'Research is the last thing on our minds, we are in crisis': Experiences of Lagos state nurses towards research and scholarly endeavours.

AIM: To explore the experiences of Nigerian nurses in research and scholarly endeavours. DESIGN: Descriptive phenomenological qualitative study design. METHOD: In-depth interviews were conducted among 30 nurses until data saturation was reached. Data were analysed using the thematic analysis method, and consolidated criteria for reporting qualitative research guidelines (COREQ) were adhered to in reporting this study. RESULTS: Three themes emerged: (1) challenges of nurses with research; (2) the state of nursing research in Lagos state; (3) strategies to improve the state of nursing research in Lagos state. Some challenges nurses in Lagos State encounter with research include heavy workload and nursing shortage due to brain drain, faulty research foundation, lack of continuing education in research and the stressful nature of conducting research in Lagos. CONCLUSION: As research is essential in addressing healthcare challenges, policymakers are encouraged to employ more nurses to reduce the workload and provide time for research activities. Training and continuing education in research can be incorporated into professional development programmes. Lagos State will benefit from nursing research units in the hospitals, and a coordinating centre for the units should be provided with adequate funding. Support could be obtained from the Institute of Nursing Research Nigeria in establishing these structures. Hospital management should embrace and welcome research output from nurses and ensure such results are implemented to improve patients' care. Nurses who excel in research might be recognised with awards and other incentives to inspire their peers.

Cost estimation alongside a multi-regional, multi-country randomized trial of antenatal ultrasound in five low-and-middle-income countries.

BACKGROUND: Improving maternal health has been a primary goal of international health agencies for many years, with the aim of reducing maternal and child deaths and improving access to antenatal care (ANC) services, particularly in low-and-middle-income countries (LMICs). Health interventions with these aims have received more attention from a clinical effectiveness perspective than for cost impact and economic efficiency. METHODS: We collected data on resource use and costs as part of a large, multi-country study assessing the use of routine antenatal screening ultrasound (US) with the aim of considering the implications for economic efficiency. We assessed typical antenatal outpatient and hospital-based (facility) care for pregnant women, in general, with selective complication-related data collection in women participating in a large maternal health registry and clinical trial in five LMICs. We estimated average costs from a facility/health system perspective for outpatient and inpatient services. We converted all country-level currency cost estimates to 2015 United States dollars (USD). We compared average costs across countries for ANC visits, deliveries, higher-risk pregnancies, and complications, and conducted sensitivity analyses. RESULTS: Our study included sites in five countries representing different regions. Overall, the relative cost of individual ANC and delivery-related healthcare use was consistent among countries, generally corresponding to country-specific income levels. ANC outpatient visit cost estimates per patient among countries ranged from 15 to 30 USD, based on average counts for visits with and without US. Estimates for antenatal screening US visits were more costly than non-US visits. Costs associated with higher-risk pregnancies were influenced by rates of hospital delivery by cesarean section (mean per person delivery cost estimate range: 25-65 USD). CONCLUSIONS: Despite substantial differences among countries in infrastructures and health system capacity, there were similarities in resource allocation, delivery location, and country-level challenges. Overall, there was no clear suggestion that adding antenatal screening US would result in either major cost savings or major cost increases. However, antenatal screening US would have higher training and maintenance costs. Given the lack of clinical effectiveness evidence and greater resource constraints of LMICs, it is unlikely that introducing antenatal screening US would be economically efficient in these settings--on the demand side (i.e., patients) or supply side (i.e., healthcare providers). TRIAL REGISTRATION: Trial number: NCT01990625 (First posted: November 21, 2013 on https://clinicaltrials.gov ).

Association of haemoglobin levels in the first trimester and at 26-30 weeks with fetal and neonatal outcomes: a secondary analysis of the Global Network for Women's and Children's Health's ASPIRIN Trial.

