COVID-19 Vaccine Acceptance, Hesitancy, and Uptake in People with Diabetes in Australia.

Background: This study explored vaccination hesitancy, diabetes-specific COVID-19 vaccination concerns, and whether they predicted vaccination uptake in people with diabetes. Methods: Quantitative, cross-sectional, and predictive approaches were used. An online survey was conducted with people with diabetes attending four Australian health services, using convenience sampling (n = 842). The survey data collected included clinico-demographic characteristics, COVID-19 vaccine hesitancy, and attitudes around COVID-19 vaccine confidence and complacency. Clinico-demographic characteristics that predicted vaccination status, vaccine hesitancy, and vaccine-related attitudes were identified using regression analyses. Results: Most participants received at least one COVID-19 vaccine dose. Younger age and type 1 diabetes were associated with lower vaccination status, and they were partially mediated through higher vaccine hesitancy. Younger age and English as a dominant language were associated with higher negative attitudes towards speed of vaccine development. Conclusions: Despite an overall high vaccination rate, general and diabetes-specific COVID-19 vaccine concerns are a barrier to uptake for some people with diabetes, particularly in those who are younger or have type 1 diabetes. A detailed understanding of concerns for particular subgroups can help tailor information to increase vaccine acceptance, particularly in the context of requiring booster doses.

Improving early detection of colorectal cancer in Aotearoa New Zealand; how do the direct access criteria perform?

AIM: Colorectal cancer (CRC) is a common malignancy in New Zealand, and there is increasing pressure on investigative resources for diagnosis. The national direct access referral guidelines from the Ministry of Health (MoH) guide who should be referred for investigation, but their performance in detecting CRC and other significant diseases has not been reported previously. This paper describes the yield, by direct access criterion, of all referrals through the direct access pathway to the Canterbury District Health Board (CDHB) during 2018. METHODS: First referrals received through the direct access colonoscopy/computed tomography colonography (CTC) pathway for 2018 were audited. Patients were assigned to symptom groups corresponding to the MoH direct access criteria, and demographic data were captured. Diagnostic outcomes were collected through analysis of all endoscopy, CT colonography and histology reports in the 18 months following referral for primary analysis, with further follow-up through to May 2021 to detect missed pathology. RESULTS: Three thousand two hundred referrals were analysed, and 88.5% underwent colorectal investigation. 128 CRC were diagnosed, 176 advanced polyps, 49 cases of inflammatory bowel disease (IBD) and there were 56 other significant findings. The yield by category for the direct access criteria varied between 0-15.0%, and one urgent criterion had a CRC yield lower than two semi-urgent categories. For patients whose symptoms met at least one of the criteria, excluding those referred with suspected IBD, the combined CRC yield was 4.9%, compared with 1.8% in those who did not meet criteria. The sensitivity and specificity of the criteria for CRC (excluding IBD) was 90% and 23% respectively. There were no CRC detected during the extended follow-up period. CONCLUSION: In this referred population, the MoH direct access colonoscopy/CTC criteria varied significantly in their CRC yield, with an arbitrary distinction between urgent and semi-urgent categories. The low specificity of the criteria means the number needed to investigate to detect one CRC was one in 22. Improved diagnostic algorithms are urgently required to improve both the sensitivity and specificity, thereby more appropriately allocating finite resources to those patients who are most in need of investigation.

Development, validation and clinical utility of a risk prediction model for adverse pregnancy outcomes in women with gestational diabetes: The PeRSonal GDM model.

