Utility of surveillance data for planning for dengue elimination in Yogyakarta, Indonesia: a scenario-tree modelling approach.

INTRODUCTION: Field trials and modelling studies suggest that elimination of dengue transmission may be possible through widespread release of Aedes aegypti mosquitoes infected with the insect bacterium Wolbachia pipientis (wMel strain), in conjunction with routine dengue control activities. This study aimed to develop a modelling framework to guide planning for the potential elimination of locally acquired dengue in Yogyakarta, a city of almost 400 000 people in Java, Indonesia. METHODS: A scenario-tree modelling approach was used to estimate the sensitivity of the dengue surveillance system (including routine hospital-based reporting and primary-care-based enhanced surveillance), and time required to demonstrate elimination of locally acquired dengue in Yogyakarta city, assuming the detected incidence of dengue decreases to zero in the future. Age and gender were included as risk factors for dengue, and detection nodes included the probability of seeking care, probability of sample collection and testing, diagnostic test sensitivity and probability of case notification. Parameter distributions were derived from health system data or estimated by expert opinion. Alternative simulations were defined based on changes to key parameter values, separately and in combination. RESULTS: For the default simulation, median surveillance system sensitivity was 0.131 (95% PI 0.111 to 0.152) per month. Median confidence in dengue elimination reached 80% after a minimum of 13 months of zero detected dengue cases and 90% confidence after 25 months, across different scenarios. The alternative simulations investigated produced relatively small changes in median system sensitivity and time to elimination. CONCLUSION: This study suggests that with a combination of hospital-based surveillance and enhanced clinic-based surveillance for dengue, an acceptable level of confidence (80% probability) in the elimination of locally acquired dengue can be reached within 2 years. Increasing the surveillance system sensitivity could shorten the time to first ascertainment of elimination of dengue and increase the level of confidence in elimination.

Systematic scoping review of the implementation, adoption, use, and effectiveness of digital contact tracing interventions for COVID-19 in the Western Pacific Region.

A systematic scoping review of digital contact tracing (DCT) interventions for COVID-19 was conducted to describe the implementation, adoption, use and effectiveness of DCT interventions implemented as part of the COVID-19 response in the Western Pacific Region (WPR). A systematic search identified 341 studies and 128 grey literature sources, of which 18 studies and 41 grey literature sources were included. 17 (46%) WPR countries and areas implemented DCT interventions. Adoption ranged from 14.6% to 92.7% in different adult populations and epidemiological contexts. Trust in authorities, and privacy concerns and beliefs, were the most frequent determinants of adoption and use. Only two studies analysed DCT effectiveness, which showed limited to no effectiveness of DCT interventions in low transmission settings. Overall, there is limited evidence available to evaluate the contribution of DCT to mitigating COVID-19 in the WPR. Preparedness for future health emergencies should include developing robust frameworks for DCT effectiveness evaluations.

The Australian 2019/2020 Black Summer Bushfires: Analysis of the Pathology, Treatment Strategies and Decision Making About Burnt Livestock.

In 2019/2020, Australia experienced a severe bushfire event, with many tens of thousands of livestock killed or euthanized. Little systematic research has occurred to understand livestock bushfire injuries, risk factors for injury, or how to make decisions about management of bushfire-injured livestock. Addressing this research gap is important as there is an increasing bushfire incidence globally. This paper presents qualitative research findings about bushfire-injured and killed livestock in the south-east of Australia after the 2019/2020 Australian bushfires. We describe observed pathology, treatments used, and risk factors for injury, then use thematic analysis to understand decision making about managing fire-injured livestock. Livestock injured by the fires showed pathology predominantly associated with the common integument (feet, hooves and skin) and signs of acute respiratory damage. It could take several days for the full extent of burns to become apparent, leaving prognostic doubt. Treatment strategies included immediate euthanasia, salvage slaughter, retention for later culling, treatment and recovery on farm, hospitalization and intensive treatment, or no intervention. Risk factors reported for livestock injury included lack of warnings about an impending fire, the type and amount of vegetation around livestock and the weather conditions on the day the fire reached livestock. Moving stock to an area with little vegetation before fire arrived was seen as protective. Decision making regarding injured livestock appeared influenced by three main themes: (1) observations on the severity of pathology, clinical signs and level of prognostic doubt, (2) pre-existing beliefs about animal welfare (responsibility to minimize unnecessary suffering) and (3) assumptions about the future. The management of livestock was largely appropriate due to the rapid provision of veterinary expertise. However, it is likely that some injured livestock were euthanized due to conservative veterinary advice driven by a lack of opportunity to re-assess stock, with impacts on farmers. In future, resourcing regular revisits of injured livestock to manage risks of gradual progression of burn pathology may facilitate more accurate prognostic assessment, provided injured animals can receive appropriate pain relief. In addition, a more comprehensive burns classification system linked to prognosis that can be rapidly applied in the field may assist assessments.

