Identifying the Unmet Needs of People Living With Amyotrophic Lateral Sclerosis: A National Survey to Inform Interdisciplinary Palliative Care.

Introduction/Aims: This national survey builds on previous qualitative research examining potential palliative care needs among people living with ALS (pALS) by quantifying and investigating relationships among pALS' stage of illness progression; physical, emotional, social, spiritual, and intimacy-related concerns; advance care planning behaviors; perceptions of feeling heard and understood by healthcare providers; and overall quality of life. Methods: Researchers partnered with national organizations to recruit pALS to participate in a one-time survey comprising items from validated instruments (eg, the ALS Specific Quality of Life Instrument-Revised) and researcher-generated measures. Data were analyzed using logistic and linear regression. Results: Among pALS (n = 112), many respondents indicated they had discussed their wishes for end-of-life care with family or friends, shared their wishes with providers, and documented their wishes in writing (79.5%, 49.1%, and 63.4%, respectively). Mean (M) quality of life scores were moderate (M ≈ 6 of 10). Illness stage was associated with documentation of end-of-life care wishes but not with having discussed these wishes with others or with overall quality of life. Reported emotional intimacy received was comparable to that desired (difference = .01 of 10); however, a greater desire for physical intimacy relative to that received was indicated (difference = 1.75 of 10). Discussion: Interdisciplinary palliative care teams may enhance ALS care by promoting advance care planning behaviors (particularly discussing one's wishes with healthcare providers), providing interventions to improve quality of life, and supporting pALS in navigating challenges related to physical intimacy.

Cue utilisation reduces the impact of response bias in histopathology.

Histopathologists make diagnostic decisions that are thought to be based on pattern recognition, likely informed by cue-based associations formed in memory, a process known as cue utilisation. Typically, the cases presented to the histopathologist have already been classified as 'abnormal' by clinical examination and/or other diagnostic tests. This results in a high disease prevalence, the potential for 'abnormality priming', and a response bias leading to false positives on normal cases. This study investigated whether higher cue utilisation is associated with a reduction in positive response bias in the diagnostic decisions of histopathologists. Data were collected from eighty-two histopathologists who completed a series of demographic and experience-related questions and the histopathology edition of the Expert Intensive Skills Evaluation 2.0 (EXPERTise 2.0) to establish behavioural indicators of context-related cue utilisation. They also completed a separate, diagnostic task comprising breast histopathology images where the frequency of abnormality was manipulated to create a high disease prevalence context for diagnostic decisions relating to normal tissue. Participants were assigned to higher or lower cue utilisation groups based on their performance on EXPERTise 2.0. When the effects of experience were controlled, higher cue utilisation was specifically associated with a greater accuracy classifying normal images, recording a lower positive response bias. This study suggests that cue utilisation may play a protective role against response biases in histopathology settings.

Two-week-wait referrals in otolaryngology in a tertiary centre: cross-sectional study of benign outcomes, with a systematic review.

OBJECTIVE: The two-week-wait referral is designed to improve early detection in cancer patients. This retrospective study analysed those ENT two-week-wait referrals to out-patient clinics in a tertiary head and neck oncology centre, from January to June 2018, which were not compliant with National Institute for Health and Care Excellence guidelines (2015 update). METHODS: Referral symptoms were statistically analysed against National Institute for Health and Care Excellence guidelines, with detailed analysis of reasons for non-compliance. In addition, a systematic review of similar previously published articles was conducted. RESULTS: There were 1107 patients referred through the two-week-wait pathway. Of these referrals, 52 per cent were compliant with National Institute for Health and Care Excellence 2015 guidelines. Six errors were identified for non-compliant referrals, most commonly inconsistencies in referral (e.g. globus sensation) and intermittent disease course (e.g. intermittent hoarseness). Of all patients referred, 93 per cent were diagnosed with benign conditions, with laryngopharyngeal reflux being the commonest. Twenty-two per cent of referred patients were discharged after the first visit. CONCLUSION: Two-week-wait referral is inappropriately overused. There are many non-compliant referrals, and most of the outcomes are benign.

Period-Prevalence and Risk Factors for Delirium in a Tertiary Referral ICU: A prospective cohort study.

