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1.  Cost and resource utilization in cervical cancer management: a real-world retrospective cost analysis 
Current Oncology  2016;23(Suppl 1):S14-S22.
We set out to assess the health care resource utilization and cost of cervical cancer from the perspective of a single-payer health care system.
Retrospective observational data for women diagnosed with cervical cancer in British Columbia between 2004 and 2009 were analyzed to calculate patient-level resource utilization patterns from diagnosis to death or 5-year discharge. Domains of resource use within the scope of this cost analysis were chemotherapy, radiotherapy, and brachytherapy administered by the BC Cancer Agency; resource utilization related to hospitalization and outpatient visits as recorded by the B.C. Ministry of Health; medically required services billed under the B.C. Medical Services Plan; and prescriptions dispensed under British Columbia’s health insurance programs. Unit costs were applied to radiotherapy and brachytherapy, producing per-patient costs.
The mean cost per case of treating cervical cancer in British Columbia was $19,153 (standard error: $3,484). Inpatient hospitalizations, at 35%, represented the largest proportion of the total cost (95% confidence interval: 32.9% to 36.9%). Costs were compared for subgroups of the total cohort.
As health care systems change the way they manage, screen for, and prevent cervical cancer, cost-effectiveness evaluations of the overall approach will require up-to-date data for resource utilization and costs. We provide information suitable for such a purpose and also identify factors that influence costs.
PMCID: PMC4780585  PMID: 26985142
Cost of care; cervical cancer
2.  Population-based trends in systemic therapy use and cost for cancer patients in the last year of life 
Current Oncology  2016;23(Suppl 1):S32-S41.
The use of systemic therapy near the end of life can expose cancer patients to severe toxicity for minimal survival gain and comes with a high cost. Early palliative care is recommended, but there is evidence that aggressive care remains common. To better understand those patterns, the present study set out to describe trends in systemic therapy use and cost for cancer patients in the last year of life.
Using the BC Cancer Registry, a retrospective population-based cohort of cancer decedents (2002–2007) was identified and linked to systemic therapy records. The outcomes of interest were any systemic therapy use and total systemic therapy costs during the last year of life. Multiple logistic regression (systemic therapy use) and generalized linear regression (costs) were conducted, adjusting for age, sex, and survival. Subgroup analyses were performed for patients with primary colorectal, lung, prostate, or breast cancer.
From 2002 to 2007, use of systemic therapy in the last 12–4 months of life increased by 21% (95% ci: 10% to 33%); no significant change in use in the last 3 months of life was observed. Costs for both periods increased over time, by 48% (95% ci: 36% to 63%) and by 33% (95% ci: 19% to 49%) respectively. The trends varied across cancer sites, with the greatest increases being observed for lung and colorectal cancer patients.
The use and costs of systemic therapy have generally been increasing, putting pressure on health care providers and payers, but the quality-of-life implications for patients must be better understood.
PMCID: PMC4780587  PMID: 26985144
Systemic therapy; chemotherapy; costs; end-of-life care; palliative care
3.  Temporal association between home nursing and hospital costs at end of life in three provinces 
Current Oncology  2016;23(Suppl 1):S42-S51.
Research has demonstrated that increases in palliative homecare nursing are associated with a reduction in the rate of subsequent hospitalizations. However, little evidence is available about the cost-savings potential of palliative nursing when accounting for both increased nursing costs and potentially reduced hospital costs.
Our retrospective cohort study included cancer decedents from British Columbia, Ontario, and Nova Scotia who received any palliative nursing in the last 6 months of life. A Poisson regression analysis was used to determine the association of increased nursing costs (in 2-week blocks) on the relative average hospital costs in the subsequent 2-week block and on the overall total cost (hospital costs plus nursing costs in the preceding 2-week block).
The cohort included 58,022 cancer decedents. Results of the analysis for the last month of life showed an association between increased nursing costs and decreased relative hospital costs in comparisons with a reference group (>0 to 1 hour nursing in the block): the maximum decrease was 55% for Ontario, 31% for British Columbia, and 38% for Nova Scotia. Also, increased nursing costs in the last month were almost always associated with lower total costs in comparison with the reference. For example, cost savings per person-block ranged from $376 (>10 nursing hours) to $1,124 (>4 to 6 nursing hours) in British Columbia.
