Magnitude and determinants of excess total, age-specific and sex-specific all-cause mortality in 24 countries worldwide during 2020 and 2021: results on the impact of the COVID-19 pandemic from the C-MOR project.

INTRODUCTION: To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age. METHODS: Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015-2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015-2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models. RESULTS: Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively. CONCLUSION: This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.

Post implementation quarantine recommendations that support preparedness: A systematic review and quarantine implementation capability framework.

BACKGROUND: During COVID-19, countries utilised various quarantine systems to achieve specific outcomes. At different stages and durations, voluntary and mandatory quarantine occurred in homes, hotels and facilities based on local and national elimination strategies. Countries are incorporating quarantine lessons from COVID-19 into revising pandemic plans as part of the World Health Organization's Preparedness and Resilience for Emerging Threats (PRET) activities. This review aimed to amalgamate quarantine post implementation recommendations from a whole-of-system perspective. METHODS: This review utilised MEDLINE, Embase, CINAHL, APA, and PsycINFO. To capture all pandemics, no date restriction was applied. Recommendations were synthesised and inductively grouped into quarantine capability categories. This review was registered in PROSPERO (CRD42023420765). RESULTS: A total of 449 published articles were screened, with 51 articles included and 156 recommendations extracted. Recommendations were grouped into 15 quarantine capability categories, comprising governance, preparation, infection prevention and control, ventilation, compliance, data, information and technology, safety-quality-risk, communication, healthcare model, home quarantine, hotel quarantine, facility quarantine, workforce, and resident considerations. The capability categories were further consolidated into strategic, structural, and operational domains to support the whole-of-system perspective. CONCLUSION: The quarantine implementation capability framework generated provides comprehensive and deeper insights into the essential capabilities required for quarantine systems to support governments in PRET activities, including reviewing and revising pandemic plans and developing quarantine preparedness exercises.

Demographic Characteristics of Unvaccinated Asymptomatic and Symptomatic SARS-CoV-2 Cases in Barwon South West, Victoria, Australia.

We investigated 328 SARS-CoV-2 cases in Barwon South West, Victoria, Australia, in the 2020 pre-vaccination period, comparing infections with symptoms to those that remained asymptomatic. De-identified self-reported data on case characteristics and symptom progression from three sequential questionnaires were examined. Multivariable logistic regression was used to model associations between demographic profiles and symptoms. Asymptomatic infections were more than three times as likely to be seen in ethnic minority groups than the Caucasian population after adjusting for gender and age [OR 3.2, 95% CI 1.5-6.7, p < 0.01] and were more common among cases of Asian background [OR 2.8, 95%CI 1.2-6.4]. Asymptomatic infections were also more common in youth and younger adults, but cases were approximately seven times more likely to be in seniors (≥65 years) compared with those 24 years of age or younger after adjusting for sex and ethnicity [OR 6.9, 95% CI 1.3-35.8]. The overrepresentation of ethnic minority groups among asymptomatic infections is suggestive of genetic haplotype variability by ethnic group, conferring greater cross-protection from other coronaviruses in the initial phase of the COVID-19 pandemic. Replication of this analysis in the post-vaccination era and reassessment of symptom expression according to ethnicity in a community with established vaccine and infection-induced immunity would determine whether this is a sustained association or one confined to the early stages of a pandemic in an immunologically naive population. These findings may, in part, reflect differences in testing patterns by ethnicity and true differences in disease expression, both of which are important to understand in order to inform transmission prevention strategies and tailored risk messaging according to ethnic background.

Forecasting pandemic quarantine in New Zealand and Australia: A scoping review of quarantine characteristics and capabilities within preparedness plans and pandemic exercise reports from 2002 to 2019.

