The top 10 research priorities in diabetes and pregnancy according to women, support networks and healthcare professionals.

AIMS: To undertake a Priority Setting Partnership (PSP) to establish priorities for future research in diabetes and pregnancy, according to women with experience of pregnancy, and planning pregnancy, with any type of diabetes, their support networks and healthcare professionals. METHODS: The PSP used established James Lind Alliance (JLA) methodology working with women and their support networks and healthcare professionals UK-wide. Unanswered questions about the time before, during or after pregnancy with any type of diabetes were identified using an online survey and broad-level literature search. A second survey identified a shortlist of questions for final prioritisation at an online consensus development workshop. RESULTS: There were 466 responses (32% healthcare professionals) to the initial survey, with 1161 questions, which were aggregated into 60 unanswered questions. There were 614 responses (20% healthcare professionals) to the second survey and 18 questions shortlisted for ranking at the workshop. The top 10 questions were: diabetes technology, the best test for diabetes during pregnancy, diet and lifestyle interventions for diabetes management during pregnancy, emotional and well-being needs of women with diabetes pre- to post-pregnancy, safe full-term birth, post-natal care and support needs of women, diagnosis and management late in pregnancy, prevention of other types of diabetes in women with gestational diabetes, women's labour and birth experiences and choices and improving planning pregnancy. CONCLUSIONS: These research priorities provide guidance for research funders and researchers to target research in diabetes and pregnancy that will achieve greatest value and impact.

Prolonged elevation of D-dimer levels in convalescent COVID-19 patients is independent of the acute phase response.

BACKGROUND: Persistent fatigue, breathlessness, and reduced exercise tolerance have been reported following acute COVID-19 infection. Although immuno-thrombosis has been implicated in acute COVID-19 pathogenesis, the biological mechanisms underpinning long COVID remain unknown. We hypothesized that pulmonary microvascular immuno-thrombosis may be important in this context. METHODS: One hundred fifty COVID-19 patients were reviewed at St James's Hospital Dublin between May and September 2020 at a median of 80.5 (range 44-155) days after initial diagnosis. These included patients hospitalized during initial illness (n = 69) and others managed entirely as out-patients (n = 81). Clinical examination, chest x-ray, and 6-min walk tests were performed. In addition, a range of coagulation and inflammatory markers were assessed. RESULTS: Increased D-dimer levels (>500 ng/ml) were observed in 25.3% patients up to 4 months post-SARS-CoV-2 infection. On univariate analysis, elevated convalescent D-dimers were more common in COVID-19 patients who had required hospital admission and in patients aged more than 50 years (p < .001). Interestingly, we observed that 29% (n = 11) of patients with elevated convalescent D-dimers had been managed exclusively as out-patients during their illness. In contrast, other coagulation (prothrombin time, activated partial thromboplastin time, fibrinogen, platelet count) and inflammation (C-reactive protein, interleukin-6, and sCD25) markers had returned to normal in >90% of convalescent patients. CONCLUSIONS: Elucidating the biological mechanisms responsible for sustained D-dimer increases may be of relevance in long COVID pathogenesis and has implications for clinical management of these patients.

Effect of social deprivation on the admission rate and outcomes of adult respiratory emergency admissions.

