Predictors of spine metastases at initial presentation of pediatric brain tumor patients: a single-institution study.

PURPOSE: Given the rarity of disseminated disease at the time of initial evaluation for pediatric brain tumor patients, we sought to identify clinical and radiographic predictors of spinal metastasis (SM) at the time of presentation. METHODS: We performed a single-institution retrospective chart review of pediatric brain tumor patients who first presented between 2004 and 2018. We extracted information regarding patient demographics, radiographic attributes, and presenting symptoms. Univariate and multivariate logistic regression was used to estimate the association between measured variables and SMs. RESULTS: We identified 281 patients who met our inclusion criteria, of whom 19 had SM at initial presentation (6.8%). The most common symptoms at presentation were headache (n = 12; 63.2%), nausea/vomiting (n = 16; 84.2%), and gait abnormalities (n = 8; 41.2%). Multivariate models demonstrated that intraventricular and posterior fossa tumors were more frequently associated with SM (OR: 5.28, 95% CI: 1.79-15.59, p = 0.003), with 4th ventricular (OR: 7.42, 95% CI: 1.77-31.11, p = 0.006) and cerebellar parenchymal tumor location (OR: 4.79, 95% CI: 1.17-19.63, p = 0.030) carrying the highest risk for disseminated disease. In addition, evidence of intracranial leptomeningeal enhancement on magnetic resonance imaging (OR: 46.85, 95% CI: 12.31-178.28, p < 0.001) and hydrocephalus (OR: 3.19; 95% CI: 1.06-9.58; p = 0.038) were associated with SM. CONCLUSIONS: Intraventricular tumors and the presence of intracranial leptomeningeal disease were most frequently associated with disseminated disease at presentation. These findings are consistent with current clinical expectations and offer empirical evidence that heightened suspicion for SM may be prospectively applied to certain subsets of pediatric brain tumor patients at the time of presentation.

Prognostic factors for patients with anal cancer treated with conformal radiotherapy-a systematic review.

AIMS: Anal cancer is primarily treated using concurrent chemoradiotherapy (CRT), with conformal techniques such as intensity modulated radiotherapy (IMRT) and volumetric arc therapy (VMAT) now being the standard techniques utilised across the world. Despite this, there is still very limited consensus on prognostic factors for outcome following conformal CRT. This systematic review aims to evaluate the existing literature to identify prognostic factors for a variety of oncological outcomes in anal cancer, focusing on patients treated with curative intent using contemporary conformal radiotherapy techniques. MATERIALS AND METHODS: A literature search was conducted using Medline and Embase to identify studies reporting on prognostic factors for survival and cancer-related outcomes after conformal CRT for anal cancer. The prognostic factors which were identified as significant in univariable and multivariable analysis, along with their respective factor effects (where available) were extracted. Only factors reported as prognostic in more than one study were included in the final results. RESULTS: The results from 19 studies were analysed. In both univariable and multivariable analysis, N stage, T stage, and sex were found to be the most prevalent and reliable clinical prognostic factors for the majority of outcomes explored. Only a few biomarkers have been identified as prognostic by more than one study - pre-treatment biopsy HPV load, as well as the presence of leukocytosis, neutrophilia and anaemia at baseline measurement. The results also highlight the lack of studies with large cohorts exploring the prognostic significance of imaging factors. CONCLUSION: Establishing a set of prognostic and potentially predictive factors for anal cancer outcomes can guide the risk stratification of patients, aiding the design of future clinical trials. Such trials will in turn provide us with greater insight into how to effectively treat this disease using a more personalised approach.

Combined PET-CT and MRI for response evaluation in patients with squamous cell anal carcinoma treated with curative-intent chemoradiotherapy.

