Lower versus Higher Glycemic Criteria for Diagnosis of Gestational Diabetes.

BACKGROUND: Treatment of gestational diabetes improves maternal and infant health, although diagnostic criteria remain unclear. METHODS: We randomly assigned women at 24 to 32 weeks' gestation in a 1:1 ratio to be evaluated for gestational diabetes with the use of lower or higher glycemic criteria for diagnosis. The lower glycemic criterion was a fasting plasma glucose level of at least 92 mg per deciliter (≥5.1 mmol per liter), a 1-hour level of at least 180 mg per deciliter (≥10.0 mmol per liter), or a 2-hour level of at least 153 mg per deciliter (≥8.5 mmol per liter). The higher glycemic criterion was a fasting plasma glucose level of at least 99 mg per deciliter (≥5.5 mmol per liter) or a 2-hour level of at least 162 mg per deciliter (≥9.0 mmol per liter). The primary outcome was the birth of an infant who was large for gestational age (defined as a birth weight above the 90th percentile according to Fenton-World Health Organization standards). Secondary outcomes were maternal and infant health. RESULTS: A total of 4061 women underwent randomization. Gestational diabetes was diagnosed in 310 of 2022 women (15.3%) in the lower-glycemic-criteria group and in 124 of 2039 women (6.1%) in the higher-glycemic-criteria group. Among 2019 infants born to women in the lower-glycemic-criteria group, 178 (8.8%) were large for gestational age, and among 2031 infants born to women in the higher-glycemic-criteria group, 181 (8.9%) were large for gestational age (adjusted relative risk, 0.98; 95% confidence interval, 0.80 to 1.19; P = 0.82). Induction of labor, use of health services, use of pharmacologic agents, and neonatal hypoglycemia were more common in the lower-glycemic-criteria group than in the higher-glycemic-criteria group. The results for the other secondary outcomes were similar in the two trial groups, and there were no substantial between-group differences in adverse events. Among the women in both groups who had glucose test results that fell between the lower and higher glycemic criteria, those who were treated for gestational diabetes (195 women), as compared with those who were not (178 women), had maternal and infant health benefits, including fewer large-for-gestational-age infants. CONCLUSIONS: The use of lower glycemic criteria for the diagnosis of gestational diabetes did not result in a lower risk of a large-for-gestational-age infant than the use of higher glycemic criteria. (Funded by the Health Research Council of New Zealand and others; GEMS Australian New Zealand Clinical Trials Registry number, ACTRN12615000290594.).

Prophylactic Oral Dextrose Gel and Neurosensory Impairment at 2-Year Follow-up of Participants in the hPOD Randomized Trial.

Importance: Prophylactic oral dextrose gel reduces neonatal hypoglycemia, but later benefits or harms remain unclear. Objective: To assess the effects on later development of prophylactic dextrose gel for infants born at risk of neonatal hypoglycemia. Design, Setting, and Participants: Prospective follow-up of a multicenter randomized clinical trial conducted in 18 Australian and New Zealand hospitals from January 2015 to May 2019. Participants were late preterm or term at-risk infants; those randomized in 9 New Zealand centers (n = 1359) were included and followed up between January 2017 and July 2021. Interventions: Infants were randomized to prophylactic 40% dextrose (n = 681) or placebo (n = 678) gel, 0.5 mL/kg, massaged into the buccal mucosa 1 hour after birth. Main Outcomes and Measures: The primary outcome of this follow-up study was neurosensory impairment at 2 years' corrected age. There were 44 secondary outcomes, including cognitive, language, and motor composite Bayley-III scores (mean [SD], 100 [15]; higher scores indicate better performance). Results: Of eligible infants, 1197 (91%) were assessed (581 females [49%]). Neurosensory impairment was not significantly different between the dextrose and placebo gel groups (20.8% vs 18.7%; unadjusted risk difference [RD], 2.09% [95% CI, -2.43% to 6.60%]; adjusted risk ratio [aRR], 1.13 [95% CI, 0.90 to 1.41]). The risk of cognitive and language delay was not significantly different between the dextrose and placebo groups (cognitive: 7.6% vs 5.3%; RD, 2.32% [95% CI, -0.46% to 5.11%]; aRR, 1.40 [95% CI, 0.91 to 2.17]; language: 17.0% vs 14.7%; RD, 2.35% [95% CI, -1.80% to 6.50%]; aRR, 1.19 [95% CI, 0.92 to 1.54]). However, the dextrose gel group had a significantly higher risk of motor delay (2.5% vs 0.7%; RD, 1.81% [95% CI, 0.40% to 3.23%]; aRR, 3.79 [95% CI, 1.27 to 11.32]) and significantly lower composite scores for cognitive (adjusted mean difference [aMD], -1.30 [95% CI, -2.55 to -0.05]), language (aMD, -2.16 [95% CI, -3.86 to -0.46]), and motor (aMD, -1.40 [95% CI, -2.60 to -0.20]) performance. There were no significant differences between groups in the other 27 secondary outcomes. Conclusions and Relevance: Among late preterm and term infants born at risk of neonatal hypoglycemia, prophylactic oral 40% dextrose gel at 1 hour of age, compared with placebo, resulted in no significant difference in the risk of neurosensory impairment at 2 years' corrected age. However, the study may have been underpowered to detect a small but potentially clinically important increase in risk, and further research including longer-term follow-up is required. Trial Registration: anzctr.org.au Identifier: ACTRN12614001263684.

