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PubMed1999

The impact of radiotherapy dose and other treatment-related and clinical factors on in-field control in stage I and II non-Hodgkin's lymphoma.

PURPOSE/OBJECTIVE: To assess local (in-field) disease control, identify potential prognostic factors, and elucidate the optimal radiotherapy dose in various clinical settings of Stage I and II non-Hodgkin's lymphoma (non-CNS). MATERIALS & METHODS: A total of 285 consecutive patients with Stage I and II non-Hodgkin's lymphoma were treated with curative intent, including 159 with radiotherapy (RT) alone and 126 with combined-modality therapy (CMT). Of these, 72 patients had low-grade lymphomas (LGL), 92 had intermediate or high-grade lymphomas (I/HGL), and 21 had unclassified lymphomas. Clinical and treatment variables with potential prognostic significance for in-field disease control, freedom from relapse (FFR), and absolute survival (AS) were evaluated by univariate and multivariate analyses. RESULTS: The 5-, 10-, and 20-year actuarial AS rates were 73%, 46%, and 33% for patients with LGL and 64%, 44%, and 18% for patients with I/HGL, respectively. The 5-, 10-, and 20-year actuarial FFR rates were 62%, 59%, and 49% for patients with LGL and 66%, 57%, and 57% for patients with I/HGL, respectively. Significant prognostic factors identified by the multivariate analysis were age, tumor size, and histology for AS; tumor size and treatment for FFR; and only tumor size for in-field disease control. There were 95 total failures, with only 12 occurring infield. Most failures (65%) were in contiguous unirradiated sites. All 4 in-field failures in patients with LGL occurred after RT doses < 30 Gy, although none occurred in 10 patients with small-volume LGL of the orbit treated with doses < 30 Gy. The 8 in-field failures in patients with I/HGL were distributed evenly throughout the RT dose range; 5 occurred in patients treated with CMT, all with tumors > 6 cm, and 4 with less than a complete response (CR) to chemotherapy. CONCLUSION: Our analysis suggests that the overwhelming problem in the treatment of non-Hodgkin's lymphoma is not in-field failure but, rather, failure in contiguous unirradiated sites. A dose of 20-25 Gy may be sufficient for small-volume LGL of the orbit. A dose of 30 Gy is sufficient for LGL in general, as well as for patients with nonbulky (< or = 6 cm) I/HGL treated with CMT who have a CR. However, patients with I/HGL treated with CMT for tumors > 6 cm and/or without a CR may benefit from doses > or = 40 Gy.

Actuarial Analysis↗
PubMed1995

Complications of peripheral arteriography: a new system to identify patients at increased risk.

PURPOSE: The most quoted literature on arteriographic complications is based on self-reports collected during the mid 1970s. We sought to determine whether those results remain valid despite changes in arteriographic practice and whether patient subgroups at increased risk could be identified. METHODS: Five hundred forty-nine consecutive patients were examined after arteriography and twice over 72 hours. Patients were telephoned at least 2 weeks later to identify delayed complications. The sample was divided into two groups to allow independent validation of suspected prognostic factors. RESULTS: The rate of major complications was 2.9% (16/549), but varied from 0.7% to 9.1% among three strata of relative risk. Rates were highest in patients studied for suspected aortic dissection, mesenteric ischemia, gastrointestinal bleeding, or symptomatic carotid artery stenosis and lowest in patients with trauma or aneurysmal disease. Patients studied for claudication or limb-threatening ischemia had intermediate risk (2.0%). Within these strata, congestive heart failure and furosemide use were the only variables independently associated with a significantly increased complication rate. CONCLUSIONS: Previous reports have overestimated the risk of arteriography for trauma or aneurysm but substantially underestimate the risk for patients with other common conditions. Such stratified complication rates are essential to understand relative costs and benefits of arteriography and other vascular imaging modalities in specific clinical situations.

Acute Kidney Injury↗
PubMed2001

Correlation between serum transaminase activity and virus load among patients with chronic liver disease type B.

