Opioid-prescribing patterns, storage, handling, and disposal in postoperative pediatric urology patients.

BACKGROUND: Emerging research on surgeons and the opioid epidemic have focused on the adult population. Consequently, little is known regarding opioid-prescribing practices in the pediatric population. The goal of this study is to examine postoperative opioid-prescribing and consumption patterns, as well as storage and disposal trends for specific pediatric urologic procedures. STUDY DESIGN: Patients undergoing surgery associated with specified Current Procedural Terminology codes were retrospectively identified, and details regarding opioid medications were obtained through our pharmacy database. Patients' guardians were contacted two weeks postoperatively to determine opioid usage. Opioids were prescribed at a standard dosing of 0.1 mg/kg per dose or the equivalent. RESULTS: Of the 171 identified patients, 117 patients were successfully contacted, with 67 (39%) completing telephone surveys. The 3 most common pediatric urology procedures were inguinal hernia repair (N = 39), circumcision (N = 27), and cystoscopy (N = 16). Across all procedures, there was an average excess of 9.8 doses prescribed, corresponding to an overprescription rate of 64%. Of the patients prescribed opioids, 41 (62%) had leftover opioid medication two weeks postoperatively. Thirty-two of 41 (78%) patients did not dispose of their leftover medication. Only 13 patients received perioperative counseling on appropriate storage and disposal of opiates. DISCUSSION: Prescribing practices for an array of pediatric urologic procedures are non-standardized and often generously excessive. We show universal overprescribing for all our reviewed urologic procedures. Sixty-two percent of pediatric urology patients did not use their entire prescribed opiate, leaving a significant pool of medicine within the pediatric family home. Given the low incidence of perioperative education, unsurprisingly a majority of our patients improperly handled and disposed off excess opioid medication. CONCLUSION: There is general overprescription of postoperative opioids and poor perioperative opioid education in the pediatric urology population.

Implementation and evaluation of a transit dosimetry system for treatment verification.

PURPOSE: To evaluate a formalism for transit dosimetry using a phantom study and prospectively evaluate the protocol on a patient population undergoing 3D conformal radiotherapy. METHODS: Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. The measured EPID dose map was back-projected using the planning CT images to calculate dose at pre-specified points within the patient using commercially available software, EPIgray (DOSIsoft, France). This software compared computed back-projected dose with treatment planning system dose. A series of tests were performed on solid water phantoms (linearity, field size effects, off-axis effects). 37 patients were enrolled in the prospective study. RESULTS: The EPID dose response was stable and linear with dose. For all tested field sizes the agreement was good between EPID-derived and treatment planning system dose in the central axis, with performance stability up to a measured depth of 18cm (agreement within -0.5% at 10cm depth on the central axis and within -1.4% at 2cm off-axis). 126 transit images were analysed of 37 3D-conformal patients. Patient results demonstrated the potential of EPIgray with 91% of all delivered fields achieved the initial set tolerance level of ΔD of 0±5-cGy or %ΔD of 0±5%. CONCLUSIONS: The in vivo dose verification method was simple to implement, with very few commissioning measurements needed. The system required no extra dose to the patient, and importantly was able to detect patient position errors that impacted on dose delivery in two of cases.

Investigation into the effects of high-Z nano materials in proton therapy.

High-Z nano materials have been previously shown to increase the amount of dose deposition within the tumour due to an increase in secondary electrons. This study evaluates the effects of high-Z nano materials in combination with protons, and the impact of proton energy, nanoparticle material and concentration. These effects were studied in silico through Monte Carlo simulation and experimentally through a phantom study, with particular attention to macroscale changes to the Bragg peak in the presence of nanoparticles. Three nanoparticle materials were simulated (gold, silver and platinum) at three concentrations (0.01, 0.1 and 6.5 mg ml(-1)) at two clinical proton energies (60 and 226 MeV). Simulations were verified experimentally using Gafchromic film measurements of gold nanoparticles suspended in water at two available high concentrations (5.5 mg ml(-1) and 1.1 mg ml(-1)). A significant change to Bragg peak features was evident, where at 226 MeV and 6.5 mg ml(-1), simulations of gold showed a 4.7 mm longitudinal shift of the distal edge and experimentally at 5.5 mg ml(-1), a shift of 2.2 mm. Simulations showed this effect to be material dependent, where platinum having the highest physical density caused the greatest shift with increasing concentration. A dose enhancement of 6% ± 0.05 and 5% ± 0.15 (60 MeV and 226 MeV, respectively) was evident with gold at 6.5 mg ml(-1) to water alone, compared to the 21% ± 0.53 observed experimentally as dose to film with 5.5 mg ml(-1) of gold nanoparticles suspended in water at 226 MeV. The introduction of nanoparticles has strong potential to enhance dose in proton therapy, however the changes to the Bragg peak distribution that occur with high concentrations need to be accounted for to ensure tumour coverage.