Background: The ability to calculate the absolute risk of adverse pregnancy outcomes for an individual woman with gestational diabetes mellitus (GDM) would allow preventative and therapeutic interventions to be delivered to women at high-risk, sparing women at low-risk from unnecessary care. We aimed to develop, validate and evaluate the clinical utility of a prediction model for adverse pregnancy outcomes in women with GDM. Methods: A prediction model development and validation study was conducted on data from a observational cohort. Participants included all women with GDM from three metropolitan tertiary teaching hospitals in Melbourne, Australia. The development cohort comprised those who delivered between 1 July 2017 to 30 June 2018 and the validation cohort those who delivered between 1 July 2018 to 31 December 2018. The main outcome was a composite of critically important maternal and perinatal complications (hypertensive disorders of pregnancy, large-for-gestational age neonate, neonatal hypoglycaemia requiring intravenous therapy, shoulder dystocia, perinatal death, neonatal bone fracture and nerve palsy). Model performance was measured in terms of discrimination and calibration and clinical utility evaluated using decision curve analysis. Findings: The final PeRSonal (Prediction for Risk Stratified care for women with GDM) model included body mass index, maternal age, fasting and 1-hour glucose values (75-g oral glucose tolerance test), gestational age at GDM diagnosis, Southern and Central Asian ethnicity, East Asian ethnicity, nulliparity, past delivery of an large-for-gestational age neonate, past pre-eclampsia, GWG until GDM diagnosis, and family history of diabetes. The composite adverse pregnancy outcome occurred in 27% (476/1747) of women in the development (1747 women) and in 26% (244/955) in the validation (955 women) cohorts. The model showed excellent calibration with slope of 0.99 (95% CI 0.75 to 1.23) and acceptable discrimination (c-statistic 0.68; 95% CI 0.64 to 0.72) when temporally validated. Decision curve analysis demonstrated that the model was useful across a range of predicted probability thresholds between 0.15 and 0.85 for adverse pregnancy outcomes compared to the alternatives of managing all women with GDM as if they will or will not have an adverse pregnancy outcome. Interpretation: The PeRSonal GDM model comprising of routinely available clinical data shows compelling performance, is transportable across time, and has clinical utility across a range of predicted probabilities. Further external validation of the model to a more disparate population is now needed to assess the generalisability to different centres, community based care and low resource settings, other healthcare systems and to different GDM diagnostic criteria. Funding: This work is supported by the Mothers and Gestational Diabetes in Australia 2 NHMRC funded project #1170847.

TNF-α inhibitor tanfanercept (HBM9036) improves signs and symptoms of dry eye in a phase 2 trial in the controlled adverse environment in China.

PURPOSE: This study evaluated the clinical safety and efficacy of tanfanercept (HBM9036) ophthalmic solution as a novel treatment for dry eye disease (DED) in a controlled adverse environment (CAE) study conducted in China. METHODS: In a single-center, double-masked, randomized, placebo-controlled study, 100 patients received 0.25% tanfanercept, or placebo, twice daily for eight weeks. A mobile international CAE® DE Model was used for patient selection with a standardized challenge endpoint. Primary efficacy endpoint was fluorescein inferior corneal staining score (ICSS) pre- to post-CAE challenge from baseline. Secondary endpoints included Schirmer's Tear Test, Tear-Film Break-Up Time, Ocular Discomfort Score, Ora Calibra® Ocular Discomfort and 4-Symptom Questionnaire, total corneal staining score (TCSS), and drop comfort. Signs and symptoms were assessed both pre- and post-CAE to evaluate the efficacy of tanfanercept on both environmental and CAE endpoints. RESULTS: The tanfanercept treatment group showed improvement in ICSS pre- to post-CAE change from baseline scores when compared to placebo (- 0.61 ± 0.11 and - 0.54 ± 0.11, respectively; mean difference = 0.07, p = 0.65). TCSS pre-post-CAE change from baseline scores was also in favor of active when compared to placebo (- 1.03 ± 0.21 and - 0.67 ± 0.21, respectively; mean difference = 0.37, p = 0.23). Schirmer's score improvement was demonstrated in favor of active (1.87 ± 0.62 mm) as compared to placebo (1.28 ± 0.62 mm; mean difference = 0.59 mm, p = 0.50). Change from baseline in mean Tear-Film Break-up Time favored active treatment over placebo (mean difference = 1.21 s, p = 0.45). Notably, the tanfanercept showed more obvious benefits for each DED sign in a subgroup of subjects ≥ 35 years of age. Tanfanercept was well tolerated with no serious adverse events occurring during the study. CONCLUSION: Tanfanercept demonstrated improvements in favor of active as compared to placebo in the signs of DED, being safe and well tolerated. These data support further evaluation of tanfanercept for the treatment of DED in China. TRIAL REGISTRATION: This study was retrospectively registered at ClinicalTrials.gov (NCT04092907) on September 17, 2019.