Newly developed hepatitis B virus (HBV)-DNA quantitative assays, transcription-mediated amplification and hybridization protection assay (TMA-HPA) and branched-DNA assay were clinically evaluated. The subjects consisted of 160 chronic HBV carriers; 48 were hepatitis Be antigen (HBeAg)-positive, whereas 109 were anti-HBe-positive (three were both negative). All subjects with HBeAg, except one, showed high HBV-DNA replication levels (>/=10(5.8) copies/ml). In HBeAg negative subjects, there was a strong correlation between the serum HBV-DNA and alanine aminotransferase (ALT) levels; ALT level was usually normal if the samples tested showed an HBV-DNA level less than 10(5)/ml, whereas, the majority of the sera with an HBV-DNA concentration greater than 10(7)copies/ml showed elevation in serum ALT level. An intermediate range of HBV-DNA level (10(5)-10(7) copies/ml) was associated with variable ALT activity. In conclusion, a serum HBV-DNA level associated with ALT elevation was lower in patients with type B chronic liver disease negative for HBeAg compared with their HBeAg-positive counterparts. There was usually no or mild liver disease activity when patients with chronic HBV infection have serum HBV-DNA levels less than 10(5)copies/ml.

Journal Article↗
PubMed1998

Coupled activation of the donor and the acceptor side of photosystem II during photoactivation of the oxygen evolving cluster.

Photoactivation of photosystem II has been studied in the FUD 39 mutant of Chlamydomonas reinhardtii that lacks the 23 kDa extrinsic subunit of photosystem II. We have taken advantage of the slow photoactivation rate of FUD 39, earlier demonstrated in Rova, E. M., et al. [(1996) J. Biol. Chem. 271, 28918-28924], to study events in photosystem II during intermediate stages of the process. By measuring the EPR multiline signal, the decay of the variable fluorescence after single flashes, and electron transfer from water to the QB site, we found a good correlation between the building of a tetrameric Mn cluster, longer recombination times between QA- and the donor side of photosystem II, and the achievement of water splitting ability. An increased rate of electron transfer from QA- to the QB site on the acceptor side of photosystem II, mainly due to enhanced efficiency of binding of QB to its site, was found to precede the building of the Mn cluster. We also showed that TyrD was oxidized simultaneously with this increase in electron-transfer rate. Thus, it appears that photoactivation is sequential, with an increased rate of electron transfer on the acceptor side occurring together with the oxidation of TyrD in the first step, followed by the assembly of the Mn cluster. We suggest that a conformational change of photosystem II is induced early in the photoactivation process facilitating electron transfer from the primary donor to the acceptor side. As a consequence, TyrD, an auxiliary electron donor to P680+/TyrZ*, is oxidized. That this occurs before the Mn cluster is fully functional serves to protect photosystem II against donor side induced photodamage.

Animals↗
PubMed1996

Synthetic Strategies To Obtain V-P-O Open Frameworks Containing Organic Species as Structural Directing Agents. Crystal Structure of the V(IV)-Fe(III) Bimetallic Phosphate [H(3)N(CH(2))(2)NH(3)](2)[H(3)N(CH(2))(2)NH(2)][Fe(III)(H(2)O)(2)(V(IV)O)(8)(OH)(4)(HPO(4))(4)(PO(4))(4)].4H(2)O.

A general synthetic approach to rationalize the solution preparative chemistry of oxovanadium phosphates containing organic species as structural directing agents is presented. Careful attention is payed to the hydrolysis and condensation processes involving the ionic species in solution, and a simple restatement of the partial charge model (PCM) has been used in order to organize the experimental results. The structure of a new V(IV)-Fe(III) bimetallic oxovanadium phosphate, [H(3)N(CH(2))(2)NH(3)](2)[H(3)N(CH(2))(2)NH(2)] [Fe(III)(H(2)O)(2)(V(IV)O)(8)(OH)(4)(HPO(4))(4)(PO(4))(4)].4H(2)O, has been determined by X-ray single crystal diffraction methods. This compound crystallizes in the monoclinic system, space group P2(1)/n and the cell dimensions are as follows: a = 14.383(3) Å, b = 10.150(2) Å, c = 18.355(4) Å, and beta = 90.39(3) degrees (Z = 2). The existence of a complex intercrossing channel system, including a very large channel of 18.4 Å of diameter (in which both water molecules and ethylenediamine species are located), is the more interesting feature of this structure. Thermal decomposition, including the dehydration/rehydration process, has been studied by thermal analysis and variable temperature X-ray powder diffraction techniques. A complementary SEM study of the different intermediate decomposition products is presented.

Journal Article↗
PubMed2005

Superexchange and sequential mechanisms in charge transfer with a mediating state between the donor and acceptor.

