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1.  Characterizing Non-Tuberculous Mycobacteria Infection in Bronchiectasis 
Chronic airway infection is a key aspect of the pathogenesis of bronchiectasis. A growing interest has been raised on non-tuberculous mycobacteria (NTM) infection. We aimed at describing the clinical characteristics, diagnostic process, therapeutic options and outcomes of bronchiectasis patients with pulmonary NTM (pNTM) disease. This was a prospective, observational study enrolling 261 adult bronchiectasis patients during the stable state at the San Gerardo Hospital, Monza, Italy, from 2012 to 2015. Three groups were identified: pNTM disease; chronic P. aeruginosa infection; chronic infection due to bacteria other than P. aeruginosa. NTM were isolated in 32 (12%) patients, and among them, a diagnosis of pNTM disease was reached in 23 cases. When compared to chronic P. aeruginosa infection, patients with pNTM were more likely to have cylindrical bronchiectasis and a “tree-in-bud” pattern, a history of weight loss, a lower disease severity and a lower number of pulmonary exacerbations. Among pNTM patients who started treatment, 68% showed a radiological improvement, and 37% achieved culture conversion without recurrence, while 21% showed NTM isolation recurrence. NTM isolation seems to be a frequent event in bronchiectasis patients, and few parameters might help to suspect NTM infection. Treatment indications and monitoring still remain an important area for future research.
PMCID: PMC5133910  PMID: 27854334
non-cystic fibrosis bronchiectasis; non-tuberculous mycobacteria; pulmonary infection
2.  Role of cephalosporins in the era of Clostridium difficile infection 
The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise. This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011–12 to 2012–13, respectively. While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence. Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI. Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations. We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes.
PMCID: PMC5161048  PMID: 27659735
3.  Chromogranin A levels and mortality in patients with severe sepsis 
Chromogranin A (CgA) is a novel biomarker with potential to assess mortality risk of patients with severe sepsis.
Assess association of CgA levels and mortality risk of severely septic patients.
Serum CgA levels were measured in 50 hospitalized, severely septic patients with organ failure <48 hours.
Higher CgA levels trended towards higher ICU and hospital mortality. Patients without cardiovascular disease who died in the ICU had higher median (IQR) CgA levels 602.3 (343.3, 1134.3) ng/ml vs. 205.5 (130.7, 325.9) ng/ml, p=0.01.
High CgA levels predict ICU mortality in severely septic patients without prior cardiovascular disease.
PMCID: PMC5027645  PMID: 26154393
Chromogranin A; sepsis; biological marker; mortality; cardiovascular diseases
4.  A systematic review of the burden of vaccine preventable pneumococcal disease in UK adults 
Invasive pneumococcal disease (IPD) and pneumococcal pneumonia are common and carry a significant morbidity and mortality. Current strategies to prevent pneumococcal disease are under review in the United Kingdom (UK). We conducted a systematic review to evaluate the burden of vaccine type adult pneumococcal disease specifically in the UK.
A systematic review conducted and reported according to MOOSE guidelines. Relevant studies from 1990 to 2015 were included. The primary outcome was the incidence of vaccine type pneumococcal disease, focussing on the pneumococcal polysaccharide vaccine (PPSV), the 13-valent conjugate vaccine (PCV13) and the 7-valent conjugate vaccine (PCV7).
Data from surveillance in England and Wales from 2013/14 shows an incidence of 6.85 per 100,000 population across all adult age groups for IPD, and an incidence of 20.58 per 100,000 population in those aged >65 years. The corresponding incidences for PCV13 serotype IPD were 1.4 per 100,000 and 3.72 per 100,000. The most recent available data for community-acquired pneumonia (CAP) including non-invasive disease showed an incidence of 20.6 per 100,000 for adult pneumococcal CAP and 8.6 per 100,000 population for PCV13 serotype CAP. Both IPD and CAP data sources in the UK suggest an ongoing herd protection effect from childhood PCV13 vaccination causing a reduction in the proportion of cases caused by PCV13 serotypes in adults. Despite this, applying the incidence rates to UK population estimates suggests more than 4000 patients annually will be hospitalised with PCV13 serotype CAP and more than 900 will be affected by IPD, although with a trend for these numbers to decrease over time.
There was limited recent data on serotype distribution in high risk groups such as those with chronic respiratory or cardiac disease and no data available for vaccine type (VT) CAP managed in the community where there is likely to be a considerable unmeasured burden.
The most recent available data suggests that VT pneumococcal disease continues to have a high burden in UK adults despite the impact of childhood PCV13 vaccination. IPD estimates represent only a fraction of the total burden of pneumococcal disease.
Study registration
PROSPERO CRD42015025043
Electronic supplementary material
The online version of this article (doi:10.1186/s12890-016-0242-0) contains supplementary material, which is available to authorized users.
PMCID: PMC4864929  PMID: 27169895
Vaccine; Pneumonia; Infection; Epidemiology; Mortality
5.  The EMBARC European Bronchiectasis Registry: protocol for an international observational study 
ERJ Open Research  2016;2(1):00081-2015.
Bronchiectasis is one of the most neglected diseases in respiratory medicine. There are no approved therapies and few large-scale, representative epidemiological studies.
The EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration) registry is a prospective, pan-European observational study of patients with bronchiectasis. The inclusion criterion is a primary clinical diagnosis of bronchiectasis consisting of: 1) a clinical history consistent with bronchiectasis; and 2) computed tomography demonstrating bronchiectasis. Core exclusion criteria are: 1) bronchiectasis due to known cystic fibrosis; 2) age <18 years; and 3) patients who are unable or unwilling to provide informed consent.
The study aims to enrol 1000 patients by April 2016 across at least 20 European countries, and 10 000 patients by March 2020. Patients will undergo a comprehensive baseline assessment and will be followed up annually for up to 5 years with the goal of providing high-quality longitudinal data on outcomes, treatment patterns and quality of life. Data from the registry will be available in the form of annual reports. and will be disseminated in conference presentations and peer-reviewed publications.
The European Bronchiectasis Registry aims to make a major contribution to understanding the natural history of the disease, as well as guiding evidence-based decision making and facilitating large randomised controlled trials.
The European Bronchiectasis Registry will recruit 10 000 patients over 5 years
PMCID: PMC5005162  PMID: 27730179
6.  Clinical Tuberculosis 
Breathe  2015;11(3):231.
Despite advances in public health and chemotherapy, we remain far from the objective of tuberculosis (TB) control and elimination globally. There are more than 9 million new cases worldwide each year, with 1.5 million deaths. TB is second only to HIV/AIDS as the greatest worldwide cause of infectious death.
Book review: Clinical Tuberculosis by PDO Davies et al.
PMCID: PMC4666451
7.  Ethnicity & First Birth: Age, Smoking, Delivery, Gestation, Weight & Feeding: Scottish Health & Ethnicity Linkage Study 
European journal of public health  2014;24(6):910-915.
We linked census and health service datasets to address the shortage of information comparing maternal characteristics and pregnancy outcomes by ethnic group in Scotland.
Retrospective cohort study linking the 2001 national Census for Scotland and hospital obstetric data (2001-2008); comparing maternal age, smoking status, gestational age, caesarean section rates, birthweight, preterm and breastfeeding rates by ethnic group.
144,344 women were identified as having had a first birth between 1 May 2001 and 30 April 2008. White Scottish mothers were younger (mean age 27.3 years, 95% CI 27.3, 27.4) than other White groups and most non-White groups. They had the highest smoking rates (25.8%, CI 25.5, 26.0) and the lowest rates of breastfeeding at 6-8 weeks (23.4%, CI 23.1, 23.6), with most of the other groups being around 40%.
Women from non-White minority ethnic groups in Scotland tended to have babies of lower birthweight (eg Pakistani mean birthweight - 3105 Grams, White Scottish - 3356 Grams), even after adjustment for gestational age, maternal age, education, smoking and housing tenure. This effect was more noticeable for women born in the UK. White English, Irish, and Other White babies tended to have higher birthweights. There was little variation between groups in Caesarean section rates.
Pregnant women from ethnic minority populations in Scotland have more favourable health behaviour than the White Scottish, although the non-white groups tend to have lower birthweight. Further exploration of the reasons for these differences has potential to benefit women from the majority population.
PMCID: PMC4140759  PMID: 24843052
Ethnicity; Maternal health; Birth Weight; Breast Feeding
8.  Doing science: how to get credit for your scientific work 
Breathe  2015;11(2):153-155.
Everyone deserves to be acknowledged for their efforts and contributions to a shared goal, and getting credit for your scientific work should be part of a natural process and should be fair and straightforward. However, credit cannot be objectively measured despite it having a big influence and, unfortunately, getting appropriate credit can occasionally be both complicated and challenging.
PMCID: PMC4487371  PMID: 26306117
9.  STOPPIT Baby Follow-Up Study: The Effect of Prophylactic Progesterone in Twin Pregnancy on Childhood Outcome 
PLoS ONE  2015;10(4):e0122341.
To determine the long-term effects of in utero progesterone exposure in twin children.
This study evaluated the health and developmental outcomes of all surviving children born to mothers who participated in a double-blind, placebo-controlled trial of progesterone given for the prevention of preterm birth in twin pregnancies (STOPPIT, ISRCTN35782581). Follow-up was performed via record linkage and two parent-completed validated questionnaires, the Child Development Inventory and the Health Utilities Index.
Record linkage was successfully performed on at least one record in 759/781 (97%) children eligible for follow-up. There were no differences between progesterone-exposed and placebo-exposed twins with respect to incidence of death, congenital anomalies and hospitalisation, nor on routine national child health assessments. Questionnaire responses were received for 324/738 (44%) children. The mean age at questionnaire follow-up was 55.5 months. Delay in at least one developmental domain on the Child Development Inventory was observed in 107/324 (33%) children, with no evidence of difference between progesterone-exposed and placebo-exposed twins. There was no evidence of difference between the progesterone and placebo groups in global health status assessed using the Health Utilities Index: 89% of children were rated as having ‘excellent’ health and a further 8% as having ‘very good’ health.
In this cohort of twin children there was no evidence of a detrimental or beneficial impact on health and developmental outcomes at three to six years of age due to in utero exposure to progesterone.