BACKGROUND: Delirium is common in intensive care and leads to increases in morbidity, mortality, Intensive Care Unit (ICU) length of stay, and hospital length of stay. Certain risk factors predict the appearance of delirium. STUDY OBJECTIVES: To determine the rates of delirium, the rate of risk factors, and their relationship to the occurrence of delirium in an adult ICU. METHODS: Single-centre, prospective, observational study. Demographic and treatment data were collected. The Confusion Assessment Method for ICU (CAM-ICU) was performed twice daily to assess for delirium continuously during a 3-week period. Statistical analysis was used to determine the relationship between risk factors and the occurrence of delirium. RESULTS: 86 patients were screened, 44 patients were included, and 260 patient-days were analyzed. The incidence of delirium was 42.9%, the prevalence of delirium in ICU was 50%. Urinary catheters and use of opioids were the most common factors with a positive association for occurrence of delirium. Exposure to daylight and sleeping for more than 4 hours at night were the factors most commonly associated with a lack of delirium. CONCLUSION: The rates of delirium in ICU were high and risk factors occurred frequently. Addressing modifiable risk factors, including the promotion of adequate sleep, could improve outcomes.

Outcome of two-week head and neck cancer pathway for the otolaryngology department in a tertiary centre.

BACKGROUND: The two-week-wait head and neck cancer referral pathway was introduced by the Department of Health, and refined through National Institute for Health and Care Excellence guidelines which were updated in 2015. METHODS: A retrospective study was conducted of two-week-wait referrals to out-patient ENT from January to June 2018. The analysis included demographics, referral symptoms according to National Institute for Health and Care Excellence 2015 guidelines, cancer pick-up rates and positive predictive values. RESULTS: A total of 1107 patients were referred for suspected head and neck cancer over six months, with 6 per cent diagnosed with cancer. Neck lump, persistent hoarseness and throat pain were the most common presenting symptoms. Neck lump had the highest positive predictive value, followed by oral swelling. Oral bleeding and persistent unilateral sore throat showed significant positive predictive values. Investigation for metastatic head and neck cancer of an unknown primary or the involvement of other multidisciplinary teams could hinder the achievement of a 62-day treatment target. CONCLUSION: The cancer pick-up rate from two-week-wait referrals is only 1.5 times higher than routine referrals. The 'red flag' symptoms given in the 2015 National Institute for Health and Care Excellence update would benefit from further review.

Management of Lower Urinary Tract Symptoms after Prostate Radiation.

PURPOSE OF REVIEW: To present urologists with guidance on how to approach and manage lower urinary tract symptoms (LUTS) in patients who have undergone radiation therapy (RT) for prostate cancer. RECENT FINDINGS: There are few studies that specifically examine treatment approaches for LUTS in patients who have undergone prostate cancer RT. LUTS after prostate RT are unique when compared to de novo LUTS. Understanding these distinctions is important for urologists' practice as well as patients' quality of life. Discussion of the risks and management of post-RT LUTS should be included in the shared decision-making process when counseling patients on various treatment options for prostate cancer. Further studies evaluating treatments for storage and voiding symptoms after RT are needed to help guide future care.

Association of Anaesthetists: anaesthesia and peri-operative care for Jehovah's Witnesses and patients who refuse blood.

There are approximately 8.5 million Jehovah's Witnesses and around 150,000 live in Great Britain and Ireland. Based on their beliefs and core values, Jehovah's Witnesses refuse blood component transfusion (including red cells, plasma and platelets). They regard non-consensual transfusion as a physical violation. Consent to treatment is at the heart of this guideline. Refusal of treatment by an adult with capacity is lawful. The reasons why a patient might refuse transfusion and the implications are examined. The processes and products that are deemed acceptable or unacceptable to Jehovah's Witnesses are described. When a team is faced with a patient who refuses transfusion, a thorough review of the clinical situation is advocated and all options for treatment should be explored. After discussion, a plan should then be made that is acceptable to the patient and appropriate consent obtained. When agreement cannot be reached between the doctor and the patient, referral for a second opinion should be considered. When the patient is a child, the same strategy should be used but on occasion the clinical team may have to obtain legal help.

Fibre degradation of wheat straw by Pleurotus erygnii under low moisture conditions during solid-state fermentation.