BACKGROUND: This scoping review aims to identify and critically review quarantine preparedness in New Zealand and Australia pre-COVID-19 by categorising, comparing, and evaluating quarantine information contained within pandemic plans and exercises from both countries. METHODS: Parliamentary websites, including Archives New Zealand, ParlInfo and Google Scholar, were searched for publicly available plans and exercise reports from 2002 to 2019. Data were extracted from documents meeting the inclusion criteria and analysed using directive content analysis based on the Australian Disaster Preparedness Framework categories. This scoping review followed the Joanna Briggs Institute methodology for scoping reviews, which guided the data extraction, analysis, and presentation of results. RESULTS: A total of 16 documents mentioned quarantine and were included in this scoping review. The emphasis and level of detail regarding quarantine characteristics and capabilities varied between New Zealand's five documents (one plan and four exercise reports) and Australia's 11 documents (one Influenza pandemic plan, eight state plans and two exercise reports). New Zealand's plan forecasted the need for both voluntary quarantine at home and involuntary quarantine in facilities for incoming travellers, whilst the Australian Influenza pandemic plan and state plans primarily considered voluntary quarantine within private residences. Capability gaps identified during exercises were not consistently incorporated into revised plans. Some government documents containing information on quarantine may not be publicly available, limiting the available evidence for this review. CONCLUSION: This scoping review highlights the need to incorporate a range of possible quarantine options into plans and preparation activities to test and identify gaps in government and responsible agencies' capabilities. Pandemic preparedness will be strengthened by incorporating quarantine scale and duration variables into exercise scenarios.

A cross-disciplinary view of current and emerging COVID-19 developments.

The emergency phase of the coronavirus disease 2019 (COVID-19) pandemic is over. Still, the work goes on in understanding the SARS-CoV-2 virus and its evolution, infection impacts - acute and long term - as well as therapeutics and the lessons for preventing and responding to future pandemics. Research into the long-term post-infection effects and therapeutic interventions also expands as the post-infection period lengthens. We provide an overview of the leading edge of COVID-19 research across clinical, epidemiological and social domains.

Pandemic policing and the construction of publics: an analysis of COVID-19 lockdowns in public housing.

COVID-19 responses have cast a spotlight on the uneven impacts of public health policy with particular populations or sites targeted for intervention. Perhaps the starkest example in Australia was the 'hard' lockdown of nine public housing complexes in inner-city Melbourne from 4 to 18 July 2020, where residents were fully confined to their homes. These complexes are home to diverse migrant communities and the lockdown drew public criticism for unfairly stigmatising ethnic minorities. This article draws on media articles published during the lockdown and the Victorian Ombudsman's subsequent investigation to explore the implications of broad, top-down public health measures for culturally and linguistically diverse (CALD) communities. Drawing on Lea's (2020) conceptualisation of policy ecology, we analyse the lockdown measures and community responses to explore the normative assumptions underpinning health policy mechanisms, constituting 'target populations' in narrow, exclusionary terms. We argue that the lockdown measures and use of police as compliance officers positioned tower residents as risky subjects in risky places. Tracing how such subject positions are produced, and resisted at the grassroots level, we highlight how policy instruments are not neutral interventions, but rather instantiate classed and racialised patterns of exclusion, reinforcing pervasive social inequalities in the name of public health.

Impact of the COVID-19 pandemic on total, sex- and age-specific all-cause mortality in 20 countries worldwide during 2020: results from the C-MOR project.

BACKGROUND: To understand the impact of the COVID-19 pandemic on mortality, this study investigates overall, sex- and age-specific excess all-cause mortality in 20 countries, during 2020. METHODS: Total, sex- and age-specific weekly all-cause mortality for 2015-2020 was collected from national vital statistics databases. Excess mortality for 2020 was calculated by comparing weekly 2020 observed mortality against expected mortality, estimated from historical data (2015-2019) accounting for seasonality, long- and short-term trends. Crude and age-standardized rates were analysed for total and sex-specific mortality. RESULTS: Austria, Brazil, Cyprus, England and Wales, France, Georgia, Israel, Italy, Northern Ireland, Peru, Scotland, Slovenia, Sweden, and the USA displayed substantial excess age-standardized mortality of varying duration during 2020, while Australia, Denmark, Estonia, Mauritius, Norway, and Ukraine did not. In sex-specific analyses, excess mortality was higher in males than females, except for Slovenia (higher in females) and Cyprus (similar in both sexes). Lastly, for most countries substantial excess mortality was only detectable (Austria, Cyprus, Israel, and Slovenia) or was higher (Brazil, England and Wales, France, Georgia, Italy, Northern Ireland, Sweden, Peru and the USA) in the oldest age group investigated. Peru demonstrated substantial excess mortality even in the <45 age group. CONCLUSIONS: This study highlights that excess all-cause mortality during 2020 is context dependent, with specific countries, sex- and age-groups being most affected. As the pandemic continues, tracking excess mortality is important to accurately estimate the true toll of COVID-19, while at the same time investigating the effects of changing contexts, different variants, testing, quarantine, and vaccination strategies.