PMCID: PMC4400139  PMID: 25881289
10.  Breastfeeding is Associated with Reduced Childhood Hospitalization: Evidence from a Scottish Birth Cohort (1997-2009) 
The Journal of Pediatrics  2015;166(3):620-625.e4.
To evaluate the risk of childhood hospitalization associated with infant feeding patterns at 6-8 weeks of age in Scotland.
Study design
A retrospective population level study based on the linkage of birth, death, maternity, infant health, child health surveillance, and admission records for children born as single births in Scotland between 1997 and 2009 (n = 502 948) followed up to March 2012. Descriptive analyses, Kaplan Meier tests, and Cox regression were used to quantify the association between the mode of infant feeding and risk of childhood hospitalization for respiratory, gastrointestinal, and urinary tract infections, and other common childhood ailments during the study period.
Within the first 6 months of life, there was a greater hazard ratio (HR) of hospitalization for common childhood illnesses among formula-fed infants (HR 1.40; 95% CI 1.35-1.45) and mixed-fed infants (HR 1.18; 95% CI 1.11-1.25) compared with infants exclusively breastfed after adjustment for parental, maternal, and infant health characteristics. Within the first year of life and beyond, a greater relative risk of hospitalization was observed among formula-fed infants for a range of individual illnesses reported in childhood including gastrointestinal, respiratory, and urinary tract infections, otitis media, fever, asthma, diabetes, and dental caries.
Using linked administrative data, we found greater risks of hospitalization in early childhood for a range of common childhood illnesses among Scottish infants who were not exclusively breastfed at 6-8 weeks of age.
PMCID: PMC4344374  PMID: 25556021
HR, Hazard ratio; PAF, Population-attributable fraction
11.  A prospective cohort study of the use of domiciliary intravenous antibiotics in bronchiectasis 
We introduced domiciliary intravenous (IV) antibiotic therapy in patients with bronchiectasis to promote patient-centred domiciliary treatment instead of hospital inpatient treatment.
To assess the efficacy and safety of domiciliary IV antibiotic therapy in patients with non-cystic fibrosis bronchiectasis.
In this prospective study conducted over 5 years, we assessed patients’ eligibility for receiving domiciliary treatment. All patients received 14 days of IV antibiotic therapy and were monitored at baseline/day 7/day 14. We assessed the treatment outcome, morbidity, mortality and 30-day readmission rates.
A total of 116 patients received 196 courses of IV antibiotics. Eighty courses were delivered as inpatient treatment, 32 as early supported discharge (ESD) and 84 as domiciliary therapy. There was significant clinical and quality of life improvement in all groups, with resolution of infection in 76% in the inpatient group, 80% in the ESD group and 80% in the domiciliary group. Morbidity was recorded in 13.8% in the inpatient group, 9.4% in the ESD group and 14.2% in the domiciliary IV group. No mortality was recorded in either group. Thirty-day readmission rates were 13.8% in the inpatient group, 12.5% in the ESD group and 14.2% in the domiciliary group. Total bed days saved was 1443.
Domiciliary IV antibiotic therapy in bronchiectasis is clinically effective and was safe in our cohort of patients.
PMCID: PMC4373503  PMID: 25340361
12.  Evaluation of Health in Pregnancy grants in Scotland: a protocol for a natural experiment 
BMJ Open  2014;4(10):e006547.
A substantial proportion of low birth weight is attributable to the mother's cultural and socioeconomic circumstances. Early childhood programmes have been widely developed to improve child outcomes. In the UK, the Health in Pregnancy (HiP) grant, a universal conditional cash transfer of £190, was introduced for women reaching the 25th week of pregnancy with a due date on/or after 6 April 2009 and subsequently withdrawn for women reaching the 25th week of pregnancy on/or after 1 January 2011. The current study focuses on the evaluation of the effectiveness and cost-effectiveness of the HiP grant.
Methods and analysis
The population under study will be all singleton births in Scotland over the periods of January 2004 to March 2009 (preintervention), April 2009 to April 2011 (intervention) and May 2011 to December 2013 (postintervention). Data will be extracted from the Scottish maternity and neonatal database. The analysis period 2004–2013 should yield over 585 000 births. The primary outcome will be birth weight among singleton births. Other secondary outcomes will include gestation at booking, booking before 25 weeks; measures of size and stage; gestational age at delivery; weight-for-dates, term at birth; birth outcomes and maternal smoking. The main statistical method we will use is interrupted time series. Outcomes will be measured on individual births nested within mothers, with mothers themselves clustered within data zones. Multilevel regression models will be used to determine whether the outcomes changed during the period in which the HiP grants was in effect. Subgroup analyses will be conducted for those groups most likely to benefit from the payments.
Ethics and dissemination
Approval for data collection, storage and release for research purpose has been given (6 May 2014, PAC38A/13) by the Privacy Advisory Committee. The results of this study will be disseminated through peer-reviewed publications in journals, national and international conferences.
PMCID: PMC4202003  PMID: 25324327
13.  Varying gestational age patterns in cesarean delivery: an international comparison 
While international variations in overall cesarean delivery rates are well documented, less information is available for clinical sub-groups. Cesarean data presented by subgroups can be used to evaluate uptake of cesarean reduction policies or to monitor delivery practices for high and low risk pregnancies based on new scientific evidence. We studied differences and patterns in cesarean delivery rates by multiplicity and gestational age in Europe and the United States.