The application of solid-state fermentation offers an alternative to conventional, submerged approaches for a variety of bioconversion processes, including animal feeds, biofuels and fungal bioproducts. Optimizing solid-state fermentation under low moisture conditions could significantly impact the proportion of dry biomass that could be processed and improve the commercial viability of this approach, because of reduced input costs and higher yields of final products. Pleurotus erygnii that appeared to show tolerance to low moisture conditions was grown on saturated and desaturated wheat straw. Pleurotus erygnii showed insignificant fibre degradation although showed significantly lower biomass decomposition on desaturated wheat straw. Fibre decomposition by the fungus on wheat straw containing wheat bran showed marginally higher decomposition when saturated although there was no difference in biomass decomposition. The levels of delignification achieved were similar under different saturation conditions. It would appear that the fungus effectively decomposed fibre under low moisture conditions often resulting in lower biomass losses. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, a white rot fungus, Pleurotus erygnii, effectively decomposed fibre under low moisture conditions when grown on wheat straw at similar levels under higher moisture conditions. However, the addition of wheat bran to wheat straw created a heterogeneous system that appeared to allow P. erygnii to thrive under much lower moisture conditions although lower levels of fibre decomposition was obtained. These factors could influence the preparation of solid-state fermentation.

Association of Anaesthetists guidelines: cell salvage for peri-operative blood conservation 2018.

The use of cell salvage is recommended when it can be expected to reduce the likelihood of allogeneic (donor) red cell transfusion and/or severe postoperative anaemia. We support and encourage a continued increase in the appropriate use of peri-operative cell salvage and we recommend that it should be available for immediate use 24 h a day in any hospital undertaking surgery where blood loss is a recognised potential complication (other than minor/day case procedures).

A mass spectrometry method for the determination of the species of origin of gelatine in foods and pharmaceutical products.

Gelatine is a component of a wide range of foods. It is manufactured as a by-product of the meat industry from bone and hide, mainly from bovine and porcine sources. Accurate food labelling enables consumers to make informed decisions about the food they buy. Since labelling currently relies heavily on due diligence involving a paper trail, there could be benefits in developing a reliable test method for the consumer industries in terms of the species origin of gelatine. We present a method to determine the species origin of gelatines by peptide mass spectrometry methods. An evaluative comparison is also made with ELISA and PCR technologies. Commercial gelatines were found to contain undeclared species. Furthermore, undeclared bovine peptides were observed in commercial injection matrices. This analytical method could therefore support the food industry in terms of determining the species authenticity of gelatine in foods.

Standardised reporting protocol for endoscopic resection for Barrett oesophagus associated neoplasia: expert consensus recommendations.

Endoscopic resection (ER) is considered the therapy of choice for intraepithelial neoplasia associated with visible lesions and T1a adenocarcinoma. Pathologists are bound to encounter specimens collected via these techniques more frequently in their practice. A standardised protocol for handling, grossing, and assessing ER specimens should be adopted to ensure that all prognostic information and characteristics influencing treatment are included in reports (see Supplementary Video Abstract, http://links.lww.com/PAT/A22). The entire specimen should be appropriately oriented, processed and assessed. An ER specimen will commonly show intraepithelial neoplasia or invasive carcinoma. There are essential features that should be recorded if invasive carcinoma is found as they dictate further management and follow-up. These features are the margin status, depth of invasion, degree of differentiation and presence or absence of lymphovascular invasion. Important features such as duplication of muscularis mucosae should be recognised to avoid misinterpretation of depth of invasion. Key diagnostic and prognostic elements that are essential for optimal clinical decisions have been included in the reporting format proposed by the Structured Pathology Reporting committee of the Royal College of Pathologists of Australasia (RCPA).

Where did platelets go in 2012? A survey of platelet transfusion practice in the North of England.

OBJECTIVES: To record the fate of transfused platelet doses in the North of England, and thereby assist with demand-planning and help target teaching on appropriate use. BACKGROUND: Platelet use has risen recently to the extent that donation practice has changed to meet demand. Two national comparative audits have shown inappropriate use and the 2010 audit concluded that current U.K. guidelines for platelet usage should be completely implemented at a local level. It is necessary to know how platelets are used and by whom in order to facilitate guideline concordance. METHODS: All hospital trusts in the North East and Cumbria recorded data on all platelet doses transfused in two separate 4-week periods in 2012. Data were entered onto an electronic survey tool. RESULTS: One thousand and five hundred and seventy-four reports were received, documenting 1937 transfused doses--96% of total issues for the study periods. One thousand and forty-five platelet doses (54%) were given for haematological indications. The second commonest indication was cardiac surgery (201 doses, 10% of the total) followed by non-haematological oncology (127 doses, 6.5%), critical care (106 doses, 5%) and liver disease (50 doses, 2.5%). The commonest haematological indication was acute myeloid leukaemia, 310 doses, (16% of all platelet use), followed by stem cell transplantation, 271 doses (14%). Seventy-two percent of platelet doses were given prophylactically, the majority without any planned procedure. CONCLUSION: The commonest indication for platelet use, where reinforcement of guidelines will be productive, is prophylaxis in haematological disease. Use of platelets in cardiac surgery is also worthy of close scrutiny.