Molecular Epidemiology of Penicillin-Susceptible Staphylococcus aureus Bacteremia in Australia and Reliability of Diagnostic Phenotypic Susceptibility Methods to Detect Penicillin Susceptibility.

BACKGROUND: Defined by the emergence of antibiotic resistant strains, Staphylococcus aureus is a priority bacterial species with high antibiotic resistance. However, a rise in the prevalence of penicillin-susceptible S. aureus (PSSA) bloodstream infections has recently been observed worldwide, including in Australia, where the proportion of methicillin-susceptible S. aureus causing bacteremia identified phenotypically as penicillin-susceptible has increased by over 35%, from 17.5% in 2013 to 23.7% in 2020. OBJECTIVES: To determine the population structure of PSSA causing community- and hospital-onset bacteremia in Australia and to evaluate routine phenotypic antimicrobial susceptibility methods to reliably confirm penicillin resistance on blaZ-positive S. aureus initially classified as penicillin-susceptible by the Vitek® 2 automated microbiology system. RESULTS: Whole genome sequencing on 470 PSSA collected in the 2020 Australian Group on Antimicrobial Resistance Australian Staphylococcus aureus Sepsis Outcome Programme identified 84 multilocus sequence types (STs), of which 79 (463 isolates) were grouped into 22 clonal complexes (CCs). The dominant CCs included CC5 (31.9%), CC97 (10.2%), CC45 (10.0%), CC15 (8.7%), and CC188 (4.9%). Many of the CCs had multiple STs and spa types and, based on the immune evasion cluster type, isolates within a CC could be classified into different strains harboring a range of virulence and resistance genes. Phylogenetic analyses of the isolates showed most CCs were represented by one clade. The blaZ gene was identified in 45 (9.6%) PSSA. Although multiclonal, approximately 50% of blaZ-positive PSSA were from CC15 and were found to be genetically distant from the blaZ-negative CC15 PSSA. The broth microdilution, Etest® and cefinase, performed poorly; however, when the appearance of the zone edge was considered; as per the EUCAST and CLSI criteria, disc diffusion detected 100% of blaZ-positive PSSA. CONCLUSIONS: In Australia, PSSA bacteremia is not caused by the expansion of a single clone. Approximately 10% of S. aureus classified as penicillin-susceptible by the Vitek® 2 harbored blaZ. Consequently, we recommend that confirmation of Vitek® 2 PSSA be performed using an alternative method, such as disc diffusion with careful interpretation of the zone edge.

Prevalence of chronic non-communicable diseases in Ethiopia: A systematic review and meta-analysis of evidence.

