Comparative effectiveness of metformin versus insulin for gestational diabetes in New Zealand.

PURPOSE: To measure the comparative effectiveness of metformin versus insulin for initial pharmacological management of gestational diabetes mellitus (GDM). METHODS: We conducted a population-based retrospective cohort study using administrative claims, maternity care, and laboratory result data from New Zealand. We followed pregnant women aged 15 to 45 from GDM diagnosis through delivery and assessed outcomes using maternity care and hospitalization data. We adjusted for covariates using inverse probability of treatment weights and multiple imputation for missing covariate information. We estimated unadjusted and adjusted risk ratios (RRs), risk differences (RDs) per 100, and 95% confidence intervals (CIs). Linear regression was used to estimate the association of treatment with birthweight. We stratified analyses by ethnicity and infant sex in prespecified sensitivity analyses. RESULTS: We compared 3818 metformin-treated pregnancies with 3450 insulin-treated pregnancies. We observed differences in treatment initiation by ethnicity, socioeconomic status, region, and calendar year. Treatment groups were similar in age, body mass index (BMI), and timing of diagnosis/treatment initiation. After adjustment, metformin was associated with reduced absolute risk of planned elective c-section (RD = -2.3, 95% CI, -4.3 to -0.3), large for gestational age (RD = -3.7, 95% CI, -5.5 to -1.8), and neonatal hypoglycemia (RD = -5.0, 95% CI, -6.9 to -3.2) compared with insulin. There were no clinically meaningful differences in average birthweight between metformin- and insulin-treated pregnancies. We observed variation in estimates by ethnicity and infant sex for some neonatal outcomes. CONCLUSION: Metformin appears to be an effective treatment for women with GDM and may reduce risk of some adverse neonatal outcomes when compared with insulin.

Association of Long-term Child Growth and Developmental Outcomes With Metformin vs Insulin Treatment for Gestational Diabetes.

Importance: Metformin is an emerging option for treating gestational diabetes (GDM). However, because metformin crosses the placenta, patients and clinicians are concerned with its long-term effect on child health. Objective: To estimate the association of treating GDM with metformin vs insulin with child growth and development. Design, Setting, and Participants: Population-based cohort study of New Zealand women treated with metformin or insulin for GDM from 2005 to 2012 and their children. This study linked national health care data to create a cohort of mothers and their children, including data from maternity care, pharmaceutical dispensing, hospitalizations, demographic records, and the B4 School Check (B4SC) preschool health assessment. Women treated pharmacologically with metformin or insulin during pregnancy were included. We excluded pregnancies with evidence of diabetes and deliveries prior to 2013. Liveborn infants were linked to their B4SC results. Data were analyzed between January 2017 and May 2018. Exposures: Pharmacologic treatment for GDM with metformin or insulin, measured using pharmaceutical claims data. Main Outcomes and Measures: Child growth (weight and height) and Strengths and Difficulties Questionnaire (SDQ) scores for behavioral development. All outcomes were derived from the B4SC screening program. Linear and log-binomial regression with inverse probability of treatment weighting was used to estimate the association of child growth and psychosocial outcomes with metformin vs insulin treatment for GDM. Results: In both treatment groups, the mean (SD) maternal age was 32 (5) years. A large proportion of mothers who were treated with insulin identified as New Zealand European (867 [44.9%]) while 576 mothers who were treated with metformin (28.9%) identified as New Zealand European. Approximately one-third of mothers who were treated with metformin (n = 639) identified as Asian. We identified 3928 pregnancies treated with metformin (n = 1996) or insulin (n = 1932). After adjustment, we observed no meaningful difference in weight for height z scores between children exposed to metformin compared with insulin (mean difference, -0.10; 95% CI, -0.20 to 0.01). Risk of being 85th percentile or greater for weight for height was similar between treatment groups (adjusted risk ratio, 0.92; 95% CI, 0.83-1.02). Mean SDQ scores were not meaningfully different between the treatment groups, Children of metformin-treated mothers were not significantly more likely to have parent-reported SDQ scores of 14 or more (adjusted risk ratio, 1.13; 95% CI, 0.88-1.46) than those of insulin-treated mothers. Conclusions and Relevance: Our study compares long-term outcomes among school-aged children following maternal use of metformin vs insulin treatment for GDM. Children of metformin-treated mothers were indistinguishable on growth and developmental assessments from those of insulin-treated mothers. These results will help inform future GDM treatment guidelines.

