Open-Source Automated Insulin Delivery in Type 1 Diabetes.

BACKGROUND: Open-source automated insulin delivery (AID) systems are used by many patients with type 1 diabetes. Data are needed on the efficacy and safety of an open-source AID system. METHODS: In this multicenter, open-label, randomized, controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio to use an open-source AID system or a sensor-augmented insulin pump (control). The patients included both children (defined as 7 to 15 years of age) and adults (defined as 16 to 70 years of age). The AID system was a modified version of AndroidAPS 2.8 (with a standard OpenAPS 0.7.0 algorithm) paired with a preproduction DANA-i insulin pump and Dexcom G6 CGM, which has an Android smartphone application as the user interface. The primary outcome was the percentage of time in the target glucose range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) between days 155 and 168 (the final 2 weeks of the trial). RESULTS: A total of 97 patients (48 children and 49 adults) underwent randomization (44 to open-source AID and 53 to the control group). At 24 weeks, the mean (±SD) time in the target range increased from 61.2±12.3% to 71.2±12.1% in the AID group and decreased from 57.7±14.3% to 54.5±16.0% in the control group (adjusted difference, 14 percentage points; 95% confidence interval, 9.2 to 18.8; P<0.001), with no treatment effect according to age (P = 0.56). Patients in the AID group spent 3 hours 21 minutes more in the target range per day than those in the control group. No severe hypoglycemia or diabetic ketoacidosis occurred in either group. Two patients in the AID group withdrew from the trial owing to connectivity issues. CONCLUSIONS: In children and adults with type 1 diabetes, the use of an open-source AID system resulted in a significantly higher percentage of time in the target glucose range than the use of a sensor-augmented insulin pump at 24 weeks. (Supported by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12620000034932.).

Real time continuous glucose monitoring in high-risk people with insulin-requiring type 2 diabetes: A randomised controlled trial.

AIMS: To investigate the impact of real-time continuous glucose monitoring (rtCGM) on glycaemia in a predominantly indigenous (Maori) population of adults with insulin-requiring type 2 diabetes (T2D) in New Zealand. METHODS: Twelve-week, multicentre randomised controlled trial (RCT) of adults with T2D using ≥0.2 units/kg/day of insulin and elevated glycated haemoglobin (HbA1c) ≥64 mmol/mol (8.0%). Following a 2-week blinded CGM run-in phase, participants were randomised to rtCGM or control (self-monitoring blood glucose [SMBG]). The primary outcome was time in the target glucose range (3.9-10 mmol/L; TIR) during weeks 10-12, with data collected by blinded rtCGM in the control group. RESULTS: Sixty-seven participants entered the RCT phase (54% Maori, 57% female), median age 53 (range 16-70 years), HbA1c 85 (IQR 74, 94) mmol/mol (9.9 [IQR 8.9, 10.8]%), body mass index (36.7 ± 7.7 kg/m2). Mean (±SD) TIR increased from 37 (24)% to 53 (24)% [Δ 13%; 95% CI 4.2 to 22; P = 0.007] in the rtCGM group but did not change in the SMBG group [45 (21)% to 45 (25)%, Δ 2.5%, 95% CI -6.1 to 11, P = 0.84]. Baseline-adjusted between-group difference in TIR was 10.4% [95% CI -0.9 to 21.7; P = 0.070]. Mean HbA1c (±SD) decreased in both groups from 85 (18) mmol/mol (10.0 [1.7]%) to 64 (16) mmol/mol (8.0 [1.4]%) in the rtCGM arm and from 81 (12) mmol/mol (9.6 [1.1]%) to 65 (13) mmol/mol (8.1 [1.2]%) in the SMBG arm (P < 0.001 for both). There were no severe hypoglycaemic or ketoacidosis events in either group. CONCLUSIONS: Real-time CGM use in a supportive treat-to-target model of care likely improves glycaemia in a population with insulin-treated T2D and elevated HbA1c.

Fear avoidance and return to work after mild traumatic brain injury.

