BackgroundInvasive Group B streptococcus (GBS) is a major cause of serious neonatal infection. Current strategies to reduce early-onset GBS disease have no impact on late-onset disease (LOD). Although GBS LOD is viewed as a sporadic event in the community, LOD arising within the neonatal intensive care unit (ICU) raises questions about mode of acquisition.MethodsFollowing a cluster of 4 GBS LOD cases, enhanced surveillance for all GBS LOD was undertaken over 2 years in the neonatal ICU supported by neonatal rectal screening. GBS isolates were serotyped and genome-sequenced.ResultsTwelve late -onset invasive GBS episodes were identified (incidence 0.6/1000 live births). Genomic analysis revealed that 11/12 GBS isolates (92%) were linked to at least one other LOD isolate. Isolates from the first cluster were serotype V, resistant to macrolides and lincosamides, and sequencing confirmed isolates were indistinguishable, or distinguishable by only one SNP difference, from each other. Rectal carriage was rare. Prospective surveillance identified three further clusters of LOD due to serotypes Ia (3 cases), Ib (2 cases), and III (2 cases), that would not have been identified without surveillance and genome sequencing, leading to a re-evaluation of interventions required to prevent GBS LOD.ConclusionAcquisition routes for LOD GBS in the neonatal ICU are poorly understood; cases may not necessarily be sporadic. Within this neonatal ICU, our data suggest that a single case of LOD GBS sepsis should be considered a potential nosocomial transmission event warranting prompt investigation, heightened infection prevention vigilance and action where required.
Objectives To examine variations in screening status category with time for 20,862 invasive breast cancers diagnosed in the West Midlands between 1989 and 2006, and to provide 10-year relative survival rates for each category. Method Population-based breast screening was introduced in the West Midlands from 1988. Primary invasive breast cancers diagnosed from 1 April 1989 to 31 March 2006 in women eligible for breast screening were identified from the West Midlands Cancer Intelligence Unit's cancer registration database. A screening status was determined for each case using previously published methodology. Results Screening status rates are affected initially by the gradual rollout of the screening programme and more recently by the need to wait for three years before interval cancers and cancers in lapsed and non-attenders can be identified. In the steady-state period 1994 -2003, 40.6% of invasive breast cancers were screen-detected, 36.3% were interval cancers and 11.2% were cancers in non-attenders (NA). Ten-year relative survival was 89.6% for screen-detected breast cancers, 73.3% for interval cancers and 51.9% for cancers in NA. Conclusion The detection of invasive breast cancers by screening has improved over time, with an equivalent reduction in the numbers of interval cancers. This, together with a stable rate of cancers in NA and an improvement in the survival of women with interval cancers, suggests that further improvements in breast cancer mortality can be predicted. International comparisons of interval cancer rates are difficult due to interprogramme differences in the time between screens.
BACKGROUND: Prior literature has suggested synergy between immune checkpoint therapy (ICT) and radiotherapy (RT) for the treatment of brain metastases (BrM), but to the authors' knowledge the optimal timing of therapy to maximize this synergy is unclear. METHODS: A total of 199 patients with melanoma and non-small cell lung cancer with BrM received ICT and RT between 2007 and 2016 at the study institution. To reduce selection biases, individual metastases were included only if they were treated with RT within 90 days of ICT. Concurrent treatment was defined as RT delivered on the same day as or in between doses of an ICT course; all other treatment was considered to be nonconcurrent. Multivariable Cox proportional hazards models were used to assess time to response and local disease recurrence on a per-metastasis basis, using a sandwich estimator to account for intrapatient correlation. RESULTS: The final cohort included 110 patients with 340 BrM, with 102 BrM treated concurrently and 238 BrM treated nonconcurrently. Response rates were higher with the use of concurrent treatment (70% vs 47%; P < .001), with correspondingly lower rates of progressive disease (5% vs 26%; P < .001). On multivariable analysis, concurrent treatment was found to be associated with improved time to response (hazard ratio, 1.76; 95% CI, 1.18-2.63 [P = .006]) and decreased local recurrence (hazard ratio, 0.42; 95% CI, 0.23-0.78 [P = .006]). This effect appeared to be greater for melanoma than for non-small cell lung cancer, although interaction tests were not statistically significant. Only 1 of 103 metastases which had a complete response later developed disease progression. CONCLUSIONS: Concurrent RT and ICT may improve response rates and decrease local recurrence of brain metastases compared with treatment that was nonconcurrent but delivered within 90 days. Further study of this combination in prospective, randomized trials is warranted.
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