Evaluation of oral dextrose gel for prevention of neonatal hypoglycemia (hPOD): A multicenter, double-blind randomized controlled trial.

BACKGROUND: Neonatal hypoglycemia is common and can cause brain injury. Buccal dextrose gel is effective for treatment of neonatal hypoglycemia, and when used for prevention may reduce the incidence of hypoglycemia in babies at risk, but its clinical utility remains uncertain. METHODS AND FINDINGS: We conducted a multicenter, double-blinded, placebo-controlled randomized trial in 18 New Zealand and Australian maternity hospitals from January 2015 to May 2019. Babies at risk of neonatal hypoglycemia (maternal diabetes, late preterm, or high or low birthweight) without indications for neonatal intensive care unit (NICU) admission were randomized to 0.5 ml/kg buccal 40% dextrose or placebo gel at 1 hour of age. Primary outcome was NICU admission, with power to detect a 4% absolute reduction. Secondary outcomes included hypoglycemia, NICU admission for hypoglycemia, hyperglycemia, breastfeeding at discharge, formula feeding at 6 weeks, and maternal satisfaction. Families and clinical and study staff were unaware of treatment allocation. A total of 2,149 babies were randomized (48.7% girls). NICU admission occurred for 111/1,070 (10.4%) randomized to dextrose gel and 100/1,063 (9.4%) randomized to placebo (adjusted relative risk [aRR] 1.10; 95% CI 0.86, 1.42; p = 0.44). Babies randomized to dextrose gel were less likely to become hypoglycemic (blood glucose < 2.6 mmol/l) (399/1,070, 37%, versus 448/1,063, 42%; aRR 0.88; 95% CI 0.80, 0.98; p = 0.02) although NICU admission for hypoglycemia was similar between groups (65/1,070, 6.1%, versus 48/1,063, 4.5%; aRR 1.35; 95% CI 0.94, 1.94; p = 0.10). There were no differences between groups in breastfeeding at discharge from hospital (aRR 1.00; 95% CI 0.99, 1.02; p = 0.67), receipt of formula before discharge (aRR 0.99; 95% CI 0.92, 1.08; p = 0.90), and formula feeding at 6 weeks (aRR 1.01; 95% CI 0.93, 1.10; p = 0.81), and there was no hyperglycemia. Most mothers (95%) would recommend the study to friends. No adverse effects, including 2 deaths in each group, were attributable to dextrose gel. Limitations of this study included that most participants (81%) were infants of mothers with diabetes, which may limit generalizability, and a less reliable analyzer was used in 16.5% of glucose measurements. CONCLUSIONS: In this placebo-controlled randomized trial, prophylactic dextrose gel 200 mg/kg did not reduce NICU admission in babies at risk of hypoglycemia but did reduce hypoglycemia. Long-term follow-up is needed to determine the clinical utility of this strategy. TRIAL REGISTRATION: ACTRN 12614001263684.