OBJECTIVES: Fear avoidance is associated with symptom persistence after mild traumatic brain injury (mTBI). In this study, we investigated whether fear avoidance was associated with other outcomes such as return to work-related activity (RTW). MATERIALS AND METHODS: We analyzed associations between fear avoidance and RTW 6-9 months after mTBI, in two merged prospective mTBI cohorts. Adult participants aged 16 or over (n=175), presenting to outpatient services in New Zealand within 3 months of their injury, who were engaged in work-related activity at the time of injury, were included. Participants completed the Fear Avoidance Behavior after Traumatic Brain Injury (FAB-TBI) questionnaire at enrollment and 6 months later. Associations between FAB-TBI scores and RTW outcome were analyzed using multivariate approaches. RESULTS: Overall, 53% of participants had RTW by 6-9 months after mTBI. While early fear avoidance was weakly associated with RTW, persistent high fear avoidance between study assessments or increasing avoidance with time were associated with greater odds of still being off work 6-9 months after injury. CONCLUSIONS: Pervasive and increasing avoidance of symptom triggers after mTBI were associated with lower rates of RTW 6-9 months after mTBI. Further research is needed to better understand transition points along the recovery trajectory where fear avoidance behaviors fade or increase after mTBI.

Predicting regression of cervical intraepithelial neoplasia grade 2 in women under 25 years.

BACKGROUND: A number of retrospective and prospective studies have documented substantial rates of regression in cervical intraepithelial neoplasia grade 2 lesions in young women. Initial observational management of cervical intraepithelial neoplasia grade 2 is increasingly accepted as appropriate for women under 25 years of age with screen-detected abnormalities and is included in a number of clinical guidelines. However, there has been a paucity of large prospective studies on observational management with strict inclusion criteria. A number of important questions remain, specifically regarding the clinical variables that are associated with the risk of progression or persistence of disease. To investigate these factors and to ensure that young women with cervical intraepithelial neoplasia grade 2 undergoing observational management were being managed in a well-monitored and an appropriately informed fashion, we conducted a large, multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 in women under 25 years. OBJECTIVE: This study aimed to determine the regression rates and clinical, cytologic, and pathologic predictors of regression of cervical intraepithelial neoplasia grade 2 in women under 25 years undergoing observational management over 24 months. STUDY DESIGN: This study was a multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 (ie, repeat colposcopy, cytology, and cervical biopsy every 6 months) for up to 24 months. A total of 615 consenting women under 25 years with newly-diagnosed, biopsy-proven cervical intraepithelial neoplasia grade 2 were recruited (from 2010 to 2016) through 16 hospital-based colposcopy units in New Zealand and Australia. RESULTS: At completion, 326 women had confirmed regression, 156 had persistent high-grade cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ, and 24 had unconfirmed regression (ie, first regression at the 24-month follow-up). A total of 109 women did not complete the protocol (41 because of delayed follow-up, 41 lost to follow-up, 22 elected treatment, 4 refused a biopsy, and 1 died of an unrelated cause). Confirmed regression was observed in 53% (326 of 615) of all women enrolled in the study and, when missing data were imputed, it was estimated that 64% of women (95% confidence interval, 60%-68%) would have experienced regression. Similarly, lesions regressed in 64% (326 of 506) of women who completed the observational protocol. Based on a multivariable analysis, detection of human papillomavirus 16 in a liquid-based cytology sample at the time of initial colposcopy decreased the chance of regression by 31% (risk ratio, 0.69; 95% confidence interval, 0.56-0.86; P<.001). In addition, at initial colposcopy, low-grade or normal colposcopic impression, later year of diagnosis, low-grade or normal cytology, and being a nonsmoker were all independently associated with an increased chance of regression. CONCLUSION: More than half of women under 25 years with cervical intraepithelial neoplasia grade 2 will regress to cervical intraepithelial neoplasia grade 1 or normal within 24 months without destructive treatment. The absence of human papillomavirus 16 is the most important predictor of regression.

Evaluation of guidelines for observational management of cervical intraepithelial neoplasia 2 in young women.