This study used routine aggregate data from 17 European countries and the United States on the number of singleton and multiple live births with cesarean versus vaginal delivery by week of gestation in 2008. Overall and gestation-specific cesarean delivery rates were analyzed. We computed rate differences to compare mode of delivery (cesarean vs vaginal birth) between selected gestational age groups and studied associations between rates in these subgroups namely: very preterm (26–31 weeks GA), moderate preterm (32–36 weeks GA), near term (37–38 weeks GA), term (39–41 weeks GA) and post-term (42+ weeks GA) births, using Spearman’s rank tests.
High variations in cesarean rates for singletons and multiples were observed everywhere. Rates for singletons varied from 15% in The Netherlands and Slovenia, to over 30% in the US and Germany. In singletons, rates were highest for very preterm births and declined to a nadir at 40 weeks of gestation, ranging from 8.0% in Sweden and Norway, to 22.5% in the US. These patterns differed across countries; the average rate difference between very preterm and term births was 43 percentage points, but ranged from 14% to 61%. High variations in rate differences were also observed for near term versus term births. For multiples, rates declined by gestational age in some countries, whereas in others rates were similar across all weeks of gestation. Countries’ overall cesarean rates were highly correlated with gestation-specific subgroup rates, except for very preterm births.
Gestational age patterns in cesarean delivery were heterogeneous across countries; these differences highlight areas where consensus on best practices is lacking and could be used in developing strategies to reduce cesareans.
PMCID: PMC4177602  PMID: 25217979
Cesarean delivery (CD); Cross-national comparisons; Gestational age; Plurality; Mode of delivery; Euro-Peristat
14.  The Bronchiectasis Severity Index. An International Derivation and Validation Study 
Rationale: There are no risk stratification tools for morbidity and mortality in bronchiectasis. Identifying patients at risk of exacerbations, hospital admissions, and mortality is vital for future research.
Objectives: This study describes the derivation and validation of the Bronchiectasis Severity Index (BSI).
Methods: Derivation of the BSI used data from a prospective cohort study (Edinburgh, UK, 2008–2012) enrolling 608 patients. Cox proportional hazard regression was used to identify independent predictors of mortality and hospitalization over 4-year follow-up. The score was validated in independent cohorts from Dundee, UK (n = 218); Leuven, Belgium (n = 253); Monza, Italy (n = 105); and Newcastle, UK (n = 126).
Measurements and Main Results: Independent predictors of future hospitalization were prior hospital admissions, Medical Research Council dyspnea score greater than or equal to 4, FEV1 < 30% predicted, Pseudomonas aeruginosa colonization, colonization with other pathogenic organisms, and three or more lobes involved on high-resolution computed tomography. Independent predictors of mortality were older age, low FEV1, lower body mass index, prior hospitalization, and three or more exacerbations in the year before the study. The derived BSI predicted mortality and hospitalization: area under the receiver operator characteristic curve (AUC) 0.80 (95% confidence interval, 0.74–0.86) for mortality and AUC 0.88 (95% confidence interval, 0.84–0.91) for hospitalization, respectively. There was a clear difference in exacerbation frequency and quality of life using the St. George’s Respiratory Questionnaire between patients classified as low, intermediate, and high risk by the score (P < 0.0001 for all comparisons). In the validation cohorts, the AUC for mortality ranged from 0.81 to 0.84 and for hospitalization from 0.80 to 0.88.
Conclusions: The BSI is a useful clinical predictive tool that identifies patients at risk of future mortality, hospitalization, and exacerbations across healthcare systems.
PMCID: PMC3977711  PMID: 24328736
bronchiectasis; mortality; Pseudomonas aeruginosa; exacerbation; prediction
15.  Phenotyping community-acquired pneumonia according to the presence of acute respiratory failure and severe sepsis 
Respiratory Research  2014;15(1):27.
Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission.
This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three hospitals in Italy, Spain, and Scotland between 2008 and 2010. Three groups of patients were identified: those with neither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on admission.
Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C. Patients in Group C were more severe than patients in Group B. Isolated ARF was correlated with age (p < 0.001), COPD (p < 0.001) and multilobar infiltrates (p < 0.001). The contemporary occurrence of ARF and SS was associated with age (p = 0.002), residency in nursing home (p = 0.007), COPD (p < 0.001), multilobar involvement (p < 0.001) and renal disease (p < 0.001). 4.2% of patients in Group A died, 9.3% in Group B and 26% in Group C, p < 0.001. After adjustment, the presence of only ARF had an OR for in-hospital mortality of 1.85 (p = 0.011) and the presence of both ARF and SS had an OR of 6.32 (p < 0.001).
The identification of ARF and SS on hospital admission can help physicians in classifying CAP patients into three different clinical phenotypes.
PMCID: PMC4015148  PMID: 24593040
Pneumonia; Sepsis; Severe sepsis; Acute respiratory failure; ARDS; CAP; Community-acquired pneumonia; Mortality; Oxygenation
16.  Outcomes of Induction of Labour in Women with Previous Caesarean Delivery: A Retrospective Cohort Study Using a Population Database 
PLoS ONE  2013;8(4):e60404.