Electronic information systems for One Health surveillance of antimicrobial resistance: a systematic scoping review.

INTRODUCTION: Electronic information systems (EIS) that implement a 'One Health' approach by integrating antimicrobial resistance (AMR) data across the human, animal and environmental health sectors, have been identified as a global priority. However, evidence on the availability, technical capacities and effectiveness of such EIS is scarce. METHODS: Through a qualitative synthesis of evidence, this systematic scoping review aims to: identify EIS for AMR surveillance that operate across human, animal and environmental health sectors; describe their technical characteristics and capabilities; and assess whether there is evidence for the effectiveness of the various EIS for AMR surveillance. Studies and reports between 1 January 2000 and 21 July 2021 from peer-reviewed and grey literature in the English language were included. RESULTS: 26 studies and reports were included in the final review, of which 27 EIS were described. None of the EIS integrated AMR data in a One Health approach across all three sectors. While there was a lack of evidence of thorough evaluations of the effectiveness of the identified EIS, several surveillance system effectiveness indicators were reported for most EIS. Standardised reporting of the effectiveness of EIS is recommended for future publications. The capabilities of the EIS varied in their technical design features, in terms of usability, data display tools and desired outputs. EIS that included interactive features, and geospatial maps are increasingly relevant for future trends in AMR data analytics. CONCLUSION: No EIS for AMR surveillance was identified that was designed to integrate a broad range of AMR data from humans, animals and the environment, representing a major gap in global efforts to implement One Health approaches to address AMR.

Evidence That Higher Temperatures Are Associated With a Marginally Lower Incidence of COVID-19 Cases.

Seasonal variations in COVID-19 incidence have been suggested as a potentially important factor in the future trajectory of the pandemic. Using global line-list data on COVID-19 cases reported until 17th of March 2020 and global gridded weather data, we assessed the effects of air temperature and relative humidity on the daily incidence of confirmed COVID-19 local cases at the subnational level (first-level administrative divisions). After adjusting for surveillance capacity and time since first imported case, average temperature had a statistically significant, negative association with COVID-19 incidence for temperatures of -15°C and above. However, temperature only explained a relatively modest amount of the total variation in COVID-19 cases. The effect of relative humidity was not statistically significant. These results suggest that warmer weather may modestly reduce the rate of spread of COVID-19, but anticipation of a substantial decline in transmission due to temperature alone with onset of summer in the northern hemisphere, or in tropical regions, is not warranted by these findings.

Qualitative research in epidemiology: theoretical and methodological perspectives.

Increasingly, modern epidemiology has adopted complex causal frameworks incorporating individual- and population-level determinants of health. Despite the growing use of qualitative methodologies in public health research generally, discussion of causal reasoning in epidemiology rarely considers evidence derived from qualitative research. This article argues for a coherent role of qualitative research within epidemiology through analysis of the principles of causal reasoning that underlie current debates about causal inference in epidemiology. It introduces two approaches to causal inference by Russo and Williamson (2009) and Reiss (2012) that emphasize the relevance of both the nature of causation and how knowledge is gained about causation in assessing evidence for a causal relation. Both theories have scope for incorporating multiple types of evidence to assess causal claims. We argue that these theories align with the empirical focus of epidemiology and allow for different types of evidence to evaluate causal claims, including evidence originating from qualitative research; such evidence can contribute to a mechanistic understanding of causal relations and to understanding the effects of context on health-related outcomes. Finally, we discuss this approach in light of previous literature on the role of qualitative research in epidemiology and implications for future epidemiologic research.

