Computational tissue staining of non-linear multimodal imaging using supervised and unsupervised deep learning

Hematoxylin and Eosin (H&E) staining is the ’gold-standard’ method in histopathology. However, standard H&E staining of high-quality tissue sections requires long sample preparation times including sample embedding, which restricts its application for ’real-time’ disease diagnosis. Due to this reason, a label-free alternative technique like non-linear multimodal (NLM) imaging, which is the combination of three non-linear optical modalities including coherent anti-Stokes Raman scattering, two-photon excitation fluorescence and second-harmonic generation, is proposed in this work. To correlate the information of the NLM images with H&E images, this work proposes computational staining of NLM images using deep learning models in a supervised and an unsupervised approach. In the supervised and the unsupervised approach, conditional generative adversarial networks (CGANs) and cycle conditional generative adversarial networks (cycle CGANs) are used, respectively. Both CGAN and cycle CGAN models generate pseudo H&E images, which are quantitatively analyzed based on mean squared error, structure similarity index and color shading similarity index. The mean of the three metrics calculated for the computationally generated H&E images indicate significant performance. Thus, utilizing CGAN and cycle CGAN models for computational staining is beneficial for diagnostic applications without performing a laboratory-based staining procedure. To the author’s best knowledge, it is the first time that NLM images are computationally stained to H&E images using GANs in an unsupervised manner.     

Prehospital use of paracetamol among children attending the accident and emergency department

Methods: A prospective cohort study of carers of children attending a paediatric accident and emergency (A&E) department. Carers of children completed a questionnaire to identify domestic patterns of paracetamol use. Data were collected on temperature of the child in the A&E department, administration of antipyretics in the A&E department, diagnosis, and disposal from the A&E department.

Results: Seventy five adults attending the A&E department consented to involvement. Sixty five of the children were feverish on arrival in the A&E department. Twenty one children (32.3%) had not received paracetamol before attending. There was a significant relation between knowledge of the antipyretic properties of paracetamol and administration (χ²=5.0, p<0.05). There was a significant correlation between fever and administration of paracetamol in the A&E department (χ²=23.7, p<0.01), however, 15 feverish patients (24.6%) were not treated.

Conclusions: Most carers administer paracetamol appropriately in the prehospital setting. Administration correlates significantly with knowledge of its benefits. There is scope for education of carers and A&E department staff in the in the appropriate use of antipyretics such as paracetamol.

     

Sports medicine and the accident and emergency medicine specialist

Background: Sport and exercise related injuries are responsible for about 5% of the workload in the accident and emergency (A&E) department, yet training in sports medicine is not a compulsory part of the curriculum for Higher Specialist Training.

Aim: To determine how A&E medicine consultants and specialist trainees view their role and skill requirements in relation to sports medicine.

Method: A modified Delphi study, consisting of two rounds of a postal questionnaire. Participants were invited to rate the importance of statements relating to the role and training of the A&E specialist in relation to sports injuries (six statements) and the need for knowledge and understanding of defined skills of importance in sports medicine (16 statements).

Value of research: This provides a consensus of opinion on issues in sport and exercise medicine that have educational implications for A&E specialists, and should be considered in the curriculum for Higher Specialist Training. There is also the potential for improving the health care provision of A&E departments, to the exercising and sporting population.

     

Section 136, The Mental Health Act 1983; levels of knowledge among accident and emergency doctors,senior nurses,and police constables

Objectives: Section 136 of the Mental Health Act 1983 empowers the police to detain those suspected of being mentally ill in public places, and convey them to a place of safety. In practice, accident and emergency (A&E) departments are often used. The authors assessed levels of knowledge of section 136 between A&E doctors, senior nurses, and police constables.

Methods: Doctors and senior nurses in all (A&E) departments in the Yorkshire region were asked to complete a multiple choice tick box type questionnaire, as were police constables from the Humberside Police Force.

Results: 179 completed questionnaires were returned, of which 16 were completed by consultants, 14 by SpRs, 24 by SHOs, 33 by senior nurses, and 92 by police officers. Some 24.1% of A&E staff and 10.9% of police failed to recognise that a person has to appear to be suffering from a mental disorder to be placed on a section 136; 40.2% of police did not know that section 136 is a police power; 55.2% of A&E staff and 14.1% of police incorrectly thought that a person could be placed on a section 136 in their own home; 43.75% of consultants and 50% of SpRs did not consider A&E departments to be a place of safety; 49.4% of A&E staff and 29.3% of police thought that patients could be transferred on a section 136. Only 10.3% of A&E staff and 22.8% of police had received any formal training.