The rate of intramolecular charge transfer from biphenyl to naphthalene was determined for the radical anions and radical cations of molecules with the general structure: (2-naphthyl)-(steroid spacer)-(4-biphenylyl). Varied degrees of unsaturation (one double bond, NSenB; two double bonds, NSen(2)B; and the b-ring completely aromatized, NSarB) were incorporated into the steroid spacer to examine the effect it would have on the charge transfer rate. The charge transfer rate, as inferred from the decay of the biphenyl radical ion absorption, increased in all cases relative to the completely saturated 3-(2-naphthyl)-16-(4-biphenylyl)-5alpha-androstane (NSB) reference molecule. For the anion charge transfer, the decay rates increased by factors of 1.4, 4.2, and 5.1, respectively, and for the cation, the decay rates increased by factors of 5, 276, and 470. To explain the results, the charge-transfer process was viewed as a combination of two independent mechanisms: a single-step, superexchange mechanism, and a two-step, sequential charge transfer. Using a low level of theory, simple models of the superexchange and two-step mechanisms were developed to elucidate the nature and differences between the two mechanisms. The critical variable for this analysis is the free energy of formation (DeltaG(I) degrees ) of the intermediate state: (2-naphthyl)-[spacer](1)+/--(4-biphenylyl). The conclusion from this treatment is that superexchange is the dominant mechanism when DeltaG(I) degrees is large, but at small DeltaG(I) degrees , the sequential mechanism will dominate. This is because the superexchange rate is shown to have a weak dependence on DeltaG(I) degrees , changing 10-fold for a change in DeltaG(I) degrees of 2 eV, compared to the sequential mechanism in which the rate can change over 10(3) for 0.5 V.

Journal Article↗
PubMed2003

Manipulations during the second, but not the first, week of life increase susceptibility to cocaine self-administration in female rats.

We compared the effects of manipulations during week 1 vs week 2 of life on the propensity to self-administer cocaine. Pups received daily subcutaneous saline injections, were handled briefly, or remained undisturbed during their respective treatment periods. Animals handled during the second week of life exhibited increased locomotor response to novelty when tested on postnatal day (PND) 48, compared to all other groups. Rats were implanted with jugular catheters on PND 70 and then given the opportunity to self-administer (0.125 mg/kg/infusion) cocaine for 5 consecutive days (1 h sessions). The dose was then raised to 0.25 mg/kg/infusion for 5 days and to 0.5 mg/kg/infusion for the final 5 days of testing. Only animals manipulated during the second week of life acquired drug-taking behavior. These effects were both stimulus- and gender-specific. Females handled during the second week of life acquired cocaine self-administration (SA) at the lowest dose, and females injected during the second week of life acquired at the intermediate dose. Males injected during the second week of life showed a similar, but more variable, drug-taking pattern. There were no group differences in serum corticosterone response to novelty, although relative to undisturbed animals and those manipulated in the first week of life, female animals manipulated during the second week of life had lower basal expression of hippocampal glucocorticoid receptor mRNA in adulthood. We conclude that the second week of life in the rodent is a sensitive period during which manipulations result in a more vulnerable phenotype for the acquisition of cocaine SA.

Animals↗
PubMed2005

How to choose one-dimensional basis functions so that a very efficient multidimensional basis may be extracted from a direct product of the one-dimensional functions: energy levels of coupled systems with as many as 16 coordinates.

In this paper we propose a scheme for choosing basis functions for quantum dynamics calculations. Direct product bases are frequently used. The number of direct product functions required to converge a spectrum, compute a rate constant, etc., is so large that direct product calculations are impossible for molecules or reacting systems with more than four atoms. It is common to extract a smaller working basis from a huge direct product basis by removing some of the product functions. We advocate a build and prune strategy of this type. The one-dimensional (1D) functions from which we build the direct product basis are chosen to satisfy two conditions: (1) they nearly diagonalize the full Hamiltonian matrix; (2) they minimize off-diagonal matrix elements that couple basis functions with diagonal elements close to those of the energy levels we wish to compute. By imposing these conditions we increase the number of product functions that can be removed from the multidimensional basis without degrading the accuracy of computed energy levels. Two basic types of 1D basis functions are in common use: eigenfunctions of 1D Hamiltonians and discrete variable representation (DVR) functions. Both have advantages and disadvantages. The 1D functions we propose are intermediate between the 1D eigenfunction functions and the DVR functions. If the coupling is very weak, they are very nearly 1D eigenfunction functions. As the strength of the coupling is increased they resemble more closely DVR functions. We assess the usefulness of our basis by applying it to model 6D, 8D, and 16D Hamiltonians with various coupling strengths. We find approximately linear scaling.

Journal Article↗
PubMed2003

Biodiversity as spatial insurance in heterogeneous landscapes.