Costs of inpatient hospitalisations in the last year of life in older New Zealanders: a cohort study.

BACKGROUND: Rapidly ageing populations means that many people now die in advanced age. This paper investigated public hospital and long-term care home costs in the 12 months before death in Maori and non-Maori of advanced age in New Zealand. METHODS: Data from an existing longitudinal study (LiLACS NZ) was used, in which 937 older New Zealanders were enrolled in 2010. At the time of this study, 213 Maori and 241 non-Maori in the cohort had died. National Health Index numbers were linked to the hospitalisation National Minimum Dataset to ascertain public hospitalisation and care home costs in the last year of life. RESULTS: The average total publicly funded hospital and long-term care home costs in the 12 months prior to death were $16,211 and $17,351 for Maori and non-Maori respectively. Non-Maori tended to have long lengths of stay in their last year of life, and non-Maori men had the highest proportion with high costs and long lengths of stay in care homes. Costs in the last year of life were 8.1 times higher in comparison to costs for individuals who did not die in the same time period. CONCLUSION: Despite New Zealand's commitment to providing an equitable level of healthcare, this study illustrated that ethnic and gender disparities are still apparent at the end of life. This raises questions as to whether money at the end of life is being spent appropriately, and how it could potentially be more equitably targeted to meet the diverse needs of older people and their families.

Cost burden and net monetary benefit loss of neonatal hypoglycaemia.

BACKGROUND: Neonatal hypoglycaemia is a common but treatable metabolic disorder that affects newborn infants and which, if not identified and treated adequately, may result in neurological sequelae that persist for the lifetime of the patient. The long-term financial and quality-of-life burden of neonatal hypoglycaemia has not been previously examined. METHODS: We assessed the postnatal hospital and long-term costs associated with neonatal hypoglycaemia over 80 year and 18 year time horizons, using a health-system perspective and assessing impact on quality of life using quality-adjusted life year (QALYs). A decision analytic model was used to represent key outcomes in the presence and absence of neonatal hypoglycaemia. RESULTS: The chance of developing one of the outcomes of neonatal hypoglycaemia in our model (cerebral palsy, learning disabilities, seizures, vision disorders) was 24.03% in subjects who experienced neonatal hypoglycaemia and 3.56% in those who do did not. Over an 80 year time horizon a subject who experienced neonatal hypoglycaemia had a combined hospital and post-discharge cost of NZ$72,000 due to the outcomes modelled, which is NZ$66,000 greater than a subject without neonatal hypoglycaemia. The net monetary benefit lost due to neonatal hypoglycaemia, using a value per QALY of NZ$43,000, is NZ$180,000 over an 80 year time horizon. CONCLUSIONS: Even under the most conservative of estimates, neonatal hypoglycaemia contributes a significant financial burden to the health system both during childhood and over a lifetime. The combination of direct costs and loss of quality of life due to neonatal hypoglycaemia means that this condition warrants further research to focus on prevention and effective treatment.

Cost-Utility Analysis of Prophylactic Dextrose Gel vs Standard Care for Neonatal Hypoglycemia in At-Risk Infants.

OBJECTIVE: To evaluate the long-term costs and impact on quality of life of using prophylactic dextrose gel in patients at increased risk of developing neonatal hypoglycemia. STUDY DESIGN: A cost-utility analysis was performed from the perspective of the health system, using a decision tree to model the long-term clinical outcomes of neonatal hypoglycemia, including cerebral palsy, epilepsy, vision disturbances, and learning disabilities, in patients at increased risk of neonatal hypoglycemia who received prophylactic dextrose gel vs standard care. Model parameters including likelihoods of hypoglycemia and admission to a neonatal intensive care unit, were based on the pre-Hypoglycemia Prevention with Oral Dextrose Study. Estimations of the likelihood of long-term condition(s), and their costs, were based on review of published literature. RESULTS: Patients who received prophylactic dextrose gel incurred costs to the health system of around US $14 000 over an 18-year time horizon, accruing 11.25 quality-adjusted life-years, whereas those who did not receive prophylactic treatment incurred cost of around $16 000 and experienced a utility of 11.10 quality-adjusted life-years. CONCLUSIONS: A prophylactic strategy of using dextrose gel in infants at increased risk of neonatal hypoglycemia is likely to be cost effective compared with standard care, to reduce the direct costs to the health system over an 18-year time horizon, and improve quality of life.