In the last month of life, increased palliative nursing costs (compared with costs for >0 to 1 hour of nursing in the block) were associated with lower relative hospital costs and a lower total cost in a subsequent block. Our research suggests a cost-savings potential associated with increased community-based palliative nursing.
PMCID: PMC4780588  PMID: 26985145
Palliative care; homecare; nursing; hospitalization; costing; end of life; Canadian data
4.  Association between activities related to routes of infection and clinical manifestations of melioidosis 
Clinical Microbiology and Infection  2016;22(1):79.e1-79.e3.
We sought associations between route of infection by Burkholderia pseudomallei and clinical manifestations in 330 cases of melioidosis in northeast Thailand using bivariate multivariable logistic regression models. Activities related to skin inoculation were negatively associated with bacteraemia, activities related to ingestion were associated with bacteraemia, and activities related to inhalation were associated with pneumonia. Our study suggests that route of infection is one of the factors related to clinical manifestations of melioidosis.
PMCID: PMC4721533  PMID: 26417852
Bacteraemia; Burkholderia pseudomallei; ingestion; inhalation; inoculation; melioidosis; pneumonia
5.  Impact of routine bedside infectious disease consultation on clinical management and outcome of Staphylococcus aureus bacteraemia in adults 
Staphylococcus aureus bacteraemia (SAB) is a common, serious infection that is associated with high rates of morbidity and mortality. Evidence suggests that infectious disease consultation (IDC) improves clinical management in patients with SAB. We examined whether the introduction of a routine bedside IDC service for adults with SAB improved clinical management and outcomes compared to telephone consultation. We conducted an observational cohort study of 571 adults with SAB at a teaching hospital in the United Kingdom between July 2006 and December 2012. A telephone consultation was provided on the day of positive blood culture in all cases, but an additional bedside IDC was provided after November 2009 (routine IDC group). Compared to patients in the pre-IDC group, those in the routine IDC group were more likely to have a removable focus of infection identified, echocardiography performed and follow-up blood cultures performed. They also received longer courses of antimicrobial therapy, were more likely to receive combination antimicrobial therapy and were more likely to have SAB recorded in the hospital discharge summary. There was a trend towards lower mortality at 30 days in the routine IDC group compared to the pre-IDC group (12% vs. 22%, p 0.07). Our findings suggest that routine bedside IDC should become the standard of care for adults with SAB.
PMCID: PMC4509716  PMID: 26033668
Bacteraemia; infectious disease consultation; outcome; Staphylococcus aureus; treatment
6.  Epigenomic alterations define lethal CIMP-positive ependymomas of infancy 
Nature  2014;506(7489):445-450.
Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.
PMCID: PMC4174313  PMID: 24553142
7.  First detection of livestock-associated meticillin-resistant Staphylococcus aureus CC398 in bulk tank milk in the United Kingdom, January to July 2012 
Livestock-associated meticillin-resistant Staphylococcus aureus belonging to clonal complex 398 (LA-MRSA CC398) is an important cause of zoonotic infections in several countries, but there is only a single published report of this lineage from the United Kingdom (UK). Here, we describe the isolation of LA-MRSA CC398 from bulk tank milk from five geographically dispersed farms in the UK. Our findings suggest that LA-MRSA CC398 is established in livestock in the UK. Awareness of the potential occupational risks and surveillance in other food-producing animal species should be promoted.
PMCID: PMC3867000  PMID: 23241232
8.  The newly described mecA homologue, mecALGA251, is present in methicillin-resistant Staphylococcus aureus isolates from a diverse range of host species 
Journal of Antimicrobial Chemotherapy  2012;67(12):2809-2813.
A previously unidentified mecA homologue, mecALGA251, has recently been described in methicillin-resistant Staphylococcus aureus (MRSA) from humans and dairy cattle. The origin and epidemiology of this novel homologue are unclear. The objective of this study was to provide basic descriptive information of MRSA isolates harbouring mecALGA251 from a range of host animal species.