Automated estimation of disease recurrence in head and neck cancer using routine healthcare data.

BACKGROUND: Overall survival (OS) and progression free survival (PFS) are key outcome measures for head and neck cancer as they reflect treatment efficacy, and have implications for patients and health services. The UK has recently developed a series of national cancer audits which aim to estimate survival and recurrence by relying on institutions manually submitting interval data on patient status, a labour-intensive method. However, nationally, data are routinely collected on hospital admissions, surgery, radiotherapy and chemotherapy. We have developed a technique to automate the interpretation of these routine datasets, allowing us to derive patterns of treatment in head and neck cancer patients from routinely acquired data. METHODS: We identified 122 patients with head and neck cancer and extracted treatment histories from hospital notes to provide a gold standard dataset. We obtained routinely collected local data on inpatient admission and procedures, chemotherapy and radiotherapy for these patients and analysed them with a computer algorithm which identified relevant time points and then calculated OS and PFS. We validated these by comparison with the gold standard dataset. The algorithm was then optimised to maximise correct identification of each timepoint, and minimise false identification of recurrence events. RESULTS: Of the 122 patients, 82% had locally advanced disease. OS was 88% at 1 year and 77% at 2 years and PFS was 75% and 66% at 1 and 2 years. 40 patients developed recurrent disease. Our automated method provided an estimated OS of 87% and 77% and PFS of 87% and 78% at 1 and 2 years; 98% and 82% of patients showed good agreement between the automated technique and Gold standard dataset of OS and PFS respectively (ratio of Gold standard to routine intervals of between 0.8 and 1.2). The automated technique correctly assigned recurrence in 101 out of 122 (83%) of the patients: 21 of the 40 patients with recurrent disease were correctly identified, 19 were too unwell to receive further treatment and were missed. Of the 82 patients who did not develop a recurrence, 77 were correctly identified and 2 were incorrectly identified as having recurrent disease when they did not. CONCLUSIONS: We have demonstrated that our algorithm can be used to automate the interpretation of routine datasets to extract survival information for this sample of patients. It currently underestimates recurrence rates due to many patients not being well-enough to be treated for recurrent disease. With some further optimisation, this technique could be extended to a national level, providing a new approach to measuring outcomes on a larger scale than is currently possible. This could have implications for healthcare provision and policy for a range of different disease types.

An x-ray fluorescence imaging system for gold nanoparticle detection.

Gold nanoparticles (GNPs) may be used as a contrast agent to identify tumour location and can be modified to target and image specific tumour biological parameters. There are currently no imaging systems in the literature that have sufficient sensitivity to GNP concentration and distribution measurement at sufficient tissue depth for use in in vivo and in vitro studies. We have demonstrated that high detecting sensitivity of GNPs can be achieved using x-ray fluorescence; furthermore this technique enables greater depth imaging in comparison to optical modalities. Two x-ray fluorescence systems were developed and used to image a range of GNP imaging phantoms. The first system consisted of a 10 mm(2) silicon drift detector coupled to a slightly focusing polycapillary optic which allowed 2D energy resolved imaging in step and scan mode. The system has sensitivity to GNP concentrations as low as 1 ppm. GNP concentrations different by a factor of 5 could be resolved, offering potential to distinguish tumour from non-tumour. The second system was designed to avoid slow step and scan image acquisition; the feasibility of excitation of the whole specimen with a wide beam and detection of the fluorescent x-rays with a pixellated controlled drift energy resolving detector without scanning was investigated. A parallel polycapillary optic coupled to the detector was successfully used to ascertain the position where fluorescence was emitted. The tissue penetration of the technique was demonstrated to be sufficient for near-surface small-animal studies, and for imaging 3D in vitro cellular constructs. Previous work demonstrates strong potential for both imaging systems to form quantitative images of GNP concentration.