The potential consequences of biodiversity loss for ecosystem functioning and services at local scales have received considerable attention during the last decade, but little is known about how biodiversity affects ecosystem processes and stability at larger spatial scales. We propose that biodiversity provides spatial insurance for ecosystem functioning by virtue of spatial exchanges among local systems in heterogeneous landscapes. We explore this hypothesis by using a simple theoretical metacommunity model with explicit local consumer-resource dynamics and dispersal among systems. Our model shows that variation in dispersal rate affects the temporal mean and variability of ecosystem productivity strongly and nonmonotonically through two mechanisms: spatial averaging by the intermediate-type species that tends to dominate the landscape at high dispersal rates, and functional compensations between species that are made possible by the maintenance of species diversity. The spatial insurance effects of species diversity are highest at the intermediate dispersal rates that maximize local diversity. These results have profound implications for conservation and management. Knowledge of spatial processes across ecosystems is critical to predict the effects of landscape changes on both biodiversity and ecosystem functioning and services.

Biodiversity↗
PubMed2026

Mendelian disorders of the epigenetic machinery: a decade of insights into the molecular basis.

The Mendelian disorders of the Epigenetic Machinery (MDEMs), or Chromatinopathies, are now understood to be a collectively common cause of childhood neurodevelopmental delays and intellectual disability. In the past decade, the chromatin and gene expression consequences of heterozygous chromatin regulator disruption have been investigated in various disease models, yielding insights into the molecular pathogenesis of MDEMs. In this review, we highlight some of these results - drawing upon studies of representative MDEMs - together with potential unifying concepts. We propose that MDEMs are characterized by distributed, often subtle chromatin and gene expression perturbations, which impact diverse cellular pathways and processes and are frequently shared between distinct disorders. In this sense, they occupy an intermediate space between classical monogenic disorders and complex traits. We propose potential explanations for the variable expressivity in MDEMs and conclude by considering how technological advances can now enable a deeper and more precise mechanistic characterization of this important Mendelian disease group.

Humans↗
PubMed1997

Serotype-related differences in inflammatory response to Streptococcus pneumoniae in experimental meningitis.

It has been suggested that serotype influences severity of experimental pneumococcal meningitis. This hypothesis was tested with strains of serotypes 1, 5, 6B, 7F, 14, and 23F, prevalent in Israel, in an experimental rabbit model. Cerebrospinal fluid (CSF) bacterial titers, leukocyte densities, concentrations of lactate, protein, and glucose, tumor necrosis factor-alpha levels, brain water content, and cerebral blood flow were measured 18 h after inoculation of pneumococci. Serotypes 5 and 7F exhibited mild inflammatory responses (leukocytosis <1000/mm3, lactate <4 mmol/L); types 6B, 14, and 23F showed severe inflammatory responses (leukocytosis >5000/mm3, lactate >10 mmol/L); serotype 1 had intermediate inflammatory responses but exceptionally high CSF bacterial titers. Leukocyte count correlated with all other variables; lactate with all except brain water content. On the basis of 6 Streptococcus pneumoniae serotypes, three discrete levels of inflammatory responses could be delineated in experimental pneumococcal meningitis.

Animals↗
PubMed2003

An independent evaluation of modern prognostic scores in a central European cohort of 120 patients with hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is a common cancer worldwide. As prognosis of HCC patients depends not only on tumour extension but also on liver function, TNM staging of HCC is of limited value. The Okuda score incorporating the variables of liver function and tumour extension is used widely. However, among patients with an intermediate Okuda score, survival varies considerably. Several newer scores promise to perform better than the Okuda score in stratifying HCC patients. We therefore tested the ability of several newer scores to predict survival in comparison to the Okuda score in a European cohort of HCC patients. PATIENTS AND METHODS: A total of 120 patients with sufficient follow-up data were identified retrospectively among the 130 patients with HCC first seen between 1997 and 2000 in our department. Child-Pugh score, Okuda score, Vienna survival model for HCC (VISUM-HCC) score, Chevret score, Barcelona clinic liver cancer (BCLC) classification and cancer of the liver Italian programme (CLIP) score were calculated. Survival analysis was performed for all eligible patients stratified according to each scoring system. Receiver operating characteristics analysis was performed using six months survival as the outcome measure. Univariate and stepwise logistic regression analyses were performed to identify prognostic factors. RESULTS: Survival times of HCC patients grouped according to all scores were significantly different. All scores performed similarly to the Okuda score in the receiver operating characteristic analysis. Prognostic factors for survival were albumin concentration and the presence of portal obstruction. CONCLUSION: In our central European cohort, there was no advantage of using the newer scores instead of the Okuda score.