BACKGROUND: A high rate of regression in young women with cervical intraepithelial neoplasia grade 2 has been recorded. However, there are few prospective data by which to evaluate management guidelines. OBJECTIVE: This study evaluates the American Society for Colposcopy and Cervical Pathology recommendations for follow-up of young women with cervical intraepithelial neoplasia 2 using data created by a large prospective multicenter study of observational management. MATERIALS AND METHODS: Participants were 616 women under 25 years with biopsy-diagnosed cervical intraepithelial neoplasia 2 following a referral to colposcopy for an abnormal smear with no previous high-grade abnormality. The protocol included colposcopy, cytology, and colposcopically directed biopsy at the initial visit and at 6- and 12-month follow-ups visits, and these data were analyzed. Histology from the corresponding cervical biopsy was treated as the reference diagnostic test. For young women with cervical intraepithelial neoplasia 2, we aimed to determine the following: (1) the ability of colposcopy to identify women with cervical intraepithelial neoplasia 3 or worse at 6 months; and (2) the ability of colposcopy, cytology, and a combination of cytology and colposcopy to identify residual high-grade abnormalities at 12 months. In addition, although not specified in the guidelines, we investigated the ability of high-risk human papillomavirus positivity alone or with cytology as a co-test to identify residual high-grade abnormalities at 12 months. RESULTS: At 6 months, cervical intraepithelial neoplasia 3+ colposcopic appearance identified only 28% (95% confidence interval, 18-40%) of women diagnosed with cervical intraepithelial neoplasia 3. At 12 months, a high-grade colposcopic appearance identified only 58% (95% confidence interval, 48-68%) of women with residual histological cervical intraepithelial neoplasia 2 or 3. At 12 months, high-grade cytology identified only 58% (95% confidence interval, 48-68%) of women with cervical intraepithelial neoplasia 2 or 3. However, the combination of either high-grade cytology or colposcopic appearance proved substantially more sensitive (81%; 95% confidence interval, 72-88%). High-risk human papillomavirus positivity at 12 months was a sensitive (96%; 95% confidence interval, 89-99%) indicator of persisting high-grade histology. However, this sensitivity came at the expense of specificity (52%; 95% confidence interval, 45-58%). A co-test of high-risk human papillomavirus positivity or high-grade cytology at 12 months provided a high sensitivity (97%; 95% confidence interval, 90-99%) but low specificity (51%; 95% confidence interval, 45%-58%). CONCLUSION: Colposcopy and cytology are limited in their ability to exclude persistent high-grade abnormality for young women undergoing observational management for cervical intraepithelial neoplasia 2. We recommend biopsy for all women at 12 months. High-risk human papillomavirus positivity is a sensitive indicator of persistent abnormality and should be considered in those not having a biopsy.

Development and Validation of a Predictive Model to Aid in the Management of Intact Abdominal Aortic Aneurysms.

OBJECTIVE/BACKGROUND: Predicting outcomes prior to elective abdominal aortic aneurysm repair (AAA) requires critical decision making, as the treatment offered is a prophylactic procedure to prevent death from a ruptured AAA. The aim of this work was to develop and validate a model that may predict outcomes for patients with an AAA and hence aid in clinical decision making. METHODS: A discrete event simulation model was built to simulate the natural history of a patient with an AAA and to predict the 30 day and 2-5 year survival of patients undergoing treatment and surveillance. The input parameters of AAA behavior and impact of comorbidities on survival were derived from the published literature and the New Zealand national life tables. The model was externally validated using a cohort of patients that underwent AAA repair (n = 320) and a cohort of patients undergoing small AAA surveillance (n = 376). All patients had completed at least 5 years of follow up. RESULTS: The model was run three times for each data set to test. This produced a SD < 1%, indicating excellent reproducibility. The observed 30 day mortality for the patients undergoing AAA repair was 9/320 (2.8%) and the expected (model predicted) mortality was 3.8% (c-statistic 0.87 [95 confidence interval 0.75-1.0]). The c-statistic for the predicted 2-5 year survival ranged from 0.68 to 0.71 for the repaired AAA cohort and 0.69 to 0.73 for patients with a small AAA on surveillance. CONCLUSION: The AAA clinical decision tool has the ability to accurately predict the 5 year survival of patients with an AAA. This tool can be used during clinical decision making to better inform clinicians and patients of long-term outcomes. Further validation studies in a wider AAA population are required to test the broader clinical utility of this AAA clinical decision tool.

Antenatal haemoglobin A1c centiles: does one size fit all?