A quantitative x-ray detection system for gold nanoparticle tumour biomarkers.

X-ray fluorescence techniques have proven beneficial for identifying and quantifying trace elements in biological tissues. A novel approach is being developed that employs x-ray fluorescence with an aim to locate heavy nanoparticles, such as gold, which are embedded into tissues. Such nanoparticles can be functionalized to act as markers for tumour characteristics to map the disease state, with the future aim of imaging them to inform cancer therapy regimes. The uptake of functionalized nanoparticles by cancer cells will also enable detection of small clusters of infiltrating cancer cells which are currently missed by commonly used imaging modalities. The novel system, consisting of an energy-resolving silicon drift detector with high spectral resolution, shows potential in both quantification of and sensitivity to nanoparticle concentrations typically found in tumours. A series of synchrotron measurements are presented; a linear relationship between fluorescence intensity and gold nanoparticle (GNP) concentration was found down to 0.005 mgAu ml(-1), the detection limit of the system. Successful use of a bench-top source, suitable for possible future clinical use, is also demonstrated, and found not to degrade the detection limit or accuracy of the GNP concentration measurement. The achieved system sensitivity suggests possible future clinical usefulness in measuring tumour uptake in vivo, particularly in shallow tumour sites and small animals, in ex vivo tissue and in 3D in vitro research samples.

Travel-associated Legionnaires disease in Europe in 2009.

A total of 818 cases of Legionnaires' disease with onset of illness in 2009 were reported from 22 European and two non-European countries to the European Surveillance Scheme for Travel-Associated Legionnaires' Disease (EWGLINET). This is a decrease of 52 cases compared with 2008 and 129 fewer than in 2007 - the peak year of reporting to date. A total of 794 (97.1%) cases were reported as confirmed and 24 as presumptive cases. Outcome of illness was reported for 561 (68.6%) cases. Of these cases 28 (5%) were reported to have died. More than half, of the cases in 2009 (n=469, 57.3%) were reported within 20 days of symptom onset. Cases visited 53 countries and were infected in all months of the year, with a peak in September (n=146). By country of residence of the cases, the United Kingdom (UK) reported the highest number of cases (n=173). Italy reported the second highest number of cases (n=169) and was also the country associated with the most cases by country of infection (n=209). A total of 88 new clusters (75 in Europe and 13 outside Europe) were detected in 2009 and were associated with 196 cases. The largest cluster occurred in Italy and involved seven cases. Without the scheme's international database, thirty three (37.5%) of the newly detected clusters would not have been identified. In 49 of the accommodation sites with clusters of cases, environmental samples were found to be positive for Legionella spp. Details of 10 sites were published on the European Working Group for Legionella Infections (EWGLI) website for failure to return information on the status of environmental investigations.

Characteristics of reoffending accommodation sites in Europe with clusters of Legionnaires disease, 2003-2007.

Between 2003 and 2007, 21% (n=100/477) of accommodation sites linked to clusters of two or more cases of Legionnaires' disease that were investigated by the European Surveillance Scheme for Travel-Associated Legionnaires' Disease (EWGLINET) went on to be associated with at least one further case, despite reporting that satisfactory control measures had been implemented at the time the cluster was first detected. This paper examines these sites (termed reoffenders) in order to determine whether they share any characteristics that may have contributed to the reoffence. All investigations conducted at cluster sites between 2003 and 2007 were included in the analysis, giving a total of 615 investigations conducted at 477 sites. Every country that investigated more than three cluster sites had to deal with at least one reoffence, and one site reoffended five times. The cases involved in the cluster that stayed elsewhere during their incubation periods could be used to help assess the probability of exposure, and therefore the risk, posed by particular cluster sites. A more extensive investigation and control regime may be needed in some instances to better control the risk of Legionnaires' disease at an accommodation site.

