Presentation, characteristics and management of obstructive intestinal conditions in cystic fibrosis.

Objective: Constipation and distal intestinal obstruction syndrome (DIOS) are common gastrointestinal manifestations of cystic fibrosis (CF). The primary aim was to describe the characteristics of constipation and DIOS hospitalisations in a paediatric and adult CF service over a 12-year period. The secondary aims were to determine the proportion of constipation and DIOS presentations which met the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) CF Working Group definitions and to describe management strategies of both conditions. Method: A retrospective study of children and adults with CF who were admitted with a primary diagnosis of constipation or DIOS between 1 January 2011 and 31 December 2022. ESPGHAN definitions for constipation and DIOS were retrospectively applied to all admissions to determine if the primary medical diagnosis met ESPGHAN criteria. Results: During the 12-year study period, 42 hospitalisations for constipation were recorded in 19 patients, and 33 hospitalisations for DIOS were recorded in 23 patients. 88.10% of constipation episodes met ESPGHAN definitions, compared with 3.0% of DIOS episodes. Constipation and DIOS were primarily treated with polyethylene glycol (PEG). The use of sodium amidotrizoate meglumine enemas was significantly higher in the DIOS group (p=0.045). Those admitted with DIOS were significantly less likely to be recommended a weaning dose of PEG (p=0.018). Conclusion: Children and adults with CF are more commonly admitted for the management of constipation than DIOS. There is considerable variation in diagnostic and therapeutic practice, and this study highlights the need to enhance the translation and adoption of existing best-practice guidelines.

Jacquet erosive dermatitis associated with commercial barrier cream.

Jacquet erosive dermatitis (JED) is a rare, severe form of napkin dermatitis associated with friction and irritant exposure in the napkin area. The condition typically causes erosions and erythematous punched-out ulcerations. We present two cases of JED in infants associated with the use of a common brand barrier cream Curash. This appeared to present following a change of several active ingredients.

The Edmonton Classification System for Cancer Pain in Patients with Bone Metastasis: a descriptive cohort study.

PURPOSE: We describe the prevalence of the Edmonton Classification System for Cancer Pain (ECS-CP) features in patients with bone metastasis and cancer-induced bone pain (CIBP) and the relationship between ECS-CP features, pain intensity, and opioid consumption. METHODS: We assessed ECS-CP features and recoded pain mechanisms and opioid use in adult patients with bone metastasis. Validated measures were used to assess pain intensity, incident pain, psychological distress, addictive behavior, and cognition. RESULTS: Among 147 eligible patients, 95.2% completed the assessment. Mean participant age was 73.2 years, the majority female (52.1%) with breast cancer occurring most commonly (25.7%). One or more ECS-CP features were present in 96.4% and CIBP in 75.7% of patients. The median average and worst pain scores were 3 and 6, respectively. Neuropathic pain was the most prevalent pain mechanism (45.0%) and was associated with breakthrough pain frequency (p=0.014). Three-quarters had incident pain, which was strongly associated with a higher average and worst pain scores (3.5 and 7, p<0.001 for both), background oral morphine equivalent daily dose (26.7mg, p=0.005), and frequency of daily breakthrough analgesia (1.7 doses/day, p=0.007). Psychological distress (n=90, 64.3%) was associated with a significantly higher average pain score (4, p=0.009) and a slightly higher worst pain score (7, p=0.054). Addictive behaviour and cognitive dysfunction were relatively uncommon (18.6% and 12.9%, respectively). CONCLUSION: There is a need to promote standardized assessment and classification of pain syndromes such as CIBP. The ECS-CP may allow us to consider CIBP in a systematic manner and develop personalized pain interventions appropriate to the pain profile. TRIAL REGISTRATION: Retrospectively registered in ANZCTR ACTRN12622000853741 (16/06/2022).

Feasibility of a Geriatric Oncology Longitudinal End to End (GOLDEN) Program in a Tertiary Cancer Center in Singapore.