OBJECTIVE: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes. DESIGN: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6+0 -13+6  weeks and 26+0 -30+0  weeks of gestation with fetal and neonatal outcomes. SETTING: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala. POPULATION: A total of 11 976 pregnant women. METHODS: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes. MAIN OUTCOME MEASURES: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g. RESULTS: The mean haemoglobin levels at 6+0 -13+6  weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6+0 -13+6  weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation. CONCLUSIONS: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6+0 -13+6  weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger. TWEETABLE ABSTRACT: Both lower and some higher haemoglobin concentrations were associated with adverse fetal and neonatal outcomes at 6-13 weeks and 26-30 weeks of gestation.

Impregnation of catheters with anacardic acid from cashew nut shell prevents Staphylococcus aureus biofilm development.

AIM: The effect of anacardic acid impregnation on catheter surfaces for the prevention of Staphylococcus aureus attachments and biofilm formations were evaluated. METHODS AND RESULTS: Silicon catheter tubes were impregnated using different concentrations of anacardic acids (0·002-0·25%). Anacardic acids are antibacterial phenolic lipids from cashew nut (Anacardium occidentale) shell oil. Anacardic acid-impregnated silicon catheters revealed no significant haemolytic activity and were cytocompatible against fibroblast cell line (L929). Sustained release of anacardic acids was observed for 4 days. Anacardic acid-impregnated silicon catheters efficiently inhibited S. aureus colonization and the biofilm formation on its surface. The in vivo antibiofilm activity of anacardic acid-impregnated catheters was tested in an intraperitoneal catheter-associated medaka fish infection model. Significant reduction in S. aureus colonization on anacardic acid-impregnated catheter tubes was observed. CONCLUSIONS: Our data suggest that anacardic acid-impregnated silicon catheters may help in preventing catheter-related staphylococcal infections. SIGNIFICANCE AND IMPACT OF THE STUDY: This study opens new directions for designing antimicrobial phytochemical-coated surfaces with ideal antibiofilm properties and could be of great interest for biomedical research scientists.

Routine antenatal ultrasound in low- and middle-income countries: first look - a cluster randomised trial.

OBJECTIVE: Ultrasound is widely regarded as an important adjunct to antenatal care (ANC) to guide practice and reduce perinatal mortality. We assessed the impact of ANC ultrasound use at health centres in resource-limited countries. DESIGN: Cluster randomised trial. SETTING: Clusters within five countries (Democratic Republic of Congo, Guatemala, Kenya, Pakistan, and Zambia) METHODS: Clusters were randomised to standard ANC or standard care plus two ultrasounds and referral for complications. The study trained providers in intervention clusters to perform basic obstetric ultrasounds. MAIN OUTCOME MEASURES: The primary outcome was a composite of maternal mortality, maternal near-miss mortality, stillbirth, and neonatal mortality. RESULTS: During the 24-month trial, 28 intervention and 28 control clusters had 24 263 and 23 160 births, respectively; 78% in the intervention clusters received at least one study ultrasound; 60% received two. The prevalence of conditions noted including twins, placenta previa, and abnormal lie was within expected ranges. 9% were referred for an ultrasound-diagnosed condition, and 71% attended the referral. The ANC (RR 1.0 95% CI 1.00, 1.01) and hospital delivery rates for complicated pregnancies (RR 1.03 95% CI 0.89, 1.20) did not differ between intervention and control clusters nor did the composite outcome (RR 1.09 95% CI 0.97, 1.23) or its individual components. CONCLUSIONS: Despite availability of ultrasound at ANC in the intervention clusters, neither ANC nor hospital delivery for complicated pregnancies increased. The composite outcome and the individual components were not reduced. TWEETABLE ABSTRACT: Antenatal care ultrasound did not improve a composite outcome that included maternal, fetal, and neonatal mortality.

A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry.

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.

Global Network for Women's and Children's Health Research: probable causes of stillbirth in low- and middle-income countries using a prospectively defined classification system.