Background: Non-communicable diseases (NCDs) are a growing global health challenge disproportionately impacting low- and middle-income settings, including Ethiopia. Currently, the body of evidence describing the burden of NCDs is fragmented, inconsistent, health facility- or institution-based, and out-dated in Ethiopia. We conducted a systematic review of the literature and meta-analysis of the prevalence of NCDs in community settings in Ethiopia. Review methodology: Community-based quantitative studies published in English between January 1st, 2012, and June 30th, 2022, that reported on the prevalence of NCDs in Ethiopia were included. A systematic search of Medline, Embase, Scopus, CINAHL, and Global Health using pretested search terms related to NCDs was conducted, and data were extracted using a piloted data extraction proforma adapted from the Joanna Briggs Institute tool. Meta-analysis was performed using Stata 16. While the pooled prevalence of Diabetes Mellitus (DM) and undiagnosed (DM) was computed and presented using forest plots, then overall prevalence of NCDs and other various types of NCDs were narratively synthesized. I 2 was used to assess heterogeneity. Studies that did not fulfill the criteria (used similar tool to measure the types of NCDs) for meta-analysis were narratively synthesized. Results: Twenty-two studies met the inclusion criteria. Five studies measured the prevalence of NCDs (all NCDs together), ranging from 29 to 35% (prevalence estimates not pooled). The pooled prevalence of Diabetes Mellitus (DM) across ten studies was 5% (95% CI: 4-7%). Three studies each reported on the prevalence of undiagnosed DM (pooled prevalence 5%, 95% CI: 4-7%) and pre-DM (pooled prevalence 7%, 95% CI: 3-14%%). In a narrative analysis the prevalence of cardiovascular conditions ranged from 13.4 to 32.2% (n = 3 studies), cancer mortality ranged from 4 to 18% (n = 3 studies) and respiratory conditions ranged from 1 to 18% (n = 3 studies). Some studies have determined more than one NCDs and that is why the total number of studies are exceeding more than twenty studies. Conclusion and recommendations: Our analysis found that approximately one-third of Ethiopians have an NCD, with cardiovascular diseases the most common of all NCDs. The prevalence of respiratory conditions also appears high, but there are insufficient data for a pooled estimate. Whilst the prevalence of DM appears relatively low, there is evidence that the magnitude is increasing. Public health actions to address the high burden of cardiovascular and respiratory diseases, as well as the increasing magnitude of DM in Ethiopia, must be prioritized. Systematic review registration: PROSPERO [CRD42020196815].

The Magnitude of NCD Risk Factors in Ethiopia: Meta-Analysis and Systematic Review of Evidence.

BACKGROUND: Non-communicable Diseases (NCDs) and their risk factors are the leading contributors to morbidity and mortality globally, particularly in low- and middle-income countries including Ethiopia. To date, there has been no synthesis of the literature on the relative prevalence of NCD risk factors in Ethiopia. METHODOLOGY: We conducted a systematic review and meta-analysis of primary studies reporting on the prevalence of NCD risk factors in Ethiopia published in English from 2012 to July 2020. Pre-tested NCD search terms were applied to Medline, Embase, Scopus, CINAHL, and Global Health. Three reviewers screened and appraised the quality of the identified papers. Data extraction was conducted using a pilot tested proforma. Meta-analysis was conducted using Stata 16 and pooled prevalence estimated with associated 95% confidence intervals. Clinically heterogeneous studies that did not fulfil the eligibility criteria for meta-analysis were narratively synthesised. I2 was used to assess statistical heterogeneity. RESULTS: 47 studies fulfilled the inclusion criteria and contributed 68 NCD risk factor prevalence estimates. Hypertension was the most frequently examined NCD risk factor, with a pooled prevalence of 21% (n = 27 studies). The pooled prevalence percentages for overweight and obesity were 19.2% and 10.3%, respectively (n = 7 studies each), with a combined prevalence of 26.8% (n = 1 study). It was not possible to pool the prevalence of alcohol consumption, smoking, metabolic disorders, or fruit consumption because of heterogeneity across studies. The prevalence of alcohol use, as reported from the included individual studies, ranged from 12.4% to 13.5% (n = 7 studies). More than 90% of participants met the WHO-recommended level of physical activity (n = 5 studies). The prevalence of smoking was highly variable, ranging between 0.8% and 38.6%, as was the prevalence of heavy alcohol drinking (12.4% to 21.1%, n = 6 studies) and metabolic syndrome (4.8% to 9.6%, n = 5 studies). Fruit consumption ranged from 1.5% up to the recommended level, but varied across geographic areas (n = 3 studies). CONCLUSION AND RECOMMENDATIONS: The prevalence of NCD risk factors in Ethiopia is relatively high. National NCD risk factor surveillance is required to inform the prioritisation of policies and interventions to reduce the NCD burden in Ethiopia.

Random amplified polymorphic DNA analysis reveals no clear link between Staphylococcus epidermidis and acute mastitis.

Mastitis is commonly experienced by breastfeeding women. While Staphylococcus aureus is usually implicated in infectious mastitis, coagulase-negative staphylococci (CoNS) are a possible alternative pathogen. This case-control study examined the role of CoNS in mastitis using isolates cultured from breast milk of 20 women with mastitis and 16 women without mastitis. Gene sequencing determined bacterial species, and random amplified polymorphic DNA (RAPD) analysis investigated strain-level variation. The majority of CoNS isolates were Staphylococcus epidermidis (182/199; 91%). RAPD analysis identified 33 unique S. epidermidis profiles, with no specific profile associated with mastitis cases.