There is evidence that induction of labour (IOL) around term reduces perinatal mortality and caesarean delivery rates when compared to expectant management of pregnancy (allowing the pregnancy to continue to await spontaneous labour or definitive indication for delivery). However, it is not clear whether IOL in women with a previous caesarean section confers the same benefits. The aim of this study was to describe outcomes of IOL at 39–41 weeks in women with one previous caesarean delivery and to compare outcomes of IOL or planned caesarean delivery to those of expectant management.
Methods and Findings
We performed a population-based retrospective cohort study of singleton births greater than 39 weeks gestation, in women with one previous caesarean delivery, in Scotland, UK 1981–2007 (n = 46,176). Outcomes included mode of delivery, perinatal mortality, neonatal unit admission, postpartum hemorrhage and uterine rupture. 40.1% (2,969/7,401) of women who underwent IOL 39–41 weeks were ultimately delivered by caesarean. When compared to expectant management IOL was associated with lower odds of caesarean delivery (adjusted odds ratio [AOR] after IOL at 39 weeks of 0.81 [95% CI 0.71–0.91]). There was no significant effect on the odds of perinatal mortality but greater odds of neonatal unit admission (AOR after IOL at 39 weeks of 1.29 [95% CI 1.08–1.55]). In contrast, when compared with expectant management, elective repeat caesarean delivery was associated with lower perinatal mortality (AOR after planned caesarean at 39 weeks of 0.23 [95% CI 0.07–0.75]) and, depending on gestation, the same or lower neonatal unit admission (AOR after planned caesarean at 39 weeks of 0.98 [0.90–1.07] at 40 weeks of 1.08 [0.94–1.23] and at 41 weeks of 0.77 [0.60–1.00]).
A more liberal policy of IOL in women with previous caesarean delivery may reduce repeat caesarean delivery, but increases the risks of neonatal complications.
PMCID: PMC3615029  PMID: 23565242
17.  Outcomes of elective induction of labour compared with expectant management: population based study 
The BMJ  2012;344:e2838.
Objective To determine neonatal outcomes (perinatal mortality and special care unit admission) and maternal outcomes (mode of delivery, delivery complications) of elective induction of labour compared with expectant management.
Design Retrospective cohort study using an unselected population database.
Setting Consultant and midwife led obstetric units in Scotland 1981-2007.
Participants 1 271 549 women with singleton pregnancies of 37 weeks or more gestation.
Interventions Outcomes of elective induction of labour (induction of labour with no recognised medical indication) at 37, 38, 39, 40, and 41 weeks’ gestation compared with those of expectant management (continuation of pregnancy to either spontaneous labour, induction of labour or caesarean section at a later gestation).
Main outcome measures Extended perinatal mortality, mode of delivery, postpartum haemorrhage, obstetric anal sphincter injury, and admission to a neonatal or special care baby unit. Outcomes were adjusted for age at delivery, parity, year of birth, birth weight, deprivation category, and, where appropriate, mode of delivery.
Results At each gestation between 37 and 41 completed weeks, elective induction of labour was associated with a decreased odds of perinatal mortality compared with expectant management (at 40 weeks’ gestation 0.08% (37/44 764) in the induction of labour group versus 0.18% (627/350 643) in the expectant management group; adjusted odds ratio 0.39, 99% confidence interval 0.24 to 0.63), without a reduction in the odds of spontaneous vertex delivery (at 40 weeks’ gestation 79.9% (35 775/44 778) in the induction of labour group versus 73.7% (258 665/350 791) in the expectant management group; adjusted odds ratio 1.26, 1.22 to 1.31). Admission to a neonatal unit was, however, increased in association with elective induction of labour at all gestations before 41 weeks (at 40 weeks’ gestation 8.0% (3605/44 778) in the induction of labour group compared with 7.3% (25 572/350 791) in the expectant management group; adjusted odds ratio 1.14, 1.09 to 1.20).
Conclusion Although residual confounding may remain, our findings indicate that elective induction of labour at term gestation can reduce perinatal mortality in developed countries without increasing the risk of operative delivery.
PMCID: PMC3349781  PMID: 22577197
18.  Cardiovascular disease and air pollution in Scotland: no association or insufficient data and study design? 
BMC Public Health  2012;12:227.
Coronary heart disease and stroke are leading causes of mortality and ill health in Scotland, and clear associations have been found in previous studies between air pollution and cardiovascular disease. This study aimed to use routinely available data to examine whether there is any evidence of an association between short-term exposure to particulate matter (measured as PM10, particles less than 10 micrograms per cubic metre) and hospital admissions due to cardiovascular disease, in the two largest cities in Scotland during the years 2000 to 2006.
The study utilised an ecological time series design, and the analysis was based on overdispersed Poisson log-linear models.
No consistent associations were found between PM10 concentrations and cardiovascular hospital admissions in either of the cities studied, as all of the estimated relative risks were close to one, and all but one of the associated 95% confidence intervals contained the null risk of one.
This study suggests that in small cities, where air quality is relatively good, then either PM10 concentrations have no effect on cardiovascular ill health, or that the routinely available data and the corresponding study design are not sufficient to detect an association.
