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1.  The impact of staffing on central venous catheter-associated bloodstream infections in preterm neonates – results of nation-wide cohort study in Germany 
Very low birthweight (VLBW) newborns on neonatal intensive care units (NICU) are at increased risk for developing central venous catheter-associated bloodstream infections (CVC BSI). In addition to the established intrinsic risk factors of VLBW newborns, it is still not clear which process and structure parameters within NICUs influence the prevalence of CVC BSI.
The study population consisted of VLBW newborns from NICUs that participated in the German nosocomial infection surveillance system for preterm infants (NEO-KISS) from January 2008 to June 2009. Structure and process parameters of NICUs were obtained by a questionnaire-based enquiry. Patient based date and the occurrence of BSI derived from the NEO-KISS database. The association between the requested parameters and the occurrance of CVC BSI and laboratory-confirmed BSI was analyzed by generalized estimating equations.
We analyzed data on 5,586 VLBW infants from 108 NICUs and found 954 BSI cases in 847 infants. Of all BSI cases, 414 (43%) were CVC-associated. The pooled incidence density of CVC BSI was 8.3 per 1,000 CVC days. The pooled CVC utilization ratio was 24.3 CVC-days per 100 patient days. A low realized staffing rate lead to an increased risk of CVC BSI (OR 1.47; p=0.008) and also of laboratory-confirmed CVC BSI (OR 1.78; p=0.028).
Our findings show that low levels of realized staffing are associated with increased rates of CVC BSI on NICUs. Further studies are necessary to determine a threshold that should not be undercut.
PMCID: PMC3643825  PMID: 23557510
Staffing; CVC; BSI; NICU; VLBW
2.  Late-onset bloodstream infections of Very-Low-Birth-Weight infants: data from the Polish Neonatology Surveillance Network in 2009–2011 
BMC Infectious Diseases  2014;14:339.
Late-Onset Bloodstream Infections (LO-BSI) continue to be one of the most important complications associated with hospitalization of infants born with very low birth weight (VLBW). The aims of this study were to assess the epidemiology of LO-BSI together with the risk factors and the distribution of causative pathogens at six Polish neonatal intensive care units that participated in the Polish Neonatology Surveillance Network from January 1, 2009 to December 31, 2011.
The surveillance covered 1,695 infants whose birth weights were <1501 grams (VLBW) in whom LO-BSI was diagnosed >72 hours after delivery. Case LO-BSI patients were defined according to NeoKISS.
Four hundred twenty seven episodes of LO-BSI were diagnosed with a frequency of 25.3% and an incidence density of 6.7/1000 patient-days (pds). Results of our multivariate analysis demonstrated that surgical procedures and lower gestational age were significantly associated with the risk of LO-BSI. Intravascular catheters were used in infants with LO-BSI significantly more frequently and/or for longer duration: Central venous cathters (CVC) (OR 1.29) and Peripheral venous catheters (PVC) (OR 2.8), as well as, the total duration of total parenteral nutrition (13 vs. 29 days; OR 1.81). Occurrence of LO-BSI was significantly associated with increased the length of mechanical ventilation (MV) (OR 2.65) or the continuous positive airway pressure (CPAP) (OR 2.51), as well as, the duration of antibiotic use (OR 2.98). The occurrence of more than one infection was observed frequently (OR 9.2) with VLBW with LO-BSI. Microorganisms isolated in infants with LO-BSI were dominated by Gram-positive cocci, and predominantly by coagulase-negative staphylococci (62.5%).
Independent risk factor for LO-BSI in VLBV infants are: low gestational age and requirement for surgery. The incidence rates of LO-BSI especially CVC-BSI were higher in the Polish NICUs surveillance than those of other national networks, similar to the central- and peripheral utilization ratio.
PMCID: PMC4074408  PMID: 24939563
3.  The Impact of Statistical Choices on Neonatal Intensive Care Unit Quality Ratings Based on Nosocomial Infection Rates 
To examine the extent to which performance assessment methodologies affect the percent of neonatal intensive care units (NICUs) and very low birth weight (VLBW) infants included in performance assessments, distribution of NICU performance ratings, and level of agreement in those ratings.
Cross-sectional study based on risk-adjusted nosocomial infection rates.
NICUs belonging to the California Perinatal Quality Care Collaborative 2007–2008.
126 California NICUs and 10,487 VLBW infants.
Main Exposure
Three performance assessment choices: 1. Excluding “low-volume” NICUs (those caring for < 30 VLBW infants in a year) vs. a criterion based on confidence intervals, 2. Using Bayesian vs. frequentist hierarchical models, and 3. Pooling data across one vs. two years.
Main Outcome Measures
Proportion of NICUs and patients included in quality assessment, distribution of ratings for NICUs, and agreement between methods using the kappa statistic.
Depending on the methods applied, between 51% and 85% of NICUs were included in performance assessment, the percent of VLBW infants included in performance assessment ranged from 72% to 96%, between 76–87% NICUs were considered “average,” and the level of agreement between NICU ratings ranged from 0.26 to 0.89.
The percent of NICUs included in performance assessment and their ratings can shift dramatically depending on performance measurement methodology. Physicians, payers, and policymakers should continue to closely examine which existing performance assessment methodologies are most appropriate for evaluating pediatric care quality.
PMCID: PMC4104272  PMID: 21536958
Quality; quality improvement; performance incentives; pay-for-performance; public reporting; neonatal intensive care units; Very Low Birth Weight infants; Nosocomial infections
4.  Individual units rather than entire hospital as the basis for improvement: the example of two Methicillin resistant Staphylococcus aureus cohort studies 
Two MRSA surveillance components exist within the German national nosocomial infection surveillance system KISS: one for the whole hospital (i.e. only hospital based data and no rates for individual units) and one for ICU-based data (rates for each individual ICU). The objective of this study was to analyze which surveillance system (a hospital based or a unit based) leads to a greater decrease in incidence density of nosocomial MRSA
Two cohort studies of surveillance data were used: Data from a total of 224 hospitals and 359 ICUs in the period from 2004 to 2009. Development over time was described first for both surveillance systems. In a second step only data were analyzed from those hospitals/ICUs with continuous participation for at least four years. Incidence rate ratios (IRR) with 95% confidence intervals were calculated to compare incidence densities between different time intervals.
In the baseline year the mean MRSA incidence density of hospital acquired MRSA cases was 0.25 and the mean incidence density of ICU-acquired MRSA was 1.25 per 1000 patient days. No decrease in hospital-acquired MRSA rates was found in a total of 111 hospitals with continuous participation in the hospital- based system. However, in 159 ICUs with continuous participation in the unit-based system, a significant decrease of 29% in ICU-acquired MRSA was identified.
A unit-based approach of surveillance and feedback seems to be more successful in decreasing nosocomial MRSA rates, compared to a hospital-based approach. Therefore each surveillance system should provide unit-based data to stimulate activities on the unit level.
PMCID: PMC3436609  PMID: 22958320
Infection prevention; Surveillance; MRSA; Quality management
5.  Linkage, Evaluation and Analysis of National Electronic Healthcare Data: Application to Providing Enhanced Blood-Stream Infection Surveillance in Paediatric Intensive Care 
PLoS ONE  2013;8(12):e85278.
Linkage of risk-factor data for blood-stream infection (BSI) in paediatric intensive care (PICU) with bacteraemia surveillance data to monitor risk-adjusted infection rates in PICU is complicated by a lack of unique identifiers and under-ascertainment in the national surveillance system. We linked, evaluated and performed preliminary analyses on these data to provide a practical guide on the steps required to handle linkage of such complex data sources.
Data on PICU admissions in England and Wales for 2003-2010 were extracted from the Paediatric Intensive Care Audit Network. Records of all positive isolates from blood cultures taken for children <16 years and captured by the national voluntary laboratory surveillance system for 2003-2010 were extracted from the Public Health England database, LabBase2. “Gold-standard” datasets with unique identifiers were obtained directly from three laboratories, containing microbiology reports that were eligible for submission to LabBase2 (defined as “clinically significant” by laboratory microbiologists). Reports in the gold-standard datasets were compared to those in LabBase2 to estimate ascertainment in LabBase2. Linkage evaluated by comparing results from two classification methods (highest-weight classification of match weights and prior-informed imputation using match probabilities) with linked records in the gold-standard data. BSI rate was estimated as the proportion of admissions associated with at least one BSI.