Premature mortality attributable to COVID-19: potential years of life lost in 17 countries around the world, January-August 2020.

BACKGROUND: Understanding the impact of the burden of COVID-19 is key to successfully navigating the COVID-19 pandemic. As part of a larger investigation on COVID-19 mortality impact, this study aims to estimate the Potential Years of Life Lost (PYLL) in 17 countries and territories across the world (Australia, Brazil, Cape Verde, Colombia, Cyprus, France, Georgia, Israel, Kazakhstan, Peru, Norway, England & Wales, Scotland, Slovenia, Sweden, Ukraine, and the United States [USA]). METHODS: Age- and sex-specific COVID-19 death numbers from primary national sources were collected by an international research consortium. The study period was established based on the availability of data from the inception of the pandemic to the end of August 2020. The PYLL for each country were computed using 80 years as the maximum life expectancy. RESULTS: As of August 2020, 442,677 (range: 18-185,083) deaths attributed to COVID-19 were recorded in 17 countries which translated to 4,210,654 (range: 112-1,554,225) PYLL. The average PYLL per death was 8.7 years, with substantial variation ranging from 2.7 years in Australia to 19.3 PYLL in Ukraine. North and South American countries as well as England & Wales, Scotland and Sweden experienced the highest PYLL per 100,000 population; whereas Australia, Slovenia and Georgia experienced the lowest. Overall, males experienced higher PYLL rate and higher PYLL per death than females. In most countries, most of the PYLL were observed for people aged over 60 or 65 years, irrespective of sex. Yet, Brazil, Cape Verde, Colombia, Israel, Peru, Scotland, Ukraine, and the USA concentrated most PYLL in younger age groups. CONCLUSIONS: Our results highlight the role of PYLL as a tool to understand the impact of COVID-19 on demographic groups within and across countries, guiding preventive measures to protect these groups under the ongoing pandemic. Continuous monitoring of PYLL is therefore needed to better understand the burden of COVID-19 in terms of premature mortality.

COVID-19 infection and the broader impacts of the pandemic on healthcare workers.

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease or COVID-19 pandemic is associated with more than 230 million cases and has challenged healthcare systems globally. Many healthcare workers (HCWs) have acquired the infection, often through their workplace, with a significant number dying. The epidemiology of COVID-19 infection in HCWs continues to be explored, with manifold exposure risks identified, leading to COVID-19 being recognised as an occupational disease for HCWs. The physical illness due to COVID-19 in HCWs is similar to the general population, with some HCWs experiencing a long-term illness, which may impact their ability to return to work. HCWs have also been affected by the immense workplace and psychosocial disruption caused by the pandemic. The impacts on the psychological well-being of HCWs globally have been profound, with high prevalence estimates for mental health symptoms, including emotional exhaustion. Globally, governments, healthcare organisations and employers have key responsibilities, including: to be better prepared for crises with comprehensive disaster response management plans, and to protect and preserve the health workforce from the physical and psychological impacts of the pandemic. While prioritising HCWs in vaccine rollouts globally has been critical, managing exposures and outbreaks occurring in healthcare settings remains challenging and continues to lead to substantial disruption to the health workforce. Safeguarding healthcare workforces during crises is critical as we move forward on the new path of 'COVID normal'.

Learning to live with COVID-19 in Australia: time for a new approach.

The emergence of the Delta variant of SARS-CoV-2 has made Australia's 'COVID-zero' strategy unviable. As signalled by the Australian Government's National plan to transition Australia's national COVID-19 response, we need to plan a pathway forward for life beyond lockdown. However, this plan must be guided by long overdue discussions on our tolerance for serious illness, and hospital and intensive care unit capacity. The modelling that informs the national transition plan remains relevant, even with increases in case numbers, but one crucial thing that does change if cases continue to escalate is the effectiveness of test, trace and isolate models. As we move into suppression mode with higher rates of the population fully vaccinated, we will no longer need to find every case. This is among the many shifts in approach that will shape our transition by early 2022 to living with - and controlling - the disease.