OBJECTIVE: We sought to classify causes of stillbirth for six low-middle-income countries using a prospectively defined algorithm. DESIGN: Prospective, observational study. SETTING: Communities in India, Pakistan, Guatemala, Democratic Republic of Congo, Zambia and Kenya. POPULATION: Pregnant women residing in defined study regions. METHODS: Basic data regarding conditions present during pregnancy and delivery were collected. Using these data, a computer-based hierarchal algorithm assigned cause of stillbirth. Causes included birth trauma, congenital anomaly, infection, asphyxia, and preterm birth, based on existing cause of death classifications and included contributing maternal conditions. MAIN OUTCOME MEASURES: Primary cause of stillbirth. RESULTS: Of 109 911 women who were enrolled and delivered (99% of those screened in pregnancy), 2847 had a stillbirth (a rate of 27.2 per 1000 births). Asphyxia was the cause of 46.6% of the stillbirths, followed by infection (20.8%), congenital anomalies (8.4%) and prematurity (6.6%). Among those caused by asphyxia, 38% had prolonged or obstructed labour, 19% antepartum haemorrhage and 18% pre-eclampsia/eclampsia. About two-thirds (67.4%) of the stillbirths did not have signs of maceration. CONCLUSIONS: Our algorithm determined cause of stillbirth from basic data obtained from lay-health providers. The major cause of stillbirth was fetal asphyxia associated with prolonged or obstructed labour, pre-eclampsia and antepartum haemorrhage. In the African sites, infection also was an important contributor to stillbirth. Using this algorithm, we documented cause of stillbirth and its trends to inform public health programs, using consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. TWEETABLE ABSTRACT: Major causes of stillbirth are asphyxia, pre-eclampsia and haemorrhage. Infections are important in Africa.

Pregnancy outcome in chronic myeloid leukemia patients on imatinib therapy.

INTRODUCTION: Imatinib is a first-line therapy to treat chronic myeloid leukemia (CML) patients. MATERIALS AND METHODS: We selected 22 CML cases of pregnancies and reported 9 accidental and 13 planned pregnancies that were on imatinib therapy. Willing female patients remaining in complete hematological, cytogenetic and major molecular responses for at least 2 years planned for pregnancy and were advised to stop imatinib for 1 month prior to conception and 3 months after conception (first trimester). Willing male patients stopped therapy 1 month prior to conception of their wives. In unplanned cases, all patients were in exposure to imatinib during conception. Twenty-two pregnancies resulted in seven male children and eight female children. There were three spontaneous abortions and four elective abortions along with one case of hypospadia and another one of mild hydrocephalus. CONCLUSION: We may suggest that planned pregnancy during therapy may be encouraged but imatinib therapy in unplanned pregnancy can cause spontaneous abortion or congenital anomaly.

Birth attendants as perinatal verbal autopsy respondents in low- and middle-income countries: a viable alternative?

OBJECTIVE: To assess the feasibility of using birth attendants instead of bereaved mothers as perinatal verbal autopsy respondents. METHODS: Verbal autopsy interviews for early neonatal deaths and stillbirths were conducted separately among mothers (reference standard) and birth attendants in 38 communities in four developing countries. Concordance between maternal and attendant responses was calculated for all questions, for categories of questions and for individual questions. The sensitivity and specificity of individual questions with the birth attendant as respondent were assessed. FINDINGS: For early neonatal deaths, concordance across all questions was 94%. Concordance was at least 95% for more than half the questions on maternal medical history, birth attendance and neonate characteristics. Concordance on any given question was never less than 80%. Sensitivity and specificity varied across individual questions, more than 80% of which had a sensitivity of at least 80% and a specificity of at least 90%. For stillbirths, concordance across all questions was 93%. Concordance was 95% or greater more than half the time for questions on birth attendance, site of delivery and stillborn characteristics. Sensitivity and specificity varied across individual questions. Over 60% of the questions had a sensitivity of at least 80% and over 80% of them had a specificity of at least 90%. Overall, the causes of death established through verbal autopsy were similar, regardless of respondent. CONCLUSION: Birth attendants can substitute for bereaved mothers as verbal autopsy respondents. The questions in existing harmonized verbal autopsy questionnaires need further refinement, as their sensitivity and specificity differ widely.

Do practicing clinicians agree with expert ratings of neonatal intensive care unit quality measures?