Reporting gaps were identified in 548/2596 lab-months of LabBase2. Ascertainment of clinically significant BSI in the remaining months was approximately 80-95%. Prior-informed imputation provided the least biased estimate of BSI rate (5.8% of admissions). Adjusting for ascertainment, the estimated BSI rate was 6.1-7.3%.
Linkage of PICU admission data with national BSI surveillance provides the opportunity for enhanced surveillance but analyses based on these data need to take account of biases due to ascertainment and linkage error. This study provides a generalisable guide for linkage, evaluation and analysis of complex electronic healthcare data.
PMCID: PMC3869925  PMID: 24376874
6.  Characteristics of HIV seroprevalence of visitors to public health centers under the national HIV surveillance system in Korea: cross sectional study 
BMC Public Health  2009;9:123.
In Korea, the cumulative number of HIV-infected individuals was smaller than those of other countries. Mandatory HIV tests, dominating method until 1990's, have been gradually changed to voluntary HIV tests. We investigated HIV seroprevalence status and its characteristics of visitors to Public Health Centers (PHCs), which conducted both mandatory test and voluntary test under the national HIV/STI surveillance program.
We used HIV-testing data from 246 PHCs in 2005 through the Health Care Information System. The number of test taker was calculated using the code distinguished by the residential identification number. The subjects were classified into four groups by reason for testing; General group, HIV infection suspected group (HIV ISG), HIV test recommended group (HIV TRG), and sexually transmitted infection (STI) risk group.
People living with HIV/AIDS were 149 (124 male and 25 female) among 280,456 individuals tested at PHCs. HIV seroprevalence was 5.3 per 10,000 individuals. Overall, the male revealed significantly higher seroprevalence than the female (adjusted Odds Ratio (adj. OR): 6.2; CI 3.8–10.2). Individuals aged 30–39 years (adj. OR: 2.6; CI 1.7–4.0), and 40–49 years (adj. OR: 3.8; CI 2.4–6.0) had higher seroprevalence than 20–29 years. Seroprevalence of HIV ISG (voluntary test takers and cases referred by doctors) was significantly higher than those of others. Foreigners showed higher seroprevalence than native Koreans (adj. OR: 3.8; CI 2.2–6.4). HIV ISG (adj. OR: 4.9; CI 3.2–7.5), and HIV TRG (adj. OR: 2.6; CI 1.3–5.4) had higher seroprevalence than General group.
A question on the efficiency of current mandatory test is raised because the seroprevalence of mandatory test takers was low. However, HIV ISG included voluntary test takers was high in our result. Therefore, we suggest that Korea needs to develop a method encouraging more people to take voluntary tests at PHCs, also to expand the anonymous testing centers and Voluntary Counselling and Testing Program (VCT) for general population to easily access to HIV testing.
PMCID: PMC2689198  PMID: 19416524
7.  Decreased Bone Mineral Density in Adults Born with Very Low Birth Weight: A Cohort Study 
PLoS Medicine  2009;6(8):e1000135.
Petteri Hovi and colleagues evaluate skeletal health in 144 adults born preterm with very low birth weight and show that as adults these individuals have significantly lower bone mineral density than do their term-born peers.
Very-low-birth-weight (VLBW, <1,500 g) infants have compromised bone mass accrual during childhood, but it is unclear whether this results in subnormal peak bone mass and increased risk of impaired skeletal health in adulthood. We hypothesized that VLBW is associated with reduced bone mineral density (BMD) in adulthood.
Methods and Findings
The Helsinki Study of Very Low Birth Weight Adults is a multidisciplinary cohort study representative of all VLBW births within the larger Helsinki area from 1978 to 1985. This study evaluated skeletal health in 144 such participants (all born preterm, mean gestational age 29.3 wk, birth weight 1,127 g, birth weight Z score 1.3), and in 139 comparison participants born at term, matched for sex, age, and birth hospital. BMD was measured by dual energy X-ray absorptiometry at age 18.5 to 27.1 y. Adults born with VLBW had, in comparison to participants born at term, a 0.51-unit (95% confidence interval [CI] 0.28–0.75) lower lumbar spine Z score and a 0.56-unit (95% CI 0.34–0.78) lower femoral neck Z score for areal BMD. These differences remained statistically significant after adjustment for the VLBW adults' shorter height and lower self-reported exercise intensity.
Young adults born with VLBW, when studied close to the age of peak bone mass, have significantly lower BMD than do their term-born peers. This suggests that compromised childhood bone mass accrual in preterm VLBW children translates into increased risk for osteoporosis in adulthood, warranting vigilance in osteoporosis prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Most pregnancies last 40 weeks but some babies arrive earlier than expected. Sadly, babies born before 37 weeks of pregnancy—premature babies—are more likely to die than full-term babies, although recent improvements in neonatal care have increased their chances of survival. Premature babies also often have serious long-term health problems, particularly those born before 32 weeks of pregnancy. Such extremely premature babies have poorly developed internal organs and are usually very small—babies whose birth weight is less than 1,500 g are called very-low-birth-weight (VLBW) babies; the average full-term birth weight is about 3,500 g. Furthermore, their bones are not as well developed as those of full-term babies. The human skeleton initially consists of a soft fibrous material called cartilage. This is gradually transformed into bone by a process called bone mineralization. The last third of pregnancy is a crucial period for bone mineralization although the process continues throughout infancy and childhood. Thus, VLBW babies often have subnormal skeletal mineralization and their accrual of bone mass during childhood is frequently compromised.
Why Was This Study Done?
It is not known whether the childhood bone deficits of VLBW babies persist into adulthood because the first generation of these infants not to die soon after birth is only just reaching adulthood. Peak bone mass is reached in early adulthood (bone mass begins to decrease from the age of 35 years onward) and is an important indicator of whether an individual will develop osteoporosis (thinning of the bones) and be susceptible to bone fractures later in life. If adults with VLBW (about 1% of live births in high-income countries are now VLBW births) do have a subnormal peak bone mass and reduced bone mineral density (BMD), they may be able reduce their risk of developing osteoporosis by eating a healthy diet and exercising regularly. In this study (part of the Helsinki Study of Very Low Birth Weight Adults), the researchers investigate the skeletal health of people who were born with VLBW in the Helsinki area between 1978 and 1985.
What Did the Researchers Do and Find?
The researchers compared the skeletal health of 144 young adults who were born prematurely with VLBW and subnormal BMD with that of 139 age- and sex-matched individuals who were born at term. They measured the BMD of the participants (average age 22.6 years) using “dual energy X-ray absorptiometry” and determined a “Z score” for the spine in the lower back (the lower lumbar spine) and the hip (two sites that are routinely examined in assessments of skeletal health). Z scores indicate whether an individual's BMD is significantly different from the average BMD of healthy age- and sex-matched people; in this study, reduced BMD was defined as a Z score of −1.0 or less. The researchers found that adults born with VLBW had an average Z score of −0.51 at the lower lumbar spine and −0.56 at the hip when compared with the adults born at term. Furthermore, 44% of the VLBW participants but only 26% of the term-born participants had a lumbar spine Z score of −1.0 or less. Adjustment for the shorter height of the VLBW participants slightly reduced these differences in BMD but the differences remained statistically significant.
What Do These Findings Mean?
These findings show that, when studied close to the age of peak bone mass, young adults born with VLBW have a significantly lower BMD than their term-born peers and a 2-fold greater risk of having a lumbar spine Z score of below −1.0; a unit decrease in Z score approximately doubles the risk of bone fractures. Because BMD measurements were only taken at one age, it remains possible, however, that the BMD of the VLBW adults might eventually match that of their full-term peers. Recently born VLBW babies still have a lower than average BMD during their childhood, note the researchers, even though their care has changed since the people included in this study were born. Thus, these findings suggest that people who were VLBW infants should be encouraged to eat food rich in vitamin D and calcium and to do regular weight-bearing exercise throughout their lives to improve their bone health and reduce their risk of developing osteoporosis.