A number of S. aureus isolates from historical animal isolate collections were chosen for investigation based on their similarity to known mecALGA251 MRSA isolates. The presence of mecALGA251 was determined using a multiplex PCR and antimicrobial susceptibility testing performed by disc diffusion.
MRSA harbouring mecALGA251 were found in isolates from a domestic dog, brown rats, a rabbit, a common seal, sheep and a chaffinch. All of the isolates were phenotypically MRSA, although this depended on which test was used; some isolates would be considered susceptible with certain assays. All isolates were susceptible to linezolid, rifampicin, kanamycin, norfloxacin, erythromycin, clindamycin, fusidic acid, tetracycline, trimethoprim/sulfamethoxazole and mupirocin. Five multilocus sequence types were represented (2273, 130, 425, 1764 and 1245) and six spa types (t208, t6293, t742, t6594, t7914 and t843).
The discovery of MRSA isolates possessing mecALGA251 from a diverse range of host species, including different taxonomic classes, has important implications for the diagnosis of MRSA in these species and our understanding of the epidemiology of this novel mecA homologue.
PMCID: PMC3494845  PMID: 22941897
animal infections; animal reservoirs; wildlife; MRSA
9.  Prevalence and characterization of human mecC methicillin-resistant Staphylococcus aureus isolates in England 
There are limited data available on the epidemiology and prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the human population that encode the recently described mecA homologue, mecC. To address this knowledge gap we undertook a prospective prevalence study in England to determine the prevalence of mecC among MRSA isolates.
Patients and methods
Three hundred and thirty-five sequential MRSA isolates from individual patients were collected from each of six clinical microbiology laboratories in England during 2011–12. These were tested by PCR or genome sequencing to differentiate those encoding mecA and mecC. mecC-positive isolates were further characterized by multilocus sequence typing, spa typing, antimicrobial susceptibility profile and detection of PBP2a using commercially available kits.
Nine out of the 2010 MRSA isolates tested were mecC positive, indicating a prevalence among MRSA in England of 0.45% (95% CI 0.24%–0.85%). The remainder were mecA positive. Eight out of these nine mecC MRSA isolates belonged to clonal complex 130, the other being sequence type 425. Resistance to non-β-lactam antibiotics was rare among these mecC MRSA isolates and all were phenotypically identified as MRSA using oxacillin and cefoxitin according to BSAC disc diffusion methodology. However, all nine mecC isolates gave a negative result using three different commercial PBP2a detection assays.
mecC MRSA are currently rare among MRSA isolated from humans in England and this study provides an important baseline prevalence rate to monitor future changes, which may be important given the increasing prevalence of mecC MRSA reported in Denmark.
PMCID: PMC3956372  PMID: 24284779
MRSA; mec genes; S. aureus; surveillance
10.  Prevalence and properties of mecC methicillin-resistant Staphylococcus aureus (MRSA) in bovine bulk tank milk in Great Britain 
mecC methicillin-resistant Staphylococcus aureus (MRSA) represent a newly recognized form of MRSA, distinguished by the possession of a divergent mecA homologue, mecC. The first isolate to be identified came from bovine milk, but there are few data on the prevalence of mecC MRSA among dairy cattle. The aim of this study was to conduct a prevalence study of mecC MRSA among dairy farms in Great Britain.
Test farms were randomly selected by random order generation and bulk tank samples were tested for the presence of mecC MRSA by broth enrichment and plating onto chromogenic agar. All MRSA isolated were screened by PCR for mecA and mecC, and mecC MRSA were further characterized by multilocus sequence typing, spa typing and antimicrobial susceptibility testing.
mecC MRSA were detected on 10 of 465 dairy farms sampled in England and Wales (prevalence 2.15%, 95% CI 1.17%–3.91%), but not from 625 farms sampled in Scotland (95% CI of prevalence 0%–0.61%). Seven isolates belonged to sequence type (ST) 425, while the other three belonged to clonal complex 130. Resistance to non-β-lactam antibiotics was uncommon. All 10 isolates produced a negative result by slide agglutination for penicillin-binding protein 2a. mecA MRSA ST398 was detected on one farm in England.
mecC MRSA is widely distributed among dairy farms in Great Britain, but this distribution is not uniform across the whole country. These results provide an important baseline dataset to monitor the epidemiology of this emerging form of MRSA.
