BACKGROUND

The role of public reporting in improving hospital quality of care is controversial. Reporting of hospital-acquired infection rates has been introduced in multiple health care systems, but its relationship to infection rates has been understudied. Our objective was to determine whether mandatory public reporting by hospitals is associated with a reduction in hospital rates of Clostridium difficile infection.

RESULTS

We conducted a longitudinal, population-based cohort study in Ontario (Canada's largest province) between April 1, 2002, and March 31, 2010. We included all patients (>1 y old) admitted to 180 acute care hospitals. Using Poisson regression, we developed a model to predict hospital- and age-specific monthly rates of C. difficile disease per 10,000 patient-days prior to introduction of public reporting on September 1, 2008. We then compared observed monthly rates of C. difficile infection in the post-intervention period with rates predicted by the pre-intervention predictive model. In the pre-intervention period there were 33,634 cases of C. difficile infection during 39,221,113 hospital days, with rates increasing from 7.01 per 10,000 patient-days in 2002 to 10.79 in 2007. In the first calendar year after the introduction of public reporting, there was a decline in observed rates of C. difficile colitis in Ontario to 8.92 cases per 10,000 patient-days, which was significantly lower than the predicted rate of 12.16 (95% CI 11.35-13.04) cases per 10,000 patient-days (p<0.001). Over this period, public reporting was associated with a 26.7% (95% CI 21.4%-31.6%) reduction in C. difficile cases, or a projected 1,970 cases averted per year (95% CI 1,476-2,500). The effect was specific to C. difficile, with rates of community-acquired gastrointestinal infections and urinary tract infections unchanged. A limitation of our study is that this observational study design cannot rule out the influence of unmeasured temporal confounders.

CONCLUSIONS

Public reporting of hospital C. difficile rates was associated with a substantial reduction in the population burden of this infection. Future research will be required to discern the direct mechanism by which C. difficile infection rates may have been reduced in response to public reporting. Please see later in the article for the Editors' Summary.

BACKGROUND

Health services for victims of rape are recognised as a particularly neglected area of the health sector internationally. Efforts to strengthen these services need to be guided by clinical research. Expert medical evidence is widely used in rape cases, but its contribution to the progress of legal cases is unclear. Only three studies have found an association between documented bodily injuries and convictions in rape cases. This article aims to describe the processing of rape cases by South African police and courts, and the association between documented injuries and DNA and case progression through the criminal justice system.

RESULTS

We analysed a provincially representative sample of 2,068 attempted and completed rape cases reported to 70 randomly selected Gauteng province police stations in 2003. Data sheets were completed from the police dockets and available medical examination forms were copied. 1,547 cases of rape had medical examinations and available forms and were analysed, which was at least 85% of the proportion of the sample having a medical examination. We present logistic regression models of the association between whether a trial started and whether the accused was found guilty and the medico-legal findings for adult and child rapes. Half the suspects were arrested (n = 771), 14% (209) of cases went to trial, and in 3% (31) of adults and 7% (44) of children there was a conviction. A report on DNA was available in 1.4% (22) of cases, but the presence or absence of injuries were documented in all cases. Documented injuries were not associated with arrest, but they were associated with children's cases (but not adult's) going to trial (adjusted odds ratio [AOR] for having genital and nongenital injuries 5.83, 95% confidence interval [CI] 1.87-18.13, p = 0.003). In adult cases a conviction was more likely if there were documented injuries, whether nongenital injuries alone AOR 6.25 (95% CI 1.14-34.3, p = 0.036), ano-genital injuries alone (AOR 7.00, 95% CI 1.44-33.9, p = 0.017), or both nongenital and ano-genital injuries (AOR 12.34, 95% CI 2.87-53.0, p = 0.001). DNA was not associated with case outcome.

CONCLUSIONS

This is the first study, to our knowledge, to show an association between documentation of ano-genital injuries, trials commencing, and convictions in rape cases in a developing country. Its findings are of particular importance because they show the value of good basic medical practices in documentation of injuries, rather than more expensive DNA evidence, in assisting courts in rape cases. Health care providers need training to provide high quality health care responses after rape, but we have shown that the core elements of the medico-legal response require very little technology. As such they should be replicable in low- and middle-income country settings. Our findings raise important questions about the value of evidence that requires the use of forensic laboratories at a population level in countries like South Africa that have substantial inefficiencies in their police services. Please see later in the article for the Editors' Summary.

