APTC-EC-2A: A Lytic Phage Targeting Multidrug Resistant E. coli Planktonic Cells and Biofilms

Escherichia coli (E. coli) are common bacteria that colonize the human and animal gastrointestinal tract, where they help maintain a balanced microbiome. However, some E. coli strains are pathogenic and can cause serious infectious diseases and life-threatening complications. Due to the overuse of antibiotics and limited development of novel antibiotics, the emergence of antibiotic-resistant strains has threatened modern medicine, whereby common infections can become lethal. Phage therapy has once again attracted interest in recent years as an alternative treatment option to antibiotics for severe infections with antibiotic-resistant strains. The aim of this study was to isolate and characterize phage against multi-drug resistant E. coli isolated from clinical samples and hospital wastewater. For phage isolation, wastewater samples were collected from The Queen Elizabeth Hospital (Adelaide, SA, Australia) followed by phage enrichment as required. Microbiological assays, electron microscopy and genomic sequencing were carried out to characterize the phage. From the 10 isolated E. coli phages, E. coli phage APTC-EC-2A was the most promising and could lyse 6/7 E. coli clinical isolates. APTC-EC-2A was stable at a broad pH range (3–11) and could lyse the host E. coli at temperatures ranging between 30–50 °C. Furthermore, APTC-EC-2A could kill E. coli in planktonic and biofilm form. Electron microscopy and genomic sequencing indicated the phage to be from the Myoviridae family and of lytic nature. In conclusion, the newly isolated phage APTC-EC-2A has the desired properties that support its potential for development as a therapeutic agent against therapy refractory E. coli infections.

The feasibility of conducting acute sarcopenia research in hospitalised older patients: a prospective cohort study

Purpose To assess feasibility of conducting acute sarcopenia research in complex populations of hospitalised older adults. Methods Patients ≥ 70 years old were recruited to three cohorts: elective colorectal surgery, emergency (abdominal) surgery, medical patients with infections. Participants were recruited to the elective cohort in preoperative assessment clinic, and acutely admitted participants from surgical and medical wards at the Queen Elizabeth Hospital Birmingham. Serial measures of muscle quantity (ultrasound quadriceps, bioelectrical impedance analysis), muscle function (hand grip strength, physical performance), and questionnaires (mini-nutritional assessment, physical function) were performed at baseline, within 7 (± 2) days of admission/surgery, and 13 (± 1) weeks post-admission/surgery. Feasibility outcomes were assessed across timepoints including recruitment and drop-out rates, and procedure completion rates. Results Eighty-one participants were recruited (mean age 79, 38.3% females). Recruitment rates were higher in elective (75%, 24/32) compared to emergency surgery (37.2%, 16/43), and medical participants (45.1%, 41/91; p = 0.003). Drop-out rates varied from 8.3 to 19.5% at 7 days, and 12.5–43.9% at 13 weeks. Age and gender did not differ between patients assessed for eligibility, approached, or recruited. Completion rates were highest for ultrasound quadriceps (98.8%, 80/81 across all groups at baseline). Gait speed completion rates were lower in medical (70.7%, 29/41) compared to elective participants (100%, 24/24) at baseline. Conclusion Higher participation refusal and drop-out rates should be expected for research involving recruitment of participants from the acute setting. Assessment of muscle quantity/quality through ultrasound is recommended in early-stage trials in the acute setting, where completion rates of physical performance testing are expected to be lower.