OBJECTIVES: To assess the effectiveness of fluorine-18 fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for response assessment post curative-intent chemoradiotherapy (CRT) in anal squamous cell carcinoma (ASCC). METHODS: Consecutive ASCC patients treated with curative-intent CRT at a single centre between January 2018 and April 2020 were retrospectively identified. Clinical meta-data including progression-free survival (PFS) and overall survival (OS) outcomes were collated. Three radiologists evaluated PET-CT and MRI using qualitative response assessment criteria and agreed in consensus. Two-proportion z test was used to compare diagnostic performance metrics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy). Kaplan-Meier analysis (Mantel-Cox log-rank) was performed. RESULTS: MRI (accuracy 76%, PPV 44.8%, NPV 95.7%) and PET-CT (accuracy 69.3%, PPV 36.7%, NPV 91.1%) performance metrics were similar; when combined, there were statistically significant improvements (accuracy 94.7%, PPV 78.9%, NPV 100%). Kaplan-Meier analysis demonstrated significant differences in PFS between responders and non-responders at PET-CT (p = 0.007), MRI (p = 0.005), and consensus evaluation (p < 0.001). Cox regression analysis of PFS demonstrated a lower hazard ratio (HR) and narrower 95% confidence intervals for consensus findings (HR = 0.093, p < 0.001). Seventy-five patients, of which 52 (69.3%) were females, with median follow-up of 17.8 months (range 5-32.6) were included. Fifteen of the 75 (20%) had persistent anorectal and/or nodal disease after CRT. Three patients died, median time to death 6.2 months (range 5-18.3). CONCLUSION: Combined PET-CT and MRI response assessment post-CRT better predicts subsequent outcome than either modality alone. This could have valuable clinical benefits by guiding personalised risk-adapted patient follow-up. KEY POINTS: • MRI and PET-CT performance metrics for assessing response following chemoradiotherapy (CRT) in patients with anal squamous cell carcinoma (ASCC) were similar. • Combined MRI and PET-CT treatment response assessment 3 months after CRT in patients with ASCC was demonstrated to be superior to either modality alone. • A combined MRI and PET-CT assessment 3 months after CRT in patients with ASCC has the potential to improve accuracy and guide optimal patient management with a greater ability to predict outcome than either modality alone.

Social care and support needs of community-dwelling people with dementia and concurrent visual impairment.

OBJECTIVES: This study explored the social care and support needs of people with dementia and visual impairment, and the barriers and facilitators for meeting these needs. METHOD: Twenty-six semi-structured interviews were conducted: 21 joint and 5 individual interviews with the person with dementia and visual impairment (n=4) or their family/paid carer (n=1). Interviews were analysed thematically. RESULTS: Three themes are presented. (1) Social care needs: having dementia can reduce an individual's ability to cope with their visual impairment, and lead to increased dependency and reduced daily stimulation. (2) Barriers to using technology to meet social care needs: difficulties were reported with learning to use unfamiliar technology and the cost of visual impairment aids, and for some, the presence of dementia made visual impairment aids unusable and vice versa. (3) Familiarity as a facilitator for meeting social care needs: living at home or taking furnishings and ornaments into a new home facilitated independence, and continuity of paid carers/volunteers facilitated the caring relationship between the individual and staff/volunteer. CONCLUSION: Care workers will better serve older people if they are aware of the social care and support needs that arise from having both dementia and visual impairment.

The association of gender and body mass index with postoperative pain scores when undergoing ankle fracture surgery.

BACKGROUND: Intraoperative administration of opiates for postoperative analgesia requires a dosing strategy without clear indicators of pain in an anesthetized patient. Preoperative patient characteristics such as body mass index (BMI), gender, age, and other patient characteristics may provide important information regarding opiate requirements. This study intends to determine if there is an association between gender or BMI and the immediate postoperative pain scores after undergoing an open reduction and internal fixation (ORIF) of an ankle fracture with general anesthesia and morphine only analgesia. MATERIALS AND METHODS: Using a retrospective cohort design, the perioperative records were reviewed at a university healthcare hospital. One hundred and thirty-seven cases met all inclusion and no exclusion criteria. Postanesthesia care unit (PACU) records were reviewed for pain scores at first report and 30 min later as well as PACU opiate requirements. T-test, chi-square, and Mann-Whitney tests compared univariate data and multivariate analysis was performed by linear regression. RESULTS: There were no statistically significant PACU pain score group differences based on gender or BMI. Post hoc analysis revealed that in the setting of similar pain scores, obese patients received a similar weight based intraoperative morphine dose when using adjusted body weight (ABW) compared to nonobese subjects. A further finding revealed a negative correlation between age and pain score (P = 0.001). CONCLUSION: This study did not find an association between obesity or gender and postoperative pain when receiving morphine only preemptive analgesia. This study does support the use of ABW as a means to calculate morphine dosing for obese patients and that age is associated with lower immediate pain scores.