Adult↗
PubMedDate not supplied

Stress myocardial perfusion imaging in the diagnosis and prognosis of women with suspected coronary artery disease.

Coronary artery disease is the single largest killer of women in the United States and claims the lives of more than 250,000 women each year. For several decades, there was the misperception that coronary artery disease was a "man's disease." The fact is that women are indeed vulnerable to coronary artery disease; however, they typically develop the disease 10 to 15 years later than men. Once coronary artery disease is evident, women have worse outcomes as compared with men.Therefore, early and accurate diagnosis of coronary artery disease is crucial for reducing heart disease mortality in women. Stress myocardial perfusion imaging using contemporary techniques has been shown to have significant value in the diagnosis and prognosis of coronary artery disease in women. Myocardial perfusion imaging with exercise or pharmacologic stress has been shown to add incremental value to the use of clinical variables or exercise electrocardiogram stress testing alone in the risk stratification of women with an intermediate clinical pretest likelihood of coronary artery disease. This review provides an overview of the role of stress myocardial perfusion imaging in the clinical evaluation of women with suspected coronary artery disease.

Algorithms↗
PubMed2003

Length and statistical weight of bubbles in DNA melting.

We present measurements of the length of the bubble versus temperature in the melting transition of DNA oligomers. The sequences are clamped at the ends of GC pairs (strong binding), and have AT rich (weaker binding) middle regions of variable length B relative to the molecule size. We use a quenching technique to trap intermediate states. We find that the average relative bubble size grows from zero for increasing temperature, but reaches a plateau at a length of order B, producing a discontinuous transition with finite bubble size. The statistical weight of the bubble states decreases as B is reduced, the transition becoming more cooperative.

Base Sequence↗
PubMed2002

Whom should we profile? Examining diabetes care practice variation among primary care providers, provider groups, and health care facilities.

OBJECTIVE: To evaluate the amount of variation in diabetes practice patterns at the primary care provider (PCP), provider group, and facility level, and to examine the reliability of diabetes care profiles constructed using electronic databases. DATA SOURCES/STUDY SETTING: Clinical and administrative data obtained from the electronic information systems at all facilities in a Department of Veterans Affairs' (VA) integrated service network for a study period of October 1997 through September 1998. STUDY DESIGN: This is a cohort study. The key variables of interest are different types of diabetes quality indicators, including measures of technical process, intermediate outcomes, and resource use. DATA COLLECTION/EXTRACTION METHODS: A coordinated registry of patients with diabetes was constructed by integrating laboratory, pharmacy, utilization, and primary care provider data extracted from the local clinical information system used at all VA medical centers. The study sample consisted of 12,110 patients with diabetes, 258 PCPs, 42 provider groups, and 13 facilities. PRINCIPAL FINDINGS: There were large differences in the amount of practice variation across levels of care and for different types of diabetes care indicators. The greatest amount of variance tended to be attributable to the facility level. For process measures, such as whether a hemoglobin A1c was measured, the facility and PCP effects were generally comparable. However, for three resource use measures the facility effect was at least six times the size of the PCP effect, and for inter-mediate outcome indicators, such as hyperlipidemia, facility effects ranged from two to sixty times the size of the PCP level effect. A somewhat larger PCP effect was found (5 percent of the variation) when we examined a "linked" process-outcome measure linking hyperlipidemia and treatment with statins). When the PCP effect is small (i.e., 2 percent), a panel of two hundred diabetes patients is needed to construct profiles with 80 percent reliability. CONCLUSIONS: little of the variation in many currently measured diabetes care practices is attributable to PCPs and, unless panel sizes are large, PCP profiling will be inaccurate. If profiling is to improve quality, it may be best to focus on examining facility-level performance variations and on developing indicators that promote specific, high-priority clinical actions.

Cohort Studies↗
PubMed2006

Genetic variation among isolates of Sarcocystis neurona, the agent of protozoal myeloencephalitis, as revealed by amplified fragment length polymorphism markers.