Additional Information
Please access these Web sites via the online version of this summary at
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on preterm birth (in English and Spanish)
The Nemours Foundation, another nonprofit organization for child health, also provides information on premature babies (in English and Spanish)
MedlinePlus provides links to other information on premature babies and to information on osteoporosis (in English and Spanish)
The US National Institute of Arthritis and Musculoskeletal and Skin Diseases and the UK National Health Service also provide detailed information on all aspects of osteoporosis
Further details about the Helsinki Study of Very Low Birth Weight Adults are available
PMCID: PMC2722726  PMID: 19707270
8.  Decreasing healthcare-associated infections (HAI) is an efficient method to decrease healthcare-associated Methicillin-resistant S.aureus (MRSA) infections Antimicrobial resistance data from the German national nosocomial surveillance system KISS 
By analysing the data of the intensive care unit (ICU) component of the German national nosocomial infection surveillance system (KISS) during the last ten years, we have observed a steady increase in the MRSA rates (proportions) from 2001 to 2005 and only a slight decrease from 2006 to 2010. The objective of this study was to investigate the development of the incidence density of nosocomial MRSA infections because this is the crucial outcome for patients.
Data from 103 ICUs with ongoing participation during the observation period were included. The pooled incidence density of nosocomial MRSA infections decreased significantly from 0.37 per 1000 patient days in 2001 to 0.15 per 1000 patient days in 2010 (RR = 0.40; CI95 0.29-0.55). This decrease was proportional to the significant decrease of all HCAI during the same time period (RR = 0.61; CI95 0.58-0.65).
The results underline the need to concentrate infection control activities on measures to control HCAI in general rather than focusing too much on specific MRSA prevention measures. MRSA rates (proportions) are not a very useful indicator of the situation.
PMCID: PMC3415117  PMID: 22958746
Surveillance; MRSA; epidemiology; Staphylococcus aureus
9.  Associations between Mode of HIV Testing and Consent, Confidentiality, and Referral: A Comparative Analysis in Four African Countries 
PLoS Medicine  2012;9(10):e1001329.
A study carried out by Carla Obermeyer and colleagues examines whether practices regarding consent, confidentiality, and referral vary depending on whether HIV testing is provided through voluntary counseling and testing or provider-initiated testing.
Recommendations about scaling up HIV testing and counseling highlight the need to provide key services and to protect clients' rights, but it is unclear to what extent different modes of testing differ in this respect. This paper examines whether practices regarding consent, confidentiality, and referral vary depending on whether testing is provided through voluntary counseling and testing (VCT) or provider-initiated testing.
Methods and Findings
The MATCH (Multi-Country African Testing and Counseling for HIV) study was carried out in Burkina Faso, Kenya, Malawi, and Uganda. Surveys were conducted at selected facilities. We defined eight outcome measures related to pre- and post-test counseling, consent, confidentiality, satisfactory interactions with providers, and (for HIV-positive respondents) referral for care. These were compared across three types of facilities: integrated facilities, where testing is provided along with medical care; stand-alone VCT facilities; and prevention of mother-to-child transmission (PMTCT) facilities, where testing is part of PMTCT services. Tests of bivariate associations and modified Poisson regression were used to assess significance and estimate the unadjusted and adjusted associations between modes of testing and outcome measures. In total, 2,116 respondents tested in 2007 or later reported on their testing experience. High percentages of clients across countries and modes of testing reported receiving recommended services and being satisfied. In the unadjusted analyses, integrated testers were less likely to meet with a counselor before testing (83% compared with 95% of VCT testers; p<0.001), but those who had a pre-test meeting were more likely to have completed consent procedures (89% compared with 83% among VCT testers; p<0.001) and pre-test counseling (78% compared with 73% among VCT testers; p = 0.015). Both integrated and PMTCT testers were more likely to receive complete post-test counseling than were VCT testers (59% among both PMTCT and integrated testers compared with 36% among VCT testers; p<0.001). Adjusted analyses by country show few significant differences by mode of testing: only lower satisfaction among integrated testers in Burkina Faso and Uganda, and lower frequency of referral among PMTCT testers in Malawi. Adjusted analyses of pooled data across countries show a higher likelihood of pre-test meeting for those testing at VCT facilities (adjusted prevalence ratio: 1.22, 95% CI: 1.07–1.38) and higher satisfaction for stand-alone VCT facilities (adjusted prevalence ratio: 1.15; 95% CI: 1.06–1.25), compared to integrated testing, but no other associations were statistically significant.
Overall, in this study most respondents reported favorable outcomes for consent, confidentiality, and referral. Provider-initiated ways of delivering testing and counseling do not appear to be associated with less favorable outcomes for clients than traditional, client-initiated VCT, suggesting that testing can be scaled up through multiple modes without detriment to clients' rights.
Please see later in the article for the Editors' Summary
Editors' Summary
In 2007, World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) issued a joint guidance document on “provider-initiated” HIV testing and counseling. They noted that previous testing strategies that relied on “client-initiated” testing (also referred to as VCT, for voluntary counseling and testing) had failed to reach enough people, both in high-income and resource-constrained countries—in Africa, for example, at that time, just 12% of men and 10% of women had ever been tested. They argued that many opportunities to diagnose and counsel people that visit health facilities for other reasons are being missed, and that provider-initiated HIV testing and counseling can help expand access to HIV treatment, care, and support. They made it clear, however, that mandatory testing is not acceptable. All provider-initiated testing must therefore give individuals the option to not be tested. In addition, the guidelines stressed that all testing must continue to observe “the three Cs” (informed consent, counseling, and confidentiality) and be accompanied by an “enabling environment” including the availability of antiretroviral therapy, prevention and support services, and a supportive social, policy, and legal framework. A number of advocates have subsequently criticized the guidelines for failing to recognize that health-care services and staff in some countries do not always observe the three Cs. Critics have also questioned the appropriateness of the strategy for settings where antiretroviral therapy is not always available or where stigma and discrimination remain widespread.
Why Was This Study Done?
To inform the debate surrounding scale-up of HIV testing in general and provider-initiated testing in particular with data on “real-life” testing, researchers have since carried out a number of studies. One of them, called MATCH (for Multi-Country African Testing and Counseling for HIV), was designed to allow systematic comparisons across African countries of different ways of HIV testing. Its goal was to investigate the uptake of testing, to analyze differences in the experience of testing across countries and modes of testing, and to use the results to devise better strategies to increase knowledge of HIV status and referral to care. MATCH used different means to collect information, including surveys and interviews. People from Burkina Faso, Kenya, Malawi, and Uganda participated. Some had undergone HIV testing, others had not. This study used a subset of the survey data collected for the MATCH study and asked whether there were systematic differences depending on the type of testing people had experienced.
What Did the Researchers Do and Find?
The data the researchers used were from 2,116 people who had undergone testing in the two previous years at different facilities in the four countries. The different facilities were grouped into three “modes” of testing: VCT-only testing, integrated testing (which included hospitals and other medical facilities where provider-initiated and client-initiated testing were both available, along with other medical services), and prevention of mother-to-child transmission (PMTCT) testing at medical facilities offering services to pregnant women. Analyzing the survey responses, the researchers categorized them as related to eight different “outcomes”: pre-test meeting, pre-test counseling, consent, confidentiality, satisfaction with the person-to-person interactions, post-test meeting to receive results, post-test counseling, and referral to care.
They found that across countries and different facilities, the majority of participants reported having received most of the testing-related services. More than 90% reported having a pre-test meeting, and around 80% were satisfied with the personal interactions, with the consent process, and with confidentiality. About 50% of participants reported receiving all post-test services, and 71% of those who had tested positive for HIV reported appropriate referral to care.
When they looked for differences between different modes of testing, the researchers found that while they existed, they did not consistently favor one mode over another. Some outcomes scored higher in VCT facilities, some in PMTCT facilities, and some in integrated facilities.
What Do These Findings Mean?