The use of master protocols for efficient trial design to evaluate radiotherapy interventions: a systematic review.

The aim of this review was to highlight why the use of master protocols trial design is particularly useful for radiotherapy intervention trials where complex setup pathways (including quality assurance, user training, and integrating multiple modalities of treatment) may hinder clinical advances. We carried out a systematic review according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, reviewing the findings using a landscape analysis. Results were summarized descriptively, reporting on trial characteristics highlighting the benefits, limitations, and challenges of developing and implementing radiotherapy master protocols, with three case studies selected to explore these issues in more detail. Twelve studies were suitable for inclusion (4 platform trials, 3 umbrella trials, and 5 basket trials), evaluating a mix of solid tumor sites in both curative and palliative settings. The interventions were categorized into 1) novel agent and radiotherapy combinations; 2) radiotherapy dose personalization; and 3) device evaluation, with a case study provided for each intervention. Benefits of master protocol trials for radiotherapy intervention include protocol efficiency for implementation of novel radiotherapy techniques; accelerating the evaluation of novel agent drug and radiotherapy combinations; and more efficient translational research opportunities, leading to cost savings and research efficiency to improve patient outcomes. Master protocols offer an innovative platform under which multiple clinical questions can be addressed within a single trial. Due to the complexity of radiotherapy trial setup, cost and research efficiency savings may be more apparent than in systemic treatment trials. Use of this research approach may be the change needed to push forward oncological innovation within radiation oncology.

School closures during COVID-19: an overview of systematic reviews.

OBJECTIVES: To assess the benefits and drawbacks of school closures and in-school mitigations during the COVID-19 pandemic. DESIGN: Overview of systematic reviews (SRs). SEARCH METHODS: We searched six databases and additional resources on 29 July 2022: MEDLINE, Embase, Google Scholar, Cochrane Library, COVID-END inventory of evidence synthesis, and Epistemonikos. ELIGIBILITY CRITERIA: We selected SRs written in English that answered at least one of four specific questions concerning the efficacy and drawbacks of school closures. Their primary studies were conducted in primary and secondary schools, including pupils aged 5-18. Interventions included school closures or mitigations (such as mask usage) introduced in schools. DATA COLLECTION AND ANALYSIS: We used AMSTAR 2 to assess confidence in the included SRs, and GRADE was used to assess certainty of evidence. We performed a narrative synthesis of the results, prioritising higher-quality SRs, those which performed GRADE assessments and those with more unique primary studies. We also assessed the overlap between primary studies included in the SRs. MAIN OUTCOME MEASURES: Our framework for summarising outcome data was guided by the following questions: (1) What is the impact of school closures on COVID-19 transmission, morbidity or mortality in the community? (2) What is the impact of COVID-19 school closures on mental health (eg, anxiety), physical health (eg, obesity, domestic violence, sleep) and learning/achievement of primary and secondary pupils? (3) What is the impact of mitigations in schools on COVID-19 transmission, morbidity or mortality in the community? and (4) What is the impact of COVID-19 mitigations in schools on mental health, physical health and learning/achievement of primary and secondary pupils? RESULTS: We identified 578 reports, 26 of which were included. One SR was of high confidence, 0 moderate, 10 low and 15 critically low confidence. We identified 132 unique primary studies on the effects of school closures on transmission/morbidity/mortality, 123 on learning, 164 on mental health, 22 on physical health, 16 on sleep, 7 on domestic violence and 69 on effects of in-school mitigations on transmission/morbidity/mortality.Both school closures and in-school mitigations were associated with reduced COVID-19 transmission, morbidity and mortality in the community. School closures were also associated with reduced learning, increased anxiety and increased obesity in pupils. We found no SRs that assessed potential drawbacks of in-school mitigations on pupils. The certainty of evidence according to GRADE was mostly very low. CONCLUSIONS: School closures during COVID-19 had both positive and negative impacts. We found a large number of SRs and primary studies. However, confidence in the SRs was mostly low to very low, and the certainty of evidence was also mostly very low. We found no SRs assessing the potential drawbacks of in-school mitigations on children, which could be addressed moving forward. This overview provides evidence that could inform policy makers on school closures during future potential waves of COVID-19.