Early life acetaminophen exposure, glutathione S-transferase genes, and development of adolescent asthma in a high-risk birth cohort.

BACKGROUND: Although the impact of early life acetaminophen on asthma risk is still not clear, potential interactions with glutathione S-transferase (GST) genes due to reduced antioxidant function in particular polymorphisms, and possible impact on lung function, have never been investigated in adolescents. OBJECTIVE: We aimed to investigate associations between early life acetaminophen use and adolescent asthma and lung function and to assess potential interactions by GST polymorphisms. METHODS: Acetaminophen use was recorded 18 times up to age 2 years (n = 575 [92.7%]). Participants were genotyped for GST polymorphisms (GSTM1/T1/P1) (n = 429 [69.2%]). Asthma and lung function were measured at 12 (n = 365 [58.9%]) and 18 years (n = 413 [66.6%]). Regression models assessed associations and interactions. RESULTS: Doubling of days of acetaminophen use was associated with reduced prebronchodilator FEV1/forced vital capacity (ß coefficient, -0.10; 95% CI, -0.19 to -0.01) and midexpiratory flow (-0.09; 95% CI, -0.18 to 0) at 18 years, but this association was not found when restricted for nonrespiratory reasons, suggesting confounding by indication. However, in children with GSTM1 null and GSTT1 present, increasing acetaminophen use for nonrespiratory reasons was associated with reduced FEV1 and midexpiratory flow at 18 years (interaction between GSTM1/T1 and acetaminophen P < .05). Increased acetaminophen use was associated with asthma at 18 years for children with GSTP1 Ile/Ile (odds ratio, 1.66; 95% CI, 1.07 to 2.57), but not other GSTP1 genotypes. CONCLUSIONS: These novel findings need to be investigated for consistency in other studies but suggest that children carrying risk genotypes may be susceptible to respiratory consequences from acetaminophen use.

Early-Life Exposure to Oral Antibiotics and Lung Function Into Early Adulthood.

BACKGROUND: Although there is ongoing debate regarding the impact of early postnatal exposure to antibiotics on the development of asthma, the possibility that antibiotic exposure may impair lung function has not previously been examined. Furthermore, it is unclear if specific types of antibiotics may have a greater effect, or if children with genetic mutations in the oxidative stress response glutathione S-transferase (GST) superfamily may be at greater risk. METHODS: Parent-reported data of childhood antibiotic use from birth to 2 years, including type and indication, were collected from a birth cohort of 620 infants with a family history of allergy. Spirometry was performed at age 12 and 18 years, and results are presented as z scores. Participants were genotyped for GST-P, GST-M, and GST-T polymorphisms. Linear regression models were used to investigate the associations while adjusting for confounding factors. RESULTS: Neither increasing days of exposure nor earlier exposure to antibiotics was associated with reduced FEV1 (at 18 years, per doubling of days of exposure = -0.03 z score units; 95% CI, -0.11 to 0.04) or FVC (< 0.01; 95% CI, -0.08 to 0.07). There was no evidence that GST-risk polymorphisms (M1, P1, and T1) increased susceptibility, and specific types of antibiotics also did not increase risk of lung function deficits. CONCLUSIONS: Increasing exposure to oral antibiotics in early postnatal life was not associated with reduced lung function in children with a family history of allergic diseases. Although unwarranted use of antibiotics in children should be minimized, concerns regarding long-term lung health should not be a driving influence for this rationalization of use.

Pollen exposure at birth and adolescent lung function, and modification by residential greenness.

