Recognition of child maltreatment in emergency departments in Europe: Should we do better?

OBJECTIVES: To evaluate the different policies to recognize child maltreatment in emergency departments (EDs) in Europe in order to define areas of improvement. METHODS: A survey was conducted on the recognition of child maltreatment in EDs in European countries with a focus on screening methods, parental risk factors, training and hospital policies. The survey was distributed through different key members from the EUSEM, REPEM and the EuSEN. A summary score based on the NICE guideline (4 questions on child characteristics, 4 questions on parental characteristics and 5 questions on hospital policy) was calculated. RESULTS: We analysed 185 completed surveys, representing 148 hospitals from 29 European countries. Of the respondents, 28.6% used a screening tool, and 31.8% had guidelines on parental risk factors. A total of 42.2% did not follow training based on child characteristics, and 57.6% did not follow training on parental characteristics. A total of 71.9% indicated that there was a need for training. 50.8% of the respondents reported a standardized policy for the detection of child maltreatment. Translating the survey results to NICE summary scores of the EDs in Europe, we found that 25.6% (34/133) met most, 22.6% (30/133) met some and 51.9% (69/133) met few of the NICE guideline recommendations. More specifically, with respect to hospital policies, 33.8% (45/133) met most, 15.0% (20/133) met some and 51.1% (68/133) met few of the NICE guideline recommendations. CONCLUSION: There is high variability regarding policies for child maltreatment detection and only a quarter of the EDs met most of the NICE guideline recommendations for child maltreatment. There is a need for the use of screening tools, training of ED staff and implementation of local hospital policies.

A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA.

T Follicular helper cells (TFH) are considered critical for B cell antibody response, and recent efforts have focused on promoting TFH in order to enhance vaccine efficacy. We studied the frequency and function of TFH in nasopharynx-associated lymphoid tissues (NALT) from children and adults, and its role in anti-influenza antibody response following stimulation by a live-attenuated influenza vaccine (LAIV) or an inactivated seasonal virus antigen (sH1N1). We further studied whether CpG-DNA promotes TFH and by which enhances anti-influenza response. We showed NALT from children aged 1.5-10 years contained abundant TFH, suggesting efficient priming of TFH during early childhood. Stimulation by LAIV induced a marked increase in TFH that correlated with a strong production of anti-hemagglutinin (HA) IgA/IgG/IgM antibodies in tonsillar cells. Stimulation by the inactivated sH1N1 antigen induced a small increase in TFH which was markedly enhanced by CpG-DNA, accompanied by enhanced anti-HA antibody responses. In B cell co-culture experiment, anti-HA responses were only seen in the presence of TFH, and addition of plasmacytoid dendritic cell to TFH-B cell co-culture enhanced the TFH-mediated antibody production following CpG-DNA and sH1N1 antigen stimulation. Induction of TFH differentiation from naïve T cells was also shown following the stimulation. Our results support a critical role of TFH in human mucosal anti-influenza antibody response. Use of an adjuvant such as CpG-DNA that has the capacity to promote TFH by which to enhance antigen-induced antibody responses in NALT tissue may have important implications for future vaccination strategies against respiratory pathogens.

Physical activity and risk of bleeding in elderly patients taking anticoagulants.

BACKGROUND: Although the possibility of bleeding during anticoagulant treatment may limit patients from taking part in physical activity, the association between physical activity and anticoagulation-related bleeding is uncertain. OBJECTIVES: To determine whether physical activity is associated with bleeding in elderly patients taking anticoagulants. PATIENTS/METHODS: In a prospective multicenter cohort study of 988 patients aged ≥ 65 years receiving anticoagulants for venous thromboembolism, we assessed patients' self-reported physical activity level. The primary outcome was the time to a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin or leading to transfusions. The secondary outcome was the time to a first clinically relevant non-major bleeding. We examined the association between physical activity level and time to a first bleeding by using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS: During a mean follow-up of 22 months, patients with a low, moderate, and high physical activity level had an incidence of major bleeding of 11.6, 6.3, and 3.1 events per 100 patient-years and an incidence of clinically relevant non-major bleeding of 14.0, 10.3, and 7.7 events per 100 patient-years, respectively. A high physical activity level was significantly associated with a lower risk of major bleeding (adjusted sub-hazard ratio 0.40, 95% confidence interval 0.22-0.72). There was no association between physical activity and non-major bleeding. CONCLUSIONS: A high level of physical activity is associated with a decreased risk of major bleeding in elderly patients receiving anticoagulant therapy.