OBJECTIVE: To assess the level of agreement when selecting quality measures for inclusion in a composite index of neonatal intensive care quality (Baby-MONITOR) between two panels: one comprised of academic researchers (Delphi) and another comprised of academic and clinical neonatologists (clinician). STUDY DESIGN: In a modified Delphi process, a panel rated 28 quality measures. We assessed clinician agreement with the Delphi panel by surveying a sample of 48 neonatal intensive care practitioners. We asked the clinician group to indicate their level of agreement with the Delphi panel for each measure using a five-point scale (much too high, slightly too high, reasonable, slightly too low and much too low). In addition, we asked clinicians to select measures for inclusion in the Baby-MONITOR based on a yes or no vote and a pre-specified two-thirds majority for inclusion. RESULT: In all, 23 (47.9%) of the clinicians responded to the survey. We found high levels of agreement between the Delphi and clinician panels, particularly across measures selected for the Baby-MONITOR. Clinicians selected the same nine measures for inclusion in the composite as the Delphi panel. For these nine measures, 74% of clinicians indicated that the Delphi panel rating was 'reasonable'. CONCLUSION: Practicing clinicians agree with an expert panel on the measures that should be included in the Baby-MONITOR, enhancing face validity.

Imatinib mesylate therapy in patients of chronic myeloid leukemia with Philadelphia chromosome positive: an experience from eastern India.

Imatinib inhibits constitutively active BCR-ABL tyrosine kinase of chronic myeloid leukemia (CML). In a long term study it was found superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. However, till date there is no major study to evaluate eastern Indian CML patients treated with imatinib mesylate. The aim of our study was to see the efficacy, tolerability, toxicity and safety of imatinib in eastern Indian subset of CML population. The present study enrolled 831 patients with CML out of which 197 were excluded due to various reasons of noncompliance, death and not being fit to receive the drug. The rest, 634 (76% of total enrolled) were selected for the evaluation. In the beginning of the study, 603 patients were in chronic phase, 27 in accelerated phase and 4 patients in blast crisis phase. Among 634 patients, 280 patients (44%) received previously either interferon alpha or hydroxyurea and other 354 patients (56%) were previously untreated. Complete hematological remission and major cytogenetic response were 91 and 67%, respectively after 1 year of treatment. Complete molecular remission was 35% after 1 year of treatment. Sixty-four patients (10.1%) were resistant to imatinib mesylate in 5 years. The disease free and overall survival at 60 months were 72.2 and 76.1% respectively. After 60 months of follow up, continuous treatment of chronic phase CML with imatinib as initial therapy was found to be safe and able to induce durable responses in a high proportion of patients.

Causes of community stillbirths and early neonatal deaths in low-income countries using verbal autopsy: an International, Multicenter Study.

OBJECTIVE: Six million stillbirths (SB) and early neonatal deaths (END) occur annually worldwide, mostly in rural settings distant from health facilities. We used verbal autopsy (VA), to understand causes of non-hospital, community-based SB and END from four low-income countries. STUDY DESIGN: This prospective observational study utilized the train-the-trainer method. VA interviewers conducted standardized interviews; in each country data were reviewed by two local physicians who assigned an underlying causes of deaths (COD). RESULT: There were 252 perinatal deaths (118 END; 134 SB) studied from pooled data. Almost half (45%) the END occurred on postnatal day 1, 19% on the second day and 16% the third day. Major early neonatal COD were infections (49%), birth asphyxia (26%), prematurity (17%) and congenital malformations (3%). Major causes of SB were infection (37%), prolonged labor (11%), antepartum hemorrhage (10%), preterm delivery (7%), cord complications (6%) and accidents (5%). CONCLUSION: Many of these SB and END were from easily preventable causes. Over 80% of END occurred during the first 3 days of postnatal life, and >90% were due to infection, birth asphyxia and prematurity. The causes of SB were more varied, and maternal infections were the most common cause. Increased attention should be targeting at interventions that reduce maternal and neonatal infections and prevent END, particularly during the first 3 days of life.

An alternative strategy for perinatal verbal autopsy coding: single versus multiple coders.