ALBUMIN CREATININE RATIO AS AN INDICATOR OF NON-HEALING FOOT WOUND FORMATION IN DIABETES

Aims: To investigate whether kidney injury, determined by albumin creatinine ratio, was associated with current non-healing foot wounds in type 2 diabetes. Materials and Methods: Eighty–nine Barbadians with diabetes were recruited. Cases had a current foot wound and controls had no current foot wound and no history of a non-healing foot wound. Cases were matched to controls using sex, age and duration of diabetes. Participants were from wound dressing and diabetes clinics at the Queen Elizabeth Hospital and Polyclinics, and from private healthcare practitioners. The relationship between albumin creatinine ratio and foot ulceration, adjusting for selected potential risk factors, was analyzed using logistic regression and presented as odds ratios. Results: Forty–four cases and 45 controls were matched, with no statistically significant difference in matching criteria. There were statistically important differences in measures of neuropathy, blood glucose, HbA1c and Albumin:creatinine ratio between cases and controls. Cases were 3 times more likely than controls to have microalbuminuria (95% CI 0.9 – 10.2; p=0.08). Cases were 7.4 times more likely than controls to have macroalbuminuria (95% CI 1.2 – 47.5; p=0.04). Conclusions: The possible association of albumin:creatinine ratio with diabetic foot wounds raises the possibility of its use in earlier identification of persons on the pathway to developing diabetic foot.

Are patients with brain tumours being given timely DVLA advice?

Aims Over 11,000 patients are diagnosed with a primary brain tumour annually in the UK, with many more being diagnosed with a secondary brain tumour. UK law stipulates that all individuals with a brain tumour must inform the Driver and Vehicle Licensing Agency (DVLA) and may be required to surrender their driving license depending on their specific tumour and symptoms. Despite this guidance, we found that patients continue to arrive at the neuro-oncology clinic without the correct DVLA advice being given. This can potentially lead to patients with brain tumours continuing to drive on the public highway, which poses a severe hazard as the risk of seizures could endanger the public. This retrospective study looks to review what information was provided to patients with brain tumours upon initial diagnosis and determine the adequacy of this; ultimately aiming to improve the quality of information given to future neuro-oncology patients. Method A structured questionnaire was designed, asking patients who have been treated for a brain tumour at the Queen Elizabeth Hospital in Birmingham about any information they received about driving when they were first diagnosed. The questionnaire comprised of 11 questions designed to gather an understanding of what information was given to patients about driving. The study secured local audit approval. 75 patients identified from the weekly neuro-oncology MDT list were contacted. All patients included in this audit were required to stop driving and inform the DVLA about their condition as per the DVLA guidelines. Their responses were collated and analysed. Using this data, we determined if there were inadequacies in the information that was given to these patients about driving, and how this process may be improved in the future. Results 60 patients (80%) possessed driving licenses when first diagnosed and 17% of these (n=10) were not told to stop driving; 8 of whom were diagnosed in primary/secondary care. 39 patients (65%) were first diagnosed in primary/secondary care, however, only 21% of these (n=8) were told to stop driving by primary/secondary care consultants. The remaining 31 patients (81%) were only told to stop driving after referral to tertiary care, by consultant neurosurgeons at the Queen Elizabeth Hospital. Conversely, of the 12 patients first diagnosed at the Queen Elizabeth Hospital, 85% were told to stop driving at diagnosis, suggesting a notable difference in informing patients between primary/secondary care and tertiary care. Patients also commented on the quality of the information received, as 10 individuals (21%) mentioned needing more information about getting their license back, and 5 individuals (11%) mentioning being given conflicting or incorrect information from different members of the MDT. Conclusion The results show that in practice, there are inconsistencies about mandatory DVLA advice which should be clearly provided to patients with a new diagnosis of a brain tumour. Only 78% of patients were told to stop driving at diagnosis, suggesting that the remainder could be liable to continue driving despite their diagnosis. Furthermore, many patients diagnosed in primary/secondary care are not being told to stop driving until after referral to tertiary care which can take weeks, causing delays in them being given this information, which can pose risks to themselves and the public. These delays may be alleviated by giving patients a simplified resource when they are first diagnosed which clearly explains the driving rules. We therefore propose developing a one-page resource based on DVLA guidance and distributing this to patients and referring healthcare professionals at first diagnosis. A subsequent re-audit can evaluate if this intervention improves the current situation.

