Economic costs associated with moderate and late preterm birth: a prospective population-based study.

OBJECTIVE: We sought to determine the economic costs associated with moderate and late preterm birth. DESIGN: An economic study was nested within a prospective cohort study. SAMPLE: Infants born between 32(+0) and 36(+6)  weeks of gestation in the East Midlands of England. A sample of infants born at ≥37 weeks of gestation acted as controls. METHODS: Data on resource use, estimated from a National Health Service (NHS) and personal social services perspective, and separately from a societal perspective, were collected between birth and 24 months corrected age (or death), and valued in pounds sterling, at 2010-11 prices. Descriptive statistics and multivariable analyses were used to estimate the relationship between gestational age at birth and economic costs. MAIN OUTCOME MEASURES: Cumulative resource use and economic costs over the first two years of life. RESULTS: Of all eligible births, 1146 (83%) preterm and 1258 (79%) term infants were recruited. Mean (standard error) total societal costs from birth to 24 months were £12 037 (£1114) and £5823 (£1232) for children born moderately preterm (32(+0) -33(+6)  weeks of gestation) and late preterm (34(+0) -36(+6)  weeks of gestation), respectively, compared with £2056 (£132) for children born at term. The mean societal cost difference between moderate and late preterm and term infants was £4657 (bootstrap 95% confidence interval, 95% CI £2513-6803; P < 0.001). Multivariable regressions revealed that, after controlling for clinical and sociodemographic characteristics, moderate and late preterm birth increased societal costs by £7583 (£874) and £1963 (£337), respectively, compared with birth at full term. CONCLUSIONS: Moderate and late preterm birth is associated with significantly increased economic costs over the first 2 years of life. Our economic estimates can be used to inform budgetary and service planning by clinical decision-makers, and economic evaluations of interventions aimed at preventing moderate and late preterm birth or alleviating its adverse consequences. TWEETABLE ABSTRACT: Moderate and late preterm birth is associated with increased economic costs over the first 2 years of life.

Validation and clinical application of molecular methods for the identification of molds in tissue.

BACKGROUND: Invasive fungal infections due to less-common molds are an increasing problem, and accurate diagnosis is difficult. METHODS: We used our previously established molecular method, which allows species identification of molds in histological tissue sections, to test sequential specimens from 56 patients with invasive fungal infections who were treated at our institution from 1982 to 2000. RESULTS: The validity of the method was demonstrated with the establishment of a molecular diagnosis in 52 cases (93%). Confirmation of the causative organism was made in all cases in which a mold had been cultured from the tissue specimen. Less-common molds were identified in 7% of cases and appear to be an increasing problem. CONCLUSIONS: Our previously established method has proven to be of value in determining the incidence of invasive infection caused by less-common molds. Institutions should continue to pursue diagnosis of invasive fungal infections by means of tissue culture and microbiologic analysis.

Fusarium dimerum infection in a stem cell transplant recipient treated successfully with voriconazole.

We report the first case, to our knowledge, of a proven Fusarium dimerum soft-tissue infection in a stem cell transplant recipient treated successfully with voriconazole. There is a well-documented increase in the incidence, diversity and antifungal resistance of invasive mould infections in the immunocompromised patient population. The management of these infections is changing as new, more efficacious and less toxic antifungal agents become available. We present the case of a 19-year-old female diagnosed with a proven F. dimerum soft-tissue infection of the foot and possible pulmonary infection with the same organism 10 days following a sibling allogeneic stem cell transplant for severe aplastic anaemia. The infection developed despite treatment with 3 mg/kg AmBisome for a concurrent chest infection. She was treated successfully with voriconazole.

Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study.

In order to update the epidemiological and mycological profile of candidaemia in Europe, the European Confederation of Medical Mycology conducted a prospective, sequential, hospital population-based study from September 1997 to December 1999. A total of 2,089 cases were documented by 106 institutions in seven European countries. Rates of candidaemia ranging from 0.20 to 0.38 per 1,000 admissions were reported. Candida albicans was identified in 56% of cases. Non-albicans Candida species were most frequently isolated from patients with haematological malignancies (65%). With increasing age, an increasing incidence of Candida glabrata was seen. The 30-day mortality rate was 37.9%. The survey results underline the burden of candidaemia in a wide range of patient populations, confirm the importance of non- albicans species, and provide baseline data for future surveillance studies at a European level.