Travel-associated Legionnaires disease in Europe in 2008.

In 2008, the European Surveillance Scheme for Travel Associated Legionnaires Disease (EWGLINET) received reports of 866 cases of travel-associated Legionnaires disease, 42 of whom were reported to have died. 824 of the cases were classified as confirmed and 42 were presumptive. As in previous years, a very low proportion of clinical isolates were obtained (63 cases, 7.3%). Males outnumbered females by 2.8:1 in the 2008 dataset and had a median age of 60 years compared with women, whose median age was 63 years. Travel outside Europe was reported for 12% of the cases. The scheme identified 108 new clusters in 2008. Sixteen were located in countries outside EWGLINET and 38 (35.2%) involved only one case from each reporting country, and would not ordinarily have been detected by national surveillance schemes alone. The largest cluster (six cases) was associated with travel to Spain. The 108 clusters were associated with 144 environmental investigations, 35 of which were at re-offending sites, (sites which had previously been investigated and where additional cases had subsequently occurred). At 61 (42.1%) of the sites Legionella species were detected. The names of 12 sites were published on the EWGLINET website.

Legionnaires disease in Europe 2007-2008.

Each spring, countries that participate in the European Surveillance Scheme for Travel Associated Legionnaires Disease (EWGLINET) are requested to submit their annual dataset of all cases of Legionnaires disease in residents of their country with onset of illness in the preceding year. These data have been collected annually since 1994 and are used to analyse epidemiological and microbiological trends within and between countries over time. This paper presents an overview of the data collected for 2007 and 2008. A total of 5,907 cases were reported by 33 countries in 2007 and 5,960 cases by 34 countries in 2008, a similar two-year total to that recorded in 2005 and 2006 [1]. The only countries with a major difference in case numbers between 2007 and 2008 were Russia, due to a large outbreak in 2007, and Italy where cases increased by 256 in 2008 mainly due to an increase in community-acquired infections. The 779 reported deaths give a two-year case fatality rate of 6.6%. Some 243 outbreaks or clusters were detected, 150 of which were linked to travel-associated infections. As in previous years, the overall main method of diagnosis was by urinary antigen detection and the proportion of cases diagnosed by culture remained low at 8.8%, although isolation rates by country ranged from under 1% to over 40%.

Travel-associated Legionnaires disease in Europe in 2007.

Nine hundred and forty six cases of travel-associated Legionnaires disease were reported to the European Surveillance Scheme for Travel Associated Legionnaires Disease (EWGLINET) with onset during 2007; 890 were confirmed and 56 were presumptive. Twenty eight cases died, giving a case fatality rate of 3.0%. 8.2% of cases were diagnosed by culture, an important increase from 5.2% in 2006. One hundred and twelve new clusters were identified; the largest involved nine cases. Sixteen of these clusters (14.3%) occurred in countries outside EWGLINET, and three involved cruise ships. Twenty nine of the new clusters (25.9%) would not have been detected without the EWGLINET scheme. A total of 151 investigations were conducted in Europe, 42 of which were conducted at re-offending sites (where additional cases had onset after a report was received to say that investigations and control measures had been satisfactorily conducted). The names of 13 accommodation sites were published on the European Working Group for Legionella Infections (EWGLI) website; 11 of these were situated in Turkey.

Weather patterns and Legionnaires' disease: a meteorological study.

This study examined the impact of meteorological conditions on sporadic, community-acquired cases of Legionnaires' disease in England and Wales (2003-2006), with reference to the 2006 increase in cases. A case-crossover methodology compared each case with self-controlled data using a conditional logistic regression analysis. Effect modification by quarter and year was explored. In total, 674 cases were entered into the dataset and two meteorological variables were selected for study based on preliminary analyses: relative humidity during a case's incubation period, and temperature during the 10-14 weeks preceding onset. For the quarter July-September there was strong evidence to suggest a year, humidity and temperature interaction (Wald chi2=30.59, 3 d.f., P<0.0001). These findings have implications for future case numbers and resource requirements.