Households or Hotspots? Defining Intervention Targets for Malaria Elimination in Ratanakiri Province, Eastern Cambodia.

BACKGROUND: Malaria "hotspots" have been proposed as potential intervention units for targeted malaria elimination. Little is known about hotspot formation and stability in settings outside sub-Saharan Africa. METHODS: Clustering of Plasmodium infections at the household and hotspot level was assessed over 2 years in 3 villages in eastern Cambodia. Social and spatial autocorrelation statistics were calculated to assess clustering of malaria risk, and logistic regression was used to assess the effect of living in a malaria hotspot compared to living in a malaria-positive household in the first year of the study on risk of malaria infection in the second year. RESULTS: The crude prevalence of Plasmodium infection was 8.4% in 2016 and 3.6% in 2017. Living in a hotspot in 2016 did not predict Plasmodium risk at the individual or household level in 2017 overall, but living in a Plasmodium-positive household in 2016 strongly predicted living in a Plasmodium-positive household in 2017 (Risk Ratio, 5.00 [95% confidence interval, 2.09-11.96], P < .0001). There was no consistent evidence that malaria risk clustered in groups of socially connected individuals from different households. CONCLUSIONS: Malaria risk clustered more clearly in households than in hotspots over 2 years. Household-based strategies should be prioritized in malaria elimination programs in this region.

A Critical Enquiry into Variability of Insecticidal Net Use in Cambodia: Implications for Assessing Appropriateness of Malaria Elimination Interventions.

Distributing long-lasting insecticidal nets (LLINs) to individuals living in malaria-endemic regions is a cornerstone of global malaria control. National malaria control programs aim to achieve "universal coverage" of at-risk populations to reach LLINs' full potential to reduce malaria, progress of which is then measured by indicators constructed from standardized questionnaires. Through an exploration of variability in LLIN use in Cambodia, we argue that indicators of universal coverage of LLINs are not sufficiently commensurate with the realities they are intended to measure, limiting the suitability of the data to serve program and policy purposes in a malaria elimination era. Reflecting on the various sources of variability in LLIN use, we apply and extend the concept of "appropriateness" as a third prong to the widely used "efficacy" and "effectiveness" criteria for evaluating LLINs as a tool for malaria prevention. Describing first the different dimensions of the intervention and the sociocultural context separately, we will further show how the variability underlying both is affected and induced by inappropriate aspects of the intervention and the measurements of its impact. We consider the gap between "net use" and the numerical representations of such local net use justifies further exploration of potential strategies to improve LLIN use in subgroups where persisting malaria transmission clusters.

Forest Goers and Multidrug-Resistant Malaria in Cambodia: An Ethnographic Study.

Multidrug-resistant Plasmodium falciparum malaria on the Cambodia-Thailand border is associated with working in forested areas. Beyond broad recognition of "forest-going" as a risk factor for malaria, little is known about different forest-going populations in this region. In Oddar Meanchey Province in northwestern Cambodia, qualitative ethnographic research was conducted to gain an in-depth understanding of how different populations, mobility and livelihood patterns, and activities within the forest intersect with potentiate malaria risk and impact on the effectiveness of malaria control and elimination strategies. We found that most forest-going in this area is associated with obtaining precious woods, particularly Siamese rosewood. In the past, at-risk populations included large groups of temporary migrants. As timber supplies have declined, so have these large migrant groups. However, groups of local residents continue to go to the forest and are staying for longer. Most forest-goers had experienced multiple episodes of malaria and were well informed about malaria risk. However, economic realities mean that local residents continue to pursue forest-based livelihoods. Severe constraints of available vector control methods mean that forest-goers have limited capacity to prevent vector exposure. As forest-goers access the forest using many different entry and exit points, border screening and treatment interventions will not be feasible. Once in the forest, groups often converge in the same areas; therefore, interventions targeting the mosquito population may have a potential role. Ultimately, a multisectoral approach as well as innovative and flexible malaria control strategies will be required if malaria elimination efforts are to be successful.

