A novel electronic health record-based, machine-learning model to predict severe hypoglycemia leading to hospitalizations in older adults with diabetes: A territory-wide cohort and modeling study.

BACKGROUND: Older adults with diabetes are at high risk of severe hypoglycemia (SH). Many machine-learning (ML) models predict short-term hypoglycemia are not specific for older adults and show poor precision-recall. We aimed to develop a multidimensional, electronic health record (EHR)-based ML model to predict one-year risk of SH requiring hospitalization in older adults with diabetes. METHODS AND FINDINGS: We adopted a case-control design for a retrospective territory-wide cohort of 1,456,618 records from 364,863 unique older adults (age ≥65 years) with diabetes and at least 1 Hong Kong Hospital Authority attendance from 2013 to 2018. We used 258 predictors including demographics, admissions, diagnoses, medications, and routine laboratory tests in a one-year period to predict SH events requiring hospitalization in the following 12 months. The cohort was randomly split into training, testing, and internal validation sets in a 7:2:1 ratio. Six ML algorithms were evaluated including logistic-regression, random forest, gradient boost machine, deep neural network (DNN), XGBoost, and Rulefit. We tested our model in a temporal validation cohort in the Hong Kong Diabetes Register with predictors defined in 2018 and outcome events defined in 2019. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) statistics, and positive predictive value (PPV). We identified 11,128 SH events requiring hospitalization during the observation periods. The XGBoost model yielded the best performance (AUROC = 0.978 [95% CI 0.972 to 0.984]; AUPRC = 0.670 [95% CI 0.652 to 0.688]; PPV = 0.721 [95% CI 0.703 to 0.739]). This was superior to an 11-variable conventional logistic-regression model comprised of age, sex, history of SH, hypertension, blood glucose, kidney function measurements, and use of oral glucose-lowering drugs (GLDs) (AUROC = 0.906; AUPRC = 0.085; PPV = 0.468). Top impactful predictors included non-use of lipid-regulating drugs, in-patient admission, urgent emergency triage, insulin use, and history of SH. External validation in the HKDR cohort yielded AUROC of 0.856 [95% CI 0.838 to 0.873]. Main limitations of this study included limited transportability of the model and lack of geographically independent validation. CONCLUSIONS: Our novel-ML model demonstrated good discrimination and high precision in predicting one-year risk of SH requiring hospitalization. This may be integrated into EHR decision support systems for preemptive intervention in older adults at highest risk.

Systematic Review of Hypofractionated Radiation Therapy for the Treatment of Oesophageal Squamous Cell Carcinoma and Oesophageal Adenocarcinoma.

BACKGROUND AND AIM: There has been limited progress made in improving the suboptimal outcomes delivered by conventionally fractionated radiotherapy (RT) for oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). A greater biological effect may be achieved using hypofractionated RT (HFRT), though the toxicity, tolerability and efficacy of this approach in OAC and OSCC is uncertain. METHODS: A systematic literature review was carried out in accordance with Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane, CINAHL, Scopus and Web of Science databases were searched for terms relating to HFRT (>2.4Gy per fraction) for OAC or OSCC. All relevant clinical studies published between January 2000 and April 2023 were included. Study quality was assessed using predefined criteria. RESULTS: Ninety-six studies were screened and 20 subsequently included, together incorporating 1208 patients. Fourteen studies focussed on neoadjuvant or definitive treatment. These were predominantly retrospective (n = 10, 71%) though two (n = 2, 14%) early phase trials were identified. Most focussed on OSCC (n = 7, 47%) or mixed OSCC/OAC (n = 6, 43%) populations. Four (28.6%) included a conventionally fractionated chemoradiotherapy (CRT) comparator, against which median overall (mOS) and progression free survival outcomes from HFRT did not differ. Reported mOS for HFRT ranged between 29-36 months at 2.5-3.125Gy per fraction (total dose 50-60Gy) for OAC and OSCC combined. Toxicity and tolerability with HFRT was comparable with conventionally fractionated CRT up to, but not exceeding, 5Gy. Three (50%) of the six palliative-intent studies were early phase trials and most (n = 4, 67%) focussed on OAC and OSCC. Response rates with HFRT in the palliative setting were 63.6-88.0%. CONCLUSION: These data provide evidence in OAC/OSCC for promising efficacy and an acceptable toxicity profile for moderately HFRT, alone or with concurrent chemotherapy. These data should prompt prospective, randomised comparisons of HFRT and conventionally fractionated CRT and single-modality RT schedules. REGISTRATION DETAILS: PROSPERO; CRD42023457791.