Lower versus higher diagnostic criteria for the detection of gestational diabetes for reducing maternal and perinatal morbidity: study protocol for the GEMS randomised trial.

BACKGROUND: Gestational diabetes mellitus (GDM) has lifelong implications for the woman and her infant. Treatment reduces adverse maternal and perinatal outcomes although uncertainty remains about the optimal diagnostic criteria. The GEMS Trial aims to assess whether detection and treatment of women with GDM using the lower International Association of Diabetes in Pregnancy Study Groups diagnostic criteria compared with the higher criteria recommended in New Zealand reduces infant morbidity without increasing maternal morbidity. METHODS: GEMS is a multicentre, randomised trial. Women with a singleton pregnancy at 24 to 34 weeks' gestation are eligible who give written informed consent. Women are randomly allocated to the Lower Criteria Group or the Higher Criteria Group. Women with a normal OGTT by their allocated criteria receive routine care (Higher criteria: fasting plasma glucose < 5.5 mmol/L, AND 2 hour < 9.0 mmol/L; Lower criteria: fasting plasma glucose < 5.1 mmol/L, AND 1 hour < 10.0 mmol/L, AND 2 hour < 8.5 mmol/l). Women with GDM on OGTT by their allocated criteria receive standard care for GDM (Higher criteria: fasting plasma glucose ≥ 5.5 mmol/L, OR 2 hour ≥ 9.0 mmol/L; Lower criteria: fasting plasma glucose ≥ 5.1 mmol/L, OR 1 hour ≥ 10.0 mmol/L, OR 2 hour ≥ 8.5 mmol/L). The primary outcome is large for gestational age (birth weight > 90th centile). Secondary outcomes for the infant include a composite of serious outcomes, gestational age, anthropometry, Apgar score < 4 at 5 minutes, lung disease, use of respiratory support, hypoglycaemia, hyperbilirubinaemia, infection, and encephalopathy; and for the woman, a composite of serious outcomes, preeclampsia, induction of labour, mode of birth, weight gain, postpartum haemorrhage and infectious morbidity. A study with 4,158 women will detect an absolute difference of 2.9% in the proportion of large for gestational age infants from 10.0% using the lower criteria to 12.9% with the higher criteria. DISCUSSION: The GEMS Trial will provide high-level evidence relevant for clinical practice. If use of the lower diagnostic criteria results in significantly fewer large for gestational age infants and/or improves maternal and perinatal outcomes these criteria should be recommended for diagnosis of gestational diabetes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry registration number ACTRN12615000290594 . Date registered: 27th March 2015.

Prolonged Postoperative Ileus Significantly Increases the Cost of Inpatient Stay for Patients Undergoing Elective Colorectal Surgery: Results of a Multivariate Analysis of Prospective Data at a Single Institution.

BACKGROUND: Prolonged postoperative ileus is a common major complication after abdominal surgery. Retrospective data suggest that ileus doubles the cost of inpatient stay. However, current economic impact data are based on retrospective studies that rely on clinical coding to diagnose ileus. OBJECTIVE: The aim of this study was to determine the economic burden of ileus for patients undergoing elective colorectal surgery. DESIGN: Economic data were audited from a prospective database of patients who underwent surgery at Auckland City Hospital between September 2012 and June 2014. SETTINGS: Auckland City Hospital is a large tertiary referral center, using an enhanced recovery after surgery protocol. PATIENTS: Patients were prospectively diagnosed with prolonged postoperative ileus using a standardized definition. MAIN OUTCOME MEASURES: The cost of inpatient stay was analyzed with regard to patient demographics and operative and postoperative factors. A multivariate analysis was performed to determine the cost of ileus when accounting for other significant covariates. RESULTS: Economic data were attained from 325 patients, and 88 patients (27%) developed ileus. The median inpatient cost (New Zealand dollars) for patients with prolonged ileus, including complication rates and length of stay, was $27,981 (interquartile range= $20,198 to $42,174) compared with $16,317 (interquartile range = $10,620 to $23,722) for other patients, a 71% increase in cost (p < 0.005). Ileus increased all associated healthcare costs, including medical/nursing care, radiology, medication, laboratory costs, and allied health (p < 0.05). Multivariate analysis showed that ileus remained a significant financial burden (p < 0.005) when considering rates of major complications and length of stay. LIMITATIONS: This is a single-institution study, which may impact the generalizability of our results. CONCLUSIONS: Prolonged ileus causes a substantial financial burden on the healthcare system, in addition to greater complication rates and length of stay in these patients. This is the first study to assess the financial impact of prolonged ileus, diagnosed prospectively using a standardized definition. See Video Abstract at http://links.lww.com/DCR/A825.