BACKGROUND: Patients with respiratory disorders constitute a major source of activity for Acute Medicine. We have examined the impact of Socio-Economic Status (SES) and weather factors on the outcomes (30-day in-hospital mortality) of emergency hospitalisations with a respiratory presentation. METHODS: All emergency respiratory admissions to St. James Hospital, Dublin, from 2002 to 2014 were evaluated. Patients were categorized by quintile of Deprivation Index, and evaluated against hospital admission rate (/1000 population) and 30-day in-hospital mortality. Univariate and multivariable risk estimates (Odds Ratios (OR) or Incidence Rate Ratios (IRR)) were calculated, using logistic or zero truncated Poisson regression as appropriate. RESULTS: There were 32,538 episodes in 14,093 patients, representing 39.5% of medical emergency episodes over the 13-yr period. Deprivation Quintile independently predicted the admission rate, with incidence rate ratios (IRR) of Q3 2.02 (95% CI: 1.27, 3.23), Q4 2.55 (95% CI: 1.35, 4.83) and Q5 5.68 (95% CI: 3.56, 9.06). The 30-day in-hospital mortality for the highest quintile was increased (p < 0.01), Q5 1.31 (95% CI: 1.07, 1.61). Particulate matter (PM10) was predictive for the top two quintiles (>17.2 and 23.8 µg/m3 respectively) with an OR for a worse outcome of Q4 1.22 (95% CI: 1.07, 1.40) and Q5 1.24 (95% CI: 1.08, 1.42). Weather (season) and the daily temperature did not affect the admission rate but were significantly associated with worse outcome. CONCLUSION: Socio-Economic Status influences the admission rate incidence and hospital mortality of respiratory emergency admissions; local environmental conditions (air pollution and temperature) appear only relevant to the mortality outcomes.

Blood cultures in emergency medical admissions: a key patient cohort.

OBJECTIVES: Blood cultures are performed in the emergency room when sepsis is suspected, and a cohort of patients is thereby identified. The present study investigated the outcomes (mortality and length of hospital stay) in this group following an emergency medical admission. METHODS: Prospective assessment of all emergency medical admissions presenting to the emergency department at St James's Hospital, Dublin, over an 11-year period (2002-2012) was carried out. Outcomes including 30-day in-hospital mortality and length of stay were explored in the context of an admission blood culture. Generalized estimating equations, logistic or zero-truncated Poisson multivariate models were used, with adjustment for confounding variables including illness severity, comorbidity, and chronic disabling disease, to assess the effect of an urgent blood culture on mortality and length of stay. RESULTS: A total of 60 864 episodes were recorded in 35 168 patients admitted over the time period assessed. Patients more likely to undergo blood cultures in the emergency department were male, younger, and had more comorbidity. Univariate and multivariate analyses showed that those who had a blood culture, irrespective of result, had increased mortality and a longer in-hospital stay. This was highest for those with a positive culture, irrespective of the organism isolated. CONCLUSION: A clinical decision to request a blood culture identified a subset of emergency admissions with markedly worse outcomes. This patient cohort warrants close monitoring in the emergency setting.

Serum potassium levels as an outcome determinant in acute medical admissions.

The relationship between serum potassium levels and mortality in acute medical admissions is uncertain. In particular, the relevance of minor abnormalities in potassium level or variations within the normal range remains to be determined. We performed a retrospective cohort study of all emergency medical admissions to St James's Hospital (Dublin, Ireland) between 2002 and 2012. We used a stepwise logistic regression model to predict in-hospital mortality, adjusting risk estimates for major predictor variables. There were 67,585 admissions in 37,828 patients over 11 years. After removing long-stay patients, 60,864 admissions in 35,168 patients were included in the study. Hypokalaemia was present in 14.5% and hyperkalaemia in 4.9%. In-hospital mortality was 3.9, 5.0, and 18.1% in the normokalaemic, hypokalaemic and hyperkalaemic groups respectively. Hypokalaemic patients had a univariate odds ratio (OR) of 1.29 for in-hospital mortality (95% confidence interval (CI) 1.16-1.43; p<0.001). Hyperkalaemic patients had a univariate OR for in-hospital mortality of 5.2 (95% CI 4.7-5.7; p<0.001). The ORs for an in-hospital death for potassium between 4.3 and 4.7 mmol/l, and 4.7 and 5.2 mmol/l, were 1.73 (95% CI 1.51-1.99) and 2.97 (95% CI 2.53-3.50) respectively. Hyperkalaemia and hypokalaemia are associated with increased mortality.

Factors associated with length of stay following an emergency medical admission.