Risk of falls and bleeding in elderly patients with acute venous thromboembolism.

OBJECTIVE: Whether or not a high risk of falls increases the risk of bleeding in patients receiving anticoagulants remains a matter of debate. METHODS: We conducted a prospective cohort study involving 991 patients ≥ 65 years of age who received anticoagulants for acute venous thromboembolism (VTE) at nine Swiss hospitals between September 2009 and September 2012. The study outcomes were as follows: the time to a first major episode of bleeding; and clinically relevant nonmajor bleeding. We determined the associations between the risk of falls and the time to a first episode of bleeding using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS: Four hundred fifty-eight of 991 patients (46%) were at high risk of falls. The mean duration of follow-up was 16.7 months. Patients at high risk of falls had a higher incidence of major bleeding (9.6 vs. 6.6 events/100 patient-years; P = 0.05) and a significantly higher incidence of clinically relevant nonmajor bleeding (16.7 vs. 8.3 events/100 patient-years; P < 0.001) than patients at low risk of falls. After adjustment, a high risk of falls was associated with clinically relevant nonmajor bleeding [subhazard ratio (SHR) = 1.74, 95% confidence interval (CI) = 1.23-2.46], but not with major bleeding (SHR = 1.24, 95% CI = 0.83-1.86). CONCLUSION: In elderly patients who receive anticoagulants because of VTE, a high risk of falls is significantly associated with clinically relevant nonmajor bleeding, but not with major bleeding. Whether or not a high risk of falls is a reason against providing anticoagulation beyond 3 months should be based on patient preferences and the risk of VTE recurrence.

Determination of (210)Pb and (226)Ra/(228)Ra in continental water using HIDEX 300SL LS-spectrometer with TDCR efficiency tracing and optimized α/ß-discrimination.

An analytical method for determination of (210)Pb, (226)Ra and (228)Ra is presented based on adsorption on 3M Empore RadDiscs, and measurement applying liquid scintillation spectrometry (LSC) after elution. The LSC measurement was performed with optimized α/ß-discrimination and isotope standardization using the triple to double coincidence ratio (TDCR). The consistency of measurement results between radioactive parent-daughter pairs (210)Pb/(210)Bi, (226)Ra/(222)Rn and (228)Ra/(228)Ac was checked in long-term counting experiments and the influence ofinterference of in-growing daughters from (226)Ra into the ß-spectrum of (228)Ra+(228)Ac was studied as well. Recommendations for optimized LSC (228)Ra measurement besides presence of (226)Ra are given.

Prospective, multicenter validation of prediction scores for major bleeding in elderly patients with venous thromboembolism.

BACKGROUND: The Outpatient Bleeding Risk Index (OBRI) and the Kuijer, RIETE and Kearon scores are clinical prognostic scores for bleeding in patients receiving oral anticoagulants for venous thromboembolism (VTE). We prospectively compared the performance of these scores in elderly patients with VTE. METHODS: In a prospective multicenter Swiss cohort study, we studied 663 patients aged ≥ 65 years with acute VTE. The outcome was a first major bleeding at 90 days. We classified patients into three categories of bleeding risk (low, intermediate and high) according to each score and dichotomized patients as high vs. low or intermediate risk. We calculated the area under the receiver-operating characteristic (ROC) curve, positive predictive values and likelihood ratios for each score. RESULTS: Overall, 28 out of 663 patients (4.2%, 95% confidence interval [CI] 2.8-6.0%) had a first major bleeding within 90 days. According to different scores, the rate of major bleeding varied from 1.9% to 2.1% in low-risk, from 4.2% to 5.0% in intermediate-risk and from 3.1% to 6.6% in high-risk patients. The discriminative power of the scores was poor to moderate, with areas under the ROC curve ranging from 0.49 to 0.60 (P = 0.21). The positive predictive values and positive likelihood ratios were low and varied from 3.1% to 6.6% and from 0.72 to 1.59, respectively. CONCLUSION: In elderly patients with VTE, existing bleeding risk scores do not have sufficient accuracy and power to discriminate between patients with VTE who are at a high risk of short-term major bleeding and those who are not.