Development and Optimization of a Machine-Learning Prediction Model for Acute Desquamation After Breast Radiation Therapy in the Multicenter REQUITE Cohort.

Purpose: Some patients with breast cancer treated by surgery and radiation therapy experience clinically significant toxicity, which may adversely affect cosmesis and quality of life. There is a paucity of validated clinical prediction models for radiation toxicity. We used machine learning (ML) algorithms to develop and optimise a clinical prediction model for acute breast desquamation after whole breast external beam radiation therapy in the prospective multicenter REQUITE cohort study. Methods and Materials: Using demographic and treatment-related features (m = 122) from patients (n = 2058) at 26 centers, we trained 8 ML algorithms with 10-fold cross-validation in a 50:50 random-split data set with class stratification to predict acute breast desquamation. Based on performance in the validation data set, the logistic model tree, random forest, and naïve Bayes models were taken forward to cost-sensitive learning optimisation. Results: One hundred and ninety-two patients experienced acute desquamation. Resampling and cost-sensitive learning optimisation facilitated an improvement in classification performance. Based on maximising sensitivity (true positives), the "hero" model was the cost-sensitive random forest algorithm with a false-negative: false-positive misclassification penalty of 90:1 containing m = 114 predictive features. Model sensitivity and specificity were 0.77 and 0.66, respectively, with an area under the curve of 0.77 in the validation cohort. Conclusions: ML algorithms with resampling and cost-sensitive learning generated clinically valid prediction models for acute desquamation using patient demographic and treatment features. Further external validation and inclusion of genomic markers in ML prediction models are worthwhile, to identify patients at increased risk of toxicity who may benefit from supportive intervention or even a change in treatment plan.

Metallic foreign body adjacent to the round window: a rare cause for chronic tympanic membrane perforation with hearing loss.

Welding injuries to the tympanic membrane (TM) or middle ear are rare but can cause significant damage. These injuries occur when a hot spark or molten slag drops directly into the external auditory canal and through the action of gravity (because the ear is upright during such an injury), then risks burning through the TM. This can lead to a multitude of adverse consequences including chronic TM perforation, secondary purulent otorrhoea, facial palsy, taste disturbance, vertigo and hearing loss. We present the case of a welding injury to the right TM, resulting in a chronic perforation and hearing loss. The patient required surgical intervention for removal of the metallic foreign body and repair of the TM. The patient obtained a good surgical result with no sensorineural hearing loss. This is a preventable occupational injury, which can be avoided by use of ear protection and increased awareness of this potential risk.

Concurrent versus sequential chemoradiotherapy for unresectable locally advanced stage III non-small cell lung cancer: Retrospective analysis in a single United Kingdom cancer centre.

INTRODUCTION: Stage III unresectable locally advanced non-small cell lung cancer (NSCLC) is a complex disease group with poor long-term survival. Clinical data suggests curative intent concurrent chemoradiotherapy (CCRT) is superior to a sequential (SCRT) approach but comes with additional toxicities. We report real world data regarding overall survival and toxicity to aid clinical decision making in balancing optimal management and treatment tolerability. METHODS: Retrospective analysis of survival data, treatment toxicities, and rates of treatment completion were performed for 241 patients who underwent chemoradiotherapy for unresectable stage III NSCLC within Leeds Cancer Centre from January 2011 to December 2014. RESULTS: Median survival was 18.8 months following SCRT compared to 22.7 months following CCRT HR 0.90 (95% CI 0.67-1.20, P = 0.46). Median follow up was 21 months. The clinical benefit rate for CCRT compared to SCRT was 22.7% versus 24%. In the CCRT group 63.8% patients completed treatment compared to 46% in the SCRT arm (P < 0.01). 90-day mortality rates were low in CCRT and SCRT cohorts at 4.3% and 1% respectively. There was greater pulmonary toxicity following CCRT versus SCRT (13.5% versus 1.0%, P < 0.01). CONCLUSION: This study provides real world data regarding the radical treatment of unresectable stage III NSCLC. Increased hospital admissions and pneumonitis toxicities did not adversely affect treatment completion for those undergoing CCRT; this was likely due to careful patient selection based on performance status. SCRT still remains an important treatment modality for patients who cannot tolerate the upfront CCRT approach but could still be treated with curative intent.