OBJECTIVE: To determine the comparability between cause of death (COD) by a single physician coder and a two-physician panel, using verbal autopsy. METHODS: The study was conducted between May 2007 and June 2008. Within a week of a perinatal death in 38 rural remote communities in Guatemala, the Democratic Republic of Congo, Zambia and Pakistan, VA questionnaires were completed. Two independent physicians, unaware of the others decisions, assigned an underlying COD, in accordance with the causes listed in the chapter headings of the International classification diseases and related health problems, 10th revision (ICD-10). Cohen's kappa statistic was used to assess level of agreement between physician coders. RESULTS: There were 9461 births during the study period; 252 deaths met study enrolment criteria and underwent verbal autopsy. Physicians assigned the same COD for 75% of stillbirths (SB) (K = 0.69; 95% confidence interval: 0.61-0.78) and 82% early neonatal deaths (END) (K = 0.75; 95% confidence interval: 0.65-0.84). The patterns and proportion of SBs and ENDs determined by the physician coders were very similar compared to causes individually assigned by each physician. Similarly, rank order of the top five causes of SB and END was identical for each physician. CONCLUSION: This study raises important questions about the utility of a system of multiple coders that is currently widely accepted and speculates that a single physician coder may be an effective and economical alternative to VA programmes that use traditional two-physician panels to assign COD.

Early postnatal hypotension is not associated with indicators of white matter damage or cerebral palsy in extremely low gestational age newborns.

OBJECTIVE: To evaluate, in extremely low gestational age newborns (ELGANs), relationships between indicators of early postnatal hypotension and cranial ultrasound indicators of cerebral white matter damage imaged in the nursery and cerebral palsy diagnoses at 24 months follow-up. STUDY DESIGN: The 1041 infants in this prospective study were born at <28 weeks gestation, were assessed for three indicators of hypotension in the first 24 postnatal hours, had at least one set of protocol cranial ultrasound scans and were evaluated with a structured neurological exam at 24 months corrected age. Indicators of hypotension included: (1) lowest mean arterial pressure (MAP) in the lowest quartile for gestational age; (2) treatment with a vasopressor; and (3) blood pressure lability, defined as the upper quartile of the difference between each infant's lowest and highest MAP. Outcomes included indicators of cerebral white matter damage, that is, moderate/severe ventriculomegaly or an echolucent lesion on cranial ultrasound and cerebral palsy diagnoses at 24 months gestation. Logistic regression was used to evaluate relationships among hypotension indicators and outcomes, adjusting for potential confounders. RESULT: Twenty-one percent of surviving infants had a lowest blood pressure in the lowest quartile for gestational age, 24% were treated with vasopressors and 24% had labile blood pressure. Among infants with these hypotension indicators, 10% percent developed ventriculomegaly and 7% developed an echolucent lesion. At 24 months follow-up, 6% had developed quadriparesis, 4% diparesis and 2% hemiparesis. After adjusting for confounders, we found no association between indicators of hypotension, and indicators of cerebral white matter damage or a cerebral palsy diagnosis. CONCLUSION: The absence of an association between indicators of hypotension and cerebral white matter damage and or cerebral palsy suggests that early hypotension may not be important in the pathogenesis of brain injury in ELGANs.

Using verbal autopsy to ascertain perinatal cause of death: are trained non-physicians adequate?

OBJECTIVES: To develop a standardized verbal autopsy (VA) training program and evaluate whether its implementation resulted in comparable knowledge required to classify perinatal cause of death (COD) by physicians and non-physicians. METHODS: Training materials, case studies, and written and mock scenarios for this VA program were developed using conventional VA and ICD-10 guidelines. This program was used to instruct physicians and non-physicians in VA methodology using a train-the-trainer model. Written tests of cognitive and applied knowledge required to classify perinatal COD were administered before and after training to evaluate the effect of the VA training program. RESULTS: Fifty-three physicians and non-physicians (nurse-midwives/nurses and Community Health Workers [CHW]) from Pakistan, Zambia, the Democratic Republic of Congo, and Guatemala were trained. Cognitive and applied knowledge mean scores among all trainees improved significantly (12.8 and 28.8% respectively, P < 0.001). Cognitive and applied knowledge post-training test scores of nurse-midwives/nurses were comparable to those of physicians. CHW (high-school graduates with 15 months or less formal health/nursing training) had the largest improvements in post-training applied knowledge with scores comparable to those of physicians and nurse-midwives/nurses. However, CHW cognitive knowledge post-training scores were significantly lower than those of physicians and nurses. CONCLUSIONS: With appropriate training in VA, cognitive and applied knowledge required to determine perinatal COD is similar for physicians and nurses-midwives/nurses. This suggests that midwives and nurses may play a useful role in determining COD at the community level, which may be a practical way to improve the accuracy of COD data in rural, remote, geographic areas.