BACKGROUND: In New Zealand, haemoglobin A1c measurements are routinely offered at booking, preferably before 20 weeks gestation, to detect pre-existing hyperglycaemia. A haemoglobin A1c <5.9% (41 mmol/mol) is considered normal based on the reference range for the non-pregnant population. AIMS: To determine pregnancy-specific haemoglobin A1c centiles by gestation and ethnicity. MATERIALS AND METHODS: This is a population-based observational study of pregnancies uncomplicated by diabetes (pre-existing or gestational) with ≥1 haemoglobin A1c measurement. Haemoglobin A1c centiles were calculated from data extracted from electronic laboratory and clinical records for pregnancies during 2008-2010. RESULTS: Included were 6800 pregnancies, European 80% (5462), Maori 6% (415), Pacific Islander 3% (196) and 11% (727) 'Others' (mostly Asian). Haemoglobin A1c levels fell with increasing gestation, reaching a nadir at 24 weeks, a trend verified by longitudinal data from 112 women. The 97.5th centile for haemoglobin A1c in European women was 5.76% (39.5 mmol/mol) at 8+0  weeks, 5.70% (38.8 mmol/mol) at 16+0  weeks, and 5.65% (38.3 mmol/mol) at 24+0  weeks. Non-European women had both higher plasma glucose levels (although within the range considered normal) and higher mean haemoglobin A1c levels compared with Europeans; mean (SD) difference in haemoglobin A1c in Maori +0.13% (0.05) (+1.4 mmol/mol (0.5)), Pacific +0.20% (0.03) (+2.2 mmol/mol (0.3)), 'Others' +0.10% (0.03) (+1.1 mmol/mol (0.3)). CONCLUSIONS: The New Zealand haemoglobin A1c cut-point ≥5.9% (41 mmol/mol) for identifying hyperglycaemia in early pregnancy is greater than the 97.5th centile in European and 'Other' women. Utilising population haemoglobin A1c centiles adjusted by gestation may thus better guide management decisions.

Survival Disparity Following Abdominal Aortic Aneurysm Repair Highlights Inequality in Ethnic and Socio-economic Status.

OBJECTIVES: Socio-economic status (SES) and ethnicity have been reported as markers influencing the likelihood of increased mortality. The aim of this study was to investigate how SES and ethnicity impacted patient survival after abdominal aortic aneurysm (AAA) repair. METHODS: Consecutive patients undergoing open and endovascular AAA repair during a 14.5 year period were identified. Ethnicity was defined as recorded on health records and SES (a score of 10, where 1 is least deprived and 10 being most deprived) and was linked to census data. Operative outcomes were reported at 30 days and a medium-term survival analysis used the Cox model to report adjusted hazard ratios (HR). RESULTS: A total of 6239 patients with a median age of 75 years and 78.7% males were included. The majority (5,654) were identified as New Zealand (NZ) Europeans, with 421 identified as NZ Maori, 97 identified as belonging to a Pacific ethnic group, and 67 identified as an Asian ethnic group. The median survival follow-up period was 5 years and after adjusting for confounders, those who identified as NZ Maori had the lowest survival compared with all other ethnic groups with a HR of 1.46 (95% CI 1.23-1.72). Living in areas of high social deprivation ≥ 7 was an independent predictor of short and medium-term overall mortality when compared with living in deprivation deciles 1 or 2. CONCLUSIONS: Low SES was identified as a marker of risk for all ethnic groups in relation to both reduced short and medium-term survival. However, regardless of SES, NZ Maori had worse overall medium-term survival following AAA repair than the other ethnic groups. Therefore it appears that both SES and being Maori were markers of increased exposure to risk that negatively impact upon survival after AAA repair. There is a need to ensure systemic processes support initiatives that reduce this inequality.

Management of Modifiable Vascular Risk Factors Improves Late Survival following Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-Analysis.

BACKGROUND: The main determinants of survival following abdominal aortic aneurysm (AAA) repair are preexisting risk factors rather than the method of repair chosen. The main aim of this meta-analysis was to assess the effect of modifiable risk factors on late survival following AAA repair. METHODS: Electronic databases were searched to identify all relevant articles reporting the influence of modifiable risk factors on long-term survival (≥1 year) following elective open aneurysm repair and endovascular aneurysm repair. RESULTS: Twenty-four studies which comprised 53,118 patients, published between 1989 and 2015, were included in the analysis. The use of statin, aspirin, beta-blockers, and a higher hemoglobin level was all significant predictors of improved survival following repair with a hazard ratio (HR) and 95% confidence interval (CI) of 0.75 (0.70-0.80), 0.81 (0.73-0.89), 0.75 (0.61-0.93), and 0.84 (0.74-0.96), respectively. Smoking history and uncorrected coronary disease were associated with a worse long-term survival of HR 1.27 (95% CI 1.07-1.51) and HR 2.59 (95% CI 1.14-5.88), respectively. CONCLUSIONS: Addressing cardiovascular risk factors in patients preoperatively improves long-term survival following AAA repair. Global strategies to improve risk factor modifications in these patients are warranted to optimize long-term outcomes.