While there is room for improvement in HIV testing services (especially post-test services) across the countries and facilities included, the study did not reveal major problems with consent or confidentiality. The results also suggest that services at PMTCT and integrated facilities are not any worse than those at VCT-only sites. It seems therefore reasonable to continue expanding access to HIV testing and to include all facilities in the scale-up. That said, this is only one of a number of studies examining issues surrounding HIV testing, and decisions should be based on all available evidence. The results here are consistent with some of the other studies, but there are also reports that counseling might become neglected as testing is scaled up, and that offering testing routinely at every doctor's visit makes it seem mandatory even if there is the possibility to “opt out.” Other analyses of the MATCH study use in-depth interviews to understand in more detail the feelings, experiences, and attitudes of participants who have been tested as well as those who have not been tested. It will be important to see whether their results are consistent with the ones here, which are based on a survey of people who have been tested.
Additional Information
Please access these websites via the online version of this summary at
WHO has published a toolkit for scaling up HIV testing and counseling services in resource-limited settings, as well as the report Service Delivery Approaches to HIV Testing and Counselling (HSC): A Strategic HTC Programme Framework
In response to reactions to the 2007 joint WHO/UNAIDS guidelines Guidance on Provider-Initiated HIV Testing and Counselling in Health Facilities, the UNAIDS Reference Group on HIV and Human Rights issued a Statement and Recommendations on Scaling up HIV Testing and Counselling
The NAM/aidsmap website has a section on HIV testing policies and guidelines.
PMCID: PMC3479110  PMID: 23109914
10.  IL-10, IL-6 and CD14 polymorphisms and sepsis outcome in ventilated very low birth weight infants 
BMC Medicine  2006;4:10.
Genetic variation in the innate immune system of the host may play a role in determining the risk of developing infection, as well as outcome from infection.
Infectious complications were retrospectively determined in 293 (233 African-American (AA), 57 Caucasian and 3 Hispanic) mechanically ventilated very low birth weight (VLBW) infants (<1500 grams at birth) who were genotyped for the IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T single nucleotide polymorphisms (SNPs).
The IL-6 -174C allele was associated with an increased incidence of late blood stream infection (BSI) in AA but not Caucasian infants. In AA infants with the C allele the incidence of late BSI was 20/29 (69%) compared to 94/204 (46%) in homozygous GG infants (RR 2.6, 95% CI: 1.1–6.0, p = 0.021). The IL-10 -1082A allele was associated with an increased incidence of late BSI. One or more episodes of late BSI developed in 14 (35%) of 40 infants with the GG genotype, 71 (49%) of 145 infants with the GA genotype and 63 (58%) of 108 infants with the AA genotype (p = 0.036). Infants with the A allele (AA or GA genotypes) had an incidence of late BSI that was 134/253 (53%) compared to 14/40 (35%) in homozygous GG infants (RR 2.1, 95% CI: 1.04–4.19, p = 0.035). The CD14 -260 C/T SNP did not alter the overall risk for BSI in ventilated VLBW infants. Multiple BSI episodes were more common in the TT genotype group (CC: 17%, CT: 11%, TT: 30%, p = 0.022). This effect was due to the strong effect of the TT genotype on the incidence of multiple BSI in AA infants (CC: 15%, CT: 11%, TT: 39%, p = 0.003).
The IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T SNPs may alter risk for BSI in ventilated VLBW infants.
PMCID: PMC1513390  PMID: 16611358
11.  Nosocomial Infection Reduction in VLBW Infants With a Statewide Quality-Improvement Model 
Pediatrics  2011;127(3):419-426.
To evaluate the effectiveness of the California Perinatal Quality Care Collaborative quality-improvement model using a toolkit supplemented by workshops and Web casts in decreasing nosocomial infections in very low birth weight infants.
This was a retrospective cohort study of continuous California Perinatal Quality Care Collaborative members' data during the years 2002–2006. The primary dependent variable was nosocomial infection, defined as a late bacterial or coagulase-negative staphylococcal infection diagnosed after the age of 3 days by positive blood/cerebro-spinal fluid culture(s) and clinical criteria. The primary independent variable of interest was voluntary attendance at the toolkit's introductory event, a direct indicator that at least 1 member of an NICU team had been personally exposed to the toolkit's features rather than being only notified of its availability. The intervention's effects were assessed using a multivariable logistic regression model that risk adjusted for selected demographic and clinical factors.
During the study period, 7733 eligible very low birth weight infants were born in 27 quality-improvement participant hospitals and 4512 very low birth weight infants were born in 27 non–quality-improvement participant hospitals. For the entire cohort, the rate of nosocomial infection decreased from 16.9% in 2002 to 14.5% in 2006. For infants admitted to NICUs participating in at least 1 quality-improvement event, there was an associated decreased risk of nosocomial infection (odds ratio: 0.81 [95% confidence interval: 0.68–0.96]) compared with those admitted to nonparticipating hospitals.
The structured intervention approach to quality improvement in the NICU setting, using a toolkit along with attendance at a workshop and/or Web cast, is an effective means by which to improve care outcomes.
PMCID: PMC3387911  PMID: 21339273
central-line–associated bloodstream infection; nosocomial infection; quality improvement; quality-improvement toolkits; quality-improvement evaluation
12.  Best Practices in Dengue Surveillance: A Report from the Asia-Pacific and Americas Dengue Prevention Boards 
Dengue fever is a virus infection that is spread by the Aedes aegypti mosquito and can cause severe disease especially in children. Dengue fever is a major problem in tropical and sub-tropical regions of the world.
Methodology/Principal Findings
We invited dengue experts from around the world to attend meetings to discuss dengue surveillance. We reviewed literature, heard detailed reports on surveillance programs, and shared expert opinions.
Presentations by 22 countries were heard during the 2.5 day meetings. We describe the best methods of surveillance in general, the stakeholders in dengue surveillance, and the steps from mosquito bite to reporting of a dengue case to explore how best to carry out dengue surveillance. We also provide details and a comparison of the dengue surveillance programs by the presenting countries.
The experts provided recommendations for achieving the best possible data from dengue surveillance accepting the realities of the real world (e.g., limited funding and staff). Their recommendations included: (1) Every dengue endemic country should make reporting of dengue cases to the government mandatory; (2) electronic reporting systems should be developed and used; (3) at minimum dengue surveillance data should include incidence, hospitalization rates, deaths by age group; (4) additional studies should be completed to check the sensitivity of the system; (5) laboratories should share expertise and data; (6) tests that identify dengue virus should be used in patients with fever for four days or less and antibody tests should be used after day 4 to diagnose dengue; and (7) early detection and prediction of dengue outbreaks should be goals for national surveillance systems.
Author Summary
The Pediatric Dengue Vaccine Initiative organized Dengue Prevention Boards in the Asia-Pacific and the Americas regions consisting of dengue experts from endemic countries. Both Boards convened meetings to review issues in surveillance. Through presentations, facilitated discussions, and surveys, the Boards identified best practices in dengue surveillance including: (1) Dengue should be a notifiable disease in endemic countries; (2) World Health Organization regional case definitions should be consistently applied; (3) electronic reporting systems should be developed and used broadly to speed delivery of data to stakeholders; (4) minimum reporting should include incidence rates of dengue fever, dengue hemorrhagic fever, dengue shock syndrome, and dengue deaths, and hospitalization and mortality rates should be reported by age group; (5) periodic additional studies (e.g., capture/recapture) should be conducted to assess under-detection, under-reporting, and the quality of surveillance; (6) laboratory methods and protocols should be standardized; (7) national authorities should encourage laboratories to develop networks to share expertise and data; and (8) RT-PCR and virus isolation (and possibly detection of the NS1 protein) are the recommended methods for confirmation of an acute dengue infection, but are recommended only for the four days after onset of fever—after day 4, IgM-capture enzyme-linked immunosorbent assay is recommended.
PMCID: PMC2982842  PMID: 21103381
13.  Characterizing the Epidemiology of the 2009 Influenza A/H1N1 Pandemic in Mexico 
PLoS Medicine  2011;8(5):e1000436.
Gerardo Chowell and colleagues address whether school closures and other social distancing strategies were successful in reducing pandemic flu transmission in Mexico by analyzing the age- and state-specific incidence of influenza morbidity and mortality in 32 Mexican states.