What motivates Ebola survivors to donate plasma during an emergency clinical trial? The case of Ebola-Tx in Guinea.

INTRODUCTION: During the 2014 Ebola Virus Disease (EVD) epidemic, the Ebola-Tx trial evaluated the use of convalescent plasma (CP) in Guinea. The effectiveness of plasmapheresis trials depends on the recruitment of plasma donors. This paper describes what motivated or deterred EVD survivors to donate CP, providing insights for future plasmapheresis trials and epidemic preparedness. METHODS: This qualitative study, part of Ebola-Tx, researched and addressed emergent trial difficulties through interviewing, participant observation and focus group discussions. Sampling was theoretical and retroductive analysis was done in NVivo 10. RESULTS: Willingness or hesitance to participate in plasma donation depended on factors at the interface of pre-existing social dynamics; the impact of the disease and the consequent emergency response including the trial set-up. For volunteers, motivation to donate was mainly related to the feeling of social responsibility inspired by having survived EVD and to positive perceptions of plasmapheresis technology despite still unknown trial outcomes. Conversely, confidentiality concerns when volunteering due to stigmatization of survivors and perceived decrease in vital strength and in antibodies when donating, leading to fears of loss in protection against EVD, were main deterrents. The dynamic (dis)trust in Ebola Response Actors and in other survivors further determined willingness to participate and lead to the emergence/decline of rumours related to blood stealing and treatment effectiveness. Historic inter-ethnic relations in the health care setting further defined volunteering along socio-economic and ethnic lines. Finally, lack of follow-up and of dedicated care further impacted on motivation to volunteer. CONCLUSIONS: Ebola-Tx was the first trial to solicit and evaluate blood-product donation as an experimental treatment on a large scale in Sub-Saharan Africa. An effective donation system requires directly engaging with emergent social barriers and providing an effective ethical response, including improved and transparent communication, effective follow-up after donation, assuring confidentiality and determining ethical incentives.

Importance of household-level risk factors in explaining micro-epidemiology of asymptomatic malaria infections in Ratanakiri Province, Cambodia.

Heterogeneity in malaria risk is considered a challenge for malaria elimination. A cross-sectional study was conducted to describe and explain micro-epidemiological variation in Plasmodium infection prevalence at household and village level in three villages in Ratanakiri Province, Cambodia. A two-level logistic regression model with a random intercept fitted for each household was used to model the odds of Plasmodium infection, with sequential adjustment for individual-level then household-level risk factors. Individual-level risk factors for Plasmodium infection included hammock net use and frequency of evening outdoor farm gatherings in adults, and older age in children. Household-level risk factors included house wall material, crop types, and satellite dish and farm machine ownership. Individual-level risk factors did not explain differences in odds of Plasmodium infection between households or between villages. In contrast, once household-level risk factors were taken into account, there was no significant difference in odds of Plasmodium infection between households and between villages. This study shows the importance of ongoing indoor and peridomestic transmission in a region where forest workers and mobile populations have previously been the focus of attention. Interventions targeting malaria risk at household level should be further explored.

Characterization of Plasmodium falciparum and Plasmodium vivax recent exposure in an area of significantly decreased transmission intensity in Central Vietnam.