Online Oncology Careers Events to Attract the Future Oncology Medical Workforce: An Exemplar Event and Review of the Literature.

AIMS: There are too few oncologists to meet the increasing burden imposed by the rising incidence of cancer. This results from issues with the retention of established oncologists and longstanding challenges to the recruitment of adequate numbers of trainees. To counter this, the British Oncology Network for Undergraduate Societies (BONUS) devised an online oncology careers event for medical students and junior doctors who are yet to select a specialty. MATERIALS AND METHODS: An online careers event was devised with a focus on oncology practice and related subspecialties, as well as research. Event attendees were asked to respond to piloted pre- and post-event surveys. Knowledge and attitudes towards a career in oncology were evaluated using Likert scale and multiple-choice questions. A systematic literature search was carried out to contextualise these data. RESULTS: Of the 73 attendees, 44 (60%) participants completed both the pre- and post-event surveys; 79.5% of attendees believed that information on a career in oncology is lacking in medical training. This viewpoint was supported by the systematic review, which highlighted a need for relevant focussed interventions targeted at medical students and fledgling doctors. The education event led to an increase in the median reported understanding of the oncology career pathway from 6.0 to 8.0 (P < 0.05 and P < 0.001), as well as the likelihood of pursuing a career in oncology (8.0-9.0; P < 0.05). It was also associated with a proportional increase in medical and surgical oncology interest, albeit with a fall in interest in clinical and interventional oncology as well as academia. CONCLUSION: A targeted online careers event increases knowledge of and interest in a career in oncology, albeit predominantly for medical and surgical subspecialties. Broader initiatives based on our model should be developed and careers in academia as well as clinical and interventional oncology emphasised.

Reversed Holocene temperature-moisture relationship in the Horn of Africa.

Anthropogenic climate change is predicted to severely impact the global hydrological cycle1, particularly in tropical regions where agriculture-based economies depend on monsoon rainfall2. In the Horn of Africa, more frequent drought conditions in recent decades3,4 contrast with climate models projecting precipitation to increase with rising temperature5. Here we use organic geochemical climate-proxy data from the sediment record of Lake Chala (Kenya and Tanzania) to probe the stability of the link between hydroclimate and temperature over approximately the past 75,000 years, hence encompassing a sufficiently wide range of temperatures to test the 'dry gets drier, wet gets wetter' paradigm6 of anthropogenic climate change in the time domain. We show that the positive relationship between effective moisture and temperature in easternmost Africa during the cooler last glacial period shifted to negative around the onset of the Holocene 11,700 years ago, when the atmospheric carbon dioxide concentration exceeded 250 parts per million and mean annual temperature approached modern-day values. Thus, at that time, the budget between monsoonal precipitation and continental evaporation7 crossed a tipping point such that the positive influence of temperature on evaporation became greater than its positive influence on precipitation. Our results imply that under continued anthropogenic warming, the Horn of Africa will probably experience further drying, and they highlight the need for improved simulation of both dynamic and thermodynamic processes in the tropical hydrological cycle.

The impact of endoscopic ultrasound on the management and outcome of patients with oesophageal cancer: an update of a systematic review.

AIM: To provide an updated systematic review concerning the impact of endoscopic ultrasound (EUS) in the modern era of oesophageal cancer staging. MATERIALS AND METHODS: To update the previous systematic review, databases including MEDLINE and EMBASE were searched and studies published from 2005 onwards were selected. Studies reporting primary data in patients with oesophageal or gastro-oesophageal junction cancer who underwent radiological staging and treatment, regardless of intent, were included. The primary outcome was the reported change in management after EUS. Secondary outcomes were recurrence rate and overall survival. Two reviewers extracted data from included articles. This study was registered with PROSPERO (CRD42021231852). RESULTS: Eighteen studies with 11,836 patients were included comprising 2,805 patients (23.7%) who underwent EUS compared to 9,031 (76.3%) without EUS examination. Reported change of management varied widely from 0% to 56%. When used, EUS fine-needle aspiration precluded curative treatment in 37.5%-71.4%. Overall survival improvements ranged between 121 and 639 days following EUS intervention compared to patients without EUS. Smaller effect sizes were observed in a randomised controlled trial, compared to larger differences reported in observational studies. CONCLUSION: Current evidence for the effectiveness of EUS in oesophageal cancer pathways is conflicting and of limited quality. In particular, the extent to which EUS adds value to contemporary cross-sectional imaging techniques is unclear and requires formal re-evaluation.