Conclusions: The knowledge among A&E staff and the police of this difficult and complex piece of mental health legislation is poor and requires action through formal education and training. This study not only reflects the levels of knowledge within the groups, it may also reflect the different perceptions of each group as to their role and duties within section 136 of the Mental Health Act 1983.

     

Tissue donation after death in the accident and emergency department: an opportunity wasted?

OBJECTIVE: To investigate whether the accident and emergency department (A&E) is a potential source of tissues for donation, from non-heart beating donors (NHBDs). METHODS: A telephone survey of 30 A&E departments was conducted to determine current tissue harvesting practices from NHBDs. The potential number of tissue donors in our own medium sized district general hospital A&E department was estimated. Senior nursing staff were asked to complete a questionnaire to establish their knowledge, attitudes, and experience of tissue harvesting from NHBDs. RESULTS: Only seven of the 30 A&E departments surveyed (23%) had an active involvement in requesting tissue donation after a sudden death. Several others had limited experience. The level of involvement was unrelated to department size. In our own A&E department, there were 110 deaths in 1995. Tissue donation had occurred on just three occasions. However, departmental staff attitudes towards reducing this shortfall were positive. CONCLUSIONS: The A&E department is a resource of tissues for donation, which is currently under used.     

What information do general practitioners want about accident and emergency patients?

OBJECTIVES: To establish what information general practitioners (GPs) want about their patients who attend accident and emergency (A&E) departments and the GPs' preferences for the type of communication and method of delivery. METHODS: Analysis of questionnaire sent to all 350 GPs in the catchment area of one A&E department. RESULTS: 219 completed questionnaires (63%) were returned. GPs requested information about most new attendances at A&E, but only 50% of GPs wanted details of every new A&E patient. Most GPs preferred a small computer generated letter or sticky label which included details of investigation results, diagnosis, treatment, and follow up arrangements. 47% of GPs requested delivery of letters by the pathology specimen service, but 25% preferred hand delivery by the patient or a relative. Individual GPs often had widely different preferences, especially about the type of communication and method of delivery. Most GPs would value a monthly list of all their patients who have attended A&E. CONCLUSIONS: GPs need prompt and appropriate information about their patients who attend A&E. A computerised records system should be arranged so that relevant information can be produced easily and quickly in a format suitable for filing in GP records. Good communications with GPs would improve the continuity of care for A&E patients.     

Who cares for the patient with head injury now?

Objective—A recent report on head injury management from the Royal College of Surgeons of England suggests that surgeons are unsuited to the inpatient care of head injuries (ICHI) and should hand over responsibility entirely to neurosurgeons and accident and emergency (A&E) specialists. This prompted a survey of A&E consultants to establish their opinions on the current and future practice of head injury care.

Methods—Questionnaires were sent to consultant members of the British Association for Accident and Emergency medicine. Of a possible 256 A&E departments from Great Britain and Ireland with over 20 000 annual new attenders 206 (80%) replied.

Results—General surgeons contribute to ICHI for adults in 107 of 206 hospitals (52%) compared with orthopaedic surgeons in 73 of 206 (35%) and A&E consultants in 71 of 206 (34%). There was frequent criticism that surgeons are uninterested in head injury care. Fifty nine units (30%) commented on the lack of neurosurgery beds and difficulties experienced in getting patients accepted. Few hospitals seem to have well integrated rehabilitation or follow up services targeted at head injury. One in six patients with head injury admitted to a general hospital or observation ward remain after 48 hours and one in 20 stay beyond one week. Of the 132 A&E units without responsibility for ICHI 54 (41%) either wish to take on this responsibility or are willing to do so if the necessary resources are first put in place. The perceived net revenue cost required to allow 67 A&E units to take on ICHI is about 12.5 million pounds per year. This does not include the cost of further care after 48 hours, follow up or rehabilitation.

Conclusion—Only one third of A&E units at present have even part of the ICHI role recommended in the RCS report; another third are prepared to accept a new role if training and resources are provided and support is forthcoming from other specialists to take over the care after 48 hours; the remaining third are unwilling to accept responsibility for ICHI.

     

What are the ten new commandments in severe polytrauma management?