Predicting outcomes in anal cancer patients using multi-centre data and distributed learning - A proof-of-concept study.

BACKGROUND AND PURPOSE: Predicting outcomes is challenging in rare cancers. Single-institutional datasets are often small and multi-institutional data sharing is complex. Distributed learning allows machine learning models to use data from multiple institutions without exchanging individual patient-level data. We demonstrate this technique in a proof-of-concept study of anal cancer patients treated with chemoradiotherapy across multiple European countries. MATERIALS AND METHODS: atomCAT is a three-centre collaboration between Leeds Cancer Centre (UK), MAASTRO Clinic (The Netherlands) and Oslo University Hospital (Norway). We trained and validated a Cox proportional hazards regression model in a distributed fashion using data from 281 patients treated with radical, conformal chemoradiotherapy for anal cancer in three institutions. Our primary endpoint was overall survival. We selected disease stage, sex, age, primary tumour size, and planned radiotherapy dose (in EQD2) a priori as predictor variables. RESULTS: The Cox regression model trained across all three centres found worse overall survival for high risk disease stage (HR = 2.02), male sex (HR = 3.06), older age (HR = 1.33 per 10 years), larger primary tumour volume (HR = 1.05 per 10 cm3) and lower radiotherapy dose (HR = 1.20 per 5 Gy). A mean concordance index of 0.72 was achieved during validation, with limited variation between centres (Leeds = 0.72, MAASTRO = 0.74, Oslo = 0.70). The global model performed well for risk stratification for two out of three centres. CONCLUSIONS: Using distributed learning, we accessed and analysed one of the largest available multi-institutional cohorts of anal cancer patients treated with modern radiotherapy techniques. This demonstrates the value of distributed learning in outcome modelling for rare cancers.

A data science approach for early-stage prediction of Patient's susceptibility to acute side effects of advanced radiotherapy.

The prediction by classification of side effects incidence in a given medical treatment is a common challenge in medical research. Machine Learning (ML) methods are widely used in the areas of risk prediction and classification. The primary objective of such algorithms is to use several features to predict dichotomous responses (e.g., disease positive/negative). Similar to statistical inference modelling, ML modelling is subject to the class imbalance problem and is affected by the majority class, increasing the false-negative rate. In this study, seventy-nine ML models were built and evaluated to classify approximately 2000 participants from 26 hospitals in eight different countries into two groups of radiotherapy (RT) side effects incidence based on recorded observations from the international study of RT related toxicity "REQUITE". We also examined the effect of sampling techniques and cost-sensitive learning methods on the models when dealing with class imbalance. The combinations of such techniques used had a significant impact on the classification. They resulted in an improvement in incidence status prediction by shifting classifiers' attention to the minority group. The best classification model for RT acute toxicity prediction was identified based on domain experts' success criteria. The Area Under Receiver Operator Characteristic curve of the models tested with an isolated dataset ranged from 0.50 to 0.77. The scale of improved results is promising and will guide further development of models to predict RT acute toxicities. One model was optimised and found to be beneficial to identify patients who are at risk of developing acute RT early-stage toxicities as a result of undergoing breast RT ensuring relevant treatment interventions can be appropriately targeted. The design of the approach presented in this paper resulted in producing a preclinical-valid prediction model. The study was developed by a multi-disciplinary collaboration of data scientists, medical physicists, oncologists and surgeons in the UK Radiotherapy Machine Learning Network.

Supraglottic laryngeal sarcoidosis masquerading as supraglottitis.

Sarcoidosis is a rare multisystem disorder of unknown aetiology characterised by non-caseating granulomas in involved organs; it is a diagnosis of exclusion. Laryngeal involvement affects only 0.5%-5% of those with sarcoidosis. It is an uncommon but important cause of supraglottic inflammation and oedema and should be considered in the differential diagnosis in patients with supraglottitis. This case describes a 30-year-old man who presented with stridor and shortness of breath. Flexible nasendoscopic examination revealed a grossly oedematous, pale pink, diffusely hypertrophied epiglottis. Surgical biopsy revealed non-caseating granulomatous inflammation. In the context of exclusion of hepatitis, anti-neutrophil cytoplasmic antibody (ANCA) positivity, malignancy and mycobacterial infection, the diagnosis of supraglottic laryngeal sarcoid was made. He is being treated with azathioprine immunosuppression with symptomatic improvement.