Hepatitis C virus NS3 mutations in haemophiliacs.

Haemophiliacs have high hepatitis C virus (HCV) exposure risk from blood products that did not undergo heat inactivation or disease-specific screening prior to 1987. Repeated exposure to infected factor concentrates predisposes haemophiliacs to higher likelihood of HCV from multiple sources. HIV coinfection could result in impaired clearance of less fit variants resulting in enrichment of quasispecies carrying resistance mutations. We postulated that haemophiliacs demonstrate increased prevalence of baseline signature mutations in the HCV NS3/4 serine protease coding domain. We examined the prevalence of putative HCV protease inhibitor mutations, mutations, subclassified into dominant mutations if changes conferred resistance, and minor variants not associated with drug resistance, in patients with haemophilia A or B, infected with HCV or HCV/HIV, prior to HCV PI exposure. A total of 151 subjects were evaluated, including 22 haemophiliacs and 129 non-haemophilic controls. Of the 58 mutations detected, 55 (95%) were resistance mutations and three (5%) were minor variants. Dominant mutations were detected in 10 (45.5%) haemophiliacs and in 43 (33.3%) controls (OR 1.67, 95% CI 0.67-4.16). There was no statistical difference in proportion of dominant mutations (P = 0.27) or minor variants (P = 0.47) between groups, despite adjustment for HIV status (P = 0.44). No significant differences in dominant or minor resistance mutations between haemophiliacs and non-haemophiliacs were observed. HIV presence or prior HAART exposure did not affect baseline distribution. We conclude that haemophiliacs are not at higher risk for pre-existing HCV PI mutations, and prospective studies of response to PI-based regimens with HCV activity are indicated.

Selected reaction monitoring method to determine the species origin of blood-based binding agents in meats: a collaborative study.

Binding products or food 'glues' are used throughout the food industry to increase the meat use rate or to augment economic efficiency. Some of these binders contain thrombin from bovine and porcine blood. The European parliament has recently banned thrombin-based additives and labelling legislation governs their use in the US. A mass spectrometry screening method is available to detect the addition of thrombin agents to foods as there is a need to protect consumers and to avoid misleading trade practices. We report the details of an inter-laboratory trial to determine the transferability of this method to operators in various food testing laboratories, each using a different triple quadrupole mass spectrometer design. The trial was successful with the species origin of the binding agent contained in each of the 43 test materials being correctly reported by the participants. This is consistent with a false positive and false negative rate of 0%. This is the first collaborative study, as far as we are aware, which involves a liquid chromatography mass spectrometry (LC-MS/MS) application to approach a food authenticity issue.

Serial changes in the expression of breast cancer-related proteins in response to neoadjuvant chemotherapy.

BACKGROUND: Tumour expression of cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), erythroblastic leukaemia viral oncogene homologue-2 (ErbB2), Ki-67 and p53 in breast cancer are associated with poorer outcomes. We investigated in vivo changes of these proteins with neoadjuvant chemotherapy. PATIENTS AND METHODS: Four core biopsies were taken from 100 breast cancer patients at baseline, during and upon completion of neoadjuvant chemotherapy. Immunohistochemical expression of these proteins were evaluated and correlated with clinicopathological features, clinical response and progression-free survival (PFS). RESULTS: There was a statistically significant change from positivity to negativity in COX-2 expression with chemotherapy (P = 0.002), predominantly in clinical responders (P = 0.002). COX-2-positive tumours that remained positive had shorter PFS than those that turned negative. Estrogen receptor (ER)+ and COX-2+ tumours at baseline that remained COX-2+ fared worse than those that became COX-2 negative (PFS 27 versus 52 months, P = 0.002). No significant changes in IHC expression were observed for ER, progesterone receptor, ErbB2, EGFR, p53 or Ki67. CONCLUSIONS: Chemotherapy induced change in COX-2 expression from positivity to negativity predominantly among clinical responders and is associated with longer PFS. Interaction between COX-2 and ER was observed, suggesting that some hormone receptor-positive patients may benefit from combining COX-2 inhibition with hormonal therapy.

An audit of the implementation of the international consensus group's guidelines on reporting of blood films.