Mexico's local and national authorities initiated an intense public health response during the early stages of the 2009 A/H1N1 pandemic. In this study we analyzed the epidemiological patterns of the pandemic during April–December 2009 in Mexico and evaluated the impact of nonmedical interventions, school cycles, and demographic factors on influenza transmission.
Methods and Findings
We used influenza surveillance data compiled by the Mexican Institute for Social Security, representing 40% of the population, to study patterns in influenza-like illness (ILIs) hospitalizations, deaths, and case-fatality rate by pandemic wave and geographical region. We also estimated the reproduction number (R) on the basis of the growth rate of daily cases, and used a transmission model to evaluate the effectiveness of mitigation strategies initiated during the spring pandemic wave. A total of 117,626 ILI cases were identified during April–December 2009, of which 30.6% were tested for influenza, and 23.3% were positive for the influenza A/H1N1 pandemic virus. A three-wave pandemic profile was identified, with an initial wave in April–May (Mexico City area), a second wave in June–July (southeastern states), and a geographically widespread third wave in August–December. The median age of laboratory confirmed ILI cases was ∼18 years overall and increased to ∼31 years during autumn (p<0.0001). The case-fatality ratio among ILI cases was 1.2% overall, and highest (5.5%) among people over 60 years. The regional R estimates were 1.8–2.1, 1.6–1.9, and 1.2–1.3 for the spring, summer, and fall waves, respectively. We estimate that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a 29%–37% reduction in influenza transmission in spring 2009. In addition, an increase in R was observed in late May and early June in the southeast states, after mandatory school suspension resumed and before summer vacation started. State-specific fall pandemic waves began 2–5 weeks after school reopened for the fall term, coinciding with an age shift in influenza cases.
We documented three spatially heterogeneous waves of the 2009 A/H1N1 pandemic virus in Mexico, which were characterized by a relatively young age distribution of cases. Our study highlights the importance of school cycles on the transmission dynamics of this pandemic influenza strain and suggests that school closure and other mitigation measures could be useful to mitigate future influenza pandemics.
Please see later in the article for the Editors' Summary
Editors' Summary
From June 2009 to August 2010, the world was officially (according to specific World Health Organization [WHO] criteria—WHO phase 6 pandemic alert) in the grip of an Influenza A pandemic with a new strain of the H1N1 virus. The epidemic in Mexico, which had the second confirmed global case of H1N1 virus was first noted in early April 2009, when reports of respiratory hospitalizations and deaths among 62 young adults in Mexico alerted local health officials to the occurrence of atypical rates of respiratory illness. In line with its inter-institutional National Pandemic Influenza Preparedness and Response Plan, the Ministry of Health cancelled school attendance in the greater Mexico City area on April 24 and expanded these measures to the rest the country three days later. The Ministry of Health then implemented in Mexico City other “social distancing” strategies such as closing cinemas and restaurants and cancelling large public gatherings.
Why Was This Study Done?
School closures and other intense social distancing strategies can be very disruptive to the population, but as yet it is uncertain whether these measures were successful in reducing disease transmission. In addition, there have been no studies concentrating on recurrent pandemic waves in Mexico. So in this study the authors addressed these issues by analyzing the age- and state-specific incidence of influenza morbidity and mortality in 32 Mexican States and quantified the association between local influenza transmission rates, school cycles, and demographic factors.
What Did the Researchers Do and Find?
The researchers used the epidemiological surveillance system of the Mexican Institute for Social Security—a Mexican health system that covers private sector workers and their families, a group representative of the general population, that comprises roughly 40% of the Mexican population (107 million individuals), with a network of 1,099 primary health care units and 259 hospitals nationwide. Then the researchers compiled state- and age-specific time series of incident influenza-like illness and H1N1 influenza cases by day of symptom onset to analyze the geographic dissemination patterns of the pandemic across Mexico and defined three temporally distinct pandemic waves in 2009: spring (April 1–May 20), summer (May 21–August 1), and fall (August 2–December 31). The researchers then applied a mathematical model of influenza transmission to daily case data to assess the effectiveness of mandatory school closures and other social distancing measures implemented during April 24–May 11, in reducing influenza transmission rates.
The Mexican Institute for Social Security reported a total of 117,626 people with influenza-like illness from April 1 to December 31, 2009, of which 36,044 were laboratory tested (30.6%) and 27,440 (23.3%) were confirmed with H1N1 influenza. During this period, 1,370 people with influenza-like illness died of which 585 (1.5 per 100,000) were confirmed to have H1N1 influenza. The median age of people with laboratory confirmed influenza like illness (H1N1) was 18 years overall but increased to 31 years during the autumn wave. The overall case-fatality ratio among people with influenza like illness was 1.2%, but highest (5.5%) among people over 60 years. The researchers found that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a substantial (29%–37%) reduction in influenza transmission in spring 2009 but increased in late May and early June in the southeast states, after mandatory school suspension resumed and before summer vacation started. State-specific pandemic waves began 2–5 weeks after school reopened for the fall term, coinciding with an age shift in influenza cases.
What Do These Findings Mean?
These findings show that the age distribution of pandemic influenza morbidity was greater in younger age groups, while the risk of severe disease was skewed towards older age groups, and that there were substantial geographical variation in pandemic patterns across Mexico, in part related to population size. But most importantly, these findings support the effectiveness of early mitigation efforts including mandatory school closures and cancellation of large public gatherings, reinforcing the importance of school cycles in the transmission of pandemic influenza. This analysis increases understanding of the age and transmission patterns of the Mexican 2009 influenza pandemic at various geographic scales, which is crucial for designing more efficient public health interventions against future influenza pandemics.
Additional Information
Please access these Web sites via the online version of this summary at
The World Health Organization provides information about the global response to the 2009 H1N1 pandemic
PMCID: PMC3101203  PMID: 21629683
14.  Invasive fungal infection in very low birthweight infants: national prospective surveillance study 
To describe the epidemiology of invasive fungal infection in very low birthweight (VLBW: <1500 g) infants in the United Kingdom.
National prospective surveillance study between February 2003 and February 2004 using the British Paediatric Surveillance Unit reporting system reconciled with cases identified through routine laboratory reporting to the Health Protection Agency (England, Wales, and Northern Ireland), the Scottish Centre for Infection and Environmental Health, and the UK Mycology Reference Laboratory.
Ninety four confirmed cases of invasive fungal infection were identified during the surveillance period giving an incidence of estimated annual incidence of 10.0 (95% confidence interval (CI) 8.0 to 12.0) cases per 1000 VLBW live births. Eighty one (86%) of the infants were of extremely low birth weight (ELBW: <1000 g), incidence 21.1 (95% CI 16.5 to 25.7) per 1000 ELBW live births. Candida species, predominantly C albicans and C parapsilosis, were isolated in 93% of cases. Most organisms were isolated from the bloodstream and urinary tract. Death occurred in 41% of the infected infants before 37 weeks postconceptional age.
The incidence of invasive fungal infection in VLBW and ELBW infants in the United Kingdom is lower than reported in previous studies from tertiary centres in North America and elsewhere. The associated late neonatal and post‐neonatal death rates are substantially higher than expected in infants without invasive fungal infection. These data may inform decisions about the evaluation and use of antifungal infection control strategies.
PMCID: PMC2672702  PMID: 16332924
very low birth weight; candida; surveillance; fungal infection
15.  Incidence of Late Onset Neonatal Sepsis in Very Low Birth Weight Infants in a Tertiary Hospital 
Late onset neonatal septicaemia (LONS) is one of the major causes of morbidity and mortality in very low birth weight (VLBW) infants. The main objective of this study was to investigate the rate of LONS in the Neonatal Intensive Care Unit (NICU) of King Khalid University Hospital (KKUH) in Riyadh, Saudi Arabia over a three year period and compare it to international standards.
To determine the incidence of LONS, a retrospective study was undertaken and premature infants with a birth weight less than 1250 g were included, giving a total of 273 infants. Their bacterial profile and the antimicrobial susceptibility of the isolates were investigated, and the changes in trends over the study period studied.