PMCID: PMC3922150  PMID: 24155057
bovine mastitis; antibiotic resistance; molecular epidemiology
11.  Hsp27 silencing coordinately inhibits proliferation and promotes Fas-induced apoptosis by regulating the PEA-15 molecular switch 
Cell Death and Differentiation  2011;19(6):990-1002.
Heat shock protein 27 (Hsp27) is emerging as a promising therapeutic target for treatment of various cancers. Although the role of Hsp27 in protection from stress-induced intrinsic cell death has been relatively well studied, its role in Fas (death domain containing member of the tumor necrosis factor receptor superfamily)-induced apoptosis and cell proliferation remains underappreciated. Here, we show that Hsp27 silencing induces dual coordinated effects, resulting in inhibition of cell proliferation and sensitization of cells to Fas-induced apoptosis through regulation of PEA-15 (15-kDa phospho-enriched protein in astrocytes). We demonstrate that Hsp27 silencing suppresses proliferation by causing PEA-15 to bind and sequester extracellular signal-regulated kinase (ERK), resulting in reduced translocation of ERK to the nucleus. Concurrently, Hsp27 silencing promotes Fas-induced apoptosis by inducing PEA-15 to release Fas-associating protein with a novel death domain (FADD), thus allowing FADD to participate in death receptor signaling. Conversely, Hsp27 overexpression promotes cell proliferation and suppresses Fas-induced apoptosis. Furthermore, we show that Hsp27 regulation of PEA-15 activity occurs in an Akt-dependent manner. Significantly, Hsp27 silencing in a panel of phosphatase and tensin homolog on chromosome 10 (PTEN) wild-type or null cell lines, and in LNCaP cells that inducibly express PTEN, resulted in selective growth inhibition of PTEN-deficient cancer cells. These data identify a dual coordinated role of Hsp27 in cell proliferation and Fas-induced apoptosis via Akt and PEA-15, and indicate that improved clinical responses to Hsp27-targeted therapy may be achieved by stratifying patient populations based on tumor PTEN expression.
PMCID: PMC3354053  PMID: 22179576
prostate cancer; Hsp27; Akt; PEA-15/PED
13.  Correlation of Susceptibility of Cryptococcus neoformans to Amphotericin B with Clinical Outcome ▿ †  
Antimicrobial Agents and Chemotherapy  2011;55(12):5624-5630.
Testing of Cryptococcus neoformans for susceptibility to antifungal drugs by standard microtiter methods has not been shown to correlate with clinical outcomes. This report describes a modified quantitative broth macrodilution susceptibility method showing a correlation with both the patient's quantitative biological response in the cerebrospinal fluid (CSF) and the survival of 85 patients treated with amphotericin B (AMB). The Spearman rank correlation between the quantitative in vitro measure of susceptibility and the quantitative measure of the number of organisms in the patient's CSF was 0.37 (P < 0.01; 95% confidence interval [95% CI], 0.20, 0.60) for the first susceptibility test replicate and 0.46 (P < 0.001; 95% CI, 0.21, 0.62) for the second susceptibility test replicate. The median in vitro estimated response (defined as the fungal burden after AMB treatment) at 1.5 mg/liter AMB for patients alive at day 14 was 5 CFU (95% CI, 3, 8), compared to 57 CFU (95% CI, 4, 832) for those who died before day 14. These exploratory results suggest that patients whose isolates show a quantitative in vitro susceptibility response below 10 CFU/ml were more likely to survive beyond day 14.
PMCID: PMC3232814  PMID: 21947402
14.  The impact of diabetes on the pathogenesis of sepsis 
Diabetes is associated with an increased susceptibility to infection and sepsis. Conflicting data exist on whether the mortality of patients with sepsis is influenced by the presence of diabetes, fuelling the ongoing debate on the benefit of tight glucose regulation in patients with sepsis. The main reason for which diabetes predisposes to infection appears to be abnormalities of the host response, particularly in neutrophil chemotaxis, adhesion and intracellular killing, defects that have been attributed to the effect of hyperglycaemia. There is also evidence for defects in humoral immunity, and this may play a larger role than previously recognised. We review the literature on the immune response in diabetes and its potential contribution to the pathogenesis of sepsis. In addition, the effect of diabetes treatment on the immune response is discussed, with specific reference to insulin, metformin, sulphonylureas and thiazolidinediones.