BACKGROUND: In Vietnam, malaria transmission has been reduced to very low levels over the past 20 years, and as a consequence, the country aims to eliminate malaria by 2030. This study aimed to characterize the dynamics and extent of the parasite reservoir in Central Vietnam, in order to further target elimination strategies and surveillance. METHODS: A 1-year prospective cohort study (n = 429) was performed in three rural communities in Quang Nam province. Six malaria screenings were conducted between November 2014 and November 2015, including systematic clinical examination and blood sampling for malaria parasite identification, as well as molecular and serological analysis of the study population. Malaria infections were detected by light microscopy (LM) and quantitative real time PCR (qPCR), while exposure to Plasmodium falciparum and Plasmodium vivax was measured in the first and last survey by ELISA for PfAMA1, PfGLURP R2, PvAMA1, and PvMSP1-19. Classification and regression trees were used to define seropositivity and recent exposure. RESULTS: Four malaria infections (2 P. falciparum, 2 P. vivax) were detected in the same village by qPCR and/or LM. No fever cases were attributable to malaria. At the same time, the commune health centre (serving a larger area) reported few cases of confirmed malaria cases. Nevertheless, serological data proved that 13.5% of the surveyed population was exposed to P. falciparum and/or P. vivax parasites during the study period, of which 32.6% were seronegative at the start of the study, indicating ongoing transmission in the area. Risk factor analysis for seroprevalence and exposure to P. falciparum and/or P. vivax identified structural or economic risk factors and activity/behaviour-related factors, as well as spatial heterogeneity at the village level. CONCLUSIONS: Previous studies in Central Vietnam demonstrated high occurrence of asymptomatic and sub-microscopic infections. However, in this study very few asymptomatic infections were detected despite serological evidence of continued transmission. Nonetheless, the factors associated with spatial heterogeneity in transmission could be evaluated using serological classification of recent exposure, which supports the usefulness of serological methods to monitor malaria transmission.

Micro-epidemiology of malaria in an elimination setting in Central Vietnam.

BACKGROUND: In Vietnam, malaria persists in remote forested regions where infections are spatially heterogeneous, mostly asymptomatic and with low parasite density. Previous studies in Vietnam have investigated broad behavioural concepts such as 'engaging in forest activities' as risk factors for malaria infection, which may not explain heterogeneity in malaria risk, especially in malaria elimination settings. METHODS: A mixed methods study combining ethnographic research and a cross-sectional survey was embedded in a 1-year malariometric cohort study in three ethnic minority villages in South Tra My district, Quang Nam Province in Central Vietnam. Qualitative data collection included in-depth interviews, informal conversations and participant observations over a 2-month period, and the findings were used to develop the questionnaire used in the cross-sectional survey. The latter collected data on evening activities, mobility patterns and household characteristics. The primary outcome, recent exposure to malaria, was defined using the classification and regression tree method to determine significant changes in antibody titres during the year preceding the survey. Risk factor analyses for recent exposure to malaria were conducted using logistic regression. RESULTS: 22 in-depth interviews and numerous participant observations were recorded during the ethnographic research (April to June 2015), and 160 adults (86% response rate) responded to the cross-sectional survey (November to December 2015). Recent exposure to Plasmodium falciparum malaria was estimated at 22.9 and at 17.1% for Plasmodium vivax. Ongoing malaria transmission appears to be maintained by activities that delay or disrupt sleeping in a permanent structure in which a bed net could be hung, including evening drinking gatherings, fishing, logging in the forest and outdoor TV watching. CONCLUSIONS: Vector control tools for outdoor evening activities in villages as well as at farms, forest and river locations should be incorporated into current malaria elimination efforts in Central Vietnam. Micro-epidemiology studies using mixed-methods designs can provide a comprehensive understanding of the malaria risk at fine spatial scales and better inform the implementation of targeted interventions for malaria elimination.

Community sensitization and decision-making for trial participation: A mixed-methods study from The Gambia.

BACKGROUND: Ensuring individual free and informed decision-making for research participation is challenging. It is thought that preliminarily informing communities through 'community sensitization' procedures may improve individual decision-making. This study set out to assess the relevance of community sensitization for individual decision-making in research participation in rural Gambia. METHODS: This anthropological mixed-methods study triangulated qualitative methods and quantitative survey methods in the context of an observational study and a clinical trial on malaria carried out by the Medical Research Council Unit Gambia. RESULTS/DISCUSSION: Although 38.7% of the respondents were present during sensitization sessions, 91.1% of the respondents were inclined to participate in the trial when surveyed after the sensitization and prior to the informed consent process. This difference can be explained by the informal transmission of information within the community after the community sensitization, expectations such as the benefits of participation based on previous research experiences, and the positive reputation of the research institute. Commonly mentioned barriers to participation were blood sampling and the potential disapproval of the household head. CONCLUSION: Community sensitization is effective in providing first-hand, reliable information to communities as the information is cascaded to those who could not attend the sessions. However, further research is needed to assess how the informal spread of information further shapes people's expectations, how the process engages with existing social relations and hierarchies (e.g. local political power structures; permissions of heads of households) and how this influences or changes individual consent.