This review aims to provide a concise overview of the trauma management evolution in the past decade. 1) Trauma care priorities have incorporated staff protection against infection and early decision making in addition to the conventional ABCDE. 2) Five stratified levels for DAM have replaced the non-specific conventional Plans A & B. 3) CT scanning can be the tunnel to death for the hemodynamically unstable patient. 4) DPL has virtually been replaced by the FAST USG. 5) Direct whole-body MDCT provides rapid imaging diagnosis & expedites the definitive treatment but carries high radiation hazards. 6) The dynamic shock assessment by fluid resuscitation response provides more outcome-specific evaluation than the static blood volume loss model. 7) DCR comprising of permissive hypotension, hemostatic resuscitation & DCS aims to overcome the lethal triad of trauma. Early transfusion of blood components of FFP & platelet concentrates improves the outcome in massive blood transfusion. 8) DCS aims to rectify the deranged physiology and not to fully restore the damaged anatomy. 9) A pre-defined protocol for major pelvic fracture can be life-saving and the novel Pre-PPP (pre-peritoneal pelvic packing) may further reduce mortality coupled with the necessary TCAE. 10) Injury prevention is equally important if not more than the trauma resuscitation & operation.KEY WORDS: Polytrauma, Priorities, DAM, CT, MDCT, DPL, FAST, Fluid resuscitation responder, DCR, DCS, Pre-PPP, Injury preventionPolytrauma management has undergone tremendous evolution in the past decade in the assessment, diagnosis, treatment and team approach algorithms. This article aims to highlight the important changes in a concise manner.     

A profile of sports hand injuries in an accident and emergency department.

OBJECTIVE: To establish a profile of sports hand injuries requiring treatment in an urban accident and emergency (A&E) department, and to determine the extent to which these injuries resulted in morbidity. METHODS: A one year prospective observational study at the Royal Victoria Infirmary, Newcastle upon Tyne. All patients presenting to the A&E department between 29 July 1995 and 28 July 1996 with a hand injury sustained during sporting activity and who received follow up by A&E or plastic surgery units were enrolled. Patients were contacted by telephone or post at median of four months after injury (range two to 13) for their assessment of the outcome. RESULTS: 262 cases were enrolled into the study. The median age for males was 21 years (range 7 to 55) and for females 16 (range 9 to 40). Follow up data were obtained by telephone in 206 (79%), and by letter in a further 26 (10%). Fractures were the commonest injury (68%), followed by soft tissue injuries (20%) and dislocations (11%). The thumb was the site affected most commonly overall, and in 10 of 17 ski related injuries; next most frequent sites were little and ring fingers. Males sustained 79% of the injuries, and 54% of these occurred during football. Netball/basketball caused 63% of female injuries. Follow up indicated that mild impairment in terms of pain, stiffness, or deformity was common (45%), while the incidence of moderate pain or serious problems was 11%. CONCLUSIONS: Sporting injuries to the hand commonly require treatment in the A&E department. Telephone/postal follow up of such injuries indicates that significant short term and longer term impairment of function may result. Suitable target areas for injury prevention are secondary schools, football (in males), and netball/basketball.     

Notification of infectious diseases by junior doctors in accident and emergency departments.

OBJECTIVE: To assess the knowledge about notifiable infectious diseases by accident and emergency (A&E) senior house officers. METHODS: A telephone questionnaire of senior house officers was carried out over a one week period at the end of their six month attachment in A&E departments in Northern Ireland. RESULTS: 81 (91%) of the senior house officers participated in the study; 23 (29%) realised that the doctor diagnosing the notifiable disease had a statutory duty to notify that disease; nine (11%) were aware there were three statutory lists in the United Kingdom. Knowledge about which infectious diseases require notification varied from 79/81 (98%) for meningococcal disease to 15/91 (19%) for methicillin resistant S aureus. Seventy nine (98%) of the doctors thought that a poster displayed in the A&E department would be helpful. There was no significant difference between duration of qualification and performance on the questionnaire (p = 0.2). CONCLUSIONS: Despite varying experience, junior doctors in A&E do not know which infectious diseases are notifiable by statute. They felt that it would be helpful to have a poster in the A&E department listing the notifiable diseases of that region. To encourage accurate reporting, interregional variation between the statutory lists should be abolished and replaced by one nationally agreed list.     

Concocting that Magic Elixir: Successful Grant Application Writing in Dissemination and Implementation Research

Background

This paper reports core competencies for dissemination and implementation (D&I) grant application writing and provides tips for writing a successful proposal.