INTRODUCTION: In the National University Cancer Institute, Singapore (NCIS), 2 pilot programs providing (i) surgical prehabilitation before cancer surgery and (ii) geriatric oncology support for older adults planned for chemotherapy and/or radiotherapy were merged to form the Geriatric Oncology Longitudinal End to eNd (GOLDEN) program in 2019 to support patients from the time of their cancer diagnosis, through their treatment process, to cancer survivorship. METHODS AND MATERIALS: Older adults aged ≥65 years were enrolled in either surgical prehabilitation, the geriatric medical oncology (GO) arm, or both. All patients undergo a geriatric assessment. We assessed if patients had a change in treatment plans based on GOLDEN recommendations, and the impact on patient related outcomes. RESULTS: There were 777 patients enrolled in the GOLDEN program over 2 years; 569 (73%) were enrolled in surgical prehabilitation, 308 (40%) were enrolled in the GO arm, with 100 (12.8%) enrolled in both. 56.9% were females. Median age was 73. Lower gastrointestinal (51.2%) and hepatobiliary cancers (24.1%) were the most common cancer types. 43.4% were pre-frail and 11.7% were frail. Of the 308 patients in the GO arm, 86.0% had geriatric syndromes, while 60.7% had a change in their treatment plans based on GOLDEN recommendations. 31.5% reported an improved global health status, while 38.3% maintained their global health status. 226 (73%) responded that they had benefited from the GOLDEN. CONCLUSION: More than half of the population was either pre-frail or frail. Amongst those in the GO arm, the majority had geriatric syndromes and had a change in their treatment plans based on GOLDEN recommendations. Majority reported either improvement or maintenance in global health status, with most feeling they have benefited from the program. Further evaluation of the longitudinal geriatric hematology-oncology program for cancer-related outcomes and sustainability should be carried out.

Association of physical function and body composition with falls in pre-frail older adults with poor physical performance: A cross-sectional study.

BACKGROUND: Falls in pre-frail older adults is often attributed to poor physical performance, lower muscle quality and quantity. The aims of our study were to determine (i) demographics, physical function, and body composition in pre-frail older adults with poor physical performance (ii) characteristics of fallers amongst those with poor physical performance and (iii) association of physical function and body composition measures with falls in pre-frail older adults with poor physical performance. METHODS: Cross-sectional study of 328 pre-frail community-dwelling older adults ≥ 60 years. Data was collected on demographics, cognition, short physical performance battery (SPPB) and gait speed. Poor physical performance was defined by SPPB ≤ 9, 5x chair-stand time ≥12 s or gait speed <1 m/s. InBody S10 used to measure body composition. RESULTS: Mean age 72.51 years, 185(56.4%) females, 276(84.1%) of Chinese ethnicity and 257 (78.4%) had poor physical performance. Within the poor performers, SPPB balance (OR 0.50; 95% CI 0.27-0.92; p = 0.025) and 5x-chair-stand (OR 1.09; 95% CI 1.01-1.18; p = 0.038) in addition to higher body fat percentage, fat mass index, fat mass to fat free mass ratio, all segmental lean masses except for left leg and body cell mass were significantly associated with falls. CONCLUSIONS: Longer chair-stand time, lower balance, low muscle and high fat mass are associated with falls in poor performers and could serve as screening tools for those at increased risk of falls. The findings from our study need to be validated prospectively in a larger population study.

Delirium is significantly associated with hospital frailty risk score derived from administrative data.

OBJECTIVES: Delirium is highly prevalent in hospitalised older adults, under-diagnosed and associated with poor outcomes. We aim to determine (i) association of frailty measured using Hospital Frailty Risk Score (HFRS) with delirium, (ii) impact of delirium on mortality, 30-days readmission, extended length of stay (eLOS) and cost (eCOST). METHODS: Retrospective cohort study was conducted on 902 older adults ≥75 years discharged from an academic tertiary hospital between March and September 2021. Data was obtained from hospital administrative database. RESULTS: Delirium was prevalent in 39.1%, 58.1% were female with mean age 85.3 ± 6.2 years. Patients with delirium were significantly older, had higher HFRS, pneumonia, urinary tract infection (UTI), E.coli and Klebsiella infection, constipation, dehydration, stroke and intracranial bleed, with comorbidities including dementia, diabetes, hypertension, hyperlipidaemia and chronic kidney disease. In-hospital mortality, 30-days mortality, 30-days readmission, median LOS and cost was significantly higher. Delirium was significantly associated with at least intermediate frailty (OR = 3.52; CI = 2.48-4.98), dementia (OR = 2.39; CI = 1.61-3.54), UTI (OR = 1.95; CI = 1.29-2.95), constipation (OR = 2.49; CI = 1.43-4.33), Klebsiella infection (OR = 3.06; CI = 1.28-7.30), dehydration (OR = 2.01; CI = 1.40 - 2.88), 30-day mortality (OR = 2.52; CI = 1.42-4.47), 30-day readmission (OR = 2.18; CI = 1.36-3.48), eLOS (OR = 1.80; CI = 1.30-2.49) and eCOST (OR = 1.67; CI = 1.20-2.35). CONCLUSIONS: Delirium was highly prevalent in older inpatients, and associated with dementia, frailty, increased cost, LOS, 30-day readmissions and mortality. Hospital Frailty Risk Score had robust association with delirium and can be auto-populated from electronic medical records. Prospective studies are needed on multicomponent delirium preventive measures in high-risk groups identified by HFRS in acute care settings.