Large volume haemorrhage following transoral robotic surgery (TORS) as a result of fibromuscular dysplasia: first reported case.

We present a case of a 61-year-old woman who suffered a haemorrhagic complication of an aneurysmal left lingual artery, secondary to fibromuscular dysplasia, following transoral robotic surgery (TORS). She was admitted through the emergency department 3 days after resection of a central base of tongue tumour. She suffered a massive haemorrhage requiring intensive care admission, blood transfusion, intubation, operative and endovascular intervention. The diagnosis of fibromuscular dysplasia was made at angiography. During attempts to embolise the culprit left lingual artery, the vessel dissected at its origin leading to arrest of bleeding. Repeat angiograms during her admission demonstrated unchanged appearances and ruled out recanalisation of the vessel. She was extubated and remained stable on the ward, discharged home some days later in good health. To our knowledge, this is the first ever reported case of fibromuscular dysplasia affecting the lingual artery leading to aneurysmal dilation and severe haemorrhage following TORS.

A New Approach to Fear of Falls From Connections With the Posttraumatic Stress Disorder Literature.

Fear of falling (FoF) is as an important psychological problem among older people. While it has been researched for around four decades, paradoxically there is no agreed definition of FoF. Confusion over the definition of FoF inhibits current understanding of empirical findings. The objective of this article is to critique current definitions of FoF and to present a novel theoretical model that aims to resolve theoretical misunderstanding. A narrative review was conducted to present definitions of FoF and concepts often conflated with it including fall-related self-efficacy and anxiety. Then, by drawing on posttraumatic stress disorder (PTSD) theory and research, we present clear distinctions between the concepts. We argue that the presence or absence of anxiety determines whether FoF becomes maladaptive or adaptive, respectively, and that enhancing self-efficacy is key to optimizing postfall psychological recovery. The theoretical clarity presented will aid future research and application of evidence to the benefit older people.

Medical Students Teaching Medical Students Surgical Skills: The Benefits of Peer-Assisted Learning.

OBJECTIVE: Teaching surgical skills is a labor intensive process, requiring a high tutor to student ratio for optimal success, and teaching for undergraduate students by consultant surgeons is not always feasible. A surgical skills course was developed, with the aim of assessing the effectiveness of undergraduate surgical peer-assisted learning. DESIGN: Five surgical skills courses were conducted looking at eight domains in surgery, led by foundation year doctors and senior medical students, with a tutor to student ratio of 1:4. Precourse and postcourse questionnaires (Likert scales 0-10) were completed. Mean scores were compared precourse and postcourse. SETTING: Surgical skills courses took place within clinical skills rooms in the Queen Elizabeth Hospital Birmingham (UK). PARTICIPANTS: Seventy students (59 medical, 2 dental, and 9 physician associate students) from a range of academic institutions across the UK completed the course. RESULTS: There was an overall increase in mean scores across all eight domains. Mean improvement score precourse and postcourse in WHO surgical safety checklist (+3.94), scrubbing (+2.99), gowning/gloving (+3.34), knot tying (+5.53), interrupted sutures (+5.89), continuous sutures (+6.53), vertical mattress sutures (+6.46), and local anesthesia (+3.73). CONCLUSIONS: Peer-assisted learning is an effective and feasible method for teaching surgical skills in a controlled environment, subsequently improving confidence among healthcare undergraduates. Such teaching may provide the basis for feasibly mass-producing surgical skills courses for healthcare students.

High-throughput proteome analysis reveals targeted TRPM8 degradation in prostate cancer.