Does the diameter of abdominal aortic aneurysm influence late survival following abdominal aortic aneurysm repair? A systematic review and meta-analysis.

BACKGROUND: Studies reporting the influence of preoperative abdominal aortic aneurysm diameter on late survival following abdominal aortic aneurysm repair have not been consistent. AIM: To report the influence of abdominal aortic aneurysm diameter on overall long-term survival following abdominal aortic aneurysm repair. METHODS: Embase, Medline and the Cochrane electronic databases were searched to identify articles reporting the influence of abdominal aortic aneurysm diameter on late survival following open aneurysm repair and endovascular aneurysm repair published up to April 2015. Data were extracted from multivariate analysis; estimated risks were expressed as hazard ratio. RESULTS: A total of 2167 titles/abstracts were retrieved, of which 76 studies were fully assessed; 19 studies reporting on 22,104 patients were included. Preoperative larger abdominal aortic aneurysm size was associated with a worse survival compared to smaller aneurysms with a pooled hazard ratio of 1.14 (95% CI: 1.09-1.18), per 1 cm increase in abdominal aortic aneurysm diameter. Subgroup analysis of the different types of repair was performed and the hazard ratio (95% CI), for open aneurysm repair and endovascular aneurysm repair were 1.08 (1.03-1.12) and 1.20 (1.15-1.25), respectively, per 1 cm increase. There was a significant difference between the groups p < 0.02. CONCLUSIONS: This meta-analysis suggests that preoperative large abdominal aortic aneurysm independently influences overall late survival following abdominal aortic aneurysm repair, and this association was greater in abdominal aortic aneurysm repaired with endovascular aneurysm repair.

Occupational Performance Coaching for Children With Neurodisability: A Randomized Controlled Trial Protocol.

Background. Occupational Performance Coaching (OPC) is a goal-oriented approach in which client agency takes precedence in goal selection, analysis, choice of action, and evaluation of success. The intended outcomes of OPC are improved occupational performance and participation in clients' life situations. Randomized clinical trials are needed to determine the effectiveness of OPC. Purpose. This study protocol outlines a randomized controlled trial (RCT) of OPC compared to usual care with caregivers of children with neurodisability in improving child, caregiver, and family occupational performance. Method. A single-blind, 2-arm parallel-group, cluster RCT of OPC compared to usual care is planned. Therapists delivering the intervention (N = 14) are randomized to "OPC training" or "usual care" groups. The primary outcome is occupational performance improvement in caregiver (N = 84) identified goals. Implications. Findings will provide translational evidence of the effectiveness of OPC and clarify intervention processes. Areas of future OPC research and development will be indicated.

Study protocol: glycaemic outcomes in people with type 2 diabetes initiating continuous glucose monitoring: the 2GO-CGM study.

Purpose: Improving glycaemic control in type 2 diabetes (T2D) is essential to reducing social and health-economic burden of diabetes-related complications. Continuous glucose monitoring (CGM) has been established as beneficial in improving glycaemic control and reducing hypoglycaemia in people with type 1 diabetes, however data in T2D is limited. This study has been designed to assess the effect of initiating real-time CGM (rtCGM) on glycaemic control in a high-risk population of adults with T2D. Secondary objectives are to assess the cost-effectiveness and safety of rtCGM, and the effects of rtCGM on diet/lifestyle and the burden of diabetic complications, including cardiovascular risk. Methods: This multicentre randomised controlled trial (RCT) will be conducted at three sites in New Zealand (Waikato, Christchurch and Dunedin). Eighty adults with T2D on insulin with suboptimal glycaemic control (HbA1c > 8.0% or 64 mmol/mol) will be randomised 1:1 to rtCGM or routine care with self-monitoring of blood glucose levels (SMBG) for three months. This intervention phase will be followed by a three-month continuation phase where SMBG group crossover to use rtCGM. Participants will then be invited to join the extension phase with continued use of rtCGM for a further 12 months. During the extension phase, both groups will independently titrate their insulin under the remote supervision of prescribing diabetes nurse specialists following an insulin titration algorithm. The primary outcome of the study is time in target glucose range (3.9-10 mmol/L or 70-180 mg/dL; TIR). Secondary outcomes include CGM metrics as per consensus statement recommendations, and HbA1c. Additional planned analyses include cardiovascular risk profile, incremental cost-effectiveness analyses, dietary patterns, and qualitative analyses. Trial registration number: The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000889853) on 8 July 2021 and the World Health Organisation International Clinical Trial Registry Platform (Universal Trial Number U1111-1264-5822).