Study protocol of a randomised controlled trial to examine the impact of a complex intervention in pre-frail older adults.

BACKGROUND: Frailty is a multidimensional geriatric syndrome associated with functional loss. The Senior Chef (SC, nutrition) and SAYGO (strength and balance exercise) programmes are well accepted among older adults but the impact of each, or a combination of both, on the frailty syndrome in pre-frail older adults is unknown. AIMS: To determine the effectiveness and cost-effectiveness of a complex intervention consisting of the SC and/or SAYGO programmes to prevent progression of frailty in pre-frail older adults. METHODS: A multi-centre randomised controlled assessor-blinded study. The four intervention groups are SC, an 8-week nutrition education and cooking class; SAYGO, a 10-week strength and balance exercise class; SC plus SAYGO, and a social group (Control). Community-dwelling adults aged 75+ (60 + Maori and Pasifika) in New Zealand are recruited through health providers. Participants are not terminally ill or with advanced dementia, and have a score of 1 or 2 on the FRAIL questionnaire. Baseline assessments are completed using standardised questionnaires prior to randomisation. Four follow-up assessments are completed: immediately after intervention, 6, 12 and 24 months post-intervention. The primary outcome is frailty score, secondary outcomes are falls, physical function, quality of life, food intake, physical activity, and sustainability of the strategy. Study outcomes will be analysed using intention-to-treat approach. Cost analyses will be completed to determine if interventions are cost effective relative to the control group. DISCUSSION: This trial is designed to be a real world rigorous assessment of whether the two intervention strategies can prevent progression of frailty in older people. If successful, this will generate valuable information about effectiveness of this nutrition and exercise strategy, and provide insights for their implementation. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry number-ACTRN12614000827639.

Cost Analysis of Treating Neonatal Hypoglycemia with Dextrose Gel.

OBJECTIVE: To evaluate the costs of using dextrose gel as a primary treatment for neonatal hypoglycemia in the first 48 hours after birth compared with standard care. STUDY DESIGN: We used a decision tree to model overall costs, including those specific to hypoglycemia monitoring and treatment and those related to the infant's length of stay in the postnatal ward or neonatal intensive care unit, comparing the use of dextrose gel for treatment of neonatal hypoglycemia with placebo, using data from the Sugar Babies randomized trial. Sensitivity analyses assessed the impact of dextrose gel cost, neonatal intensive care cost, cesarean delivery rate, and costs of glucose monitoring. RESULTS: In the primary analysis, treating neonatal hypoglycemia using dextrose gel had an overall cost of NZ$6863.81 and standard care (placebo) cost NZ$8178.25; a saving of NZ$1314.44 per infant treated. Sensitivity analyses showed that dextrose gel remained cost saving with wide variations in dextrose gel costs, neonatal intensive care unit costs, cesarean delivery rates, and costs of monitoring. CONCLUSIONS: Use of buccal dextrose gel reduces hospital costs for management of neonatal hypoglycemia. Because it is also noninvasive, well tolerated, safe, and associated with improved breastfeeding, buccal dextrose gel should be routinely used for initial treatment of neonatal hypoglycemia. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12608000623392.

Bayesian statistical models to estimate EQ-5D utility scores from EORTC QLQ data in myeloma.