David McCoy and colleagues critique the dominance of "lives saved" models of assessing the impact of health programs, using The Global Fund as a case study. Please see later in the article for the Editors' Summary.

BACKGROUND

Some evidence suggests that proton pump inhibitors (PPIs) are an under-appreciated risk factor for hypomagnesemia. Whether hospitalization with hypomagnesemia is associated with use of PPIs is unknown.

RESULTS

We conducted a population-based case-control study of multiple health care databases in Ontario, Canada, from April 2002 to March 2012. Patients who were enrolled as cases were Ontarians aged 66 years or older hospitalized with hypomagnesemia. For each individual enrolled as a case, we identified up to four individuals as controls matched on age, sex, kidney disease, and use of various diuretic classes. Exposure to PPIs was categorized according to the most proximate prescription prior to the index date as current (within 90 days), recent (within 91 to 180 days), or remote (within 181 to 365 days). We used conditional logistic regression to estimate the odds ratio for the association of outpatient PPI use and hospitalization with hypomagnesemia. To test the specificity of our findings we examined use of histamine H2 receptor antagonists, drugs with no causal link to hypomagnesemia. We studied 366 patients hospitalized with hypomagnesemia and 1,464 matched controls. Current PPI use was associated with a 43% increased risk of hypomagnesemia (adjusted odds ratio, 1.43; 95% CI 1.06-1.93). In a stratified analysis, the risk was particularly increased among patients receiving diuretics, (adjusted odds ratio, 1.73; 95% CI 1.11-2.70) and not significant among patients not receiving diuretics (adjusted odds ratio, 1.25; 95% CI 0.81-1.91). We estimate that one excess hospitalization with hypomagnesemia will occur among 76,591 outpatients treated with a PPI for 90 days. Hospitalization with hypomagnesemia was not associated with the use of histamine H2 receptor antagonists (adjusted odds ratio 1.06; 95% CI 0.54-2.06). Limitations of this study include a lack of access to serum magnesium levels, uncertainty regarding diagnostic coding of hypomagnesemia, and generalizability of our findings to younger patients.

CONCLUSIONS

PPIs are associated with a small increased risk of hospitalization with hypomagnesemia among patients also receiving diuretics. Physicians should be aware of this association, particularly for patients with hypomagnesemia. Please see later in the article for the Editors' Summary.

It is increasingly clear that mechanotransduction pathways play important roles in regulating fundamental cellular functions. Of the basic mechanical functions, the determination of cellular morphology is critical. Cells typically use many mechanosensitive steps and different cell states to achieve a polarized shape through repeated testing of the microenvironment. Indeed, morphology is determined by the microenvironment through periodic activation of motility, mechanotesting, and mechanoresponse functions by hormones, internal clocks, and receptor tyrosine kinases. Patterned substrates and controlled environments with defined rigidities limit the range of cell behavior and influence cell state decisions and are thus very useful for studying these steps. The recently defined rigidity sensing process provides a good example of how cells repeatedly test their microenvironment and is also linked to cancer. In general, aberrant extracellular matrix mechanosensing is associated with numerous conditions, including cardiovascular disease, aging, and fibrosis, that correlate with changes in tissue morphology and matrix composition. Hence, detailed descriptions of the steps involved in sensing and responding to the microenvironment are needed to better understand both the mechanisms of tissue homeostasis and the pathomechanisms of human disease. Expected final online publication date for the Annual Review of Physiology Volume 81 is February 10, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

BACKGROUND

Nine percent of new mothers in the United States who participated in the Listening to Mothers II Postpartum Survey screened positive for meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for posttraumatic stress disorder after childbirth. Women who have had a traumatic birth experience report fewer subsequent children and a longer length of time before their second baby. Childbirth-related posttraumatic stress disorder impacts couples' physical relationship, communication, conflict, emotions, and bonding with their children.