Prospective comparison of clinical prognostic scores in elder patients with a pulmonary embolism.

BACKGROUND: The Geneva Prognostic Score (GPS), the Pulmonary Embolism Severity Index (PESI) and its simplified version (sPESI) are well-known clinical prognostic scores for a pulmonary embolism (PE). OBJECTIVES: To compare the prognostic performance of these scores in elderly patients with a PE. PATIENTS AND METHODS: In a multicenter Swiss cohort of elderly patients with venous thromboembolism, we prospectively studied 449 patients aged ≥ 65 years with a symptomatic PE. The outcome was 30-day overall mortality. We dichotomized patients as low vs. higher risk in all three scores using the following thresholds: GPS scores ≤ 2 vs. > 2, PESI risk classes I-II vs. III-V and sPESI scores 0 vs. ≥ 1. We compared 30-day mortality in low- vs. higher-risk patients and the areas under the receiver-operating characteristic curve (ROC). RESULTS: Overall, 3.8% of patients (17/449) died within 30 days. The GPS classified a greater proportion of patients as low risk (92% [413/449]) than the PESI (36.3% [163/449]) and the sPESI (39.6% [178/449]) (P < 0.001 for each comparison). Low-risk patients based on the sPESI had a mortality of 0% (95% confidence interval [CI] 0-2.1%) compared with 0.6% (95% CI 0-3.4%) for low-risk patients based on the PESI and 3.4% (95% CI 1.9-5.6%) for low-risk patients based on the GPS. The areas under the ROC curves were 0.77 (95% CI 0.72-0.81), 0.76 (95% CI 0.72-0.80) and 0.71 (95% CI 0.66-0.75), respectively (P = 0.47). CONCLUSIONS: In this cohort of elderly patients with PE, the GPS identified a higher proportion of patients as low risk but the PESI and sPESI were more accurate in predicting mortality.

Cervical cancer incidence in young women: a historical and geographic controlled UK regional population study.

BACKGROUND: The commencing age of cervical screening in England was raised from 20 to 25 years in 2004. Cervical cancer incidence in young women of England is increasing. It is not clear if this is due to either greater exposure to population risk factors or reduced cervical screening. METHODS: We measured if the relative risk of cervical cancer in younger women (20-29 years) of the north-east of England (NE) differed to that of women aged 30yrs and above since 2004. We also measured average annual percentage change (AAPC) in the 3 yr moving average incidence for all age-groups. Regional screening coverage rate and population risk factors were reviewed. Comparisons were made with Wales where screening continues to commence from the age of 20yrs. RESULTS: Cervical cancer incidence in women aged 20-29 increased annually by an average of 10.3% between 2000 and 2009. The rise in women aged 30-39 was less steep (3.5%/year) but no significant rise was observed in women aged 40-49. Socioeconomic factors remained stable or improved during the time period except for the incidence of chlamydia, herpes simplex and in particular, genital warts, which increased significantly in young women. Data from Wales show similar results. CONCLUSION: The incidence of cervical cancers in young women of the NE is increasing. The rise in incidence is unrelated to the change in screening policy in 2004. Close monitoring of incidence in young women and a greater attempt to reverse the current decline in screening coverage of women aged 25-29 years are recommended.

Birth outcomes following treatment for precancerous changes to the cervix: a population-based record linkage study.