91.5% of included infants (217/237) had 1 or more blood cultures obtained beyond the second day of life. 41% (98/237) of included infants had at least one episode of proven sepsis. The majority (71.4%) of first episode sepsis was caused by Gram-positive organisms. Coagulase negative Staphylococcus accounted for around 80% of all Gram-positive infections. Gram-negative pathogens accounted for 24.5% of the late onset infections while fungal organisms were responsible for 4%.
The rate of LONS was high and exceeded internationally reported rates in our tertiary care NICU. Gram-positive organisms continue to be major causative isolates. High priority should be placed on preventative steps to control nosocomial sepsis.
PMCID: PMC3074715  PMID: 21509234
Very low birth weight infants; Sepsis; Epidemiology
16.  Prevalence of antibiotic resistance in multi-drug resistant coagulase-negative staphylococci isolated from invasive infection in very low birth weight neonates in two Polish NICUs 
Multi-drug resistant coagulaso-negative staphylococci (CNS) have become an increasing problem in nosocomial infections connected with the presence of medical devices. The paper aimed to analyze the prevalence of antibiotic resistance in CNS isolated from invasive infection in very low birth weight (VLBW) neonates.
Continuous prospective target surveillance of infections was conducted in 2009 at two Polish NICUs that participated in the Polish Neonatology Surveillance Network (PNSN). The study covered 386 neonates with VLBW (≤1500 g), among which 262 cases of invasive infection were detected with predominance of CNS (123; 47%). Altogether, 100 CNS strains were analyzed. The resistance phenotypes were determined according to EUCAST. Resistance genes: mecA, ermA, ermB, ermC, msrA, aac(6')/aph(2''), ant(4')-Ia and aph(3')-IIIa were detected using multiplex PCR.
The most common species was S. epidermidis (63%), then S. haemolyticus (28%) and other CNS (9%). Among S. epidermidis, 98% of isolates were resistant to methicillin, 90% to erythromycin, 39% to clindamycin, 95% to gentamicin, 60% to amikacin, 36% to ofloxacin, 2% to tigecycline, 3% to linezolid and 13% to teicoplanin. Among S. haemolyticus isolates, 100% were resistant to methicillin, erythromycin and gentamicin, 18% to clindamycin, 50% to amikacin, 86% to ofloxacin, 14% to tigecycline and 4% to teicoplanin. No resistance to linezolid was detected for S. haemolyticus isolates. Moreover, all isolates of S. epidermidis and S. haemolyticus were susceptible to vancomycin. The mecA gene was detected in 98% of S. epidermidis isolates and all of S. haemolyticus ones. Among macrolide resistance isolates, the ermC was most common in S. epidermidis (60%) while msrA was prevalent in S. haemolyticus (93%). The ermC gene was indicated in all isolates with cMLSB, whereas mrsA was found in isolates with MSB phenotype. Of the aminoglycoside resistance genes, aac(6')/aph(2'') were present alone in 83% of S. epidermidis, whereas aac(6')/aph(2'') with aph(3')-IIIa were predominant in 84% of S. haemolyticus.
Knowing the epidemiology and antibiotic resistance of CNS isolated from invasive infection in VLBW neonates is a key step in developing targeted prevention strategies and reducing antibiotic consumption.
PMCID: PMC3898809  PMID: 24359473
Multi-drug resistant coagulase-negative staphylococci; Resistance genes; Very-low-birth-weight neonates; Nosocomial infections
17.  Epidemiology and Diagnosis of Hospital-Acquired Conjunctivitis Among Neonatal Intensive Care Unit Patients 
Few recent reports describe the epidemiology and risk factors for health care-associated conjunctivitis among neonatal intensive care unit (NICU) patients in developed countries. Reporting may be inaccurate in this population given that the National Nosocomial Infection Surveillance System (NNIS) definition is largely dependent on a positive culture, whereas clinical practice often consists of empiric treatment.
We describe the epidemiology of conjunctivitis among neonates in 2 level III–IV NICUs and compare the NNIS definition with our study definition: eye drainage and empiric treatment with or without a culture.
Patient demographics, clinical, device usage and conjunctivitis data collected prospectively from March 2001 through January 2003 were analyzed.
Conjunctivitis occurred in 5% (n = 154/2935) of infants, of whom 51% (n =79) were in NICU 1 and 49% (n =75) in NICU 2. Predominant pathogens included coagulase-negative staphylococci (25%), Staphylococcus aureus (19%) and Klebsiella spp. (10%). Significant predictors of conjunctivitis included low birth weight, use of ventilator or nasal cannula continuous positive airway pressure and study year. Ophthalmologic examination was an additional predictor of infection in NICU 1. Eye examination data were unavailable for NICU 2. Only 62% of cases that met the study definition for conjunctivitis met the NNIS definition, because many infants received empiric treatment.
Clinical conjunctivitis was associated with low birth weight and patient care factors that could lead to contamination of the eye with respiratory tract secretions. The NNIS definition failed to detect 38% of clinical infections. Consideration should be given to revising the definition of conjunctivitis for the NICU population.
PMCID: PMC2045635  PMID: 15998997
conjunctivitis; neonatal intensive care unit; low birth weight; premature infants
18.  Incidents and errors in neonatal intensive care: a review of the literature 
To examine the characteristics of incident reporting systems in neonatal intensive care units (NICUs) in relation to type, aetiology, outcome and preventability of incidents.
Systematic review. Search strategy: Medline, Embase, Cochrane Library. Included: relevant systematic reviews, randomised controlled trials, observational studies and qualitative research. Excluded: non‐systematic reviews, expert opinions, case reports and letters. Participants: hospital units supplying neonatal intensive care. Intervention: none. Outcome: characteristics of incident reporting systems; type, aetiology, outcome and preventability of incidents.
No relevant systematic reviews or randomised controlled trials were found. Eight prospective and two retrospective studies were included. Overall, medication incidents were most frequently reported. Available data in the NICU showed that the total error rate was much higher in studies using voluntary reporting than in a study using mandatory reporting. Multi‐institutional reporting identified rare but important errors. A substantial number of incidents were potentially harmful. When a system approach was used, many contributing factors were identified. Information about the impact of system changes on patient safety was scarce.
Multi‐institutional, voluntary, non‐punitive, system based incident reporting is likely to generate valuable information on type, aetiology, outcome and preventability of incidents in the NICU. However, the beneficial effects of incident reporting systems and consecutive system changes on patient safety are difficult to assess from the available evidence and therefore remain to be investigated.
PMCID: PMC2675366  PMID: 17376782
intensive care; neonatal; medical errors; incident reporting system; NICU; patient safety
19.  Early and Late Onset Sepsis in Very-Low-Birth-Weight Infants from a Large Group of Neonatal Intensive Care Units 
Early human development  2012;88(Suppl 2):S69-S74.
Very-low-birth-weight (VLBW, <1500 g birth weight) infants are at high risk for both early- and late-onset sepsis. Prior studies have observed a predominance of gram-negative organisms as a cause of early-onset sepsis and gram-positive organisms as a cause of late-onset sepsis. These reports are limited to large, academic neonatal intensive care units (NICUs) and may not reflect findings in other units. The purpose of this study was to determine the risk factors for sepsis, the causative organisms, and mortality following infection in a large and diverse sample of NICUs.
We analyzed the results of all cultures obtained from VLBW infants admitted to 313 NICUs from 1997 to 2010.
Over 108,000 VLBW infants were admitted during the study period. Early-onset sepsis occurred in 1032 infants, and late-onset sepsis occurred in 12,204 infants. Gram-negative organisms were the most commonly isolated pathogens in early-onset sepsis, and gram-positive organisms were most commonly isolated in late-onset sepsis. Early- and late-onset sepsis were associated with increased risk of death controlling for other confounders (odds ratio 1.45 [95% confidence interval 1.21, 1.73], and OR 1.30 [95% CI 1.21, 1.40], respectively).
This is the largest report of sepsis in VLBW infants to date. Incidence for early-onset sepsis and late-onset sepsis has changed little over this 14-year period, and overall mortality in VLBW infants with early- and late-onset sepsis is higher than in infants with negative cultures.