OBJECTIVE

The purpose of this study was to describe the meaning of women's experiences of a subsequent childbirth after a previous traumatic birth.

METHODS

Phenomenology was the research design used. An international sample of 35 women participated in this Internet study. Women were asked, "Please describe in as much detail as you can remember your subsequent pregnancy, labor, and delivery following your previous traumatic birth." Colaizzi's phenomenological data analysis approach was used to analyze the stories of the 35 women.

RESULTS

Data analysis yielded four themes: (a) riding the turbulent wave of panic during pregnancy; (b) strategizing: attempts to reclaim their body and complete the journey to motherhood; (c) bringing reverence to the birthing process and empowering women; and (d) still elusive: the longed-for healing birth experience.

CONCLUSIONS

Subsequent childbirth after a previous birth trauma has the potential to either heal or retraumatize women. During pregnancy, women need permission and encouragement to grieve their prior traumatic births to help remove the burden of their invisible pain.

Historically, the study of visual perception has followed a reductionist strategy, with the goal of understanding complex visually guided behavior by separate analysis of its elemental components. Recent developments in monitoring behavior, such as measurement of eye movements in unconstrained observers, have allowed investigation of the use of vision in the natural world. This has led to a variety of insights that would be difficult to achieve in more constrained experimental contexts. In general, it shifts the focus of vision away from the properties of the stimulus toward a consideration of the behavioral goals of the observer. It appears that behavioral goals are a critical factor in controlling the acquisition of visual information from the world. This insight has been accompanied by a growing understanding of the importance of reward in modulating the underlying neural mechanisms and by theoretical developments using reinforcement learning models of complex behavior. These developments provide us with the tools to understanding how tasks are represented in the brain, and how they control acquisition of information through use of gaze. WIREs Cogni Sci 2011 2 158-166 DOI: 10.1002/wcs.113 For further resources related to this article, please visit the WIREs website.

Neutrophils are critical to innate immunity, including host defense against bacterial and fungal infections. They achieve their host defense role by phagocytosing pathogens, secreting their granules full of cytotoxic enzymes, or expelling neutrophil extracellular traps (NETs) during the process of NETosis. NETs are weblike DNA structures decorated with histones and antimicrobial proteins released by activated neutrophils. Initially described as a means for neutrophils to neutralize pathogens, NET release also occurs in sterile inflammation, promotes thrombosis, and can mediate tissue damage. To effectively manipulate this double-edged sword to fight a particular disease, researchers must work toward understanding the mechanisms driving NETosis. Such understanding would allow the generation of new drugs to promote or prevent NETosis as needed. While knowledge regarding the (patho)physiological roles of NETosis is accumulating, little is known about the cellular and biophysical bases of this process. In this review, we describe and discuss our current knowledge of the molecular, cellular, and biophysical mechanisms mediating NET release as well as open questions in the field. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 36 is October 6, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Developmental prosopagnosia (DP) is a neurodevelopmental condition characterized by severe face identity recognition problems that results from a failure to develop the mechanisms necessary for adequate face processing (Duchaine BC, Nakayama K. Developmental prosopagnosia: a window to content-specific face processing. Curr Opin Neurobiol 2006, 16:166-173.). It occurs in children and adults with normal visual acuity, and without intellectual impairments or known brain injuries. Given the importance of face recognition in daily life, and the detrimental effects of impaired face recognition, DP is an important area of study. Yet conventions for classifying individuals as DP for research purposes are poorly defined. In this focus paper, we discuss: (1) criteria for an operational definition of DP; 2) tests of face recognition and conventions for classifying individuals as DP; and 3) important considerations regarding common associations and dissociations, and cognitive heterogeneity in DP. We also highlight issues unique to studying DP in children, a relatively new endeavor that is proving to be an important complement to the work with adults. Ultimately, we hope to identify challenges researchers face when studying DP, and offer guidelines for others to consider when embarking on their own research pursuits on the topic. For further resources related to this article, please visit the WIREs website.