It is well documented that the modelling of health-related quality of life data is difficult as the distribution of such data is often strongly right/left skewed and it includes a significant percentage of observations at one. The objective of this study is to develop a series of two-part models (TPMs) that deal with these issues. Data from the UK Medical Research Council Myeloma IX trial were used to examine the relationship between the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/QLQ-MY20 scores and the European QoL-5 Dimensions (EQ-5D) utility score. Four different TPMs were developed. The models fitted included TPM with normal regression, TPM with normal regression with variance a function of participant characteristics, TPM with log-transformed data, and TPM with gamma regression and a log link. The cohort of 1839 patients was divided into 75% derivation sample, to fit the different models, and 25% validation sample to assess the predictive ability of these models by comparing predicted and observed mean EQ-5D scores in the validation set, unadjusted R2 , and root mean square error. Predictive performance in the derivation dataset depended on the criterion used, with R2 /adjusted-R2 favouring the TPM with normal regression and mean predicted error favouring the TPM with gamma regression. The TPM with gamma regression performs best within the validation dataset under all criteria. TPM regression models provide flexible approaches to estimate mean EQ-5D utility weights from the EORTC QLQ-C30/QLQ-MY20 for use in economic evaluation.

The cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy for low risk localised prostate cancer.

BACKGROUND: Radical prostatectomy is the most common treatment for localised prostate cancer in New Zealand. Active surveillance was introduced to prevent overtreatment and reduce costs while preserving the option of radical prostatectomy. This study aims to evaluate the cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy. METHODS: Markov models were constructed to estimate the life-time cost-effectiveness of active surveillance compared to watchful waiting and radical prostatectomy for low risk localised prostate cancer patients aged 45-70 years, using national datasets in New Zealand and published studies including the SPCG-4 study. This study was from the perspective of the Ministry of Health in New Zealand. RESULTS: Radical prostatectomy is less costly than active surveillance in men aged 45-55 years with low risk localised prostate cancer, but more costly for men aged 60-70 years. Scenario analyses demonstrated significant uncertainty as to the most cost-effective option in all age groups because of the unavailability of good quality of life data for men under active surveillance. Uncertainties around the likelihood of having radical prostatectomy when managed with active surveillance also affect the cost-effectiveness of active surveillance against radical prostatectomy. CONCLUSIONS: Active surveillance is less likely to be cost-effective compared to radical prostatectomy for younger men diagnosed with low risk localised prostate cancer. The cost-effectiveness of active surveillance compared to radical prostatectomy is critically dependent on the 'trigger' for radical prostatectomy and the quality of life in men on active surveillance. Research on the latter would be beneficial.

Effect of Robotic-Assisted vs Conventional Laparoscopic Surgery on Risk of Conversion to Open Laparotomy Among Patients Undergoing Resection for Rectal Cancer: The ROLARR Randomized Clinical Trial.

Importance: Robotic rectal cancer surgery is gaining popularity, but limited data are available regarding safety and efficacy. Objective: To compare robotic-assisted vs conventional laparoscopic surgery for risk of conversion to open laparotomy among patients undergoing resection for rectal cancer. Design, Setting, and Participants: Randomized clinical trial comparing robotic-assisted vs conventional laparoscopic surgery among 471 patients with rectal adenocarcinoma suitable for curative resection conducted at 29 sites across 10 countries, including 40 surgeons. Recruitment of patients was from January 7, 2011, to September 30, 2014, follow-up was conducted at 30 days and 6 months, and final follow-up was on June 16, 2015. Interventions: Patients were randomized to robotic-assisted (n = 237) or conventional (n = 234) laparoscopic rectal cancer resection, performed by either high (upper rectum) or low (total rectum) anterior resection or abdominoperineal resection (rectum and perineum). Main Outcomes and Measures: The primary outcome was conversion to open laparotomy. Secondary end points included intraoperative and postoperative complications, circumferential resection margin positivity (CRM+) and other pathological outcomes, quality of life (36-Item Short Form Survey and 20-item Multidimensional Fatigue Inventory), bladder and sexual dysfunction (International Prostate Symptom Score, International Index of Erectile Function, and Female Sexual Function Index), and oncological outcomes. Results: Among 471 randomized patients (mean [SD] age, 64.9 [11.0] years; 320 [67.9%] men), 466 (98.9%) completed the study. The overall rate of conversion to open laparotomy was 10.1%: 19 of 236 patients (8.1%) in the robotic-assisted laparoscopic group and 28 of 230 patients (12.2%) in the conventional laparoscopic group (unadjusted risk difference = 4.1% [95% CI, -1.4% to 9.6%]; adjusted odds ratio = 0.61 [95% CI, 0.31 to 1.21]; P = .16). The overall CRM+ rate was 5.7%; CRM+ occurred in 14 (6.3%) of 224 patients in the conventional laparoscopic group and 12 (5.1%) of 235 patients in the robotic-assisted laparoscopic group (unadjusted risk difference = 1.1% [95% CI, -3.1% to 5.4%]; adjusted odds ratio = 0.78 [95% CI, 0.35 to 1.76]; P = .56). Of the other 8 reported prespecified secondary end points, including intraoperative complications, postoperative complications, plane of surgery, 30-day mortality, bladder dysfunction, and sexual dysfunction, none showed a statistically significant difference between groups. Conclusions and Relevance: Among patients with rectal adenocarcinoma suitable for curative resection, robotic-assisted laparoscopic surgery, as compared with conventional laparoscopic surgery, did not significantly reduce the risk of conversion to open laparotomy. These findings suggest that robotic-assisted laparoscopic surgery, when performed by surgeons with varying experience with robotic surgery, does not confer an advantage in rectal cancer resection. Trial Registration: isrctn.org Identifier: ISRCTN80500123.

Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study).

BACKGROUND: Neonatal hypoglycaemia is common, affecting up to 15% of newborns, and can cause brain damage. Currently, there are no strategies, beyond early feeding, to prevent neonatal hypoglycaemia. Our aim was to determine a dose of 40% oral dextrose gel that will prevent neonatal hypoglycaemia in newborn babies at risk. METHODS AND FINDINGS: We conducted a randomised, double-blind, placebo-controlled dose-finding trial of buccal dextrose gel to prevent neonatal hypoglycaemia at two hospitals in New Zealand. Babies at risk of hypoglycaemia (infant of a mother with diabetes, late preterm delivery, small or large birthweight, or other risk factors) but without indication for admission to a neonatal intensive care unit (NICU) were randomly allocated either to one of four treatment groups: 40% dextrose at one of two doses (0.5 ml/kg = 200 mg/kg, or 1 ml/kg = 400 mg/kg), either once at 1 h of age or followed by three additional doses of dextrose (0.5 ml/kg before feeds in the first 12 h); or to one of four corresponding placebo groups. Treatments were administered by massaging gel into the buccal mucosa. The primary outcome was hypoglycaemia (<2.6 mM) in the first 48 h. Secondary outcomes included admission to a NICU, admission for hypoglycaemia, and breastfeeding at discharge and at 6 wk. Prespecified potential dose limitations were tolerance of gel, time taken to administer, messiness, and acceptability to parents. From August 2013 to November 2014, 416 babies were randomised. Compared to babies randomised to placebo, the risk of hypoglycaemia was lowest in babies randomised to a single dose of 200 mg/kg dextrose gel (relative risk [RR] 0.68; 95% confidence interval [CI] 0.47-0.99, p = 0.04) but was not significantly different between dose groups (p = 0.21). Compared to multiple doses, single doses of gel were better tolerated, quicker to administer, and less messy, but these limitations were not different between dextrose and placebo gel groups. Babies who received any dose of dextrose gel were less likely to develop hypoglycaemia than those who received placebo (RR 0.79; 95% CI 0.64-0.98, p = 0.03; number needed to treat = 10, 95% CI 5-115). Rates of NICU admission were similar (RR 0.64; 95% CI 0.33-1.25, p = 0.19), but admission for hypoglycaemia was less common in babies randomised to dextrose gel (RR 0.46; 95% CI 0.21-1.01, p = 0.05). Rates of breastfeeding were similar in both groups. Adverse effects were uncommon and not different between groups. A limitation of this study was that most of the babies in the trial were infants of mothers with diabetes (73%), which may reduce the applicability of the results to babies from other risk groups. CONCLUSIONS: The incidence of neonatal hypoglycaemia can be reduced with a single dose of buccal 40% dextrose gel 200 mg/kg. A large randomised trial (Hypoglycaemia Prevention with Oral Dextrose [hPOD]) is under way to determine the effects on NICU admission and later outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000322730.