Inequity in access to continuous glucose monitoring and health outcomes in paediatric diabetes, a case for national continuous glucose monitoring funding: A cross-sectional population study of children with type 1 diabetes in New Zealand.

Background: Continuous glucose monitoring (CGM) improves glycaemia for people affected by type 1 diabetes (T1D), but is not funded in Aotearoa/New Zealand. This study explores the impact of non-funded CGM on equity of access and associated glycaemic outcomes. Methods: Cross-sectional population-based study collected socio-demographic (age, gender, prioritised ethnicity, socioeconomic status) and clinical data from all regional diabetes centres in New Zealand with children <15 years with T1D as of 1st October 2021. De-identified data were obtained from existing databases or chart review. Outcomes compared socio-demographic characteristics between those using all forms of CGM and self-monitoring of blood glucose (SMBG), and association with HbA1c. Findings: 1209 eligible children were evaluated: 70.2% European, 18.1% Maori, 7.1% Pacific, 4.6% Asian, with even distribution across socioeconomic quintiles. Median HbA1c was 64 mmol/mol (8.0%), 40.2% utilised intermittently scanned (is)CGM, and 27.2% real-time (rt)CGM. CGM utilisation was lowest with Pacific ethnicity (38% lower than Maori) and the most deprived socioeconomic quintiles (quintile 5 vs. 1 adjusted RR 0.69; 95% CI, 0.57 to 0.84). CGM use was associated with regional diabetes centre (P < 0.001). The impact of CGM use on HbA1c differed by ethnicity: Maori children had the greatest difference in HbA1c between SMBG and rtCGM (adjusted difference -15.3 mmol/mol; 95% CI, -21.5 to -9.1), with less pronounced differences seen with other ethnicities. Interpretation: Inequities in CGM use exist based on prioritised ethnicity and socioeconomic status. Importantly, CGM was independently associated with lower HbA1c, suggesting that lack of CGM funding contributes to health disparity in children with T1D. Funding: Australasian Paediatric Endocrine Group (APEG), Canterbury Medical Research Foundation, Starship Foundation.

Extended Use of an Open-Source Automated Insulin Delivery System in Children and Adults with Type 1 Diabetes: The 24-Week Continuation Phase Following the CREATE Randomized Controlled Trial.

Aim: To assess long-term efficacy and safety of open-source automated insulin delivery (AID) in children and adults (7-70 years) with type 1 diabetes. Methods: Both arms of a 24-week randomized controlled trial comparing open-source AID (OpenAPS algorithm within a modified version of AndroidAPS, preproduction DANA-i™ insulin pump, Dexcom G6 continuous glucose monitor) with sensor-augmented pump therapy (SAPT), entered a 24-week continuation phase where the SAPT arm (termed SAPT-AID) crossed over to join the open-source AID arm (termed AID-AID). Most participants (69/94) used a preproduction YpsoPump® insulin pump during the continuation phase. Analyses incorporated all 52 weeks of data, and combined between-group and within-subject differences to calculate an overall "treatment effect" of AID versus SAPT. Results: Mean time in range (TIR; 3.9-10 mmol/L [70-180 mg/dL]) was 12.2% higher with AID than SAPT (95% confidence interval [CI] 10.4 to 14.1; P < 0.001). TIR was 56.9% (95% CI 54.2 to 59.6) with SAPT and 69.1% (95% CI 67.1 to 71.1) with AID. The treatment effect did not differ by age (P = 0.39) or insulin pump type (P = 0.37). HbA1c was 5.1 mmol/mol lower [0.5%] with AID (95% CI -6.6 to -3.6; P < 0.001). There were no episodes of diabetic ketoacidosis or severe hypoglycemia with either treatment over the 48 weeks. Six participants (all in SAPT-AID) withdrew: three with hardware issues, two preferred SAPT, and one with infusion-site skin irritation. Conclusion: Further evaluation of the community derived automated insulin delivery (CREATE) trial to 48 weeks confirms that open-source AID is efficacious and safe with different insulin pumps, and demonstrates sustained glycemic improvements without additional safety concerns.