DNA has been known to be a potent immune stimulus for more than half a century. However, the underlying molecular mechanisms of DNA-triggered immune response have remained elusive until recent years. Cyclic GMP-AMP synthase (cGAS) is a major cytoplasmic DNA senor in various types of cells that detect either invaded foreign DNA or aberrantly located self-DNA. Upon sensing of DNA, cGAS catalyzes the formation of cyclic GMP-AMP (cGAMP), which in turn activates the ER-localized adaptor protein MITA (also named STING) to elicit the innate immune response. The cGAS-MITA axis not only plays a central role in host defense against pathogen-derived DNA but also acts as a cellular stress response pathway by sensing aberrantly located self-DNA, which is linked to the pathogenesis of various human diseases. In this review, we summarize the spatial and temporal mechanisms of host defense to cytoplasmic DNA mediated by the cGAS-MITA axis and discuss the association of malfunctions of this axis with autoimmune and other diseases. Expected final online publication date for the Annual Review of Immunology, Volume 38 is April 26, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Human perception is fallible and may lead patients to be inaccurate when judging whether their symptoms are improving with treatment. This article provides a narrative review of studies in psychology that describe misconceptions related to a patient's comprehension, recall, evaluation and expression. The specific misconceptions include the power of suggestion (placebo effects), desire for peace-of-mind (cognitive dissonance reduction), inconsistent standards (loss aversion), a flawed sense of time (duration neglect), limited perception (measurement error), declining sensitivity (Weber's law), an eagerness to please (social desirability bias), and subtle affirmation (personal control). An awareness of specific pitfalls might help clinicians avoid some mistakes when providing follow-up and interpreting changes in patient symptoms.

BACKGROUND

Bone mineral density is known to decrease rapidly after the menopause. There is limited evidence about the separate contributions of a woman's age, menopausal status and age at menopause to the incidence of hip fracture.

RESULTS

Over one million middle-aged women joined the UK Million Women Study in 1996-2001 providing information on their menopausal status, age at menopause, and other factors, which was updated, where possible, 3 y later. All women were registered with the UK National Health Service (NHS) and were routinely linked to information on cause-specific admissions to NHS hospitals. 561,609 women who had never used hormone replacement therapy and who provided complete information on menopausal variables (at baseline 25% were pre/perimenopausal and 75% postmenopausal) were followed up for a total of 3.4 million woman-years (an average 6.2 y per woman). During follow-up 1,676 (0.3%) were admitted to hospital with a first incident hip fracture. Among women aged 50-54 y the relative risk (RR) of hip fracture risk was significantly higher in postmenopausal than premenopausal women (adjusted RR 2.22, 95% confidence interval [CI] 1.22-4.04; p = 0.009); there were too few premenopausal women aged 55 y and over for valid comparisons. Among postmenopausal women, hip fracture incidence increased steeply with age (p<0.001), with rates being about seven times higher at age 70-74 y than at 50-54 y (incidence rates of 0.82 versus 0.11 per 100 women over 5 y). Among postmenopausal women of a given age there was no significant difference in hip fracture incidence between women whose menopause was due to bilateral oophorectomy compared to a natural menopause (adjusted RR 1.20, 95% CI 0.94-1.55; p = 0.15), and age at menopause had little, if any, effect on hip fracture incidence.

CONCLUSIONS

At around the time of the menopause, hip fracture incidence is about twice as high in postmenopausal than in premenopausal women, but this effect is short lived. Among postmenopausal women, age is by far the main determinant of hip fracture incidence and, for women of a given age, their age at menopause has, at most, a weak additional effect. Please see later in the article for the Editors' Summary.

Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most potent toxins known and cause botulism and tetanus, respectively. BoNTs are also widely utilized as therapeutic toxins. They contain three functional domains responsible for receptor-binding, membrane translocation, and proteolytic cleavage of host proteins required for synaptic vesicle exocytosis. These toxins also have distinct features: BoNTs exist within a progenitor toxin complex (PTC), which protects the toxin and facilitates its absorption in the gastrointestinal tract, whereas TeNT is uniquely transported retrogradely within motor neurons. Our increasing knowledge of these toxins has allowed the development of engineered toxins for medical uses. The discovery of new BoNTs and BoNT-like proteins provides additional tools to understand the evolution of the toxins and to engineer toxin-based therapeutics. This review summarizes the progress on our understanding of BoNTs and TeNT, focusing on the PTC, receptor recognition, new BoNT-like toxins, and therapeutic toxin engineering. Expected final online publication date for the Annual Review of Biochemistry Volume 88 is June 20, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The discovery and examination of the posttranscriptional gene regulatory mechanism known as RNA interference (RNAi) contributed to the identification of small interfering RNA (siRNA) and the comprehension of its enormous potential for clinical purposes. Theoretically, the ability of specific target gene downregulation makes the RNAi pathway an appealing solution for several diseases. Despite numerous hurdles resulting from the inherent properties of siRNA molecule and proper delivery to the target tissue, more than 50 RNA-based drugs are currently under clinical testing. In this work, we analyze the recent literature in the optimization of siRNA molecules. In detail, we focused on describing the most recent advances of siRNA field aimed at optimize siRNA pharmacokinetic properties. Special attention has been given in describing the impact of RNA modifications in the potential off-target effects (OTEs) such as saturation of the RNAi machinery, passenger strand-mediated silencing, immunostimulation, and miRNA-like OTEs as well as to recent developments on the delivery issue. The novel delivery systems and modified siRNA provide significant steps toward the development of reliable siRNA molecules for therapeutic use. WIREs RNA 2016, 7:316-329. doi: 10.1002/wrna.1337 For further resources related to this article, please visit the WIREs website.

Food insecurity affects 1 in 8 US households and has clear implications for population health disparities.We present a person-centered, multilevel framework for understanding how individuals living in food-insecure households cope with inadequate access to food themselves and within their households, communities, and broader food system. Many of these coping strategies can have an adverse impact on health, particularly when the coping strategies are sustained over time; others may be salutary for health. There exist multiple opportunities for aligning programs and policies so that they simultaneously support food security and improved diet quality in the interest of supporting improved health outcomes. Improved access to these programs and policies may reduce the need to rely on individual- and household-level strategies that may have negative implications for health across the life course. Expected final online publication date for the Annual Review of Public Health Volume 40 is April 1, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

A tutorial is provided for methods to accurately and reproducibly determine the activity of Pt-based electrocatalysts for the oxygen reduction reaction in proton exchange membrane fuel cells and other applications. The impact of various experimental parameters on electrocatalyst activity is demonstrated, and explicit experimental procedures and measurement protocols are given for comparison of electrocatalyst activity to fuel cell standards. (To listen to a podcast about this article, please go to the Analytical Chemistry multimedia page at pubs.acs.org/page/ancham/audio/index.html.).

As we grow older, we gain knowledge and experience greater emotional balance, but we also experience memory loss and difficulties in learning new associations. Which cognitive abilities decline, remain stable or improve with age depends on the health of the brain and body as well as on what skills are practiced or challenged in everyday life. Recent research provides a growing understanding of the relationship between physical and cognitive changes across the life span and reveals ways to increase mental sharpness and avoid cognitive decline. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website.

The age-associated B cell subset has been the focus of increasing interest over the last decade. These cells have a unique cell surface phenotype and transcriptional signature, and they rely on TLR7 or TLR9 signals in the context of Th1 cytokines for their formation and activation. Most are antigen-experienced memory B cells that arise during responses to microbial infections and are key to pathogen clearance and control. Their increasing prevalence with age contributes to several well-established features of immunosenescence, including reduced B cell genesis and damped immune responses. In addition, they are elevated in autoimmune and autoinflammatory diseases, and in these settings they are enriched for characteristic autoantibody specificities. Together, these features identify age-associated B cells as a subset with pivotal roles in immunological health, disease, and aging. Accordingly, a detailed understanding of their origins, functions, and physiology should make them tractable translational targets in each of these settings. Expected final online publication date for the Annual Review of Immunology, Volume 38 is April 26, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Extreme weather and climate-related events occur in a particular place, by definition, infrequently. It is therefore challenging to detect systematic changes in their occurrence given the relative shortness of observational records. However, there is a clear interest from outside the climate science community in the extent to which recent damaging extreme events can be linked to human-induced climate change or natural climate variability. Event attribution studies seek to determine to what extent anthropogenic climate change has altered the probability or magnitude of particular events. They have shown clear evidence for human influence having increased the probability of many extremely warm seasonal temperatures and reduced the probability of extremely cold seasonal temperatures in many parts of the world. The evidence for human influence on the probability of extreme precipitation events, droughts, and storms is more mixed. Although the science of event attribution has developed rapidly in recent years, geographical coverage of events remains patchy and based on the interests and capabilities of individual research groups. The development of operational event attribution would allow a more timely and methodical production of attribution assessments than currently obtained on an ad hoc basis. For event attribution assessments to be most useful, remaining scientific uncertainties need to be robustly assessed and the results clearly communicated. This requires the continuing development of methodologies to assess the reliability of event attribution results and further work to understand the potential utility of event attribution for stakeholder groups and decision makers. WIREs Clim Change 2016, 7:23-41. doi: 10.1002/wcc.380 For further resources related to this article, please visit the WIREs website.