BACKGROUND: Hospitals are under pressure to use resources in the most efficient manner. We have examined the factors predicting Length of Stay (LOS) in one institution, using a database of all episodes of emergency medical admissions prospectively collected over 12 years. AIM: To examine the ability to predict hospital LOS following an emergency medical hospital admission. METHODS: All emergency admissions (66,933 episodes; 36,271 patients) to St. James's Hospital, Dublin, Ireland over a 12-year period (2002-2013) were evaluated in relation to LOS. Predictor variables (identified univariately) were entered into a multiple logistic regression model to predict a longer or shorter LOS (bivariate at the median). The data was also modelled as count data (absolute LOS), using zero truncated Poisson regression methodology. Appropriate post-estimation techniques for model fit were then applied to assess the resulting model. RESULTS: The major predictors of LOS included Acute Illness Severity (biochemical laboratory score at admission), Charlson co-morbidity, Manchester Triage Category at admission, Diagnosis Related Group, sepsis status (based on blood culture result), and Chronic Disease Score Indicator. The full model to predict a LOS above or below the median had an Area Under Receiver Operating Characteristic (AUROC) of 0.71 (95% CI: 0.70, 0.71). The truncated Poisson model appeared to achieve a good model fit (R(2) statistic=0.76). CONCLUSION: Predictor variables strongly correlated with LOS; there were linear increases within categories and summation between variables. More predictor variables may improve model reliability but predicting LOS ranges or quantiles may be more realistic, based on these results.

Chronic disabling disease--impact on outcomes and costs in emergency medical admissions.

BACKGROUND: Chronic disabling disease is present in nearly 90% of emergency medical admissions. We have examined its impact on outcomes and costs in one institution, using a database of episodes collected prospectively over 12 years. METHODS: All emergency admissions (66,933 episodes; 36,271 patients) to St James' Hospital over a 12-year period (2002-13) were evaluated in relation to 30-day in-hospital mortality, length of stay (LOS) and hospital costs. Predictor variables (identified univariately) were entered into a multi-variable logistic regression model to predict 30-day in-hospital mortality. The data were also modelled as count data (absolute LOS, total cost) using zero-truncated Poisson regression. RESULTS: Acute illness severity was the best independent predictor of mortality; chronic disabling disease was an independent predictor (P < 0.001) for patients with 4+ disabling conditions. Age, adjusted for other predictors, was only independently predictive of mortality for patient 85+ years. Chronic disabling disease was an independent predictor of LOS increasing linearly with incidence rate ratios of 1.35 (95% CI: 1.29, 1.42), 1.59 (95% CI: 1.51, 1.66), 1.73 (95% CI: 1.65, 1.83) and 1.74 (95% CI: 1.65, 1.84) for those with 1, 2, 3 or 4+ disabling conditions, respectively. Age, as a predictor of LOS was strongly correlated with the presence of disabling disease. Chronic disabling disease independently predicted costs non-linearly; those with 2 or more disabling conditions had particularly high total hospital costs. CONCLUSION: Chronic disabling disease is an independent predictor of hospital LOS and costs in unselected emergency admissions; adjusted for illness severity, it is only a mortality predictor for those with multiple disabling conditions.

Weekly cisplatin concurrently with radiotherapy in head and neck squamous cell cancer: a retrospective analysis of a tertiary institute experience.