The Challenges of Implementing Artificial Intelligence into Surgical Practice.

BACKGROUND: Artificial intelligence is touted as the future of medicine. Classical algorithms for the detection of common bile duct stones (CBD) have had poor clinical uptake due to low accuracy. This study explores the challenges of developing and implementing a machine-learning model for the prediction of CBD stones in patients presenting with acute biliary disease (ABD). METHODS: All patients presenting acutely to Christchurch Hospital over a two-year period with ABD were retrospectively identified. Clinical data points including lab test results, demographics and ethnicity were recorded. Several statistical techniques were utilised to develop a machine-learning model. Issues with data collection, quality, interpretation and barriers to implementation were identified and highlighted. RESULTS: Issues with patient identification, coding accuracy, and implementation were encountered. In total, 1315 patients met inclusion criteria. Incorrect international classification of disease 10 (ICD-10) coding was noted in 36% (137/382) of patients recorded as having CBD stones. Patients with CBD stones were significantly older and had higher aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin and gamma-glutamyl transferase (GGT) levels (p < 0.001). The no information rate was 81% (1070/1315 patients). The optimum model developed was the gradient boosted model with a PPV of 67%, NPV of 87%, sensitivity of 37% and a specificity of 96% for common bile duct stones. CONCLUSION: This paper highlights the utility of machine learning in predicting CBD stones. Accuracy is limited by current data and issues do exist around both the ethics and practicality of implementation. Regardless, machine learning represents a promising new paradigm for surgical practice.

Factors affecting the implementation of clinical pharmacy services in China.

New policies in China have recently led to the implementation of clinical pharmacy services in hospitals. We explored the views of hospital administrators, pharmacy directors, clinical pharmacists, and dispensing pharmacists about the factors affecting clinical pharmacy services in China, using the framework approach and organizational theory. We conducted 30 interviews with 130 participants at 29 hospitals (both secondary and tertiary) in Beijing, Zhengzhou, Luoyang, and Shanghai. We found that the barriers to and facilitators of implementation of clinical pharmacy services slotted into the environment and participant dimensions of Scott's adapted version of Leavitt's organizational model. External support from government was perceived as crucial to promoting pharmacy services. It is proposed that the internationally recognized Basel Statements of the International Pharmaceutical Federation also provide a strong foundation for guiding China in implementing clinical pharmacy services.

Factors influencing pharmacy services in opioid substitution treatment.

INTRODUCTION AND AIM: Heroin dependence is a serious health burden in Australia. Opioid substitution treatment (OST) has been delivered in Australian community pharmacies since 1985. The effectiveness of pharmacy-based OST is evident and the demand is increasing; however, the participation rate of community pharmacies is low, with over 60% non-providers. While previous Australian studies have focused on perspectives of community pharmacists providing the service, the views of non-providers have not yet been explored. This study aimed to further investigate factors influencing pharmacists' participation in provision of OST in the community pharmacy setting in New South Wales, Australia. DESIGN AND METHODS: Semi-structured interviews were conducted with 35 NSW community pharmacists (20 providers, 15 non-providers). Transcripts of interviews were thematically analysed. RESULTS: Factors influencing non-providers were mainly stigma and fear, the nature of an opt-in scheme, professionals' moral responsibilities, lack of awareness and knowledge, disproportionate distribution of clients and lack of financial support for OST clients. Providers were motivated by positive attitudes, functional relationships with OST clients/stakeholders, professional satisfaction and financial rewards. Recommendations to improve participation in OST services were offered by both groups. DISCUSSION AND CONCLUSION: This study explored views from both OST providers and non-providers, revealing a number of previously undocumented barriers that affect the uptake of OST provision in New South Wales community pharmacies. There were also profound ethical issues raised for consideration. These findings may help inform future policies aimed at encouraging pharmacists' provision of OST, to address the unmet needs of the ever-increasing number of heroin-dependent clients in the community.