OBJECTIVE: To examine whether treatments for precancerous changes to the cervix are associated with adverse birth outcomes in subsequent pregnancies. DESIGN: Population-based retrospective cohort study using electronic linkage of data from the Welsh cervical screening programme and a national routine child health database. SETTING: Wales. POPULATION: A total of 174,325 women aged 20-39 years who received cervical screening between April 2001 and March 2004. METHODS: Logistic regression was used to compare the odds of each birth outcome between women who had negative cervical smears and women who received either colposcopy ± punch biopsy only or colposcopy and excisional or ablative treatments, adjusted for confounding factors (e.g. age, social deprivation and smoking). MAIN OUTCOME MEASURES: Preterm birth (before 37, 32 and 28 weeks of gestation), and low birthweight (<2500 g). RESULTS: Compared with women who had negative cervical smears, the odds ratio for preterm birth (<37 weeks) was significantly increased in women who had colposcopy only (adjusted odds ratio 1.54, 95% CI 1.32-1.80) and single excisional treatment (adjusted odds ratio 1.77, 95% CI 1.47-2.13). Similar results were observed for preterm birth at <32 weeks of gestation. There was no increased risk of preterm birth or low birthweight for women who had treatment compared with women who had colposcopy only. CONCLUSION: Women who were referred for colposcopy had an increased risk of preterm births regardless of whether or not they received treatment to the cervix. This increased risk could be the result of common risk factors for abnormal smears and preterm birth.

Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial.

BACKGROUND: Cervical screening identifies many women with low-grade abnormalities. In vitro and in vivo studies have shown that diindolylmethane (DIM) could potentially halt (cervical) carcinogenesis. We report on a randomised controlled trial of the effect of DIM in women with low-grade cervical cytological abnormalities. METHODS: We conducted a pragmatic double-blind, randomised controlled trial of 150 mg DIM (from BioResponse DIM) or placebo daily for 6 months in women with newly diagnosed, low-grade cytological abnormalities. Randomisation was in the ratio 2 (DIM) to 1 (placebo). All women were invited for colposcopy at 6 months with biopsy of any abnormality. RESULTS: Of the 551 randomised women available for analysis, 9% on DIM and 12% on placebo had cervical intraepithelial neoplasia-2 (CIN2) or worse after 6-month supplementation (risk ratio (RR) 0.7 (95% confidence interval (CI): 0.4-1.2)), whereas 4.6% and 5.1%, respectively, had CIN3 or worse (RR 0.9 (95% CI: 0.4-2.0)). A total of 27.3% of women on DIM and 34.3% on placebo had no sign of disease (negative cytology, colposcopy and human papilloma virus (HPV) tests) at 6 months (RR 0.8 (95% CI: 0.6-1.0)). Of those HPV-positive at baseline, 69% (114 out of 166) of the DIM group were positive at 6 months compared with 61% (43 out of 71) of the placebo group: RR 1.1 (95% CI: 0.9-1.4). Diindolylmethane supplementation was well tolerated. CONCLUSION: The results suggest that short-term DIM supplementation (150 mg day(-1)) is well tolerated, but is unlikely to have an effect on cytology or HPV infection. Uncertainty remains regarding its effect on CIN2+.

Sharing hard labour: developing a standard template for data summaries in guideline development.

BACKGROUND: A key objective of the Guidelines International Network (GIN) is to reduce duplication of effort. To address this objective, a working group was established to define a minimum dataset for inclusion in all evidence tables. METHODS: A literature review was conducted to identify existing evidence tables, and GIN member organisations were asked to provide the tables they use. The results were used to develop a minimum dataset (template) for studies addressing intervention questions. The template was pilot-tested by a group of guideline developers and reviewed at GIN conferences. RESULTS The literature search yielded 65 articles. These dealt with reporting standards and trial quality (eg, CONSORT statement) rather than which data should be extracted from studies. However, the checklist items given were considered useful. Nineteen GIN members provided evidence tables; 17 tables were used for analysis. The number of items included in the tables ranged from 8 to 19, with several items common to all tables. Within individual items, the level of detail varied widely. The draught template included a majority of items relating to objective data. Pilot testing revealed that the median time to read a paper and complete the template was 2 h for a randomised controlled trial and 2½ h for a non-randomised, controlled intervention study. The median rating for both relevance and clarity of items was high. CONCLUSION The template listing the items needed to summarise an interventional study is now available for large-scale testing by all organisations.

Separation techniques for low-level determination of actinides in soil samples.