Methods

Two related phases were used to collect the data: a card sorting process among D&I researchers and an expert review among a smaller set of researchers. Card sorting was completed by 123 respondents. In the second phase, a series of grant application writing tips were developed based on the combined 170 years of grant review experience of the writing team.

Results

The card sorting resulted in 12 core competencies for D&I grant application writing that covered the main sections in a grant application to the US National Institutes of Health: (a) specific aims that provide clear rationale, objectives, and an overview of the research plan; (b) significance that frames and justifies the importance of a D&I question; (c) innovation that articulates novel products and new knowledge; and (d) approach that uses a relevant D&I model, addresses measurement and the D&I context, and includes an analysis plan well‐tied to the aims and measures.

Conclusions

Writing a successful D&I grant application is a skill that can be learned with experience and attention to the core competencies articulated in this paper.     

The laws of violence

Working in an accident and emergency (A&E) department inevitably involves dealing with the consequences of violence, and a knowledge of the laws of violence is a useful adjunct to the clinical practice of A&E medicine. The police and the Crown Prosecution Service decide whether or not to charge a suspect, and which charge is appropriate. All criminal offences are initially considered in the magistrates' court but the more serious offences may be committed to crown court. Specific offences include common assault, actual bodily harm, grievous bodily harm, and grievous bodily harm with intent. If the defendant is found guilty, an appropriate sentence is imposed.     

Flying Squad response to medical emergencies.

The Flying Squad of the Accident and Emergency Department, of the Derbyshire Royal Infirmary, was established in 1955 by Collins. The initial function was to provide emergency care to victims of industrial accidents. However, the spectrum of emergencies they now respond to has expanded and includes predominantly road traffic accidents and medical emergencies. Despite the proliferation of Flying Squads their benefit has been difficult to quantify even in a trauma setting (Robertson & Steedman, 1985; Gorman & Coals, 1983). The outcome in medical emergencies is reported as dismal (Robertson & Steedman, 1985; Rowley & Collins, 1979) yet the number of calls for the flying squad to attend medical emergencies are many. Previous reports have recorded 20-30% of Squad calls responding to medical emergencies (Gorman & Coals, 1983; Rowley & Collins, 1979; Steedman & Robertson, 1986; Harrop & Bodiwala, 1983).     

Patients unaware of their HIV status present to inner city accident and emergency department with respiratory complications.

OBJECTIVE: To examine the clinical presentations and management of patients presenting to an accident and emergency (A&E) department with an AIDS defining illness (ADI). METHODS: Presentations of patients in the A&E department with ADI were reviewed retrospectively. The age, sex, ethnic origin, risk factor for HIV infection, route of referral to hospital, presenting complaint, triage category, referral from A&E, admission under medical specialists, diagnosis, and survival from ADI were noted for each patient. RESULTS: 133 patients were registered at St Mary's Hospital in London with ADI during 1994. A significant minority of these patients (25/133) presented to the hospital without prior knowledge of their HIV positive status. Thirty two patients presented to the A&E department with their ADI. Of these, 13/32 (41%) were unaware of the HIV serostatus. All 13 patients had an acute respiratory disease (Pneumocystis carinii pneumonia or pulmonary tuberculosis). In contrast, patients aware of their HIV positive status (19/32) presented to the A&E department with a wide range of non-pulmonary ADI. CONCLUSIONS: The study emphasises the importance of respiratory complications in patients who present with a ADI to emergency departments but are unaware of their HIV positivity. These patients presented solely with Pneumocystis carinii pneumonia or pulmonary tuberculosis, conditions in which early diagnosis and treatment significantly reduce morbidity and mortality.     

Analgesia in the accident and emergency department: do SHOs have the knowledge to provide optimal analgesia?

OBJECTIVE: To assess senior house officers' knowledge in prescribing emergency analgesia for acute presentations in the accident and emergency (A&E) department. DESIGN: Prospective telephone survey of a defined population of SHOs, using a standardised structured questionnaire, in the months of October and November, 1995; 231 SHOs from 215 A&E departments were interviewed. The questionnaire required responses to hypothetical scenarios. A six member expert panel from the local region was consulted for suggestions for appropriate responses. MAIN OUTCOME MEASURES: Comparisons between SHO responses and those of an expert panel. RESULTS: For choice of analgesic agent, 83% of SHO responses were appropriate, for route of administration 57%, and for the dose of drug 34%. The scenario with the best overall response was a sprained ankle. The paediatric case with partial burns faired worse. Responses to a myocardial infarction scenario were the most consistent. CONCLUSIONS: A&E SHOs lack knowledge and confidence when asked to prescribe emergency analgesia for acute conditions. Responses to certain scenarios were extremely varied, indicating a need for national analgesia guidelines and protocols. Recognised training in pain management should be more readily available.     