Survival in patients with radiological diagnoses of glioblastoma: a retrospective study of 115 patients on a best supportive care pathway

Aims Glioblastoma multiforme (GBM) is a devastating disease with notoriously poor survival. Studies examining survival in patients given best supportive care (BSC) are few and far between. All patients harbouring brain tumours referred to the Neuro-oncology service at the Queen Elizabeth Hospital in Birmingham are recorded in the Somerset Cancer Registry. We set out to analyse survival times and identify patient and tumour-related factors significantly affecting prognosis. Method We identified 126 patients from 2015 to 2019 in our Somerset Cancer Registry with radiological diagnoses of glioblastoma for whom the Neuro-oncology MDT recommended BSC. We performed a retrospective analysis of clinical records and radiological images. 11 patients were excluded (8 due to insufficient imaging data, 2 who underwent subsequent surgery, 1 patient with brain metastases). Survival was measured in completed weeks since the index MDT decision. Associations between survival time and both patient- and tumour-related factors were assessed using Kaplan-Meier curves and log-rank tests. All analyses were performed using IBM SPSS 22 (IBM Corp. Armonk, NY), with p<0.05 deemed to be indicative of statistical significance throughout. Results Data were available for N=115 patients (69 males, 46 females), with a mean age of 79 ± 8 years. All patients died within 32 weeks of diagnosis, with a median survival time of 8 weeks. Only 8 patients survived for more than 20 weeks. Survival was significantly shorter in those with a greater number of main cerebral structures affected (p=0.044), with a median of 6 vs. 10 weeks for 3 or more vs. 1 structures affected (hazard ratio: 1.61, 95% CI: 0.99-2.62). Bilateral tumours involving the corpus callosum were also associated with shorter survival (p=0.039). None of the other factors considered were found to be significantly associated with survival, including age (p=0.193), gender (p=0.371), performance status (p=0.300) and tumour size (p=0.331). Conclusion With the exception of the number of main cerebral structures affected (frontal, parietal, temporal and occipital lobes, corpus callosum, insula, basal ganglia and brain stem), patient- and tumour-factors traditionally used by the MDT to prognosticate do not correlate with survival time in patients receiving BSC for radiological diagnoses of GBM. With 50% of the cohort dying within 8 weeks it is clear that we must reconsider the timing of referrals to palliative and hospice care. Finally, the fact that some patients survived for more than half a year with no surgical or oncological treatment suggests that the process of selecting patients for BSC vs aggressive treatments needs refinement.

Development of Medical Drone for Blood Product Delivery: A Technical Assessment

Drone is the well-known technology in military and amateur application. Recently, the drone was used to deliver goods and parcels. There is an increasing need for urgent delivery of medical supplies in low resource setting due to traffic congestion and terrain obstacles. The delivery of blood in emergency cases such as postpartum hemorrhaging is challenging and can be delayed due to geographical condition in underserved area. Postpartum hemorrhaging needs an immediate blood transfusion with proper blood product to save the life of mother and baby. To address to this need, a drone that can deliver blood supply to the desired location may be a good option. Therefore, research has been conducted to identify the baseline of drone specifications for blood delivery. A Hexacopter with the ArduPilot firmware and a Lithium-Polymer battery of 16,000 mAh were used to study the applicability of blood products delivery using drone. Using several tests to assess drone limitations, experimental data was obtained and analyzed using distinctive methods. The results indicated that the thrust-to-weight ratio of the drone play a paramount role for the drone performance and flight time. The GPS guidance performance showed a reliable and stable flight with only a slight deviation of ±6 meters during the tests. Finally, a test flight was conducted to simulate the actual test location from Queen Elizabeth Hospital and Hospital Wanita dan Kanak-Kanak, Likas, Sabah. The developed drone reached a flight time of 25 minutes covering 8.38 km with 4.3 kg take-off weight.