Economic evaluation of prostate cancer screening: a systematic review.

This review, based on published papers, aims to describe the costs of prostate cancer screening and to examine whether prostate cancer screening is cost effective. The estimated cost per cancer detected ranged from €1299 in The Netherlands to US$44,355 in the USA. The estimated cost per life-year saved ranged from US$3000 to US$729,000, while the cost per quality-adjusted life year (QALY) was AU$291,817 and Can$371,100. The most appropriate data for economic evaluation of prostate cancer screening should be the cost per QALY gained. The estimated costs per QALY gained by prostate cancer screening were significantly higher than the cost-effectiveness threshold, suggesting that even when based on favorable randomized controlled trials in younger age groups, prostate cancer screening is still not cost effective.

Randomised trial of neonatal hypoglycaemia prevention with oral dextrose gel (hPOD): study protocol.

BACKGROUND: Neonatal hypoglycaemia is common, affecting up to 15% of newborn babies and 50% of those with risk factors (preterm, infant of a diabetic, high or low birthweight). Hypoglycaemia can cause brain damage and death, and babies born at risk have an increased risk of developmental delay in later life. Treatment of hypoglycaemia usually involves additional feeding, often with infant formula, and admission to Neonatal Intensive Care for intravenous dextrose. This can be costly and inhibit the establishment of breast feeding. Prevention of neonatal hypoglycaemia would be desirable, but there are currently no strategies, beyond early feeding, for prevention of neonatal hypoglycaemia. Buccal dextrose gel is safe and effective in treatment of hypoglycaemia. The aim of this trial is to determine whether 40% dextrose gel given to babies at risk prevents neonatal hypoglycaemia and hence reduces admission to Neonatal Intensive Care. DESIGN: Randomised, multicentre, placebo controlled trial. INCLUSION CRITERIA: Babies at risk of hypoglycaemia (preterm, infant of a diabetic, small or large), less than 1 h old, with no apparent indication for Neonatal Intensive Care Unit admission and mother intends to breastfeed. Trial entry & randomisation: Eligible babies of consenting parents will be allocated by online randomisation to the dextrose gel group or placebo group, using a study number and corresponding trial intervention pack. STUDY GROUPS: Babies will receive a single dose of 0.5 ml/kg study gel at 1 h after birth; either 40% dextrose gel (200 mg/kg) or 2% hydroxymethylcellulose placebo. Gel will be massaged into the buccal mucosal and followed by a breast feed. Primary study outcome: Admission to Neonatal Intensive Care. SAMPLE SIZE: 2,129 babies are required to detect a decrease in admission to Neonatal Intensive Care from 10-6% (two-sided alpha 0.05, 90% power, 5% drop-out rate). DISCUSSION: This study will investigate whether admission to Neonatal Intensive Care can be prevented by prophylactic oral dextrose gel; a simple, cheap and painless intervention that requires no special expertise or equipment and hence is applicable in almost any birth setting. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry--ACTRN 12614001263684.

Sharing risk between payer and provider by leasing health technologies: an affordable and effective reimbursement strategy for innovative technologies?

The challenge of implementing high-cost innovative technologies in health care systems operating under significant budgetary pressure has led to a radical shift in the health technology reimbursement landscape. New reimbursement strategies attempt to reduce the risk of making the wrong decision, that is, paying for a technology that is not good value for the health care system, while promoting the adoption of innovative technologies into clinical practice. The remaining risk, however, is not shared between the manufacturer and the health care payer at the individual purchase level; it continues to be passed from the manufacturer to the payer at the time of purchase. In this article, we propose a health technology payment strategy-technology leasing reimbursement scheme-that allows the sharing of risk between the manufacturer and the payer: the replacing of up-front payments with a stream of payments spread over the expected duration of benefit from the technology, subject to the technology delivering the claimed health benefit. Using trastuzumab (Herceptin) in early breast cancer as an exemplar technology, we show how a technology leasing reimbursement scheme not only reduces the total budgetary impact of the innovative technology but also truly shares risk between the manufacturer and the health care system, while reducing the value of further research and thus promoting the rapid adoption of innovative technologies into clinical practice.