AIMS: This study was carried out as part of the Pathology Benchmarking Review and it audits the implementation of the guidelines for the reporting of blood films published by the International Consensus Group for Haematology Review. METHODS: Each laboratory completed a questionnaire about the number of blood counts and blood films performed. Information was collected on the criteria that were used for preparing a blood film and whether they had followed the guidelines of the International Consensus Group. RESULTS: 74 National Health Service organisations (151 laboratory sites) participated in the study. 24 laboratories had implemented the guideline, 21 with local modification, and 3 without modification. The reasons that prevented the full implementation of the guideline included the inability of laboratory information systems to be modified to include the guideline rules, the laboratory not agreeing with the guideline criteria, and the staff time required to implement the guide to justify the perceived local benefits of implementation. CONCLUSION: This is the first study that has assessed the implementation of the International Consensus Guidelines at a national level. Many laboratories had experienced difficulty in implementing the consensus guideline partly due to the complexity of the guideline. As a result 21 of the 24 laboratories that had attempted to implement the guideline had made local modification to the guideline. Since it was not possible to estimate the impact that local modification of the guideline would have on the percentage of blood films it was not possible to establish a benchmark of practice following implementation of the guideline.

Comparative validation of c-kit exon 11 mutation analysis on cytology samples and corresponding surgical resections of gastrointestinal stromal tumours.

OBJECTIVE: Studies have shown that c-kit mutation analysis of gastrointestinal stromal tumours (GISTs) obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) can be routinely performed. We validated c-kit exon 11 mutational analysis on cell block material obtained from fine needle aspiration cytology (FNAC) for diagnostic purposes and compared it with the same analysis in formalin-fixed paraffin-embedded full sections of the corresponding resection specimens. METHODS: c-kit mutation analysis was done on cell block material obtained from ten cases encountered in our department from 1999 to 2008 on which FNAC was attempted pre-operatively. The findings were compared with analysis on full paraffin section of the corresponding resected tumours in seven cases where patients opted for resection. c-kit exon 11 was examined via bidirectional nucleic acid sequencing. RESULTS: Our results showed 100% concordance for the presence and type of exon 11 mutation in the resected and aspirated tumours in all seven cases. These mutations had diagnostic value when compared with other neoplasms that are part of the cytomorphological differential diagnosis, such as leiomyosarcoma or gastric adenocarcinomas. CONCLUSION: Molecular cytopathology is a powerful tool that can complement morphology and immunohistochemical assessment of cytological material in routine practice for the diagnosis and prognostication of GISTs. We briefly discuss the advantages and limitations of the fine needle method of obtaining tissue for the diagnosis and prognostication of GISTs, and its current therapeutic strategies.

Review of orbital imaging.

CT and MRI are commonly used in the evaluation of patients with suspected orbital disease. Many different diseases may present within this small anatomical space. The purpose of this article is to present a diagnostic strategy based on a compartment model. Localizing pathology to sinus, bone, extraconal space, muscle cone, intraconal space, optic nerve, globe or lacrimal fossa allows significant reduction in the number of differential diagnoses as these compartments contain different tissues which disease may involve or arise from. Certain diseases may also present in multiple compartments. Common diseases which might present in one or multiple compartments will be discussed.

Cholecystokinin (CCK) receptor and CCK gene expression in human pituitary adenomas and in vitro effects of CCK peptides on GH and gonadotrophin secretion.

There is growing evidence that cholecystokinin (CCK) affects growth and differentiation of anterior pituitary cells, via the CCK-B receptor. The possibility of an autocrine / paracrine role for CCK to modulate hormone secretion in human pituitary tumour cells is demonstrated here by RT-PCR and direct sequencing. In support of this conclusion, a neutralising antibody against the CCK peptide exhibited a dose dependent inhibition of hormone secretion by functionless pituitary adenomas. Total RNA was extracted from human pituitary adenomas, reverse transcribed into cDNA and subjected to PCR using primers specific for the gene for CCK, CCK-A and CCK-B receptors. PCR bands of the predicted length were observed in all tumours using human CCK gene and CCK-B receptor primers. Restriction digestion and direct sequence analysis provided further evidence that they represented both the human CCK peptide along with the CCK-A and/B receptor mRNA. CCK-33 and CCK octapeptide sulphate (CCK-8s) both powerfully stimulated phosphatidylinositol hydrolysis, providing evidence for functional activity of the CCK-A and/B receptors. A direct stimulatory effect of CCK peptides on both LH and FSH secretion is reported for the first time, whereas stimulatory effects on GH were blocked by antagonists to CCK. These results may indicate an autocrine role for CCK in the functioning and perhaps development of human pituitary tumours.