Age-specific effectiveness following each dose of acellular pertussis vaccine among infants and children in New Zealand.

BACKGROUND: Though it is believed the switch from whole cell to acellular pertussis vaccine has contributed to the resurgence of pertussis disease, few studies have evaluated vaccine effectiveness (VE) and duration of protection provided by an acellular vaccine schedule including three primary doses but no toddler-age dose. We assessed this schedule in New Zealand (NZ), a setting with historically high rates of pertussis disease, and low but recently improved immunisation coverage. We further evaluated protection following the preschool-age booster dose. METHODS: We performed a nested case-control study using national-level healthcare data. Hospitalised and non-hospitalised pertussis was detected among children 6weeks to 7years of age between January 2006 and December 2013. The NZ National Immunisation Register provided vaccination status for cases and controls. Conditional logistic regression was used to calculate dose-specific VE with duration of immunity examined by stratifying VE into ages aligned with the immunisation schedule. RESULTS: VE against pertussis hospitalisation was 93% (95% confidence interval [CI]: 87, 96) following three doses among infants aged 5-11months who received three compared to zero doses. This protection was sustained through children's fourth birthdays (VE⩾91%). VE against non-hospitalised pertussis was also sustained after three doses, from 86% (95% CI: 80, 90) among 5-11month olds to 84% (95% CI: 80, 88) among 3-year-olds. Following the first booster dose at 4years of age, the protective VE of 93% (95% CI: 90, 95) among 4-year-olds continued through 7years of age (VE⩾91%). CONCLUSIONS: We found a high level of protection with no reduction in VE following both the primary course and the first booster dose. These findings support a 3-dose primary course of acellular vaccine with no booster dose until 4years of age.

Influenza vaccine effectiveness for hospital and community patients using control groups with and without non-influenza respiratory viruses detected, Auckland, New Zealand 2014.

BACKGROUND: We aimed to estimate the protection afforded by inactivated influenza vaccine, in both community and hospital settings, in a well characterised urban population in Auckland during 2014. METHODS: We used two different comparison groups, all patients who tested negative for influenza and only those patients who tested negative for influenza and had a non-influenza respiratory virus detected, to calculate the vaccine effectiveness in a test negative study design. Estimates were made separately for general practice outpatient consultations and hospitalised patients, stratified by age group and by influenza type and subtype. Vaccine status was confirmed by electronic record for general practice patients and all respiratory viruses were detected by real time polymerase chain reaction. RESULTS: 1039 hospitalised and 1154 general practice outpatient consultations met all the study inclusion criteria and had a respiratory sample tested for influenza and other respiratory viruses. Compared to general practice patients, hospitalised patients were more likely to be very young or very old, to be Maori or Pacific Islander, to have a low income and to suffer from chronic disease. Vaccine effectiveness (VE) adjusted for age and other participant characteristics using all influenza negative controls was 42% (95% CI: 16 to 60%) for hospitalised and 56% (95% CI: 35 to 70%) for general practice patients. The vaccine appeared to be most effective against the influenza A(H1N1)pdm09 strain with an adjusted VE of 62% (95% CI:38 to 77%) for hospitalised and 59% (95% CI:36 to 74%) for general practice patients, using influenza virus negative controls. Similar results found when patients testing positive for a non-influenza respiratory virus were used as the control group. CONCLUSION: This study contributes to validation of the test negative design and confirms that inactivated influenza vaccines continue to provide modest but significant protection against laboratory-confirmed influenza.

Impact of improved treatment on disease burden of chronic hepatitis C in New Zealand.