Peptomer substrates for quantitative pattern-recognition sensing of proteases.

The utility of active proteases as biomarkers is often limited by overlapping substrate specificity. Here, this feature is leveraged to develop a quantitative pattern-recognition sensing system driven by the degradation patterns of peptide-peptoid hybrid substrates to classify proteases and estimate their concentration by multivariate data analysis.

Fluorescent Peptomer Substrates for Differential Degradation by Metalloproteases.

Proteases, especially MMPs, are attractive biomarkers given their central role in both physiological and pathological processes. Distinguishing MMP activity with degradable substrates, however, is a difficult task due to overlapping substrate specificity profiles. Here, we developed a system of peptomers (peptide-peptoid hybrids) to probe the impact of non-natural residues on MMP specificity for an MMP peptide consensus sequence. Peptoids are non-natural, N-substituted glycines with a large side-chain diversity. Given the presence of a hallmark proline residue in the P3 position of MMP consensus sequences, we hypothesized that peptoids may offer N-substituted alternatives to generate differential interactions with MMPs. To investigate this hypothesis, peptomer substrates were exposed to five different MMPs, as well as bacterial collagenase, and monitored by fluorescence resonance energy transfer and liquid chromatography-mass spectrometry to determine the rate of cleavage and the composition of degraded fragments, respectively. We found that peptoid residues are well tolerated in the P3 and P3' substrate sites and that the identity of the peptoid in these sites displays a moderate influence on the rate of cleavage. However, peptoid residues were even better tolerated in the P1 substrate site where activity was more strongly correlated with side-chain identity than side-chain position. All MMPs explored demonstrated similar trends in specificity for the peptomers but exhibited different degrees of variability in proteolytic rate. These kinetic profiles served as "fingerprints" for the proteases and yielded separation by multivariate data analysis. To further demonstrate the practical application of this tunability in degradation kinetics, peptomer substrates were tethered into hydrogels and released over distinct timescales. Overall, this work represents a significant step toward the design of probes that maximize differential MMP behavior and presents design rules to tune degradation kinetics with peptoid substitutions, which has promising implications for diagnostic and prognostic applications using array-based sensors.

Outcomes of Care by Geriatricians and Non-geriatricians in an Academic Hospital.

Introduction: While hospitalist and internist inpatient care models dominate the landscape in many countries, geriatricians and internists are at the frontlines managing hospitalized older adults in countries such as Singapore and the United Kingdom. The primary aim of this study was to determine outcomes for older patients cared for by geriatricians compared with non-geriatrician-led care teams. Materials and Methods: A retrospective cohort study of 1,486 Internal Medicine patients aged ≥75 years admitted between April and September 2021 was conducted. They were either under geriatrician or non-geriatrician (internists or specialty physicians) care. Data on demographics, primary diagnosis, comorbidities, mortality, readmission rate, Hospital Frailty Risk Score (HFRS), Age-adjusted Charlson Comorbidity Index, Length of Stay (LOS), and cost of hospital stay were obtained from the hospital database and analyzed. Results: The mean age of patients was 84.0 ± 6.3 years, 860 (57.9%) females, 1,183 (79.6%) of Chinese ethnicity, and 902 (60.7%) under the care of geriatricians. Patients under geriatrician were significantly older and had a higher prevalence of frailty, dementia, and stroke, whereas patients under non-geriatrician had a higher prevalence of diabetes and hypertension. Delirium as the primary diagnosis was significantly higher among patients under geriatrician care. Geriatrician-led care model was associated with shorter LOS, lower cost, similar inpatient mortality, and 30-day readmission rates. LOS and cost were lower for patients under geriatrician care regardless of frailty status but significant only for low and intermediate frailty groups. Geriatrician-led care was associated with significantly lower extended hospital stay (OR 0.73; 95% CI 0.56-0.95) and extended cost (OR 0.69; 95% CI 0.54-0.95). Conclusion: Geriatrician-led care model showed shorter LOS, lower cost, and was associated with lower odds of extended LOS and cost.

Remaining Agile in the COVID-19 pandemic healthcare landscape - How we adopted a hybrid telemedicine Geriatric Oncology care model in an academic tertiary cancer center.