The Ca2+-permeable ion channel TRPM8 is a hallmark of the prostate epithelium. We recently discovered that TRPM8 is an ionotropic testosterone receptor. This finding suggested that testosterone-induced TRPM8 activity regulates Ca2+ homeostasis in the prostate epithelium. Since androgens are significantly implicated in prostate cancer development, the role of the novel testosterone receptor TRPM8 in cancer was assessed in our study. Although TRPM8 mRNA levels increase at the early prostate cancer stages, we found that it is not proportionally translated into TRPM8 protein levels. High-throughput proteome analysis revealed that TRPM8 degradation is enhanced in human prostate cancer cells. This degradation is executed via a dual degradation mechanism with the involvement of both lysosomal and proteasomal proteolytic pathways. The evaluation of the TRPM8 expression pattern in prostate cancer patients further confirmed the incidence of TRPM8 removal from the plasma membrane and its internalization pattern coincided with the severity of the tumor. Together, our results indicate that enhanced TRPM8 hydrolysis in prostate cancer could present an adaptation mechanism, sustained via bypassing testosterone-induced rapid Ca2+ uptake through TRPM8, thus, diminishing the rates of apoptosis. In this light, recovery of TRPM8 may pose a novel therapeutic strategy for an anti-tumor defense mechanism.

An examination of inpatient medical record keeping in the Orthopaedic Department of Kilimanjaro Christian Medical Centre (KCMC), Moshi, Tanzania.

INTRODUCTION: There is a lack of published evidence examining the quality of patient notes in African healthcare settings. We aim to examine the completeness of the orthopaedic inpatient notes and begin development of a formal audit framework in a large Tanzanian Hospital. METHODS: A retrospective review of 155 orthopaedic inpatient notes at Kilimanjaro Christian Medical Centre (KCMC) was conducted spanning 3 months. Notes were reviewed using an agreed data collection pro forma considering 3 main outcomes; i) quantity of complete entries, ii) percentage completeness of individual sections, iii) documentation of follow-up. RESULTS PRIMARY OUTCOME: 8% (n = 13) of the inpatient documents were complete (10/10 sections). 11% (n = 17) of the inpatient documents had 9 of 10 sections completed. 30% (n = 46) of the inpatient documents had 8 of 10 sections completed. Therefore, 51% (n = 79) of inpatient entries had 7 or fewer sections filled in. SECONDARY OUTCOME: Admission information and Demographics were both completed 88% (n = 137) of the time. History and the Examination sections were complete in 96% (n = 149) of cases. Investigations were complete in 77% (n = 119) and Diagnosis in 88% (n = 137). The Treatment section was complete 85% (n = 132) of the time and the Attending doctor 50% (n = 78). Procedures were 27% (n = 42) filled in while Summary of a day and Follow-up were 32% (n = 49) and 0% (n = 0) respectively. TERTIARY OUTCOME: Follow-up was not completed in any entries. CONCLUSION: There are a number of sections of the inpatient pro forma that remain inadequately completed. Regular auditing is essential for the continued progress in patient care.

Investigating the impact of headaches on the quality of life of patients with glioblastoma multiforme: a qualitative study.

OBJECTIVES: Headaches and facial pain have been identified as the most prevalent form of pain among patients with glioblastoma multiforme, the most common malignant primary brain tumour. Despite this, minimal research has been undertaken investigating the direct and indirect impact these headaches have on their quality of life. Therefore, in this study, we aimed at gaining a personal insight into the importance and impact that these headaches have on the quality of life of patients with glioblastoma multiforme. DESIGN: Exploratory study using face-to-face semistructured interviews. Interviews were audio-recorded, transcribed verbatim and then qualitatively analysed using thematic analysis. SETTING: Participants recruited from a tertiary referral hospital in Birmingham, UK. PARTICIPANTS: Purposive sampling of 14 registered outpatients recently diagnosed with glioblastoma multiforme. RESULTS: 3 themes were identified: (1) an underlying attitude of determination and positivity; (2) impact of headache unpredictability on social interaction; (3) headaches found to act as a springboard onto thoughts regarding their disease and future. CONCLUSIONS: While the quality of life of patients with glioblastoma multiforme is clearly multifactorial, headaches do indeed play a part for some. However, it is not the direct pain of the headache as one might expect that impacts on the quality of life of these patients, but the indirect effect of headaches through limiting patients' social lives and by serving as a painful psychological reminder of having a life-threatening illness. In clinical practice, using headache diaries for these patients may help provide a more comprehensive assessment and further aid management plans. Alongside acting as an important reminder of the potential secondary implications of this disease, suggestions for future research include quantitatively investigating whether headaches can act as a prognostic indicator for quality of life within this patient demographic and determining whether these conclusions also hold true for a wider spectrum of patients with brain tumour.