Development of molecular methods for the identification of aspergillus and emerging moulds in paraffin wax embedded tissue sections.

BACKGROUND/AIMS: Invasive infection with emerging moulds is increasing in incidence and reliable methods for speciating these organisms in tissue sections need to be developed. METHODS: Two methods for extracting fungal DNA from paraffin wax embedded tissue sections, based on the TaKaRa DEXPAT kit and QIAamp DNA mini kit, were optimised and compared. DNA was amplified by PCR using pan-fungal probes, and detected by Southern blot hybridisation using a high stringency method with a probe specific for Aspergillus fumigatus and A flavus. RESULTS: The method based on the TaKaRa DEXPAT kit, with additional steps using lyticase and ethanol precipitation, was superior. Less than 10 conidia were detectable using spiked samples and a positive result was obtained with 100% of clinical samples known to be culture positive for A fumigatus. Other moulds could be identified by using species specific probes or by sequencing PCR products. CONCLUSIONS: The method based on the TaKaRa DEXPAT kit could detect less than 10 conidia/sample. The method allowed accurate identification of A fumigatus and A flavus and other species could be identified using species specific probes or by DNA sequencing. These methods will provide a valuable diagnostic tool for both patient management and future antifungal and epidemiological studies.

Treatment failure in invasive aspergillosis: susceptibility of deep tissue isolates following treatment with amphotericin B.

OBJECTIVES: To determine whether treatment failure in invasive aspergillosis (IA) is the result of resistance of Aspergillus spp. isolates to amphotericin B. METHODS: Six Aspergillus fumigatus and six Aspergillus flavus isolates cultured from deep tissue biopsies in 11 patients with haematological malignancies during 1991-1998 were tested. A method based on the NCCLS M38-A broth microdilution method, with colorimetric determination of MICs, was used to determine the MICs of amphotericin B and itraconazole. RESULTS: All A. fumigatus isolates were susceptible to amphotericin B (MIC 0.25-0.5 mg/L), as were three A. flavus isolates (MIC 1 mg/L), but three were less susceptible (MIC 2 mg/L). All isolates were susceptible to itraconazole (MIC 0.125-0.25 mg/L). All patients had been treated with amphotericin B, having received a median of 12 days of treatment when the tissue was obtained. CONCLUSION: The difficulty in treating IA may not be because of the susceptibility of the isolates, but because of poor penetration of antifungal agents into infected tissue. Aspergillus spp. invade blood vessels causing thrombosis and tissue infarction, and therefore it may be difficult for antifungal drugs to exceed MICs in infected tissues. This highlights the need for different treatment strategies, such as surgery and the administration of cytokines.

Management and outcome of bloodstream infections due to Candida species in England and Wales.

This two-year prospective hospital population-based study of candidaemia is the first to be conducted in the UK. It was carried out on behalf on the British Society for Medical Mycology (BSMM) as part of the European Confederation of Medical Mycology (ECMM) epidemiological survey of candidaemia. Six hospitals in England and Wales acted as sentinel hospitals. Main outcome measures were hospital population-based incidence and 30-day mortality. There were 18.7 episodes of candidaemia per 100,000 finished consultant episodes or 3.0/100,000 bed days and 45.4% cases occurred in intensive care unit (ICU) patients. Candida albicans was isolated in 64.7% of confirmed cases. The majority of isolates were sensitive to standard antifungal agents, including fluconazole. The overall 30-day mortality was 26.4% and removal of the central venous catheter was associated with a significant reduction in mortality. In conclusion, the incidence of candidaemia in England and Wales is similar to that of the USA, the majority of isolates remain sensitive to commonly used antifungal agents and mortality associated with this infection appears to be falling.