A national cross-sectional survey investigating the use of endoscopic ultrasound in the diagnosis and treatment of oesophageal cancer in the UK.

AIM: To evaluate variation in the pre-pandemic use of endoscopic ultrasound (EUS) for oesophageal cancer diagnosis and treatment planning up to 2019, and which factors contributed to this. MATERIALS AND METHODS: A UK-wide online survey of oesophagogastric multidisciplinary team lead clinicians was undertaken to determine perceptions towards, and the use of, EUS to aid staging and treatment planning in oesophageal cancer. RESULTS: Thirty-five responses were received, representing 97 UK National Health Service Trusts/Health Boards. A majority of centres (n=21, 60%) did not have formal written guidance for EUS use. Although all respondents had access to EUS, a perceived lack of utility (n=7) and concerns about delaying treatment start dates (n=8) each restricted EUS use for a fifth of respondents. For most centres (n=24, 68.6%), EUS use is case-specific, whereas for 10 (28.6%) EUS is used for all patients with potentially curable disease. A majority of centres use diagnostic positron-emission tomography for radiotherapy target volume delineation (TVD), whereas 22 (62.9%) use EUS. The factors contributing to decisions to use EUS for staging, TVD and surgical planning varied between centres. The proportion of centre respondents who would request EUS in each of six clinical scenarios varied considerably. CONCLUSION: There were substantial differences in the patient and disease characteristics that are perceived to be indications for EUS use for both staging and treatment planning. Research to clarify in which patients with oesophageal cancer EUS affords benefit is required, as is urgent standardisation of its role in the diagnostic pathway.

Short communication: Variation in serum immunoglobulin G concentrations from birth to 112 days of age in Holstein calves fed a commercial colostrum replacer or maternal colostrum.

Serum IgG concentrations in dairy calves change throughout their first weeks of life, peaking at 24 h and then steadily decreasing until calves begin to produce endogenous IgG. The objective of this study was to observe serum IgG dynamics from birth until 16 wk of life in calves fed either maternal colostrum (MC) or colostrum replacer (CR). A total of 44 Holstein calves were randomly assigned to 1 of the 4 colostrum treatments and followed throughout the study. Treatments consisted of feeding high-quality MC, low-quality MC supplemented with CR, or 1 of 2 distinct levels of IgG concentration from CR. Overall, the interaction between type of colostrum fed and sampling time was significant. Individual differences for this effect were found at d 1, 7, 14, 21, 28, and 98, while the other time points were not different.

Effect of converting weaned dairy calves from a component-fed diet to a total mixed ration on growth and nutrient digestibility.

The objective was to determine the effects of converting calves from a component-fed ration to a total mixed ration (TMR) at 8, 10, or 12 wk of age on intake, growth, and nutrient digestibility. Holstein calves (n = 40) were randomly assigned to 1 of 4 groups (no TMR, TMR conversion at 8, 10 or 12 wk; T0, T8, T10, and T12, respectively). Calves were weaned at 6 wk of age, housed individually, and studied from 7 to 14 wk of age. Rations, consisting of a 20% crude protein texturized starter and grass hay, were offered ad libitum as separate components or as a TMR with 85% starter and 15% grass hay on a dry matter (DM) basis. Intakes and body weights (BW) were measured weekly. Component intake for TMR was calculated from the proportion of grass hay and starter contained in the TMR. Fecal grab samples were collected every 9 h over 3 d for a total of 8 samples that formed a composite at 9, 11, and 13 wk of age from the same 4 calves per group. Rumen fluid samples were collected via esophageal tube at -1, 0, 3, and 7 d relative to conversion from component to TMR. Feed and feces were evaluated for DM, neutral detergent fiber, acid detergent fiber, and acid detergent lignin (internal flow marker) to estimate digestibility. Average daily gain and final BW tended to be least for T8. Empty BW gain was significantly less for T8 than for T0 but not different from T10 or T12 (T0 = 1.07, T8 = 0.93, T10 = 1.02, T12 = 1.04 kg/d). Hip growth tended to be least for T8 and resulted in lower final hip width (T0 = 25.9, T8 = 25.2, T10 = 25.6, T12 = 25.8 cm). Intake tended to be reduced for calves converted to TMR earlier. Throughout the study, calves fed TMR ate more hay and less starter than component-fed calves. Metabolizable energy intake was less for T8 versus T0 but not different from T10 or T12 (T0 = 8.46, T8 = 7.55, T10 = 8.01, T12 = 8.23 Mcal/d). We observed no differences in feed efficiency for the duration of the study. Differences in DM digestibility were not observed, but fiber digestibility was greater for calves fed TMR at 9, 11, and 13 wk of age. Conversion to TMR increased rumen pH. These results indicate that TMR conversion increased hay consumption and subsequently decreased starter and total DM intake. This led to reduced weight and structural growth; however, calves that were converted to TMR as early as 8 wk still achieved adequate growth. The increase in rumen pH and subsequent increase in fiber digestibility allowed for calves to be converted to a 15% grass hay TMR as early as 8 wk and still achieve desirable growth goals.