PMCID: PMC3476376  PMID: 22440092
19.  Human L-Ficolin (Ficolin-2) and Its Clinical Significance 
Human L-ficolin (P35, ficolin-2) is synthesised in the liver and secreted into the bloodstream where it is one of the major pattern recognition molecules of plasma/serum. Like other ficolins, it consists of a collagen-like tail region linked to a fibrinogen-related globular head; a basic triplet subunit arises via a collagen-like triple helix, and this then forms higher multimers (typically a 12-mer, Mr 400K). Unlike other ficolins, it has a complex set of binding sites arranged within an internal cleft enabling it to recognise a variety of molecular patterns including acetylated sugars and certain 1,3-β-glucans. It is one of the few molecules known to activate the lectin pathway of complement. Recently, some disease association studies (at either the DNA or protein level) have implicated L-ficolin in innate immunity, where it might cooperate with pentraxins and collectins. Emerging lines of evidence point to a role for L-ficolin in respiratory immunity, where its affinity for Pseudomonas aeruginosa could be significant.
PMCID: PMC3303570  PMID: 22500076
20.  Population-based trends in pregnancy hypertension and pre-eclampsia: an international comparative study 
BMJ Open  2011;1(1):e000101.
The objective of this study was to compare international trends in pre-eclampsia rates and in overall pregnancy hypertension rates (including gestational hypertension, pre-eclampsia and eclampsia).
Population data (from birth and/or hospital records) on all women giving birth were available from Australia (two states), Canada (Alberta), Denmark, Norway, Scotland, Sweden and the USA (Massachusetts) for a minimum of 6 years from 1997 to 2007. All countries used the 10th revision of the International Classification of Diseases, except Massachusetts which used the 9th revision. There were no major changes to the diagnostic criteria or methods of data collection in any country during the study period. Population characteristics as well as rates of pregnancy hypertension and pre-eclampsia were compared.
Absolute rates varied across the populations as follows: pregnancy hypertension (3.6% to 9.1%), pre-eclampsia (1.4% to 4.0%) and early-onset pre-eclampsia (0.3% to 0.7%). Pregnancy hypertension and/or pre-eclampsia rates declined over time in most populations. This was unexpected given that factors associated with pregnancy hypertension such as pre-pregnancy obesity and maternal age are generally increasing. However, there was also a downward shift in gestational age with fewer pregnancies reaching 40 weeks.
The rate of pregnancy hypertension and pre-eclampsia decreased in northern Europe and Australia from 1997 to 2007, but increased in Massachusetts. The use of a different International Classification of Diseases coding version in Massachusetts may contribute to the difference in trend. Elective delivery prior to the due date is the most likely explanation for the decrease observed in Europe and Australia. Also, the use of interventions that reduce the risk of pregnancy hypertension and/or progression to pre-eclampsia (low-dose aspirin, calcium supplementation and early delivery for mild hypertension) may have contributed to the decline.
Article summary
Article focus
The population prevalence of factors associated with increased and decreased risk of pregnancy hypertension and pre-eclampsia has changed over time, but the impact of these changes is unknown.
International comparisons of absolute population rates of pregnancy hypertension and pre-eclampsia are hindered by different diagnostic criteria and methods of data collection.
Comparing trends between countries overcomes the difficulties in comparing absolute rates.
Key message
Pregnancy hypertension and/or pre-eclampsia rates declined over time in northern Europe and Australia, but not Massachusetts (USA).
Declining hypertension rates were accompanied by a downward shift in gestational age with fewer pregnancies reaching term, the time when the pregnancy hypertension and pre-eclampsia are most likely to occur.
Strengths and limitations of this study
Strengths include numerous validation studies indicating that the hypertensive disorders are reliably reported in the population data sets used for the study and the consistency of trends across most countries.
Limitations include a different International Classification of Diseases coding version in Massachusetts and lack of available information on clinical interventions.
PMCID: PMC3191437  PMID: 22021762
Trends; pregnancy; pre-eclampsia; gestational hypertension; international classification of diseases; maternal medicine; obstetrics; hypertension; epidemiology; statistics; epidmiology; delivery; birth; infant mortality; information; public health; health economics; health policy; international health services; quality in healthcare; health and socio-economic inequalities; maternal and child health; statistics and research methods; parturition; preterm birth
21.  ICU admission and severity assessment in community-acquired pneumonia 
Critical Care  2009;13(3):156.
The past 15 years have seen major advances in our understanding of severity assessment in community-acquired pneumonia (CAP). Prognostic tools have been promoted to guide all major management decisions in CAP, including admission to the critical care unit. Several recent studies, including the study by Renaud and colleagues, have challenged us to re-evaluate how we consider severe CAP, a concept for which there is still no universally accepted definition. Existing severity scores such as the Pneumonia Severity Index and the CURB65 score are designed to predict 30-day mortality. As a result, they are heavily weighted by age and co-morbidity. They perform less well when predicting other outcomes such as requirement for ICU admission and are of limited use in the critical care environment. This commentary discusses recent attempts to develop useful severity criteria to guide the use of ICU resources in patients with severe CAP.
PMCID: PMC2717437  PMID: 19591640
22.  Incidence of oronasal haemorrhage in infancy presenting to general practice in the UK 
The frequency of oronasal haemorrhage in infancy was estimated from two national GP research databases (6% UK population). When a case was identified, other presentations in the child over the first year were available from one dataset. In the first year haemoptysis is rare. In contrast, epistaxis (7–20 cases of per 10 000 infants) was 10 times more common, and 14.3% of these infants had an injury at some other point in infancy, (four times greater than the general population). In general practice epistaxis may herald other trauma presentations, implying that such infants may be part of a high-risk group for injury.