BACKGROUND

Harm reduction strategies for combating HIV epidemics among people who inject drugs (PWID) have been implemented in several countries. However, large-scale studies using sensitive measurements of HIV incidence and intervention exposures in defined cohorts are rare. The aim of this study was to determine the association between harm reduction programs and HIV incidence among PWID.

RESULTS

The study included two populations. For 3,851 PWID who entered prison between 2004 and 2010 and tested HIV positive upon incarceration, we tested their sera using a BED HIV-1 capture enzyme immunoassay to estimate HIV incidence. Also, we enrolled in a prospective study a cohort of 4,357 individuals who were released from prison via an amnesty on July 16, 2007. We followed them with interviews at intervals of 6-12 mo and by linking several databases. A total of 2,473 participants who were HIV negative in January 2006 had interviews between then and 2010 to evaluate the association between use of harm reduction programs and HIV incidence. We used survival methods with attendance at methadone clinics as a time-varying covariate to measure the association with HIV incidence. We used a Poisson regression model and calculated the HIV incidence rate to evaluate the association between needle/syringe program use and HIV incidence. Among the population of PWID who were imprisoned, the implementation of comprehensive harm reduction programs and a lower mean community HIV viral load were associated with a reduced HIV incidence among PWID. The HIV incidence in this population of PWID decreased from 18.2% in 2005 to 0.3% in 2010. In an individual-level analysis of the amnesty cohort, attendance at methadone clinics was associated with a significantly lower HIV incidence (adjusted hazard ratio: 0.20, 95% CI: 0.06-0.67), and frequent users of needle/syringe program services had lower HIV incidence (0% in high NSP users, 0.5% in non NSP users). In addition, no HIV seroconversions were detected among prison inmates.

CONCLUSIONS

Although our data are affected by participation bias, they strongly suggest that comprehensive harm- reduction services and free treatment were associated with reversal of a rapidly emerging epidemic of HIV among PWID. Please see later in the article for the Editors' Summary.

BACKGROUND

An increase in the average age of dengue hemorrhagic fever (DHF) cases has been reported in Thailand. The cause of this increase is not known. Possible explanations include a reduction in transmission due to declining mosquito populations, declining contact between human and mosquito, and changes in reporting. We propose that a demographic shift toward lower birth and death rates has reduced dengue transmission and lengthened the interval between large epidemics.

RESULTS

Using data from each of the 72 provinces of Thailand, we looked for associations between force of infection (a measure of hazard, defined as the rate per capita at which susceptible individuals become infected) and demographic and climactic variables. We estimated the force of infection from the age distribution of cases from 1985 to 2005. We find that the force of infection has declined by 2% each year since a peak in the late 1970s and early 1980s. Contrary to recent findings suggesting that the incidence of DHF has increased in Thailand, we find a small but statistically significant decline in DHF incidence since 1985 in a majority of provinces. The strongest predictor of the change in force of infection and the mean force of infection is the median age of the population. Using mathematical simulations of dengue transmission we show that a reduced birth rate and a shift in the population's age structure can explain the shift in the age distribution of cases, reduction of the force of infection, and increase in the periodicity of multiannual oscillations of DHF incidence in the absence of other changes.