Spontaneous closure of the patent ductus arteriosus in very low birth weight infants following discharge from the neonatal unit.

OBJECTIVE: To determine the incidence of spontaneous closure of the patent ductus arteriosus (PDA) and the use of medical therapies for treatment of PDA-related conditions among very low birth weight (VLBW) infants with ductal patency at the time of initial hospital discharge. STUDY DESIGN: We conducted a single-centre, retrospective, observational study of VLBW infants (birth weight <1500 g) born during 2004 and 2005 and discharged with a PDA. PDA was defined by echocardiographic and/or clinical criteria. We identified the related discharge needs, subsequent interventions, and the post-menstrual age (PMA) at which there was no longer evidence of a PDA. RESULTS: Three hundred and ninety one VLBW infants were admitted; 310 survived to discharge. Ninety five were diagnosed with a PDA during their hospitalisations; 21 had a PDA at discharge (10 received indomethacin, 11 were never treated). Among these, mean gestational age was 28 weeks, mean birth weight was 998 g, and median duration of hospitalisation was 73 days. Two infants were discharged on oxygen, two on diuretics, and two on both. None had congestive heart failure, and none died during infancy. Spontaneous closure occurred in 18 of 21 infants at a median PMA of 48 weeks (range 34-76; interquartile range 46-56). Two infants had coil occlusion at 11 months of age. One patient had a PDA at 14 months of age. CONCLUSIONS: Among a select group of VLBW infants with a PDA at initial hospital discharge, spontaneous closure during early infancy occurred in most infants.

Bronchopulmonary dysplasia and inflammatory biomarkers in the premature neonate.

Bronchopulmonary dysplasia (BPD) is the most common, serious sequela of premature birth. Inflammation is a major contributor to the pathogenesis of BPD. Often initiated by a pulmonary fetal inflammatory response, lung inflammation is exacerbated by mechanical ventilation and exposure to supplemental oxygen. In response to these initiators of injury, a complex interaction occurs between proteins that attract inflammatory cells (ie, chemokines), proteins that facilitate the transendothelial migration of inflammatory cells from blood vessels (ie, adhesion molecules), proteins that promote tissue damage (ie, pro-inflammatory cytokines and proteases), and proteins that modulate the process (eg, anti-inflammatory cytokines, binding proteins and receptor antagonists). In addition, during recovery from inflammatory injury, growth factors and other substances that control normal lung growth and mediate repair influence subsequent lung structure. In this review, we discuss the role of each aspect of the inflammatory process in the development of BPD. This discussion will include data from measurements of biomarkers in samples of fluid aspirated from the airways of human infants relevant to each phase of inflammation. Despite their limitations, these measurements provide some insight into the role of inflammation in the development of BPD and may be useful in identifying infants at risk for the disease.

Growth and neurodevelopment at 16 to 24 months of age for infants born with gastroschisis.

OBJECTIVE: To examine growth, neurodevelopment and morbidity in infants with gastroschisis. STUDY DESIGN: We enrolled all infants with gastroschisis treated at the North Carolina Children's Hospital from March 2003 through June 2005. Neonatal data were collected. Medical history, growth and neurodevelopment were assessed at 16 to 24 months. RESULT: Of 24 infants, 17 completed follow-up. Weight and length were below the 10th percentile for five and six infants, respectively. Three infants scored less than 85 on the Bayley Scales of Infant Development, second edition. Small for gestational age (SGA) infants were smaller and had lower neurodevelopmental scores. Fourteen experienced continued bowel dysfunction; nine were rehospitalized. CONCLUSION: One-third of infants with gastroschisis experience growth delay. Infants who are SGA are at higher risk, suggesting that postnatal growth may be influenced by fetal phenomena, and may not be modifiable. Neurodevelopment is not delayed. Continued bowel dysfunction is common.