Radiotherapy combined with three weekly 100 mg/m2 of cisplatin is the accepted standard of care in head and neck squamous cell carcinoma. However, this regimen is associated with severe toxicities with devastating effects on patients. Alternative protocols like weekly 40 mg/m2 have been used in an attempt to reduce toxicities. The main objective of the present study is to identify the dose intensities and toxicities of weekly cisplatin in patients treated in a tertiary centre over a 12 month period. Included patients had squamous cell carcinoma arising in the oral cavity, oropharynx, larynx, or hypopharynx. Patients were excluded if they had nasopharyngeal squamous cell carcinoma, distant metastasis or if they had prior treatment for head and neck cancer excluding neck dissection. During the study period, 52 patients met the inclusion criteria and their data were retrospectively obtained from the patients' database of St James hospital, Dublin. The median age of the study cohort was 54 years (range 33-73). Of the patients, 40 (76.9 %) were male and 12 (20.1 %) were female. The primary tumour sites were as follows: oral cavity and oropharynx in 38 (73 %), larynx in 10 (19 %), and hypopharynx in 4 (8 %). In total, 33 (63.5 %) patients had stage IV disease, while 19 (36.5 %) had stage III disease. Treatment was definitive in 35 (67 %) patients and adjuvant in 17 (35 %). Full-dose radiotherapy was achieved in 50 (96 %) patients. Only 22 (42.3 %) patients completed the intended six cycles of chemotherapy. Cumulative dose of 200 mg/m2 or more was reached in 37 (71 %) patients. The acute adverse effects included grades 3 and 4 mucositis, which occurred in 22 (43.3 %) and 6 patients (12 %), respectively. Grade 3 and 4 neutropenia occurred in six (11.5 %) and three (5.7 %) patients, respectively. The only other haematological toxicity was grade 3 anaemia in 20 (38.4 %) patients. There was no grade 3 or 4 renal toxicity among the study cohort, although grade 2 was observed in six (11.5 %) patients. Death occurred in one patient due to neutropenic septicaemia. In conclusion, weekly cisplatin is associated with moderate to severe toxicities and might lead to suboptimal chemotherapy delivery. More prospective clinical studies are required to determine the optimal chemoradiation regimen in head and neck squamous cell carcinoma.

Management of gastrointestinal stromal tumours: a single-centre experience.

BACKGROUND: Gastrointestinal stromal tumours (GISTs), although rare, are increasingly recognized, characterized immuno-phenotypically in most cases by a mutation in C-Kit. The advent of imatinib, a tyrosine kinase inhibitor, has presented a novel and effective therapy in advanced disease. The aim of this study was to present the experience and outcomes of a single centre. METHODS: Review of prospective GIST database at St James Hospital from 1997 to 2005. Survival data were analysed using Kaplan-Meier methods. RESULTS: A total of 32 patients (19 males/13 females) with a median age of 61 years (10-84) were treated. The stomach (n = 20) was the dominant site. Surgery was the first line of treatment for all these tumours, and in seven cases this was performed laparoscopically. C-Kit was positive in 81% of cases. The median survival was 78 months with a 5-year survival of 71%. CONCLUSION: GISTs are rare and surgical resection, increasingly with minimally invasive approaches, is associated with high cure rates, particularly in gastric tumours.

Clinicopathologic factors predicting complete pathological response to neoadjuvant chemoradiotherapy in esophageal cancer.

Multimodal therapy comprising neoadjuvant chemotherapy and radiation therapy prior to radical resection is increasingly utilized in gastroesophageal cancer. The achievement of a complete pathological response (pCR) or a major response is associated with an improved survival. However, up to 70% of patients show an incomplete or no response to the neoadjuvant regimen, and the identification of factors which predict a response would be of considerable clinical benefit. A retrospective analysis of a prospectively updated esophageal cancer database was performed. The predictive values of the following clinicopathological factors were investigated: age, sex, tobacco, alcohol, weight, clinical history, tumor type, site, length, width, morphology and differentiation. Statistical analysis was performed using Chi-square test with Pearson's test or Kruskal-Wallis test. One hundred and seventy-six patients were identified who had undergone neo-adjuvant chemoradiotherapy at St James's Hospital Dublin, between January 1990 and June 2003. A complete pathological response was seen in 40 cases (23%). There was a significant (P < 0.05) relationship between response to chemoradiotherapy and pretreatment tumor length. The median tumor length in the pCR group was 2 cm (1-5 cm) compared with 3 cm (2-7 cm) in non-responders (P < 0.05). Body weight, sex, tobacco or alcohol usage, tumor site, or differentiation were not predictive of response, although a trend (P = 0.08) was observed for squamous cell cancer compared with adenocarcinoma. Smaller tumor length was predictive of a greater response to chemotherapy and radiation therapy. This may reflect different tumor biology, perhaps with acquired resistance to treatment-induced apoptosis in the larger tumors. A simpler explanation is that the existing dose and treatment schedule for combination chemoradiotherapy is suboptimal in patients with larger tumors.