Comparison of immunoglobulin G absorption in calves fed maternal colostrum, a commercial whey-based colostrum replacer, or supplemented maternal colostrum.

Successful passive transfer of antibodies in neonatal calves can be achieved by feeding an adequate quantity and quality of maternal colostrum (MC) or colostrum replacer (CR). An alternative could be feeding low-quality maternal colostrum (LMC) with added IgG from a CR. The objective of this study was to determine if a commercial whey-based CR product containing low levels of casein (Premolac PLUS Bovine IgG; Zinpro Corporation, Eden Prairie, MN) fed to replace MC or supplement LMC could lead to adequate serum IgG levels and apparent efficiency of absorption (AEA) in neonatal dairy calves. Holstein calves (n = 20 per treatment) were separated from their dam after birth and randomly assigned to be fed 3.79 L of MC (106 g/L of IgG; 401 g of IgG fed), LMC (30 g/L IgG) supplemented with CR (41 g/L IgG; 154 g of IgG total fed; LMC-CR), or 1.3 L of 1 of 2 levels of CR (110 or 150 g of IgG fed; CR-110 or CR-150) within 1.5 h of birth. Colostrum was obtained from the first (MC) or second and third milkings (LMC) of cows from Pennsylvania State University dairy and pooled by source into large batches. Blood samples were taken from calves before colostrum feeding and 24 h after birth and were analyzed for serum total protein, total IgG, hematocrit, and Brix percentage. Calves fed MC had higher 24-h IgG values (means ± SEM) than calves fed LMC-CR (27.04 ± 1.07 vs. 22.33 ± 1.08 mg/mL, respectively). Feeding 150 g of IgG from CR led to higher 24-h serum IgG values than feeding 110 g of IgG (16.90 ± 1.09 vs. 12.79 ± 1.08 mg/mL). Serum IgG levels were different between the CR-fed calves and the calves fed LMC-CR and MC, but all had average values >10 mg/mL IgG. Calves fed LMC-CR had greater AEA than calves fed MC (54.58 ± 2.39 vs. 24.38 ± 2.36%, respectively). Among calves fed CR-110 or CR-150, AEA did not differ. Serum total protein and Brix percentage had strong correlations with actual IgG values across the entire study. We found no differences in average daily gain or health variables measured, and no differences in final hip width, withers height, or body weight for calves fed MC, LMC-CR, CR-150, or CR-110. These results indicate that CR can be fed successfully as an alternative to MC or as a supplement to colostrum with low IgG.

Symposium review: Colostrum management and calf nutrition for profitable and sustainable dairy farms.

Multistate dairy management research project NC-2042, which is part of the National Institute of Food and Agriculture, has devoted an ongoing objective to calf and heifer nutrition and management. Within this objective, colostrum research has been a priority due to continued opportunities to improve this area on US dairy farms. Research has focused on heating colostrum to reduce bacterial populations and pathogens while increasing IgG absorption. Research also identified other proteins that are reduced when heating colostrum. Studies indicated an apparent upper limit to IgG absorption from colostrum fed to calves. Additional studies have shed light on absorption of IgG from colostrum replacers and evaluated the use of lactoferrin and sodium bicarbonate in both maternal colostrum and colostrum replacers. Milk replacer formulation, feeding strategies, and the effect of calfhood nutrition on future performance have also been researched. Finally, water quality and its effect on calves and heifers have been studied. This review focuses on research done by multistate research project NC-2042 member states in the area of colostrum and calf nutrition and management.