Travel-associated Legionnaires disease in Europe: 2006.

Twenty countries reported 921 cases of travel-associated Legionnaires' disease to EWGLINET (the European Surveillance Scheme for Travel-Associated Legionnaires' Disease) with onset during 2006; 875 confirmed and 46 presumptive. Thirty three cases died, giving a case fatality rate of 3.6%. Of the 124 new clusters detected in 2006, 43 would not have been identified without the EWGLINET scheme. A total of 146 investigations were conducted at cluster sites according to the standards of the EWGLINET investigation guidelines; 111 of these investigations were associated with the new clusters while 35 investigations were associated with re-offending sites (where additional cases had onset after a report was received to say that investigations and control measures had been satisfactorily conducted). The names of four accommodation sites were published on the EWGLI website. Overall, there has been an upwards trend in case numbers since the scheme was founded, which has implications for the work load of public health authorities across Europe and for the tour industry. Despite this increasing pressure on public health authorities, environmental investigations are being conducted in a timely manner.

Survey on legislation regarding wet cooling systems in European countries.

Wet cooling systems are often associated with large outbreaks of Legionnaires' disease. Several European countries have legislation for registering such systems. The authors aimed to obtain an overview of the situation in Europe. A questionnaire survey was sent to 35 of the countries that collaborate in the European Working Group for Legionella Infections. In two countries it was passed to a regional level (to three regions in both Belgium and the United Kingdom), so that 39 countries or regions were sent the survey; 37 responded. Nine countries stated having legislation for the registration of wet cooling systems. Separate legislation exists at a regional level for two regions in Belgium and all three regions in the UK, giving a total of twelve countries/regions with legislation. In nine of these countries/regions, the legislation has been introduced since 2001. All of these countries/regions require periodic microbiological monitoring between twice a year and weekly; in nine, the legislation requires periodic inspection of the systems. Regulations for the registration of wet cooling systems should be required by public health authorities. During an outbreak of legionellosis, a register of wet cooling systems can speed up the investigation process considerably. The authors believe that the European Centre for Disease Prevention and Control (ECDC) should take the initiative to propose European Community (EC) regulations for all Member States.

Legionnaires disease in Europe: 2005-2006.

Once a year, every country that participates in the European Surveillance Scheme for Travel Associated Legionnaires' Disease (EWGLINET) is asked to submit a dataset comprising all cases of Legionnaires' disease (not only travel-associated) with date of onset in the previous year. This paper presents the data collected for 2005 and 2006. In this period, 11,980 cases were reported by 35 countries, showing a continued increase compared with earlier years. 214 outbreaks or clusters were reported, involving 1028 cases. 377 cases died, giving a case fatality rate of 6.6%. The highest incidence rates in both years were recorded in Spain, while six countries reported a rate of less than one case per million population in at least one of the years. Incidence rates by age group were included in the dataset for the first time, showing an increase of the overall rate with age. Main method of diagnosis was the urinary antigen test (76.0%), whilst the percentage of cases diagnosed by culture fell from 10.0% in previous years to 8.9% in 2005-2006.

Travel-associated legionnaires' disease in Europe: 2004.

Six hundred and fifty five cases of travel-associated legionnaires' disease with onset in 2004 have been reported to the EWGLINET surveillance scheme by 25 countries. A total of 84.9% of cases were diagnosed by the urinary antigen test, and 37 cultures were obtained. Thirty seven deaths were reported, giving a case fatality rate of 5.6%. Eighty six new clusters were detected, 45% of which would not have been detected without the EWGLINET scheme. Ninety four accommodation sites were investigated and the names of four sites were published on the EWGLI website. Fifteen sites were associated with additional cases after a report was received to say that investigations and control measures had been satisfactorily carried out. Further improvements could be made in the data collected on deaths due to travel-associated legionnaires' disease, and on the number of samples taken for culture throughout Europe.

What is the probability of successive cases of Legionnaires' disease occurring in European hotels?