PMCID: PMC3303037  PMID: 21805196
16.  Measuring, and identifying predictors of, women's perceptions of three types of breast cancer risk: population risk, absolute risk and comparative risk 
British Journal of Cancer  2009;100(4):583-589.
Although a key function of cancer genetics services is to provide risk information, to date there has been little consistency in the way in which breast cancer risk perception has been measured. The aims of the study were to measure estimates of (i) population risk, (ii) absolute risk and (iii) comparative risk of developing breast cancer for Ashkenazi Jewish women, and to determine predictors of breast cancer risk perception. Of 152 women, 107 (70%) completed all questions. The mean (s.d.) estimates for population risk, absolute risk and comparative risk were 22.7% (15.9), 31.8% (20.6) and 1.9-fold (1.9), respectively. Most women overestimated population risk. Women at population risk generally overestimated the population risk and their own absolute risk, yet understood they are at the same risk as the population. Those with a family history understood that they are at increased risk, but underestimated the extent to which their familial risk is increased. Anxiety, high estimation of population risk and lesser family history predicted overestimation of absolute risk, whereas high estimation of population risk and a strong family history predicted underestimation of comparative risk.
PMCID: PMC2653735  PMID: 19209174
Ashkenazi; breast cancer; perceived risk; genetic counselling; BRCA1; BRCA2
17.  Statistical strategies to improve the efficiency of molecular studies of colorectal cancer prognosis 
British Journal of Cancer  2008;99(12):2001-2005.
The evaluation of tumour molecular markers may be beneficial in prognosis and predictive in therapy. We develop a stopping rule approach to assist in the efficient utilisation of resources and samples involved in such evaluations. This approach has application in determining whether a specific molecular marker has sufficient variability to yield meaningful results after the evaluation of molecular markers in the first n patients in a study of sample size N (n⩽N). We evaluated colorectal tumours for mutations (microsatellite instability, K-ras, B-raf, PI3 kinase, and TGFβR-II) by PCR and protein markers (Bcl2, cyclin D1, E-cadherin, hMLH1, ki67, MDM2, and P53) by immunohistochemistry. Using this method, we identified and abandoned potentially uninformative molecular markers in favour of more promising candidates. This approach conserves tissue resources, time, and money, and may be applicable to other studies.
PMCID: PMC2607226  PMID: 19018265
efficiency; stopping rule; variability; survival; molecular markers
18.  Randomised trial of high frequency oscillatory ventilation or conventional ventilation in babies of gestational age 28 weeks or less: respiratory and neurological outcomes at 2 years 
The long term outcome of children entered into neonatal trials of high frequency oscillatory ventilation (HFOV) or conventional ventilation (CV) has been rarely studied.
To evaluate respiratory and neurodevelopmental outcomes for children entered into the United Kingdom Oscillation Study, which was designed to evaluate these outcomes.
Surviving infants were followed until 2 years of age corrected for prematurity. Study forms were completed by local paediatricians at routine assessments, and parents were asked to complete a validated neurodevelopmental questionnaire.
Paediatricians' forms were returned for 73% of the 585 surviving infants. Respiratory symptoms were common in all infants, and 41% had received inhaled medication. Mode of ventilation had no effect on frequency of any symptoms. At 24 months of age, severe neurodevelopmental disability was present in 9% and other disabilities in 38% of children, but the prevalence of disability was similar in children who received HFOV or CV (relative risk 0.93; 95% confidence interval 0.74 to 1.16). The prevalence of disability did not vary by gestational age, but boys were more likely to have overall disability. Developmental scores were unaffected by mode of ventilation (relative risk 1.13; 95% confidence interval 0.78 to 1.63) and were lower in infants born before 26 weeks gestation compared with babies born at 26–28 weeks.