BACKGROUND: We describe the burden of HCV infection and estimate the effect of four different treatment strategies to reduce HCV-related morbidity and mortality. METHODS: Baseline model parameters were based upon literature review and expert consensus, focusing on New Zealand data. Four scenarios were modelled: Scenario 1 estimated the impact of increased treatment efficacy, while Scenario 2 estimated the effect of increased treatment efficacy and gradual increases in numbers treated. Scenarios 3 and 4 estimated the impact of deferred introduction of new DAAs for either 1 or 2 years. RESULTS: Prevalence of HCV infection peaked in 2010 (50,480 cases). Peak prevalence of cirrhosis and HCC will occur after 2030. Scenario 2 resulted in sizeable decreases in HCV-related morbidity and mortality. The impact of Scenario 1 was smaller. Deferring funding for new DAA treatments for a further 1 or 2 years resulted in an 18-36% increase in liver-related deaths in 2030. CONCLUSIONS: While prevalence of chronic HCV infection may have peaked, disease burden continues to grow. Increased treatment uptake and efficacy combined with efforts to reduce disease transmission, will help prevent advanced liver disease and deaths.

Prevalence distribution and risk factors for Schistosoma hematobium infection among school children in Blantyre, Malawi.

BACKGROUND: Schistosomiasis is a public health problem in Malawi but estimates of its prevalence vary widely. There is need for updated information on the extent of disease burden, communities at risk and factors associated with infection at the district and sub-district level to facilitate effective prioritization and monitoring while ensuring ownership and sustainability of prevention and control programs at the local level. METHODS AND FINDINGS: We conducted a cross-sectional study between May and July 2006 among pupils in Blantyre district from a stratified random sample of 23 primary schools. Information on socio-demographic factors, schistosomiasis symptoms and other risk factors was obtained using questionnaires. Urine samples were examined for Schistosoma hematobium ova using filtration method. Bivariate and multiple logistic regressions with robust estimates were used to assess risk factors for S. hematobium. One thousand one hundred and fifty (1,150) pupils were enrolled with a mean age of 10.5 years and 51.5% of them were boys. One thousand one hundred and thirty-nine (1,139) pupils submitted urine and S. hematobium ova were detected in 10.4% (95%CI 5.43-15.41%). Male gender (OR 1.81; 95% CI 1.06-3.07), child's knowledge of an existing open water source (includes river, dam, springs, lake, etc.) in the area (OR 1.90; 95% CI 1.14-3.46), history of urinary schistosomiasis in the past month (OR 3.65; 95% CI 2.22-6.00), distance of less than 1 km from school to the nearest open water source (OR 5.39; 95% CI 1.67-17.42) and age 8-10 years (OR 4.55; 95% CI 1.53-13.50) compared to those 14 years or older were associated with infection. Using urine microscopy as a gold standard, the sensitivity and specificity of self-reported hematuria was 68.3% and 73.6%, respectively. However, the positive predictive value was low at 23.9% and was associated with age. CONCLUSION: The study provides an important update on the status of infection in this part of sub-Saharan Africa and exemplifies the success of deliberate national efforts to advance active participation in schistosomiasis prevention and control activities at the sub-national or sub-district levels. In this population, children who attend schools close to open water sources are at an increased risk of infection and self-reported hematuria may still be useful in older children in this region.

The risk of simple febrile seizures after immunisation with a new group B meningococcal vaccine, New Zealand.

As part of safety monitoring during a group B meningococcal disease vaccination campaign in New Zealand, we examined the possible excess risk of vaccine-associated simple febrile seizures (SFS). We conducted a cohort analysis using data from active hospital-based surveillance in the South Auckland area and a national immunisation register. Based on analysis of approximately 63,000 doses, we found no statistically significant increase in SFS incidence within 1, 2, 4, or 7 days after vaccination for any/all doses administered to children aged 6 months through 4 years. We concluded that the vaccine is unlikely to induce a heightened risk of SFS.

Post-marketing safety monitoring of a new group B meningococcal vaccine in New Zealand, 2004-2006.

New Zealand introduced a new outer membrane vesicle vaccine in 2004 to combat an epidemic of group B meningococcal disease. An Independent Safety Monitoring Board oversaw intensive safety monitoring, which included hospital surveillance, health professional reporting (passive and active) and mortality monitoring. With over three million doses administered to individuals aged under 20 years, the monitoring results provide consistent evidence supporting the vaccine's safety.