PMCID: PMC3513766  PMID: 22633519
early-onset sepsis; late-onset sepsis; very-low-birth-weight infants
20.  Blood stream infection is associated with altered heptavalent pneumococcal conjugate vaccine immune responses in very low birth weight infants 
Sepsis in older children and adults modifies immune system function. We compared serotype-specific antibody responses to heptavalent pneumococcal conjugate vaccine (PCV7) in very low birth weight infants (<1500g,VLBW) with and without blood stream infection (BSI) during their birth hospitalization.
Patients and Methods
Retrospective analysis of prospectively collected data for the Neonatal Research Network study of PCV7 responses among VLBWs. Infants received PCV7 at 2, 4, and 6 months after birth with blood drawn 4–6 weeks after 3rd dose. Serotype antibodies were compared between infants with or without a history of BSI. Regression models were constructed with birth-weight groups and other confounding factors identified in the primary study.
244 infants completed the vaccine series and had serum antibody available; 82 had BSI. After adjustment, BSI was not associated with reduced odds of serum antibody ≥0.35μg/mL.
BSI was not associated with reduced odds of WHO-defined protective PCV7 responses in VLBWs.
PMCID: PMC3722279  PMID: 23370608
VLBW; immune response; vaccine; sepsis; blood stream infection
21.  Monitoring the Impact of Influenza by Age: Emergency Department Fever and Respiratory Complaint Surveillance in New York City 
PLoS Medicine  2007;4(8):e247.
The importance of understanding age when estimating the impact of influenza on hospitalizations and deaths has been well described, yet existing surveillance systems have not made adequate use of age-specific data. Monitoring influenza-related morbidity using electronic health data may provide timely and detailed insight into the age-specific course, impact and epidemiology of seasonal drift and reassortment epidemic viruses. The purpose of this study was to evaluate the use of emergency department (ED) chief complaint data for measuring influenza-attributable morbidity by age and by predominant circulating virus.
Methods and Findings
We analyzed electronically reported ED fever and respiratory chief complaint and viral surveillance data in New York City (NYC) during the 2001–2002 through 2005–2006 influenza seasons, and inferred dominant circulating viruses from national surveillance reports. We estimated influenza-attributable impact as observed visits in excess of a model-predicted baseline during influenza periods, and epidemic timing by threshold and cross correlation. We found excess fever and respiratory ED visits occurred predominantly among school-aged children (8.5 excess ED visits per 1,000 children aged 5–17 y) with little or no impact on adults during the early-2002 B/Victoria-lineage epidemic; increased fever and respiratory ED visits among children younger than 5 y during respiratory syncytial virus-predominant periods preceding epidemic influenza; and excess ED visits across all ages during the 2003–2004 (9.2 excess visits per 1,000 population) and 2004–2005 (5.2 excess visits per 1,000 population) A/H3N2 Fujian-lineage epidemics, with the relative impact shifted within and between seasons from younger to older ages. During each influenza epidemic period in the study, ED visits were increased among school-aged children, and each epidemic peaked among school-aged children before other impacted age groups.
Influenza-related morbidity in NYC was highly age- and strain-specific. The impact of reemerging B/Victoria-lineage influenza was focused primarily on school-aged children born since the virus was last widespread in the US, while epidemic A/Fujian-lineage influenza affected all age groups, consistent with a novel antigenic variant. The correspondence between predominant circulating viruses and excess ED visits, hospitalizations, and deaths shows that excess fever and respiratory ED visits provide a reliable surrogate measure of incident influenza-attributable morbidity. The highly age-specific impact of influenza by subtype and strain suggests that greater age detail be incorporated into ongoing surveillance. Influenza morbidity surveillance using electronic data currently available in many jurisdictions can provide timely and representative information about the age-specific epidemiology of circulating influenza viruses.
Don Olson and colleagues report that influenza-related morbidity in NYC from 2001 to 2006 was highly age- and strain-specific and conclude that surveillance using electronic data can provide timely and representative information about the epidemiology of circulating influenza viruses.
Editors' Summary
Seasonal outbreaks (epidemics) of influenza (a viral infection of the nose, throat, and airways) send millions of people to their beds every winter. Most recover quickly, but flu epidemics often disrupt daily life and can cause many deaths. Seasonal epidemics occur because influenza viruses continually make small changes to the viral proteins (antigens) that the human immune system recognizes. Consequently, an immune response that combats influenza one year may provide partial or no protection the following year. Occasionally, an influenza virus with large antigenic changes emerges that triggers an influenza pandemic, or global epidemic. To help prepare for both seasonal epidemics and pandemics, public-health officials monitor influenza-related illness and death, investigate unusual outbreaks of respiratory diseases, and characterize circulating strains of the influenza virus. While traditional influenza-related illness surveillance systems rely on relatively slow voluntary clinician reporting of cases with influenza-like illness symptoms, some jurisdictions have also started to use “syndromic” surveillance systems. These use electronic health-related data rather than clinical impression to track illness in the community. For example, increased visits to emergency departments for fever or respiratory (breathing) problems can provide an early warning of an influenza outbreak.
Why Was This Study Done?
Rapid illness surveillance systems have been shown to detect flu outbreaks earlier than is possible through monitoring deaths from pneumonia or influenza. Increases in visits to emergency departments by children for fever or respiratory problems can provide an even earlier indicator. Researchers have not previously examined in detail how fever and respiratory problems by age group correlate with the predominant circulating respiratory viruses. Knowing details like this would help public-health officials detect and respond to influenza epidemics and pandemics. In this study, the researchers have used data collected between 2001 and 2006 in New York City emergency departments to investigate these aspects of syndromic surveillance for influenza.
What Did the Researchers Do and Find?
The researchers analyzed emergency department visits categorized broadly into a fever and respiratory syndrome (which provides an estimate of the total visits attributable to influenza) or more narrowly into an influenza-like illness syndrome (which specifically indicates fever with cough and/or sore throat) with laboratory-confirmed influenza surveillance data. They found that emergency department visits were highest during peak influenza periods, and that the affect on different age groups varied depending on the predominant circulating viruses. In early 2002, an epidemic reemergence of B/Victoria-lineage influenza viruses caused increased visits among school-aged children, while adult visits did not increase. By contrast, during the 2003–2004 season, when the predominant virus was an A/H3N2 Fujian-lineage influenza virus, excess visits occurred in all age groups, though the relative increase was greatest and earliest among school-aged children. During periods of documented respiratory syncytial virus (RSV) circulation, increases in fever and respiratory emergency department visits occurred in children under five years of age regardless of influenza circulation. Finally, the researchers found that excess visits to emergency departments for fever and respiratory symptoms preceded deaths from pneumonia or influenza by about two weeks.
What Do These Findings Mean?
These findings indicate that excess emergency department visits for fever and respiratory symptoms can provide a reliable and timely surrogate measure of illness due to influenza. They also provide new insights into how different influenza viruses affect people of different ages and how the timing and progression of each influenza season differs. These results, based on data collected over only five years in one city, might not be generalizable to other settings or years, warn the researchers. However, the present results strongly suggest that the routine monitoring of influenza might be improved by using electronic health-related data, such as emergency department visit data, and by examining it specifically by age group. Furthermore, by showing that school-aged children can be the first people to be affected by seasonal influenza, these results highlight the important role this age group plays in community-wide transmission of influenza, an observation that could influence the implementation of public-health strategies such as vaccination that aim to protect communities during influenza epidemics and pandemics.
Additional Information.
Please access these Web sites via the online version of this summary at
• US Centers for Disease Control and Prevention provides information on influenza for patients and health professionals and on influenza surveillance in the US (in English, Spanish, and several other languages)
• World Health Organization has a fact sheet on influenza and on global surveillance for influenza (in English, Spanish, French, Russian, Arabic, and Chinese)
• The MedlinePlus encyclopedia contains a page on flu (in English and Spanish)
• US National Institute of Allergy and Infectious Diseases has a feature called “focus on flu”
• A detailed report from the US Centers for Disease Control and Prevention titled “Framework for Evaluating Public Health Surveillance Systems for Early Detection of Outbreaks” includes a simple description of syndromic surveillance
• The International Society for Disease Surveillance has a collaborative syndromic surveillance public wiki
• The Anthropology of the Contemporary Research Collaboratory includes working papers and discussions by cultural anthropologists studying modern vital systems security and syndromic surveillance
PMCID: PMC1939858  PMID: 17683196
22.  Incidence of Nosocomial Infections in a Big University Affiliated Hospital in Shiraz, Iran: A Six-month Experience 
Nosocomial infections (NIs) are one of the most important health issues, particularly in developing countries, because these infections cause high mortality and morbidity, and economic and human resource loss as a consequence. To date, most surveillance studies have been conducted in developed countries, and only a few have been performed in Iran. All of the few Iranian studies have been performed using paper-based collection forms, and none was conducted with the aid of an electronic patient data retrieving and collecting tool. The aim of this study is to determine the incidence of NIs in a big university hospital of Shiraz, with the help of specifically programmed surveillance software merging electronically the available patient data and the infection results input manually.