Defining micro-epidemiology for malaria elimination: systematic review and meta-analysis.

BACKGROUND: Malaria risk can vary markedly between households in the same village, or between villages, but the determinants of this "micro-epidemiological" variation in malaria risk remain poorly understood. This study aimed to identify factors that explain fine-scale variation in malaria risk across settings and improve definitions and methods for malaria micro-epidemiology. METHODS: A systematic review of studies that examined risk factors for variation in malaria infection between individuals, households, clusters, hotspots, or villages in any malaria-endemic setting was conducted. Four databases were searched for studies published up until 6th October 2015. Crude and adjusted effect estimates for risk factors for malaria infection were combined in random effects meta-analyses. Bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: From 743 retrieved records, 51 studies were selected, representing populations comprising over 160,000 individuals in 21 countries, in high- and low-endemicity settings. Sixty-five risk factors were identified and meta-analyses were conducted for 11 risk factors. Most studies focused on environmental factors, especially increasing distance from a breeding site (OR 0.89, 95% CI 0.86-0.92, 10 studies). Individual bed net use was protective (OR 0.63, 95% CI 0.52-0.77, 12 studies), but not household bed net ownership. Increasing household size (OR 1.08, 95% CI 1.01-1.15, 4 studies) and household crowding (OR 1.79, 95% CI 1.48-2.16, 4 studies) were associated with malaria infection. Health seeking behaviour, medical history and genetic traits were less frequently studied. Only six studies examined whether individual-level risk factors explained differences in malaria risk at village or hotspot level, and five studies reported different risk factors at different levels of analysis. The risk of bias varied from low to high in individual studies. Insufficient reporting and comparability of measurements limited the number of meta-analyses conducted. CONCLUSIONS: Several variables associated with individual-level malaria infection were identified, but there was limited evidence that these factors explain variation in malaria risk at village or hotspot level. Social, population and other factors may confound estimates of environmental risk factors, yet these variables are not included in many studies. A structured framework of malaria risk factors is proposed to improve study design and quality of evidence in future micro-epidemiological studies.

Characterizing Types of Human Mobility to Inform Differential and Targeted Malaria Elimination Strategies in Northeast Cambodia.

Human population movements currently challenge malaria elimination in low transmission foci in the Greater Mekong Subregion. Using a mixed-methods design, combining ethnography (n = 410 interviews), malariometric data (n = 4996) and population surveys (n = 824 indigenous populations; n = 704 Khmer migrants) malaria vulnerability among different types of mobile populations was researched in the remote province of Ratanakiri, Cambodia. Different structural types of human mobility were identified, showing differential risk and vulnerability. Among local indigenous populations, access to malaria testing and treatment through the VMW-system and LLIN coverage was high but control strategies failed to account for forest farmers' prolonged stays at forest farms/fields (61% during rainy season), increasing their exposure (p = 0.002). The Khmer migrants, with low acquired immunity, active on plantations and mines, represented a fundamentally different group not reached by LLIN-distribution campaigns since they were largely unregistered (79%) and unaware of the local VMW-system (95%) due to poor social integration. Khmer migrants therefore require control strategies including active detection, registration and immediate access to malaria prevention and control tools from which they are currently excluded. In conclusion, different types of mobility require different malaria elimination strategies. Targeting mobility without an in-depth understanding of malaria risk in each group challenges further progress towards elimination.

High Mobility and Low Use of Malaria Preventive Measures Among the Jarai Male Youth Along the Cambodia-Vietnam Border.