PMCID: PMC2593537  PMID: 19068161
child abuse; child protection; epistaxis; haemoptysis; infant
23.  Contribution of smoking during pregnancy to inequalities in stillbirth and infant death in Scotland 1994-2003: retrospective population based study using hospital maternity records 
Objective To quantify the contribution of smoking during pregnancy to social inequalities in stillbirth and infant death.
Design Population based retrospective cohort study.
Setting Scottish hospitals between 1994 and 2003.
Participants Records of 529 317 singleton live births and 2699 stillbirths delivered at 24-44 weeks’ gestation in Scotland from 1994 to 2003.
Main outcome measures Rates of stillbirth and infant, neonatal, and post-neonatal death for each deprivation category (fifths of postcode sector Carstairs-Morris scores); contribution of smoking during pregnancy (“no,” “yes,” or “not known”) in explaining social inequalities in these outcomes.
Results The stillbirth rate increased from 3.8 per 1000 in the least deprived group to 5.9 per 1000 in the most deprived group. For infant deaths, the rate increased from 3.2 per 1000 in the least deprived group to 5.4 per 1000 in the most deprived group. Stillbirths were 56% more likely (odds ratio 1.56, 95% confidence interval 1.38 to 1.77) and infant deaths were 72% more likely (1.72, 1.50 to 1.97) in the most deprived compared with the least deprived category. Smoking during pregnancy accounted for 38% of the inequality in stillbirths and 31% of the inequality in infant deaths.
Conclusions Both tackling smoking during pregnancy and reducing infants’ exposure to tobacco smoke in the postnatal environment may help to reduce stillbirths and infant deaths overall and to reduce the socioeconomic inequalities in stillbirths and infant deaths perhaps by as much as 30-40%. However, action on smoking on its own is unlikely to be sufficient and other measures to improve the social circumstances, social support, and health of mothers and infants are needed.
PMCID: PMC2755727  PMID: 19797343
24.  Contribution of smoking during pregnancy to inequalities in stillbirth and infant death in Scotland 1994-2003: retrospective population based study using hospital maternity records 
The BMJ  2009;339:b3754.
Objective To quantify the contribution of smoking during pregnancy to social inequalities in stillbirth and infant death.
Design Population based retrospective cohort study.
Setting Scottish hospitals between 1994 and 2003.
Participants Records of 529 317 singleton live births and 2699 stillbirths delivered at 24-44 weeks’ gestation in Scotland from 1994 to 2003.
Main outcome measures Rates of stillbirth and infant, neonatal, and post-neonatal death for each deprivation category (fifths of postcode sector Carstairs-Morris scores); contribution of smoking during pregnancy (“no,” “yes,” or “not known”) in explaining social inequalities in these outcomes.
Results The stillbirth rate increased from 3.8 per 1000 in the least deprived group to 5.9 per 1000 in the most deprived group. For infant deaths, the rate increased from 3.2 per 1000 in the least deprived group to 5.4 per 1000 in the most deprived group. Stillbirths were 56% more likely (odds ratio 1.56, 95% confidence interval 1.38 to 1.77) and infant deaths were 72% more likely (1.72, 1.50 to 1.97) in the most deprived compared with the least deprived category. Smoking during pregnancy accounted for 38% of the inequality in stillbirths and 31% of the inequality in infant deaths.
Conclusions Both tackling smoking during pregnancy and reducing infants’ exposure to tobacco smoke in the postnatal environment may help to reduce stillbirths and infant deaths overall and to reduce the socioeconomic inequalities in stillbirths and infant deaths perhaps by as much as 30-40%. However, action on smoking on its own is unlikely to be sufficient and other measures to improve the social circumstances, social support, and health of mothers and infants are needed.
PMCID: PMC2755727  PMID: 19797343
25.  The Effect of Changing Patterns of Obstetric Care in Scotland (1980–2004) on Rates of Preterm Birth and Its Neonatal Consequences: Perinatal Database Study 
PLoS Medicine  2009;6(9):e1000153.
Jane Norman and colleagues analyzed linked perinatal surveillance data in Scotland and find that between 1980 and 2004 increases in spontaneous and medically induced preterm births contributed equally to the rising rate of preterm births.
Rates of preterm birth are rising worldwide. Studies from the United States and Latin America suggest that much of this rise relates to increased rates of medically indicated preterm birth. In contrast, European and Australian data suggest that increases in spontaneous preterm labour also play a role. We aimed, in a population-based database of 5 million people, to determine the temporal trends and obstetric antecedents of singleton preterm birth and its associated neonatal mortality and morbidity for the period 1980–2004.