The study was conducted prospectively through 6 months from 21st March up to 22nd September 2006, in a 374-bedded educational hospital. All patients admitted during this period were included in the study and examined everyday for detecting four types of NIs: surgical site infection (SSI), urinary tract infection (UTI), pneumonia (PNEU), and blood stream infection (BSI). Centres for Disease Control and Prevention National Nosocomial Infection Surveillance system criteria were applied.
4013 patients were admitted in the hospital. The overall infection rate was 4.14, and UTI, SSI, BSI, and PNEU rates were 1.82, 1.22, 0.5, and 0.5, respectively, per 1000 patient days of admission.
The results of this study showed that the frequency of NI in the investigated hospital was not higher than in many other reported surveillance results from other countries. This, however, might be a bias as the administration of antibiotics was very high in this study and the quality of microbiological investigation might have influenced significantly, resulting in more false-negative results than expected. Overall, the use of the Iranian National Nosocomial Infection Surveillance System Software proved to be useful and allowed both rapid data collection and detailed data analysis.
PMCID: PMC3634177  PMID: 23626895
Iran; National nosocomial infection surveillance; nosocomial infections; surveillance
23.  Risk adjusted and population based studies of the outcome for high risk infants in Scotland and Australia 
OBJECTIVES—To compare outcomes of care in selected neonatal intensive care units (NICUs) for very low birthweight (VLBW) or preterm infants in Scotland and Australia (study 1) and perinatal care for all VLBW infants in both countries (study 2).
DESIGN—Study 1: risk adjusted cohort study; study 2: population based cohort study.
SUBJECTS—Study 1: all 2621 infants of < 1500 g birth weight or < 31 weeks' gestation admitted to a volunteer sample of hospitals comprising eight of all 17 Scottish NICUs and six of all 12 tertiary NICUs in New South Wales and Queensland in 1993-1994; study 2: all 5986infants of 500-1499 g birth weight registered as live born in Scotland and Australia in 1993-1994.
MAIN OUTCOMES—Study 1: (a) hospital death; (b) death or cerebral damage, each adjusted for gestation and CRIB (clinical risk index for babies); study 2: neonatal (28 day) mortality.
RESULTS—Study 1. Data were obtained for 1628 admissions in six Australian NICUs, 775 in five Scottish tertiary NICUs, and 148 in three Scottish non-tertiary NICUs. Crude hospital death rates were 13%, 22%, and 22% respectively. Risk adjusted hospital mortality was about 50% higher in Scottish than in Australian NICUs (adjusted mortality ratio 1.46, 95% confidence interval (CI) 1.29 to 1.63,p < 0.001). There was no difference in risk adjusted outcomes between Scottish tertiary and non-tertiary NICUs. After risk adjustment, death or cerebral damage was more common in Scottish than Australian NICUs (odds ratio 1.9, 95% CI 1.5 to 2.5). Both these risk adjusted adverse outcomes remained more common in Scottish than Australian NICUs after excluding all infants < 28 weeks' gestation from the comparison. Study 2. Population based neonatal mortality in infants of 500-1499 g was higher in Scotland (20.3%) than Australia (16.6%) (relative risk 1.22, 95% CI 1.08 to 1.39, p = 0.002). In a post hoc analysis, neonatal mortality was also higher in England and Wales than in Australia.
CONCLUSIONS—Study 1: outcome was better in the Australian NICUs. Study 2: perinatal outcome was better in Australia. Both results may be consistent, at least in part, with differences in the organisation and implementation of neonatal care.

PMCID: PMC1721047  PMID: 10685984
24.  Survival and Morbidity Outcomes of Very Low Birth Weight Infants with Down Syndrome 
Pediatrics  2010;126(6):1132-1140.
Individuals with Down syndrome (DS) are at increased risk of several morbidities with lifelong health consequences. Little is known about mortality or morbidity risks in early infancy among very-low-birth-weight (VLBW) infants with DS. Our objective was to compare survival and neonatal morbidities between VLBW infants with DS and VLBW infants with other non-DS chromosomal anomalies, other non-chromosomal birth defects, and VLBW infants without major birth defects.
Data were collected prospectively for infants weighing 401-1500 grams born and/or cared for at one of the study centers participating in the NICHD Neonatal Research Network from 1994 through 2008. Risk of death and morbidities including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD), were compared between VLBW infants with DS and infants in the other groups.
Infants with DS were at increased risk of death (adjusted relative risk [RR] 2.47, 95% confidence interval [CI] 2.00-3.07), PDA, NEC, LOS, and BPD relative to infants with no birth defects. Decreased risk of death (RR 0.40, 95% CI 0.31-0.52) and increased risks of NEC and LOS were observed when comparing infants with DS to infants with other non-DS chromosomal anomalies. Relative to infants with non-chromosomal birth defects, infants with DS were at increased risk of PDA and NEC.
The increased risk of morbidities among VLBW infants with DS provides useful information for counseling parents and for caretakers in anticipating the need for enhanced surveillance for prevention of these morbidities.
PMCID: PMC3059605  PMID: 21098157
neonatal mortality; neonatal morbidity; preterm infants; Down syndrome; trisomy 21
25.  Combined use of alcohol hand rub and gloves reduces the incidence of late onset infection in very low birthweight infants 
Ng, P | Wong, H | Lyon, D | So, K | Liu, F | Lam, R | Wong, E | Cheng, A | Fok, T
Objective: To assess the incidence of late onset (> 72 hours) infection and necrotising enterocolitis (NEC) in very low birthweight (VLBW) infants in two 36 month periods using two hand hygiene protocols: conventional handwashing (HW; first 36 month period); an alcohol hand rub and gloves technique (HR; second 36 month period).
Method: VLBW infants admitted to the neonatal intensive care unit during the period December 1993–November 1999 were eligible. A new hand hygiene protocol using alcohol handrub and gloves was introduced in December 1996. Each patient's case record was reviewed retrospectively by two independent investigators using a standard data collection form. The incidence of NEC and systemic infections, including bacterial or fungal septicaemia, meningitis, and peritonitis, in the two periods were compared.
Results: The HW and HR groups contained 161 and 176 VLBW infants respectively. The incidence of late onset systemic infection decreased from 13.5 to 4.8 episodes (including NEC)/1000 patient days after introduction of the HR regimen, representing a 2.8-fold reduction. Similarly, the incidence of Gram positive, Gram negative, and fungal infections decreased 2.5-fold, 2.6-fold, and 7-fold respectively. There was also a significant reduction in the incidence of NEC in the HR group (p < 0.0001). Subgroup analysis revealed that the incidence of methicillin resistant Staphylococcus aureus (MRSA) septicaemia was significantly decreased in the second 36 month period (p  =  0.048). The clinical data suggest that infants in the HW group had significantly earlier onset of sepsis (p < 0.05) and required oxygen supplementation for longer (p < 0.05) than those in the HR group. Significantly more VLBW infants were discharged from the neonatal intensive care unit without ever being infected (p < 0.0001), and also significantly fewer infants had more than one episode of infection in the HR group (p < 0.0001).
Conclusion: The introduction of the HR protocol was associated with a 2.8-fold reduction in the incidence of late onset systemic infection, and also a significant decrease in the incidence of MRSA septicaemia and NEC in VLBW infants. This decrease in infection rate was maintained throughout the second 36 month period.
PMCID: PMC1721714  PMID: 15210670

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