Natural history of non-functioning pituitary microadenomas: results from the UK non-functioning pituitary adenoma consortium.

OBJECTIVE: The optimal approach to the surveillance of non-functioning pituitary microadenomas (micro-NFPAs) is not clearly established. Our aim was to generate evidence on the natural history of micro-NFPAs to support patient care. DESIGN: Multi-centre, retrospective, cohort study involving 23 endocrine departments (UK NFPA consortium). METHODS: Clinical, imaging, and hormonal data of micro-NFPA cases between January, 1, 2008 and December, 21, 2021 were analysed. RESULTS: Data for 459 patients were retrieved [median age at detection 44 years (IQR 31-57)-152 males/307 females]. Four hundred and nineteen patients had more than two magnetic resonance imagings (MRIs) [median imaging monitoring 3.5 years (IQR 1.71-6.1)]. One case developed apoplexy. Cumulative probability of micro-NFPA growth was 7.8% (95% CI, 4.9%-8.1%) and 14.5% (95% CI, 10.2%-18.8%) at 3 and 5 years, respectively, and of reduction 14.1% (95% CI, 10.4%-17.8%) and 21.3% (95% CI, 16.4%-26.2%) at 3 and 5 years, respectively. Median tumour enlargement was 2 mm (IQR 1-3) and 49% of micro-NFPAs that grew became macroadenomas (nearly all >5 mm at detection). Eight (1.9%) patients received surgery (only one had visual compromise with surgery required >3 years after micro-NFPA detection). Sex, age, and size at baseline were not predictors of enlargement/reduction. At the time of detection, 7.2%, 1.7%, and 1.5% patients had secondary hypogonadism, hypothyroidism, and hypoadrenalism, respectively. Two (0.6%) developed hypopituitarism during follow-up (after progression to macroadenoma). CONCLUSIONS: Probability of micro-NFPA growth is low, and the development of new hypopituitarism is rare. Delaying the first follow-up MRI to 3 years and avoiding hormonal re-evaluation in the absence of tumour growth or clinical manifestations is a safe approach for micro-NFPA surveillance.

United Kingdom Early Detection Initiative (UK-EDI): protocol for establishing a national multicentre cohort of individuals with new-onset diabetes for early detection of pancreatic cancer.

INTRODUCTION: Pancreatic cancer is a leading cause of cancer deaths worldwide. Screening for this disease has potential to improve survival. It is not feasible, with current screening modalities, to screen the asymptomatic adult population. However, screening of individuals in high-risk groups is recommended. Our study aims to provide resources and data that will inform strategies to screen individuals with new-onset diabetes (NOD) for pancreatic cancer. METHODS AND ANALYSIS: The United Kingdom Early Detection Initiative (UK-EDI) for pancreatic cancer is a national, prospective, observational cohort study that aims to recruit 2500 individuals with NOD (<6 months postdiagnosis) aged 50 years and over, with follow-up every 6 months, over a 3-year period. For study eligibility, diagnosis of diabetes is considered to be clinical measurement of haemoglobin A1c ≥48 mmol/mol. Detailed clinical information and biospecimens will be collected at baseline and follow-up to support the development of molecular, epidemiological and demographic biomarkers for earlier detection of pancreatic cancer in the high-risk NOD group. Socioeconomic impacts and cost-effectiveness of earlier detection of pancreatic cancer in individuals with NOD will be evaluated. The UK-EDI NOD cohort will provide a bioresource for future early detection research to be conducted. ETHICS AND DISSEMINATION: The UK-EDI study has been reviewed and approved by the London-West London and GTAC Research Ethics Committee (Ref 20/LO/0058). Study results will be disseminated through presentations at national and international symposia and publication in peer-reviewed, Open Access journals.

Blood levels of adiponectin and IL-1Ra distinguish type 3c from type 2 diabetes: Implications for earlier pancreatic cancer detection in new-onset diabetes.

BACKGROUND: Screening for pancreatic ductal adenocarcinoma (PDAC) in populations at high risk is recommended. Individuals with new-onset type 2 diabetes mellitus (NOD) are the largest high-risk group for PDAC. To facilitate screening, we sought biomarkers capable of stratifying NOD subjects into those with type 2 diabetes mellitus (T2DM) and those with the less prevalent PDAC-related diabetes (PDAC-DM), a form of type 3c DM commonly misdiagnosed as T2DM. METHODS: Using mass spectrometry- and immunoassay-based methodologies in a multi-stage analysis of independent sample sets (n=443 samples), blood levels of 264 proteins were considered using Ingenuity Pathway Analysis, literature review and targeted training and validation. FINDINGS: Of 30 candidate biomarkers evaluated in up to four independent patient sets, 12 showed statistically significant differences in levels between PDAC-DM and T2DM. The combination of adiponectin and interleukin-1 receptor antagonist (IL-1Ra) showed strong diagnostic potential, (AUC of 0.91; 95% CI: 0.84-0.99) for the distinction of T3cDM from T2DM. INTERPRETATION: Adiponectin and IL-1Ra warrant further consideration for use in screening for PDAC in individuals newly-diagnosed with T2DM. FUNDING: North West Cancer Research, UK, Cancer Research UK, Pancreatic Cancer Action, UK.