BACKGROUND: Exposure to high levels of pollen in infancy is a risk factor for allergic respiratory diseases in later childhood, but effects on lung function are not fully understood. We aim to examine associations between grass pollen exposure in the first months of life and lung function at 12 and 18 years, and explore potential modification. METHODS: Using the Melbourne Atopy Cohort Study, a birth cohort of children with a family history of allergic diseases, we modeled the association between cumulative grass pollen exposure up to 3 months after birth, on FEV1 , FVC, and FEV1 /FVC ratio at 12 and 18 years. We also assessed modifying effects of residential greenness levels (derived from satellite imagery), asthma, and early life sensitization to ryegrass. RESULTS: Grass pollen exposure in the first 7 days was associated with a reduction in FEV1 (-15.5 mL; 95% CI: -27.6, -3.3 per doubling of pollen count) and FVC (-20.8 mL; -35.4, -6.1) at 12 years, but not at 18 years. Increase in cumulative grass pollen exposure up to 3 months was negatively associated with FVC at 12 and 18. Exposure to high residential greenness modified the association at 18 years. CONCLUSION: Early exposure to grass pollen was associated with decreased lung function in children and adolescents. Targeted interventions for pollen avoidance strategies that take into account local topography could be implemented alongside other clinical interventions such as immunotherapy.

Syndromic management of sexually transmissible infections in resource-poor settings: a systematic review with meta-analysis of the abnormal vaginal discharge flowchart for Neisseria gonorrhoea and Chlamydia trachomatis.

BACKGROUND: Syndromic management of sexually transmissible infections is commonly used in resource-poor settings for the management of common STIs; abnormal vaginal discharge (AVD) flowcharts are used to identify and treat cervical infection including Neisseria gonorrhoea and Chlamydia trachomatis. A systematic review and meta-analysis was undertaken to measure the diagnostic test performance of AVD flowcharts, including both World Health Organization (WHO)- and locally-adapted AVD flowcharts. METHODS: A systematic search of multiple electronic databases was conducted to locate eligible studies published between 1991 and 2014. Flowcharts were categorised into one of 14 types based on: 1) use of WHO guidelines or locally-adapted versions; 2) use of risk assessment, clinical examination or both; and 3) symptomatic entry. Summary diagnostic performance measures calculated included summary sensitivity, summary specificity and diagnostic odds ratio. RESULTS: Thirty-six studies, including data on 99 flowcharts, were included in the review. Summary sensitivity estimates for WHO flowcharts ranged from 41.2 to 43.6%, and for locally adapted flowcharts from 39.5 to 74.8%. Locally adapted flowcharts performed slightly better than the WHO flowcharts. A difference in performance was not observed between use of risk assessment or clinical examination. The AVD flowchart performed slightly better when it was not restricted to symptomatic women only. CONCLUSIONS: There was considerable variation in the performance of the AVD flowchart but overall it was a poor diagnostic tool regardless of whether risk assessment or clinical examination was included, or whether the flowchart was WHO or locally developed. Many women were treated unnecessarily and many women with cervical infection were not detected. We caution against their continued use for management of cervical infection.

Age at onset and persistence of eczema are related to subsequent risk of asthma and hay fever from birth to 18 years of age.

BACKGROUND: Few studies have simultaneously addressed the importance of age of onset and persistence of eczema for the subsequent development of asthma and hay fever, particularly into early adulthood. METHODS: A high-risk birth cohort was recruited comprising 620 infants, who were then followed up frequently until 2 years of age, annually from age 3 to 7, then at 12 and 18 years, to document any episodes of eczema, current asthma, and hay fever. The generalized estimation equation technique was used to examine asthma and hay fever outcomes at 6 (n = 325), 12 (n = 248) and 18 (n = 240) years, when there was consistency of associations across the follow-ups. RESULTS: Very early-onset persistent (onset <6 months, still present from 2 to 5 years) eczema was related to current asthma (adjusted OR = 3.2 [95% CI = 1.7-6.1]), as was very early-onset remitting eczema (onset <6 months but not present from 2-5 years, OR = 2.7, 95% CI = 1.0-7.2) and early-onset persistent eczema (onset from 6-24 months, OR = 2.3, 95% CI = 1.2-4.7). Late-onset eczema (commenced from 2-5 years) was associated with increased risk of asthma at 12 years (OR = 3.0, 95% CI=1.1-8.2) but not at age 6 years. Only very early-onset persistent eczema was associated with increased risk of hay fever (aOR = 2.4, 95% CI = 1.4-4.1). CONCLUSION AND CLINICAL RELEVANCE: Eczema which commences in early infancy and persists into toddler years is strongly associated with asthma, and to a lesser extent hay fever, in high-risk children. If these associations are causal, prevention of early-life eczema might reduce the risk of respiratory allergy.