Sarcocystis neurona causes serious neurological disease in horses and other vertebrates in the Americas. Based on epidemiological data, this parasite has recently emerged. Here, the genetic diversity of Sarcocystis neurona was evaluated using the amplified fragment length polymorphism (AFLP) method. Fifteen S. neurona taxa from different regions collected over the last 10 years were used; six isolates were from clinically diseased horses, eight isolates were from wild-caught opossums (Didelphis virginiana), and one isolate was from a cowbird (Molothrus ater). Additionally, four outgroup taxa were also fingerprinted. Nine primer pairs were used to generate AFLP patterns, with a total number of amplified fragments ranging from 30 to 60, depending on the isolate and primers tested. Based on the presence/absence of amplified AFLP fragments and pairwise similarity values, all the S. neurona isolates tested were clustered in one monophyletic group. No significant correlation could be found between genomic similarity and host origin of the S. neurona isolates. AFLP revealed significant intraspecific genetic variations, and S. neurona appeared as a highly variable species. Furthermore, linkage disequilibrium analysis suggested that S. neurona populations within Michigan have an intermediate type of population structure that includes characteristics of both clonal and panamictic population structures. AFLP is a reliable molecular technique that has provided one of the most informative approaches to ascertain phylogenetic relationships in S. neurona and its closest relatives, allowing them to be clustered by relative similarity using band matching and unweighted pair group method with arithmetic mean analysis, which may be applicable to other related protozoal species.

Animals↗
PubMed2005

Characterization of the genome composition of Bartonella koehlerae by microarray comparative genomic hybridization profiling.

Bartonella henselae is present in a wide range of wild and domestic feline hosts and causes cat-scratch disease and bacillary angiomatosis in humans. We have estimated here the gene content of Bartonella koehlerae, a novel species isolated from cats that was recently identified as an agent of human endocarditis. The investigation was accomplished by comparative genomic hybridization (CGH) to a microarray constructed from the sequenced 1.93-Mb genome of B. henselae. Control hybridizations of labeled DNA from the human pathogen Bartonella quintana with a reduced genome of 1.58 Mb were performed to evaluate the accuracy of the array for genes with known levels of sequence divergence. Genome size estimates of B. koehlerae by pulsed-field gel electrophoresis matched that calculated by the CGH, indicating a genome of 1.7 to 1.8 Mb with few unique genes. As in B. quintana, sequences in the prophage and the genomic islands were reported absent in B. koehlerae. In addition, sequence variability was recorded in the chromosome II-like region, where B. koehlerae showed an intermediate retention pattern of both coding and noncoding sequences. Although most of the genes missing in B. koehlerae are also absent from B. quintana, its phylogenetic placement near B. henselae suggests independent deletion events, indicating that host specificity is not solely attributed to genes in the genomic islands. Rather, the results underscore the instability of the genomic islands even within bacterial populations adapted to the same host-vector system, as in the case of B. henselae and B. koehlerae.

Bartonella↗
PubMed2006

Less postnatal steroids, more bronchopulmonary dysplasia: a population-based study in very low birthweight infants.

OBJECTIVE: To study the association between reduced use of postnatal steroids for bronchopulmonary dysplasia (BPD) in very low birthweight (VLBW) infants and oxygen (O(2))-dependency at 28 days of age and at 36 weeks postmenstrual age. DESIGN: Large national database study. SETTING: The Israel National VLBW Neonatal Database. PATIENTS: The sample included infants born between 1997 and 2004, of gestational age 24-32 weeks, who required mechanical ventilation or O(2) therapy. Four time periods were compared: 1997-8 (era 1, peak use), 1999-2000 (era 2, intermediate), 2001-2 (era 3, expected reduction) and 2003-4 (era 4, lowest). The outcome variable "oxygen dependency" was based on clinical criteria. Multivariate regression models were used to account for confounding variables. RESULTS: Steroid use fell significantly from 23.5% in 1997-8 to 11% in 2003-4 (p<0.005). After adjustment for relevant confounding variables, the odds ratio for O(2) therapy at 28 days in era 4 versus era 1 was 1.75, 95% confidence interval (CI) 1.47 to 2.09 and 1.41, 95% CI 1.15 to 1.73 at 36 weeks postmenstrual age. The mean duration of O(2) therapy increased from 25.3 days (95% CI 23.3 to 26.3) in era 1, to 28.0 days (95% CI 26.6 to 29.4) in era 4. Survival increased from 78.5% in era 1 to 81.6% in era 4 (p<0.005). CONCLUSIONS: The use of steroids has fallen considerably since the awareness of the adverse effects of this treatment. This change has been temporally associated with increased O(2) dependency at 28 days of age and at 36 weeks postmenstrual age. The prolongation of O(2) therapy was modest in degree.

Bronchopulmonary Dysplasia↗