Why Women Might Choose a Career in Pediatric Surgery and Ensuring There Are No Impediments to Selecting the Best.

INTRODUCTION: Although pediatric surgery in Australasia has a higher proportion of women than any other surgical specialty, women remain underrepresented. There is concern that residual impediments may still deter women from choosing this specialty as a career option. MATERIALS AND METHODS: A survey of years 2 to 6 medical students, with focused analysis on those who selected pediatric surgery as their most (or least) attractive surgical specialty and the characteristics they deemed important when considering a surgical career. RESULTS: The survey was completed by 357 students of whom 50 selected pediatric surgery as their most attractive surgical specialty and 12 as their least attractive surgical specialty, at equal gender rates. The specialty was not perceived as being prestigious, well paid, or one that emphasized technical skill but was perceived as having good work-life balance, when compared with the other surgical specialties. Those who selected pediatric surgery as their most attractive specialty were otherwise less likely to choose a career in surgery. CONCLUSION: Pediatric surgery is perceived as being less aligned to characteristics stereotypically associated with males and more with those characteristics associated with females. Overall, it seems to be more female friendly than other surgical specialties. It would behove the pediatric surgical community to better understand how it is perceived, so that perceptions can be aligned to reality and gender diversity can be increased.

Nortriptyline for pain in knee osteoarthritis: a double-blind randomised controlled trial in New Zealand general practice.

BACKGROUND: Osteoarthritis (OA) of the knee is a common cause of chronic pain. Analgesics that are currently available have limited efficacy and may be poorly tolerated. Tricyclic antidepressants are used as analgesics for other chronic conditions, but they have not been evaluated as analgesics in OA. AIM: To investigate the analgesic efficacy of nortriptyline in people with knee OA. DESIGN AND SETTING: A two-arm, parallel-group, 1:1, double-blind, randomised, placebo-controlled trial in Christchurch, New Zealand. METHOD: Participants were recruited from orthopaedic outpatient clinics, primary care, and through public advertising. Adults with knee OA and a pain score of ≥20 points on the 50-point Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain subscale were randomised to receive either nortriptyline or identical placebo for 14 weeks. The primary outcome was knee pain at 14 weeks measured using the WOMAC pain subscale. Secondary outcomes included: function; stiffness; non-steroidal anti-inflammatory drug, opioid, and/or paracetamol use; each participant's global assessment; and adverse effects at 14 weeks. RESULTS: Of the 205 randomised participants, 201 (98.0%) completed follow-up at 14 weeks. The baseline-adjusted mean WOMAC pain subscale score at week 14 was 6.2 points lower (95% confidence interval = -0.26 to 12.6, P = 0.06) in the nortriptyline arm versus the placebo arm. Differences in secondary outcomes generally favoured the nortriptyline arm, but were small and unlikely to be clinically relevant. However, the following were all more commonly reported by participants taking nortriptyline than those taking a placebo: dry mouth (86.9% versus 51.0%, respectively, P<0.001), constipation (58.6% versus 30.4%, respectively, P<0.001), and sweating (31.3% versus 20.6%, respectively, P = 0.033). CONCLUSION: This study suggests nortriptyline does not significantly reduce pain in people with knee OA. The adverse effect profile was as expected.

Impact of human papillomavirus vaccination on rates of abnormal cervical cytology and histology in young New Zealand women.