Initial mode of ventilation in very preterm infants has no impact on respiratory or neurodevelopmental morbidity at 2 years. HFOV and CV appear equally effective for the early treatment of respiratory distress syndrome.
PMCID: PMC2672829  PMID: 16690640
premature; high frequency ventilation; development; respiratory function; disability
19.  Plethysmograph and interrupter resistance measurements in prematurely born young children 
Airways obstruction in premature infants is often assessed by plethysmography, which requires sedation. The interrupter (Rint) technique does not require sedation, but has rarely been examined in children under 2 years of age.
To compare Rint results with plethysmographic measurements of airway resistance (Raw) in prematurely born, young children.
Prospective study.
Infant and Paediatric Lung Function Laboratories.
Thirty children with a median gestational age of 25–29 weeks and median postnatal age of 13 months.
Interventions and main outcome measures
The infants were sedated, airway resistance was measured by total body plethysmography (Raw), and Rint measurements were made using a MicroRint device. Further Raw and Rint measurements were made after salbutamol administration if the children remained asleep.
Baseline measurements of Raw and Rint were obtained from 30 and 26 respectively of the children. Mean baseline Rint values were higher than mean baseline Raw results (3.45 v 2.84 kPa/l/s, p  =  0.006). Limits of agreement for the mean difference between Rint and Raw were −1.52 to 2.74 kPa/l/s. Ten infants received salbutamol, after which the mean Rint result was 3.6 kPa/l/s and mean Raw was 3.1 kPa/l/s (limits of agreement −0.28 to 1.44 kPa/l/s).
The poor agreement between Rint and Raw results suggests that Rint measurements cannot substitute for plethysmographic measurements in sedated prematurely born infants.
PMCID: PMC2672703  PMID: 16239293
airways resistance; interrupter technique; premature; plethysmography
20.  Respiratory function of very prematurely born infants at follow up: influence of sex 
To test the hypothesis that male compared with female prematurely born infants would have worse lung function at follow up.
Prospective follow up study.
Tertiary neonatal intensive care units
Seventy six infants, mean (SD) gestational age 26.4 (1.5) weeks, from the United Kingdom oscillation study.
Lung function measurements at a corrected age of 1 year.
Main outcome measures
Airways resistance (Raw) and functional residual capacity (FRCpleth) measured by whole body plethysmography, specific conductance (sGaw) calculated from Raw and FRCpleth, and FRC measured by a helium gas dilution technique (FRCHe).
The 42 male infants differed significantly from the 34 female infants in having a lower birth weight for gestation, requiring more days of ventilation, and a greater proportion being oxygen dependent at 36 weeks postmenstrual age and discharge. Furthermore, mean Raw and FRCpleth were significantly higher and mean sGaw significantly lower. After adjustment for birth and current size differences, the sex differences in FRCpleth and sGaw were 15% and 26% respectively and remained significant.
Lung function at follow up of prematurely born infants is influenced by sex.
PMCID: PMC2672701  PMID: 16418306
prematurity; lung function; sex; plethysmography
21.  Risk factors for respiratory morbidity in infancy after very premature birth 
Objectives: To determine the occurrence of respiratory morbidity during infancy after very premature birth and to identify risk factors.
Design: Prospective follow up study.
Setting: The United Kingdom oscillation study.
Patients: 492 infants, all born before 29 weeks gestation.
Interventions: Structured questionnaires were completed by local paediatricians when the infants were seen in outpatients at 6 and 12 months of age corrected for prematurity.
Main outcome measures: Cough, wheeze, and treatment requirements and the composite measure of respiratory morbidity (cough, frequent cough, cough without infection, wheeze, frequent wheeze, wheeze without infection, and use of chest medicine) and their relation to 13 possible explanatory variables.
Results: At 6 and 12 months of corrected age, 27% of the infants coughed and 6% had frequent (more than once a week) cough, and 20% and 3% respectively had wheeze or frequent wheeze. At 6 and 12 months, 14% of infants had taken bronchodilators and 8% inhaled steroids. After adjustment for multiple outcome testing, four factors were associated with increased respiratory morbidity: male sex, oxygen dependency at 36 weeks postmenstrual age, having older siblings aged less than 5 years, and living in rented accommodation.