INTRODUCTION: The COVID-19 pandemic has impacted healthcare on an unprecedented scale, with healthcare resources being channeled into managing the devastating effects of the outbreak. Healthcare provision for vulnerable older adults has also been affected by lockdowns and suspension of selected medical services worldwide. In our tertiary cancer center, the National University Cancer Institute, Singapore (NCIS), our Geriatric Oncology (GO) service for older adults with cancer was halted for five months. In this paper, we describe the adoption of a hybrid telemedicine model by our GO service to continue care provision for older adults in the midst of the pandemic. MATERIALS AND METHODS: Comprehensive geriatric assessments (CGA) were done via telemedicine and virtual multidisciplinary discussions were held prior to the patients' clinic visits. A hybrid telemedicine consultation allowed geriatricians and oncologists, segregated in different sites during the pandemic, to provide a hybrid physical and video geriatric oncology consultation. Scheduled phone follow ups by GO nurses helped to monitor patients for treatment-related toxicities and geriatric syndromes. RESULTS: Two hundred fifty patients were enrolled in the program from July 2020 to August 2021. All were assessed with a CGA, with 240 receiving interventions in the one-stop clinic. The average amount of time spent per visit was shortened from four hours to two and a half hours with an average of three interventions on the same day, versus one previously. Of the patients who received interventions, 84.8% were satisfied with the hybrid telemedicine model and 80.8% of them had reported a maintained or improved quality of life after being enrolled in the program. DISCUSSION: Telemedicine has been widely adopted during the pandemic, but older adults with limited digital literacy may find it a challenge. Our hybrid telemedicine model has allowed us to continue to provide cancer care, identify issues brought about by social isolation, and render timely assistance. It has become imperative to adapt, prepare and plan for the challenges we may face amid the ongoing COVID-19 pandemic and similar future outbreaks. Only by doing so can we remain agile and resilient, to continue providing quality care to our older patients with cancer.

Interviewing anorexia: How do individuals given a diagnosis of anorexia nervosa experience Voice Dialogue with their eating disorder voice? A qualitative analysis.

A proportion of individuals given an eating disorder diagnosis describe the experience of an eating disorder 'voice' (EDV). However, methods for working with this experience are currently lacking. Voice Dialogue (Stone & Stone, 1989) involves direct communication between a facilitator and parts of the self to increase awareness, understanding, and separation from inner voices. Adapted forms of this method have shown promise in working with voices in psychosis. This study aimed to explore the experience and acceptability of Voice Dialogue amongst individuals with anorexia nervosa who experience an EDV. Nine women participated in a semistructured interview following a single Voice Dialogue session. Interview transcripts were analysed using interpretative phenomenological analysis (IPA). Three overarching themes were identified as follows: (i) "separating from the EDV"; (ii) "better understanding of the EDV"; and (iii) "hopeful, motivated, and afraid of recovery". The majority of participants found Voice Dialogue acceptable and helpful for exploring their EDV. Whilst preliminary, the results suggest that Voice Dialogue has potential in terms of helping individuals establish a more constructive relationship with their EDV and motivating change. Further research is needed to build upon these findings. Implications for addressing the EDV using voice-focused interventions are explored.

BPh3-Catalyzed [2+3] Cycloaddition of Ph3PCCO with Aldonitrones: Access to 5-Isoxazolidinones with Exocyclic Phosphonium Ylide Moieties.

A method for the generation of 5-isoxazolidinones with exocyclic phosphonium ylide functionalities via [2+3] cycloaddition of Ph3PCCO and aldonitrones has been developed and applied in the synthesis of 4-alkylidene-5-isoxazolidinones via Wittig olefination. The reaction proceeds by BPh3 catalysis under mild conditions and with a broad substrate scope. A reaction pathway involving the activation of the aldonitrone via interactions with the Lewis acid BPh3 is proposed.

Classifying dermoscopic patterns of naevi in a case-control study of melanoma.

Changes in dermoscopic patterns of naevi may be associated with melanoma; however, there is no consensus on which dermoscopic classification system is optimal. To determine whether different classification systems give comparable results and can be combined for analysis, we applied two systems to a case-control study of melanoma with 1037 participants: 573 classified using a "1/3 major feature" system, 464 classified based on rules of appearance, and 263 classified with both criteria. There was strong correlation for non-specific (Spearman R = 0.96) and reticular (Spearman R = 0.82) naevi, with a slight bias for globular naevi with the rules of appearance system. Inter-observer reliability was high for the rules of appearance system, particularly for reticular naevi (Pearson >0.97). We show that different classification systems for naevi can be combined for data analysis, and describe a method for determining what adjustments may need to be applied to combine data sets.