CONCLUSIONS

Lower birth and death rates decrease the flow of susceptible individuals into the population and increase the longevity of immune individuals. The increase in the proportion of the population that is immune increases the likelihood that an infectious mosquito will feed on an immune individual, reducing the force of infection. Though the force of infection has decreased by half, we find that the critical vaccination fraction has not changed significantly, declining from an average of 85% to 80%. Clinical guidelines should consider the impact of continued increases in the age of dengue cases in Thailand. Countries in the region lagging behind Thailand in the demographic transition may experience the same increase as their population ages. The impact of demographic changes on the force of infection has been hypothesized for other diseases, but, to our knowledge, this is the first observation of this phenomenon. Please see later in the article for the Editors' Summary.

Insufficient consumption of fruits and vegetables in childhood increases the risk of future chronic diseases, including cardiovascular disease.

To assess the effectiveness, cost effectiveness and associated adverse events of interventions designed to increase the consumption of fruit, vegetables or both amongst children aged five years and under.

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase Classic and Embase to identify eligible trials on 30 September 2016. We searched CINAHL and PsycINFO in July 2016, Proquest Dissertations and Theses in November 2016 and three clinical trial registers in November 2016 and June 2017. We reviewed reference lists of included trials and handsearched three international nutrition journals. We contacted authors of included studies to identify further potentially relevant trials.

We included randomised controlled trials, including cluster-randomised controlled trials and cross-over trials, of any intervention primarily targeting consumption of fruit, vegetables or both among children aged five years and under, and incorporating a dietary or biochemical assessment of fruit or vegetable consumption. Two review authors independently screened titles and abstracts of identified papers; a third review author resolved disagreements.

Two review authors independently extracted data and assessed the risks of bias of included studies; a third review author resolved disagreements. Due to unexplained heterogeneity, we used random-effects models in meta-analyses for the primary review outcomes where we identified sufficient trials. We calculated standardised mean differences (SMDs) to account for the heterogeneity of fruit and vegetable consumption measures.We conducted assessments of risks of bias and evaluated the quality of evidence (GRADE approach) using Cochrane procedures.

We included 50 trials with 137 trial arms and 10,267 participants. Thirty trials examined the impact of child-feeding practices (e.g. repeated food exposure) in increasing child vegetable intake. Eleven trials examined the impact of parent nutrition education in increasing child fruit and vegetable intake. Eight studies examined the impact of multicomponent interventions (e.g. parent nutrition education and preschool policy changes) in increasing child fruit and vegetable intake. One study examined the effect of a nutrition intervention delivered to children in increasing child fruit and vegetable intake.Thirteen of the 50 included trials were judged as free from high risks of bias across all domains; performance, detection and attrition bias were the most common domains judged at high risk of bias of remaining studies.Meta-analysis of trials examining child-feeding practices versus no intervention revealed a positive effect on child vegetable consumption (SMD 0.38, 95% CI 0.15 to 0.61; n = 1509; 11 studies; very low-quality evidence), equivalent to a mean difference of 4.03 grams of vegetables. There were no short-term differences in child consumption of fruit and vegetables in meta-analyses of trials examining parent nutrition education versus no intervention (SMD 0.11, 95% CI -0.05 to 0.28; n = 3023; 10 studies; very low-quality evidence) or multicomponent interventions versus no intervention (SMD 0.28, 95% CI -0.06 to 0.63; n = 1861; 4 studies; very low-quality evidence).Insufficient data were available to assess long-term effectiveness, cost effectiveness and unintended adverse consequences of interventions.Studies reported receiving governmental or charitable funds, except for two studies reporting industry funding.

Despite identifying 50 eligible trials of various intervention approaches, the evidence for how to increase fruit and vegetable consumption of children remains sparse. There was very low-quality evidence child-feeding practice interventions are effective in increasing vegetable consumption of children aged five years and younger, however the effect size was very small and long-term follow-up is required. There was very low-quality evidence that parent nutrition education and multicomponent interventions are not effective in increasing fruit and vegetable consumption of children aged five years and younger. All findings should be considered with caution, given most included trials could not be combined in meta-analyses. Given the very low-quality evidence, future research will very likely change estimates and conclusions. Such research should adopt more rigorous methods to advance the field.This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.