Conclusions: Male infants are particularly vulnerable to respiratory morbidity in infancy after very premature birth. It is important to identify a safe and effective strategy to prevent chronic oxygen dependency.
PMCID: PMC1721906  PMID: 15878935
23.  Changes in the emergency workload of the London Ambulance Service between 1989 and 1999 
Methods: All emergency responses by the LAS during week 16 in each of 1989, 1996, and 1999 were studied. For each week, 999 call responses were analysed by time and day of call, and age/sex of the patient. Call response rates were calculated using age/sex census population estimates for London. Changes in call rates over time were calculated as rate ratios.
Results: Emergency responses increased from 6624 to 13 178 in the index weeks of 1989–1999. The ratio of response rates (1999/1989) was 1.91 (95% CI: 1.85 to 1.96). The proportion of out of hours calls increased significantly, from 68.8% in 1989 to 71.3% in 1999 (p = 0.0003). Response rates rose significantly more steeply for male patients than female patients from 1989 to 1999: rate ratio (95% CI); male patients 2.00 (1.91 to 2.08), female patients 1.69 (1.62 to 1.77), p<0.0001. Response rates varied by age in each of the three years investigated. Rates were consistently highest for patients aged 75 and above, and lowest for those aged 5–14. However, there was no evidence that call rates had increased disproportionately in any particular age group (p = 0.79).
Conclusions: Demand for emergency ambulance services in London has doubled in a decade. This increase is similar for all age groups, with no evidence of a greater rise in demand among older people. Call rates have increased more steeply in men than in women. Demographic changes do not explain the observed increases in demand.
PMCID: PMC1726532  PMID: 15611549
24.  In Vitro-Clinical Correlations for Amphotericin B Susceptibility in AIDS-Associated Cryptococcal Meningitis▿ †  
Reliable measures of antifungal drug susceptibility are needed. We tested the susceptibility of Cryptococcus neoformans from patients treated with amphotericin B. In vitro susceptibility employed a modified broth macrodilution method. We demonstrate a strong correlation between the quantitative measures of in vitro amphotericin B susceptibility and the quantitative response observed in patients.
PMCID: PMC1797648  PMID: 17060519
25.  Associations between perinatal interventions and hospital stillbirth rates and neonatal mortality 
Background: Previous studies suggest that high risk and low birthweight babies have better outcomes if born in hospitals with level III neonatal intensive care units. Relations between obstetric care, particularly intrapartum interventions and perinatal outcomes, are less well understood, however.
Objective: To investigate effects of obstetric, paediatric, and demographic factors on rates of hospital stillbirths and neonatal mortality.
Methods: Cross sectional data on all 65 maternity units in all Thames Regions, 1994–1996, covering 540 834 live births and stillbirths. Hospital level analyses investigated associations between staffing rates (consultant/junior paediatricians, consultant/junior obstetricians, midwives), facilities (consultant obstetrician/anaesthetist sessions, delivery beds, special care baby unit, neonatal intensive care unit cots, etc), interventions (vaginal births, caesarean sections, forceps, epidurals, inductions, general anaesthetic), parental data (parity, maternal age, social class, deprivation, multiple births), and birthweight standardised stillbirth rates and neonatal mortality.
Results: Unifactorial analyses showed consistent negative associations between measures of obstetric intervention and stillbirth rates. Some measures of staffing, facilities, and parental data also showed significant associations. Scores for interventional, organisational, and parental variables were derived for multifactorial analysis to overcome the statistical problems caused by high intercorrelations between variables. A higher intervention score and higher number of consultant obstetricians per 1000 births were both independently and significantly associated with lower stillbirth rates. Organisational and parental factors were not significant after adjustment. Only Townsend deprivation score was significantly associated with neonatal mortality (positive correlation).
Conclusions: Birthweight adjusted stillbirth rates were significantly lower in units that took a more interventionalist approach and in those with higher levels of consultant obstetric staffing. There were no apparent associations between neonatal death rates and the hospital factors measured here.
PMCID: PMC1721633  PMID: 14711857

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