Broken hand or broken nose: A case report

We report an unusual case of a foreign body in the hand, following a type of injury commonly encountered in the accident and emergency (A&E) department.     

Rapid pseudo-H&E imaging using a fluorescence-inbuilt optical coherence microscopic imaging system

A technique using Linnik-based optical coherence microscopy (OCM), with built-in fluorescence microscopy (FM), is demonstrated here to describe cellular-level morphology for fresh porcine and biobank tissue specimens. The proposed method utilizes color-coding to generate digital pseudo-H&E (p-H&E) images. Using the same camera, colocalized FM images are merged with corresponding morphological OCM images using a 24-bit RGB composition process to generate position-matched p-H&E images. From receipt of dissected fresh tissue piece to generation of stitched images, the total processing time is <15 min for a 1-cm² specimen, which is on average two times faster than frozen-section H&E process for fatty or water-rich fresh tissue specimens. This technique was successfully used to scan human and animal fresh tissue pieces, demonstrating its applicability for both biobank and veterinary purposes. We provide an in-depth comparison between p-H&E and human frozen-section H&E images acquired from the same metastatic sentinel lymph node slice (∼10 µm thick), and show the differences, like elastic fibers of a tiny blood vessel and cytoplasm of tumor cells. This optical sectioning technique provides histopathologists with a convenient assessment method that outputs large-field H&E-like images of fresh tissue pieces without requiring any physical embedment.     

Audit of patients with chest pain presenting to an accident and emergency department over a 6-month period.

The results of a 6-month retrospective audit of patients presenting with chest pain to an accident and emergency (A&E) department to which 46,000 new patients per year present are discussed. The computer diagnostic code assigned to the patients by the A&E doctor, referral rates for second opinion and disposal after assessment in the A&E department are examined, with particular reference to patients who may have had serious cardiac pathology, such as acute myocardial infarction (AMI) or unstable angina. Audit showed that overall 61% of patients with chest pain of all causes were assessed and discharged home by A&E doctors without recourse to second opinion. Of patients thought by the A&E doctors to have chest pain of cardiac origin, who were referred to the duty medical registrar or cardiologist, 88% were admitted. As a result of these findings a policy of more open referral for second opinion was instituted to reduce the likelihood of discharging patients home with serious cardiac pathology. In addition, the clinical problems of AMI and unstable angina are emphasized to all senior house officers early in their educational programme after joining A&E. Published literature on the diagnosis and misdiagnosis of AMI and unstable angina in the A&E department is reviewed. These studies are almost exclusively from North America, and a need for similar work in the U.K. is discussed.     

Deliberate self harm assessment by accident and emergency staff--an intervention study.

OBJECTIVE: To examine the impact of specific training for accident and emergency (A&E) staff on the quality of psychosocial assessment of deliberate self harm patients. METHODS: A non-randomised intervention study that compared the psychosocial assessment of deliberate self harm patients before and after a one hour teaching session for the A&E departments nursing and junior medical staff. Adequacy of psychosocial assessment was judged by examining A&E case notes. The records of the hospital's parasuicide team were examined to assess administrative changes. Staff attitude to and knowledge of deliberate self harm were also measured before and after the intervention. RESULTS: 45 of 52 nurses and all 15 junior medical staff attended the teaching session. Sixteen (13%) of 125 sets of records before and 58 (46%) of 127 sets of records after the intervention were judged to be adequate. In the postintervention period, notes were more likely to be judged adequate when a proforma was used as part of the assessment (52 of 66 with a proforma and six of 61 without a proforma, chi2 = 60, p < 0.01). Following the intervention, communication between A&E staff and the hospitals parasuicide team improved. CONCLUSIONS: An intervention that provides teaching to A&E staff can lead to improvements in the quality of psychosocial assessment of patients with deliberate self harm.     

A critical look at accident and emergency review clinics.

The reasons for and appropriateness of referral of patients after initial visit to accident & emergency (A&E) follow-up clinics by the A&E doctors were prospectively analysed in 500 patients. Fifteen per cent of patients were judged to have been inappropriately referred. Two main reasons for referral were the need for further treatment and uncertainty about diagnosis and management. The implications of reductions of A&E clinic attendances are discussed.