Nicotine-induced proliferation of isolated rat pancreatic acinar cells: effect on cell signalling and function.

OBJECTIVES: The aim of the current study was to investigate whether nicotine treatment would induce the proliferation of isolated rat primary pancreatic acinar cells in culture by activating mitogen-activated protein kinase (MAPK) signalling and exocrine secretion. MATERIALS AND METHODS: A nicotine dose- and time-response curve was initially developed to determine the optimal dose and time used for all subsequent studies. Proliferation studies were conducted by cell counting and confirmed further by bromodeoxyuridine (BrdU) incorporation and flow cytometry assays. MAPK signalling studies were conducted by Western blot analysis. Localization of ERK1/2 signals, with or without nicotine and the MAPK inhibitor, was visualized by immunofluorescence. RESULTS: Nicotine treatment caused dose-dependent activation of extracellular signal-regulated kinases (ERK1/2), the maxima occurring at 100 micro m and at 3 min after treatment; the response was suppressed by the ERK1/2 inhibitor. Maximal nicotine-induced cell proliferation occurred at 24 h, and UO126-treatment significantly reduced this response. Exposure of cells to 100 microm nicotine for 6 min significantly enhanced both baseline and cholecystokinin-stimulated cell function, and these effects were not affected by treatment with the inhibitor of ERK1/2 but were suppressed by mecamylamine, a nicotinic receptor antagonist. CONCLUSIONS: Our results suggest that nicotine treatment induced cell proliferation of isolated pancreatic acinar cells and that this is coupled with the activation of MAPK signalling with no effect on its function. Hence, in primary cells, the mechanism of induction and regulation of these two processes, cell proliferation and cell function, by nicotine treatment are independent of each other.

Treatment strategies to prevent or close a patent ductus arteriosus in preterm infants and outcomes.

OBJECTIVE: To describe the current use of treatments to prevent or treat patent ductus arteriosus (PDA) in preterm infants, examine the association between different treatment strategies and neonatal outcomes and review the variation in these practices between centers. STUDY DESIGN: Cohort study of infants born between 23 and 30 weeks gestation managed by the Pediatrix Medical Group from 1997 to 2004. We collected data on demographics, indomethacin and ligation, and outcomes of the following five groups: prophylactic indomethacin treatment: infants treated with indomethacin on day of life (DOL) 0 or 1; indicated indomethacin treatment: infants treated with indomethacin after DOL 1; PDA without treatment: infants with a PDA without report of treatment; ligation only: infants with a PDA ligation without use of indomethacin and no PDA: infants without a PDA and without treatment. RESULTS: There were 6189 (18%) patients who received prophylactic indomethacin, 5690 (16%) patients received indicated treatment, 3886 (11%) patients had a PDA without treatment, 702 (2%) patients received ligation only and 18 136 (52%) patients had no PDA. In multivariate analysis, mortality among survivors to 2 days of age was lower (odds ratio (OR) 0.6, 95% confidence interval (CI) 0.5 to 0.7, P<0.01) and chronic lung disease, isolated intestinal perforation and severe retinopathy of prematurity (stages 3 and 4) were higher (OR 1.5, 95% CI 1.3 to 1.6, P<0.01; OR 1.5, 95% CI 1.1 to 2.0, P<0.01 and 1.4, 95% CI 1.2 to 1.6, P<0.01, respectively) in the indicated treatment group compared with the PDA without treatment group. The proportion of infants receiving prophylactic indomethacin among all infants and infants receiving indicated treatment among neonates with a report of a PDA varied by site from 0 to 59% (median 9.5%) and 0 to 100% (median 62%), respectively. CONCLUSIONS: Indomethacin use for intraventricular hemorrhage prevention and/or treatment of a PDA is common, but the selection of infants for treatment, and the decision of when and how to treat vary widely between centers. Our findings suggest the need for randomized, placebo-controlled trials of the effect of treatment of the PDA in preterm infants.