Zealand infants.

BACKGROUND: A tailor-made serogroup B outer membrane vesicle vaccine was evaluated in the context of a serogroup B meningococcal epidemic dominated by Neisseria meningitidis strain B:4:P1.7b,4. OBJECTIVE: To determine the safety, reactogenicity and immunogenicity in infants aged 6-8 months of a meningococcal B vaccine developed against the New Zealand epidemic strain. DESIGN, SETTING AND PARTICIPANTS: Observer-blind, randomised, controlled trial conducted in 296 healthy infants in Auckland, New Zealand. INTERVENTION: Infants were randomised 4:1 to receive three doses of New Zealand candidate vaccine (epidemic strain NZ98/254, B:4:P1.7b,4) or meningococcal C conjugate vaccine at 6-weekly intervals. MAIN OUTCOME MEASURES: Immune response was determined by human complement mediated serum bactericidal assay. Sero-response was a fourfold or greater rise in titre compared to baseline, with baseline titres <4 required to increase to >or=8. Blood samples were taken before vaccination, 6 weeks after dose two, and 4 weeks after dose three. Local and systemic reactions were recorded for 7 days following vaccination. RESULTS: Sero-response to the candidate vaccine strain, NZ98/254, was demonstrated in 74% of vaccinees (95% CI: 68% to 80% intention-to-treat; 67% to 79% per protocol) after three doses of New Zealand candidate vaccine. No meningococcal C conjugate vaccine recipients were sero-responders to NZ98/254 after three doses. Both vaccines were well tolerated with no vaccine related serious adverse events. CONCLUSIONS: Our data indicate that the New Zealand candidate vaccine administered in three doses to this group of 6-8-month-old infants was safe and immunogenic against the candidate vaccine strain NZ98/254 (Neisseria meningitidis B:4:P1.7b,4).

Safety and immunogenicity of New Zealand strain meningococcal serogroup B OMV vaccine in healthy adults: beginning of epidemic control.

As the first step towards control of a strain specific epidemic of meningococcal disease in New Zealand (NZ), this study, an observer-blind, randomised controlled trial in 75 healthy adults, evaluated safety and immunogenicity of two different dosages of a meningococcal group B vaccine administered in a three dose regime. The "tailor-made" outer membrane vesicle (OMV) vaccine (candidate vaccine) developed using a New Zealand meningococcal group B strain (B:4:P1.7b,4) was well tolerated with no vaccine related serious adverse events. Similar local and systemic reactions were observed in those receiving the New Zealand candidate vaccine and the control parent Norwegian vaccine (MenBvac). A four-fold rise in serum bactericidal antibodies (SBAb) against the vaccine strain 4-6 weeks after the third vaccination was achieved in 100% of New Zealand candidate vaccine 2,519 microg participants and in 87% of 50 microg participants. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using 25 microg dosage.

Bleeding gastric varices--a rare complication of ovarian cancer.

Splenic venous hypertension (or 'left-sided portal hypertension') is a rare underlying cause of gastro-oesophageal varices. Ovarian carcinoma recurring beyond 10 years, following primary treatment with no interval disease, is also a rare occurrence. We report an unusual case of bleeding gastric varices secondary to splenic venous obstruction as a result of metastatic ovarian carcinoma. This occurred 21 years following surgery and adjuvant chemotherapy for primary ovarian carcinoma. To our knowledge, until now, there have been no reported cases of splenic venous hypertension due to ovarian carcinoma. This case report illustrates the successful emergency management of this condition by splenectomy, with complete resolution of varices confirmed endoscopically at 6 weeks. It is followed by a brief discussion regarding varices due to splenic venous hypertension.

Expert system support using a Bayesian belief network for the classification of endometrial hyperplasia.

Accurate morphological classification of endometrial hyperplasia is crucial as treatments vary widely between the different categories of hyperplasia and are dependent, in part, on the histological diagnosis. However, previous studies have shown considerable inter-observer variation in the classification of endometrial hyperplasias. The aim of this study was to develop a decision support system (DSS) for the classification of endometrial hyperplasias. The system used a Bayesian belief network to distinguish proliferative endometrium, simple hyperplasia, complex hyperplasia, atypical hyperplasia and grade 1 endometrioid adenocarcinoma. These diagnostic outcomes were held in the decision node. Four morphological features were selected as diagnostic clues used routinely in the discrimination of endometrial hyperplasias. These represented the evidence nodes and were linked to the decision node by conditional probability matrices. The system was designed with a computer user interface (CytoInform) where reference images for a given clue were displayed to assist the pathologist in entering evidence into the network. Reproducibility of diagnostic classification was tested on 50 cases chosen by a gynaecological pathologist. These comprised ten cases each of proliferative endometrium, simple hyperplasia, complex hyperplasia, atypical hyperplasia and grade 1 endometrioid adenocarcinoma. The DSS was tested by two consultant pathologists, two junior pathologists and two medical students. Intra- and inter-observer agreement was calculated following conventional histological examination of the slides on two occasions by the consultants and junior pathologists without the use of the DSS. All six participants then assessed the slides using the expert system on two occasions, enabling inter- and intra-observer agreement to be calculated. Using unaided conventional diagnosis, weighted kappa values for intra-observer agreement ranged from 0.645 to 0.901. Using the DSS, the results for the four pathologists ranged from 0.650 to 0.845. Both consultant pathologists had slightly worse weighted kappa values using the DSS, while both junior pathologists achieved slightly better values using the system. The grading of morphological features and the cumulative probability curve provided a quantitative record of the decision route for each case. This allowed a more precise comparison of individuals and identified why discordant diagnoses were made. Taking the original diagnoses of the consultant gynaecological pathologist as the 'gold standard', there was excellent or moderate to good inter-observer agreement between the 'gold standard' and the results obtained by the four pathologists using the expert system, with weighted kappa values of 0.586-0.872. The two medical students using the expert system achieved weighted kappa values of 0.771 (excellent) and 0.560 (moderate to good) compared to the 'gold standard'. This study illustrates the potential of expert systems in the classification of endometrial hyperplasias.