BACKGROUND: Public health officials will normally take action at accommodation sites following an association with a cluster of cases of Legionnaires' disease. This paper seeks to determine the likelihood of such a cluster occurring at a site once it has been associated with a single case of the disease, and therefore whether more should be done at sites following individual cases. METHODS: Information for UK residents reported to the EWGLINET system between 1993 and 2000 was included in a dataset. The size and country of hotel visited by the cases were divided into six country groups (France, Italy, Spain, Turkey, other Europe and other World), and eight size groups (<20 rooms, 20-49, 50-99, 100-199, 200-299, 300-399, 400-499, 500+). The data were investigated using Cox proportional hazards regression to model the probability of at least one further case following the first. RESULTS: The dataset comprised 793 cases that had stayed at 605 sites in 51 countries between 1993 and the end of 2000. This included 605 cases that were the first case associated with a site, and 188 subsequent cases. Following the first case, 16.6% of sites were associated with at least one subsequent case during the period under study. The probability of a subsequent case occurring within 6 months of the first varied by country and size group, with some combinations returning a probability >30%; the probability of a subsequent case occurring within 2 years of the first reached over 50% in some instances. CONCLUSIONS: There may be support for early intervention at some accommodation sites following a first case of Legionnaires' disease, in specific country and size groups.

The distribution of travel-associated Legionnaires' disease within selected European countries, and a comparison with tourist patterns.

Much data has been gathered by the EWGLINET scheme on the distribution of cases of travel-associated Legionnaires' disease (TALD) by country of infection, but less analysis has been carried out on the distribution of these cases within countries. Travel-associated cases with onset in 2002 linked to France, Italy, Spain and Turkey were mapped. Rates of Legionnaires' disease per 100,000 tourists were calculated for internal and foreign visitors for the regions of each country, and mapped. Rates of 1.5 cases/100,000 and 2 cases/100,000 tourists were classified as 'high' and 'very high' respectively. Cases of TALD were concentrated in certain regions, but when rates were calculated using tourist data, the results were relatively constant throughout each country. Rates were higher among foreign visitors than internal visitors; three of the countries had at least one region with 'high' rates, whilst Turkey additionally had three regions with 'very high' rates.

Travel-associated legionnaires' disease in Europe: 2004.

Six hundred and fifty five cases of travel-associated legionnaires' disease with onset in 2004 have been reported to the EWGLINET surveillance scheme by 25 countries. A total of 84.9% of cases were diagnosed by the urinary antigen test, and 37 cultures were obtained. Thirty seven deaths were reported, giving a case fatality rate of 5.6%. Eighty six new clusters were detected, 45% of which would not have been detected without the EWGLINET scheme. Ninety four accommodation sites were investigated and the names of four sites were published on the EWGLI website. Fifteen sites were associated with additional cases after a report was received to say that investigations and control measures had been satisfactorily carried out. Further improvements could be made in the data collected on deaths due to travel-associated legionnaires' disease, and on the number of samples taken for culture throughout Europe.

Legionnaires' disease in Europe 2003-2004.

Once a year, countries that collaborate in the European Surveillance Scheme for Travel Associated Legionnaires' Disease (EWGLINET) are requested to submit a dataset that provides epidemiological and microbiological information on cases of legionnaires' disease (nosocomial (hospital-acquired), community and travel related) detected in their country for that year. This paper presents the data collected for 2003 and 2004. For this period, 9166 cases were reported to the dataset by 35 countries, of which 941 cases were associated with outbreaks. Fourteen countries reported a total of 218 detected outbreaks. National infection rates varied between countries from 28.7 to less than one case per million population. This information is valuable in that it allows countries to assess the effectiveness of their national surveillance schemes in detecting cases. Over the two year period, 748 cases were reported to have died, giving a case fatality rate of 8.2%. The lack of detailed epidemiological information on deaths from legionnaires' disease is highlighted. The establishment of the European Centre for Disease Prevention and Control is seen as an opportunity to develop European collaborations more fully, and to increase further the protection of Europeans from outbreaks of legionnaires' disease.