AIM: Determine the impact of quadrivalent human papillomavirus (HPV) vaccination on abnormal cervical cytology and histology rates in young New Zealand women. METHODS: Retrospective population-based cohort study of women born 1990-1994, with a cervical cytology or histology recorded when aged 20-24 between 1 January 2010 and 31 December 2015. Data was obtained through linking the National Immunisation Register and National Cervical Screening Programme Register. RESULTS: N=104,313 women (376,402 person years of follow up) were included. The incidence of high-grade cytology was lower in vaccinated women (at least one dose prior to 18 years) than in unvaccinated women (8.5 vs 11.3 per 1,000 person years [p1000py], incidence rate ratio [IRR 0.75], 95% CI 0.70, 0.80, p<.001). The incidence of high-grade histology was lower in vaccinated women than in unvaccinated women (6.0 vs 8.7 p1000py, IRR 0.69, 95% CI 0.64, 0.75, p<.001). There was no evidence of a difference in the incidence of high-grade histology between European and Maori women overall or after taking vaccination status into account. CONCLUSIONS: Receiving at least one dose of quadrivalent HPV vaccine prior to 18 years was associated with a 25% lower incidence of high-grade cytology and 31% lower incidence of high-grade histology in women aged 20-24 years.

Changes in human papillomavirus genotypes associated with cervical intraepithelial neoplasia grade 2 lesions in a cohort of young women (2013-2016).

In 2008, a quadrivalent human papillomavirus (HPV) vaccine (genotypes 6, 11, 16, 18) became available in New Zealand. This study investigated whether the proportion of cervical intraepithelial neoplasia grade 2 (CIN2) lesions associated with HPV genotypes 16 and 18 changed over time in young women recruited to a prospective CIN2 observational management trial (PRINCess) between 2013 and 2016. Partial HPV genotyping (16, 18, or other high risk HPV) was undertaken on n = 392 women under 25 years (mean age 21.8, range 17-24) with biopsy-diagnosed CIN2. High risk HPV genotypes were detected in 96% of women with CIN2 lesions. Between 2013 and 2016, the proportion of women whose liquid-based cytology samples were HPV 16 or 18 positive decreased from 43% to 13%. HPV vaccination status was known for 78% of women. Between 2013 and 2016, the proportion of HPV 16/18 positivity did not significantly change in HPV-vaccinated women, but decreased from 66% to 17% in unvaccinated women. The reducing proportion of HPV 16/18-related CIN2 in our cohort of young New Zealand women may be attributable to the introduction of a national HPV vaccination program. The substantial decrease in HPV 16/18 positivity observed in unvaccinated women is likely to be due to a herd effect.

Deaths from Opioid Overdosing: Implications of Coroners' Inquest Reports 2008-2012 and Annual Rise in Opioid Prescription Rates: A Population-Based Cohort Study.

INTRODUCTION: In the late 1990s multiple physicians and advocacy organizations promoted increased use of opioids for the treatment of acute, chronic and cancer pain. There has been an exponential growth in opioid prescribing in the last 20 years in the United States of America, in Australia, and in other developed Western countries. There are negative consequences associated with the liberal use of opioids. The primary aim of this population-based cohort study is to investigate the opioid-related death rate in New Zealand between 1 January 2008 and 31 December 2012. The secondary aims of this cohort study are: (1) to compare the opioid-related death rate per population in New Zealand in 2001/2002 with that between 2011/2012; (2) to investigate the number of opioid prescriptions in New Zealand between 2001 and 2012; (3) to compare the opioid-related death rate per population in New Zealand between 2001 and 2012 with the number of opioid prescriptions in New Zealand between 2001 and 2012. METHODS: Permission to access records from the Coronial Services Office in Wellington for 2008-2012 was acquired. Permission to access records for prescriptions containing opioids (dose and formulation) was obtained from the Pharmaceutical Collection. RESULTS: The rate of opioid-related deaths in New Zealand has increased by 33% from 2001 to 2012. More than half of the opioid-related deaths between 2008 and 2012 were unintentional opioid overdoses. Opioid analgesic deaths were most likely due to methadone, morphine and codeine prescribed by healthcare professionals. That 179 of these opioid-related deaths between 2008 and 2012 were unintentional opioid overdoses, and thus could have been avoided, is tragic. This study shows that there was a steady annual increases in opioid prescriptions in New Zealand from 2001 to 2012. This rise in opioid analgesic deaths was associated with the increases in the numbers of opioid prescriptions. CONCLUSION: A multifaceted national public health approach is needed to bring together the various stakeholders involved with pain management, opioid dependence, opioid availability and opioid diversion. There needs to be a targeted approach to educate current and future medical practitioners regarding the appropriate use of opioid prescriptions for the management of pain, as well as a strengthening of primary, secondary and tertiary resources to support medical practitioners managing their patients who suffer with pain.