Outcomes of Patients with Nelson's Syndrome after Primary Treatment: A Multicenter Study from 13 UK Pituitary Centers.

CONTEXT: Long-term outcomes of patients with Nelson's syndrome (NS) have been poorly explored, especially in the modern era. OBJECTIVE: To elucidate tumor control rates, effectiveness of various treatments, and markers of prognostic relevance in patients with NS. PATIENTS, DESIGN, AND SETTING: Retrospective cohort study of 68 patients from 13 UK pituitary centers with median imaging follow-up of 13 years (range 1-45) since NS diagnosis. RESULTS: Management of Cushing's disease (CD) prior to NS diagnosis included surgery+adrenalectomy (n = 30; eight patients had 2 and one had 3 pituitary operations), surgery+radiotherapy+adrenalectomy (n = 17; two received >1 courses of irradiation, two had ≥2 pituitary surgeries), radiotherapy+adrenalectomy (n = 2), and adrenalectomy (n = 19). Primary management of NS mainly included surgery, radiotherapy, surgery+radiotherapy, and observation; 10-year tumor progression-free survival was 62% (surgery 80%, radiotherapy 52%, surgery+radiotherapy 81%, observation 51%). Sex, age at CD or NS diagnosis, size of adenoma (micro-/macroadenoma) at CD diagnosis, presence of pituitary tumor on imaging prior adrenalectomy, and mode of NS primary management were not predictors of tumor progression. Mode of management of CD before NS diagnosis was a significant factor predicting progression, with the group treated by surgery+radiotherapy+adrenalectomy for their CD showing the highest risk (hazard ratio 4.6; 95% confidence interval, 1.6-13.5). During follow-up, 3% of patients had malignant transformation with spinal metastases and 4% died of aggressively enlarging tumor. CONCLUSIONS: At 10 years follow-up, 38% of the patients diagnosed with NS showed progression of their corticotroph tumor. Complexity of treatments for the CD prior to NS diagnosis, possibly reflecting corticotroph adenoma aggressiveness, predicts long-term tumor prognosis.

A Multidisciplinary Evaluation of a Virtually Supervised Home-Based High-Intensity Interval Training Intervention in People With Type 1 Diabetes.

OBJECTIVE: Adopt a multidisciplinary approach to evaluate a virtually supervised home-based high-intensity interval training (Home-HIT) intervention in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: Eleven individuals with type 1 diabetes (seven women; age 30 ± 3 years; [Formula: see text] 2.5 ± 0.2 L/min; duration of diabetes 10 ± 2 years) completed 6 weeks of Home-HIT. A heart rate monitor and mobile phone application were used to provide feedback to the participants and research team on exercise intensity (compliance) and adherence. RESULTS: Training adherence was 95 ± 2%, and compliance was 99 ± 1%. Home-HIT increased [Formula: see text] by 7% (P = 0.017) and decreased insulin dose by 13% (P = 0.012). Blood glucose concentration did not change from baseline to immediately or 1 h post Home-HIT. Qualitative perceptions of Home-HIT and the virtual-monitoring system were positive, supporting that the intervention successfully removed exercise barriers in people with type 1 diabetes. CONCLUSIONS: Virtually monitored Home-HIT resulted in high adherence alongside increased [Formula: see text] and decreased insulin dose.

High-Intensity Interval Training Improves Aerobic Capacity Without a Detrimental Decline in Blood Glucose in People With Type 1 Diabetes.

Context: We investigated whether 6 weeks of high-intensity interval training (HIT) induced improvements in cardiometabolic health markers similar to moderate-intensity continuous training (MICT) in people with type 1 diabetes (T1D), and whether HIT abolished acute reductions in plasma glucose levels observed after MICT sessions. Methods: Two groups of sedentary individuals with T1D (n = 7 per group) completed 6 weeks of thrice weekly HIT or MICT. Pre- and post-training measurements were made of 24-hour interstitial glucose profiles, using continuous glucose monitors, and cardiometabolic health markers [peak oxygen consumption (V˙o2peak), blood lipid profile, and aortic pulse wave velocity (aPWV)]. Capillary blood glucose (BG) concentrations were assessed before and after exercise to investigate changes in BG levels during exercise in the fed state. Results: Six weeks of HIT or MICT increased V˙o2peak by 14% and 15%, respectively (P < 0.001), and aPWV by 12% (P < 0.001), with no difference between groups. There was no difference in incidence or percentage of time spent in hypoglycemia after training in either group (P > 0.05). In the fed state, the mean change (±SEM) in capillary BG concentration during the HIT sessions was -0.2 ± 0.5 mmol/L, and -5.5 ± 0.4 mmol/L during MICT. Conclusions: Six weeks of HIT improved V˙o2peak and aPWV to a similar extent as MICT. That BG levels remained stable during HIT in the fed state but consistently fell during MICT suggests HIT may be the preferred training mode for some people with T1D.