Malaria control along the Vietnam-Cambodia border presents a challenge for both countries' malaria elimination targets as the region is forested, inhabited by ethnic minority populations, and potentially characterized by early and outdoor malaria transmission. A mixed methods study assessed the vulnerability to malaria among the Jarai population living on both sides of the border in the provinces of Ratanakiri (Cambodia) and Gia Lai (Vietnam). A qualitative study generated preliminary hypotheses that were quantified in two surveys, one targeting youth (N = 498) and the other household leaders (N = 449). Jarai male youth, especially in Cambodia, had lower uptake of preventive measures (57.4%) and more often stayed overnight in the deep forest (35.8%) compared with the female youth and the adult population. Among male youth, a high-risk subgroup was identified that regularly slept at friends' homes or outdoors, who had fewer bed nets (32.5%) that were torn more often (77.8%). The vulnerability of Jarai youth to malaria could be attributed to the transitional character of youth itself, implying less fixed sleeping arrangements in nonpermanent spaces or non-bed sites. Additional tools such as long-lasting hammock nets could be suitable as they are in line with current practices.

Variation in hospital caesarean section rates for preterm births.

BACKGROUND: Evidence about optimal mode of delivery for preterm birth is lacking, and there is thought to be considerable variation in practice. OBJECTIVE: To assess whether variation in hospital preterm caesarean section rates (Robson Classification Group 10) and outcomes are explained by casemix, labour or hospital characteristics. MATERIALS AND METHODS: Population-based cohort study in NSW, 2007-2011. Births were categorised according to degree of prematurity and hospital service capability: 26-31, 32-33 and 34-36 weeks' gestation. Hospital preterm caesarean rates were investigated using multilevel logistic regression models, progressively adjusting for casemix, labour and hospital factors. The association between hospital caesarean rates, and severe maternal and neonatal morbidity rates was assessed. RESULTS: At 26-31 weeks' gestation, the caesarean rate was 55.2% (seven hospitals, range 43.4-58.4%); 50.9% at 32-33 weeks (12 hospitals, 43.4-58.1%); and 36.4% at 34-36 weeks (51 hospitals, 17.4-48.3%). At 26-31 weeks and 32-33 weeks' gestation, 81% and 59% of the variation between hospitals was explained with no hospital significantly different from the state average after adjustment. At 34-36 weeks' gestation, although 59% of the variation was explained, substantial unexplained variation persisted. Hospital caesarean rates were not associated with severe maternal morbidity rates at any gestational age. At 26-31 weeks' gestation, medium and high caesarean rates were associated with higher severe neonatal morbidity rates, but there was no evidence of this association ≥32 weeks. CONCLUSION: Both casemix and practice differences contributed to the variation in hospital caesarean rates. Low preterm caesarean rates were not associated with worse outcomes.

Adjustment for compliance behavior in trials of epidural analgesia in labor using instrumental variable meta-analysis.

OBJECTIVES: Intention-to-treat (ITT) analysis of randomized controlled trials (RCTs) may cause bias when compliance is poor. Noncompliance describes failure to comply with allocation in the intervention arm, and contamination describes uptake of the intervention in the control arm. Instrumental variable (IV) analysis can be applied in addition to the primary ITT analysis to estimate the causal effect adjusted for noncompliance and contamination, assuming that noncompliers would have had the same treatment benefit as compliers. We aimed to compare ITT and IV meta-analysis of the association between epidural analgesia in labor and cesarean section. STUDY DESIGN AND SETTING: The study was restricted to 27 trials in a Cochrane Systematic Review. The association between epidural analgesia in labor and cesarean section was calculated using ITT and IV analyses. Pooled risk ratios (RRs) were calculated using fixed-effects meta-analysis. RESULTS: In 18 trials with compliance data, noncompliance was 23% and contamination was 27%. In 10 trials with outcome data stratified by compliance, the pooled RR for cesarean section following epidural analgesia was 1.37 [95% confidence interval (CI): 1.00, 1.89; P = 0.049] using IV compared with 1.19 (95% CI: 0.93, 1.51; P = 0.16) using ITT. CONCLUSION: ITT meta-analysis underestimates the effect of receiving epidural analgesia in labor on cesarean section compared with IV meta-analysis.