Low rates of dental attendance by the age of one and inequality between local government administrative areas in England.

OBJECTIVE: To describe child dental attendance (DA) by 1 year of age in England and its relationship with area deprivation. BASIC RESEARCH DESIGN: Analysis of National Health Service data for the 12 months to June 2017. Deprivation was measured by Index of Multiple Deprivation Rank of Average Score (2015) for upper-tier and unitary local authorities in England (LAs, n=151). DA rates were calculated for children under 1 year (⟨1yr) and children aged 1 year and under (⟨1yr). A Spearman's test assessed strength of association with deprivation. The Slope Index of Inequality (SII) and Relative Index of Inequality (RII) explored equity. CLINICAL SETTING: Upper-tier and unitary LAs in England. MAIN OUTCOME MEASURE: Attending an NHS primary care dental service. RESULTS: DA rates ranged from 0 to 12.3% (Median:2; IQR:1.4,3.9) in children ⟨1yr and from 3.7 to 37.6% (Median:10; IQR:7.4,17) in children ≤1yr. DA rates decreased as deprivation decreased (Spearman=-0.25, p=0.0019 in children ⟨1yr; Spearman=-0.21, p=0.0104 in children ≤1yr). The SII suggested a 2 percentage point difference in DA rate across the deprivation distribution in children ⟨1yr (SII=-0.02, 95% CI=-0.01,-0.04; p=⟨0.001); and a 5 point difference in children ≤1yr (SII=-0.05, 95% CI=-0.02,-0.09; p=0.003). The DA rate in the most deprived LA was 2.1 higher than the least deprived LA (RII=2.1, 95% CI=1.4,3.2; p=⟨0.001) in children ⟨1yr and 1.5 higher (RII=1.5, 95% CI=1.2,2; p=0.004) in children ≤1yr. CONCLUSIONS: DA rates were low for all LAs and only partially explained by deprivation. More deprived LAs were, unexpectedly, more likely to report higher DA rates.

Hypofractionated Radiotherapy in Oesophageal Cancer for Patients Unfit for Systemic Therapy: A Retrospective Single-Centre Analysis.

AIMS: Chemoradiotherapy (CRT) is established as a superior treatment option to definitive radiotherapy in the non-surgical management of oesophageal cancer. For patients precluded from CRT through choice or comorbidity there is little evidence to guide delivery of single-modality radiotherapy. In this study we outline outcomes for patients unfit for CRT who received a hypofractionated radiotherapy (HRT) regimen. MATERIALS AND METHODS: A retrospective UK single-centre analysis of 61 consecutive patients with lower- or middle-third adenocarcinoma (OAC; 61%) or squamous cell carcinoma of the oesophagus managed using HRT with radical intent between April 2009 and 2014. Treatment consisted of 50 Gy in 16 fractions (n = 49, 80.3%) or 50-52.5 Gy in 20 fractions (n = 12, 19.7%). Outcomes were referenced against a contemporaneous comparator cohort of 80 (54% OAC) consecutive patients managed with conventionally fractionated CRT within the same centre. RESULTS: Three-year and median overall survival were, respectively, 56.9% and 29 months with HRT compared with 55.5% and 26 months for CRT; adjusted hazard ratio 0.79 (95% confidence interval 0.48-1.28). Grade 3 and 4 toxicity rates were low at 16.4% (n = 10) for those receiving HRT and 40.2% (n = 32) for the CRT group. In patients with OAC, CRT delivered superior overall survival (hazard ratio 0.46; 95% confidence interval 0.25-0.85) and progression-free survival (hazard ratio 0.45; 95% confidence interval 0.23-0.88) when compared with HRT. CONCLUSIONS: The HRT regimen described here was safe and tolerable in patients unable to receive CRT, and delivered promising survival outcomes. The use of HRT for the treatment of oesophageal cancer, both alone and as a sequential or concurrent treatment with chemotherapy, requires further study. New precision radiotherapy technologies may provide additional scope for improving outcomes in oesophageal cancer using HRT-based approaches and should be evaluated.