Vascular endothelial growth factor levels in serum and plasma following esophageal cancer resection--relationship to platelet count.

In patients with cancer circulating vascular endothelial growth factor (VEGF) may be tumor-derived and have prognostic significance. Activated platelets may also be a source of VEGF, releasing it in serum formation. Debate exists as to whether serum or plasma VEGF (S-VEGF, P-VEGF) is the most appropriate surrogate marker of tumor angiogenesis. As healing wounds produce VEGF that can spill over into the circulation, we aimed to investigate the potential confounding effects of cancer surgery on both perioperative S-VEGF and P-VEGF levels and to evaluate their relationship with platelet count. S-VEGF, P-VEGF and platelet counts were measured in 23 patients undergoing esophageal cancer resection. Samples were taken preoperatively and six weeks following surgery. Seven patients were also sampled on postoperative days 1, 5 and 10. VEGF was assayed using a commercial enzyme linked immunosorbent assay. S-VEGF and P-VEGF both rose after surgery (S-VEGF; day 5: 1017 [446-1224] pg/mL and day 10: 1231 [626-2046] pg/mL versus pre-op: 329 [189-599] pg/mL. P-VEGF; day 1: 55 [46-104] pg/mL and day 10: 58 [20-154] pg/mL versus pre-op: 23 [13-46] pg/mL), falling towards preoperative levels by six weeks. Platelet count correlated with S-VEGF (rho=0.281; p<0.05, Spearman's rank) and P-VEGF (rho=0.330; p<0.01, Spearman's rank). Platelets may contribute to VEGF levels in plasma as well as in serum. The effects of surgery on S-VEGF or P-VEGF levels are mainly transient. Care must be exercised when interpreting circulating VEGF levels in the early postoperative period.

Increased nm23 immunoreactivity is associated with selective inhibition of systemic tumour cell dissemination.

AIMS: In vitro transfection experiments show that the nm23 gene suppresses metastasis, although the evidence from clinical studies is contradictory. The purpose of this study was to investigate whether nm23 selectively influences systemic, pleural, and lymphatic metastasis in non-small cell lung cancer (NSCLC). METHODS: Forty two patients undergoing resection of NSCLC and lymph node sampling were enrolled prospectively. In each case, a bone marrow aspirate, pleural lavage, and lymph nodes were assessed using immunohistochemistry for epithelial antigens and morphology. The intensity of nm23-H1 immunoreactivity of the primary tumour was compared with the internal control of normal bronchial epithelium in 32 cases where available. The microvessel count (MVC) of each tumour was determined using immunohistochemistry for the endothelial cell marker CD34. RESULTS: Tumour cell dissemination was detected in the bone marrow in 18 patients, in the pleura in seven, and in the lymph nodes in 21. Increased immunoreactivity for nm23 was found in the primary tumour in six patients, with none having tumour cells in the bone marrow, compared with 12 of 26 patients who showed nm23 immunoreactivity equal to or less than the control (Fisher's exact test: p = 0.043). This effect was confirmed to be independent of the MVC on multivariate analysis. There was no significant difference in the incidence of pleural or lymphatic tumour cell dissemination between the two groups. CONCLUSION: nm23 appears to be a suppressor of systemic, but not lymphatic, metastasis in primary NSCLC.

Multi-drug resistant Pseudomonas aeruginosa outbreak in a burns unit--an infection control study.

A newly introduced, multi-drug resistant (MDR) strain of Pseudomonas aeruginosa was isolated from four patients admitted to the Concord Hospital Burns Unit (BU) between December 1997 and March 1998. It was the cause of recurrent episodes of bacteraemia in two. This strain was resistant in vitro to gentamicin, piperacillin and ciprofloxacin. The isolates were confirmed as a clonal strain by pulse field gel electrophoresis (PFGE). Multiple environmental swabs were taken to search for an environmental reservoir, but no source was identified. Random cultures of staff members' hands failed to demonstrate ongoing carriage. In the absence of a demonstrable point source for the outbreak, direct cross-transmission patient to patient, via transient staff hand contamination, was the most likely route of infection. Following study commencement no new cases of infection with the MDR strain were detected. It would appear that the infection cycle has been interrupted, and the outbreak terminated following the discharge of the last infected patient from the BU. Contamination of a neutral detergent in the BU with Klebsiella oxytoca was detected incidentally during environmental surveillance. A potential hospital-wide outbreak was averted.