Methods and Findings
There were 1.49 million births in Scotland over the study period, of which 5.8% were preterm. We found a percentage increase in crude rates of both spontaneous preterm birth per 1,000 singleton births (10.7%, p<0.01) and medically indicated preterm births (41.2%, p<0.01), which persisted when adjusted for maternal age at delivery. The greater proportion of spontaneous preterm births meant that the absolute increase in rates of preterm birth in each category were similar. Of specific maternal complications, essential and pregnancy-induced hypertension, pre-eclampsia, and placenta praevia played a decreasing role in preterm birth over the study period, with gestational and pre-existing diabetes playing an increasing role. There was a decline in stillbirth, neonatal, and extended perinatal mortality associated with preterm birth at all gestation over the study period but an increase in the rate of prolonged hospital stay for the neonate. Neonatal mortality improved in all subgroups, regardless of obstetric antecedent of preterm birth or gestational age. In the 28 wk and greater gestational groups we found a reduction in stillbirths and extended perinatal mortality for medically induced but not spontaneous preterm births (in the absence of maternal complications) although at the expense of a longer stay in neonatal intensive care. This improvement in stillbirth and neonatal mortality supports the decision making behind the 34% increase in elective/induced preterm birth in these women. Although improvements in neonatal outcomes overall are welcome, preterm birth still accounts for over 66% of singleton stillbirths, 65% of singleton neonatal deaths, and 67% of infants whose stay in the neonatal unit is “prolonged,” suggesting this condition remains a significant contributor to perinatal mortality and morbidity.
In our population, increases in spontaneous and medically induced preterm births have made equal contributions to the rising rate of preterm birth. Despite improvements in related perinatal mortality, preterm birth remains a major obstetric and neonatal problem, and its frequency is increasing.
Please see later in the article for the Editors' Summary
Editors' Summary
Most pregnancies last about 40 weeks but increasing numbers of babies are being born preterm, before they reach 37 weeks of gestation (gestation is the period during which a baby develops in its mother). Nowadays in the US, for example, more than half a million babies arrive earlier than expected every year (1 in 8 babies). Although improvements in the care of newborn babies (neonatal care) mean that preterm babies are more likely to survive than in the past, preterm birth remains the single biggest cause of infant death in many developed countries, and many preterm babies who survive have long-term health problems and disabilities, particularly those born before 32 weeks of gestation. Preterm births can be spontaneous or medically induced. At present, it impossible to predict which mothers will spontaneously deliver early and there is no effective way to prevent these preterm births; medically induced early labor is undertaken when either the unborn baby or mother would be at risk if the pregnancy continued to full term.
Why Was This Study Done?
Preterm birth rates need to be reduced, but before this can be done it is important to know how the causes of preterm birth, the numbers of preterm stillbirths, and the numbers of preterm babies who die at birth (neonatal deaths) or soon after (perinatal deaths) are changing with time. If, for example, the rise in preterm births is mainly due to an increase in medically induced labor and if this change in practice has reduced neonatal deaths, it would be unwise to try to reduce the preterm birth rate by discouraging medically induced preterm births. So far, data from the US and Latin America suggest that the increase in preterm births in these countries is solely due to increased rates of medically induced preterm births. However, in Europe and Australia, the rate of spontaneous preterm births also seems to be increasing. In this study, the researchers examine the trends over time and causes of preterm birth and of neonatal death and illness in Scotland over a 25-year period.
What Did the Researchers Do and Find?
By searching a Scottish database of linked maternity records and infant health and death records, the researchers identified 1.49 million singleton births that occurred between 1980 and 2004 of which nearly 90,000 were preterm births. Over the study period, the rates of spontaneous and of medically induced preterm births per 1,000 births increased by 10.7% and 41.2%, respectively, but because there were more spontaneous preterm births than medically induced preterm births, the absolute increase in the rates of each type of birth was similar. Several maternal complications including preeclampsia (a condition that causes high blood pressure) and placenta previa (covering of the opening of the cervix by the placenta) played a decreasing role in preterm births over the study period, whereas gestational and preexisting diabetes played an increasing role. Finally, there was a decline in stillbirths and in neonatal and perinatal deaths among preterm babies, although more babies remained in the hospital longer than 7 days after birth. More specifically, after 28 weeks of gestation, stillbirths and perinatal deaths decreased among medically induced preterm births but not among spontaneous preterm births.
What Do These Findings Mean?
These findings indicate that in Scotland between 1980 and 2004, increases in spontaneous and medically induced preterm births contributed equally to the rising rate of preterm births. Importantly, they also show that the increase in induced preterm births helped to reduce stillbirths and neonatal and perinatal deaths, a finding that supports the criteria that clinicians currently use to decide whether to induce an early birth. Nevertheless, preterm births still account for two-thirds of all stillbirths, neonatal deaths, and extended neonatal stays in hospital and thus cause considerable suffering and greatly increase the workload in neonatal units. The rates of such births consequently need to be reduced and, for Scotland at least, ways will have to be found to reduce the rates of both spontaneous and induced preterm births to achieve this goal while continuing to identify those sick babies who need to be delivered early to give them the best chance of survival.
Additional Information
Please access these Web sites via the online version of this summary at
Tommys is a nonprofit organization that funds research and provides information on the causes and prevention of miscarriage, premature birth, and stillbirth
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)
The US Centers for Disease Control and Prevention provides information on maternal and infant health (in English and Spanish)
The US National Women's Health Information Center has detailed information about pregnancy, including a section on pregnancy complications
MedlinePlus provides links to other information on premature babies and to information on pregnancy (in English and Spanish)
PMCID: PMC2740823  PMID: 19771156

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