Fasted High-Intensity Interval and Moderate-Intensity Exercise Do Not Lead to Detrimental 24-Hour Blood Glucose Profiles.

Aims: To compare the effect of a bout of high-intensity interval training (HIT) with a bout of moderate-intensity continuous training (MICT) on glucose concentrations over the subsequent 24-hour period. Methods: Fourteen people with type 1 diabetes [T1D (duration of T1D, 8.2 ± 1.4 years)], all on a basal-bolus regimen, completed a randomized, counterbalanced, crossover study. Continuous glucose monitoring was used to assess glycemic control after a single bout of HIT (six 1-minute intervals) and 30 minutes of MICT on separate days compared with a nonexercise control day (CON). Exercise was undertaken after an overnight fast with omission of short-acting insulin. Capillary blood glucose samples were recorded before and after exercise to assess the acute changes in glycemia during HIT and MICT. Results: There was no difference in the incidence of or percentage of time spent in hypoglycemia, hyperglycemia, or target glucose range over the 24-hour and nocturnal period (12:00 am to 6:00 am) between CON, HIT, and MICT (P > 0.05). Blood glucose concentrations were not significantly (P = 0.49) different from pre-exercise to post-exercise, with HIT (0.39 ± 0.42 mmol/L) or MICT (-0.39 ± 0.66 mmol/L). There was no difference between exercise modes (P = 1.00). Conclusions: HIT or 30 minutes of MICT can be carried out after an overnight fast with no increased risk of hypoglycemia or hyperglycemia. If the pre-exercise glucose concentration is 7 to 14 mmol/L, no additional carbohydrate ingestion is necessary to undertake these exercises. Because HIT is a time-efficient form of exercise, the efficacy and safety of long-term HIT should now be explored.

A cost-benefit analysis of twice-daily consultant ward rounds and clinical input on investigation and pharmacy costs in a major teaching hospital in the UK.

OBJECTIVES: Misuse of investigations, medications and hospital beds is costing the National Health Service (NHS) billions of pounds with little evidence that approaches centred on reducing overuse are sustainable. Our previous study demonstrated that twice-daily consultant ward rounds reduce inpatient length of stay and suggested a reduction in overuse of investigations and medications. This study aims to assess the impact of daily consultant ward rounds on the use of investigations and medications and estimate the potential cost benefit. SETTINGS: The study was performed on two medical wards in a major city university teaching hospital in Liverpool, UK, receiving acute admissions from medical assessment and emergency departments. PARTICIPANTS AND INTERVENTION: The total number of patients admitted, investigations performed and pharmacy costs incurred were collected for 2 years before and following a change in the working practice of consultants from twice-weekly to twice-daily consultant ward rounds on the two medical wards. OUTCOME MEASURES: We performed a cost-benefit analysis to assess the net amount of money saved by reducing inappropriate investigations and pharmacy drug use following the intervention. RESULTS: Despite a 70% increase in patient throughput (p<0.01) the investigations and pharmacy, costs per patient reduced by 50% over a 12-month period (p<0.01) and were sustained for the next 12 months. The reduction in investigations and medication use did not have any effect on the readmission or mortality rate (p=NS), whereas, the length of stay was almost halved (p<0.01). Daily senior clinician input resulted in a net cost saving of £336,528 per year following the intervention. CONCLUSIONS: Daily consultant input has a significant impact on reducing the inappropriate use of investigations and pharmacy costs saving the NHS more than £650K on the two wards over a 2-year period.

The impact of twice-daily consultant ward rounds on the length of stay in two general medical wards.

Excess average length of stay (ALoS) not only results in an increased cost to hospitals but also increases the risk of hospital-acquired infection and thromboembolism. Various factors suggested to affect ALoS have yet to demonstrate a significant impact in clinical practice. Increased consultant input has been identified as an important factor influencing ALoS. As a result, a radical and innovative consultant job plan, replacing twice-weekly with twice-daily ward rounds (WRs) on a university teaching hospital's two medical words has been designed. The number of discharges (NoDs) significantly increased (p < 0.01), ALoS reduced (p < 0.01), whereas, readmission rate and mortality remained unchanged (p = NS) over 12 months following twice-daily WRs compared to two other wards with twice-weekly WRs. This innovative model resulted in almost doubling the NoDs and halving the ALoS. This study suggests that ALoS can be reduced and sustained with a cultural and behavioural shift in consultant working patterns, without affecting readmission rate or inpatient mortality.