The separation methods for soil samples applied at PSI are based on extraction chromatography and ion exchange. After sample leaching, the actinides are pre-concentrated via precipitation using oxalic acid. Besides the classical separation methods applying the extraction chromatographic resins U/TEVA (for U, Th), TRU (Pu, Am), new methods were recently implemented to increase the radiochemical recovery of particularly trivalent Am and Cm. These methods do not require initial reduction of Pu(IV) to Pu(III) but stabilize Pu on the tetravalent oxidation state using a mixture of NaNO(2)/H(2)O(2) in strong acidic medium. The Pu-fraction is then fixed along with Th onto Dowex AG 1-X2 anion exchanger resin. Th is eluted via complexation with 10M HCl, Pu via reduction with HI. The fractions of Am+Cm and U are loaded onto DGA resin. This resin shows extraordinary high distribution coefficients (k'-values) exceeding 10(4) (for Am) in strong nitric acid medium. The separation between U and Am is obtained quantitatively by decreasing the HNO(3) concentration from 3 to 0.25 M (stripping of the U-fraction) while Am can be easily eluted thereafter using 0.25 M HCl as complexation compound.

Does Young's syndrome exist?

BACKGROUND AND METHODS: Young's syndrome describes a combination of male infertility, azoospermia, bronchiectasis and sinusitis. Although Young's syndrome is a well accepted disorder within the realms of infertility medicine, it is also accepted as being a potential cause of sino-nasal disease which is rarely seen by otolaryngologists. However, the significance of the sinus component within this triad is not fully understood. To gain further insight into the relationship of sinusitis with Young's syndrome, we reviewed all of the currently available published literature. RESULTS: Within the reviewed literature, the diagnosis of sinusitis in Young's syndrome was crude and poorly defined; there was little emphasis on sinus disease in most publications. CONCLUSIONS: The prevalence of Young's syndrome is reported to be declining, and the level of evidence regarding sinus disease within this syndrome is limited to case series only. There is, in fact, little evidence to support Young's syndrome being a significant aetiological factor for sinus disease, nor indeed to support the existence of Young's syndrome as an entity in its own right. The only documented aetiological factor is mercury exposure in childhood, an event that is seldom currently encountered; this would support our theory of the extinction of the condition. As an incidental finding, we found that the term Young's syndrome refers to two different medical conditions.

Human papillomavirus prevalence in women attending routine cervical screening in South Wales, UK: a cross-sectional study.

In this cross-sectional population-based study we determine human papillomavirus (HPV) prevalence in South Wales to provide comprehensive baseline data for future assessment of the impact of prophylactic HPV vaccination and to help inform future screening strategies. Liquid-based cytology samples from women attending routine cervical screening were collected (n=10 000: mean age 38 years, 93% cytology negative, and 64.8% from the 50% least deprived LSOA according to social deprivation score (SDS)). High-Risk (HR) and Low-Risk HPV screening was performed using HPV PCR-EIA with genotyping of HR positives and data correlated with age, SDS and cytology. Overall HPV prevalence was 13.5% (9.3% age standardised) and the most frequent HR types were HPV 16, 31, 18 and 58. In HR HPV-positive cases 42.4% had a single HR type and they were predominant in women with severe cytological abnormalities. Here, 66% of all HR HPV cases were in women aged 30 years of age or less and SDS had no significant effect on HPV status. HPV prevalence increased significantly with degree of dyskaryosis from 7% in cytology negative samples to 80% in samples with severe cytological abnormalities (P-value <0.0001). Overall, 46% of HR HPV cases were positive for the two HR types targeted by the prophylactic vaccines (HPV 16 and HPV 18). The data presented represents the largest type-specific investigation of HPV prevalence in an unselected UK population.

Radioisotope contaminations from releases of the Tomsk-Seversk nuclear facility (Siberia, Russia).

Soils have been sampled in the vicinity of the Tomsk-Seversk facility (Siberia, Russia) that allows us to measure radioactive contaminations due to atmospheric and aquatic releases. Indeed soils exhibit large inventories of man-made fission products including 137Cs (ranging from 33,000 to 68,500 Bq m(-2)) and actinides such as plutonium (i.e. 239+240Pu from 420 to 5900 Bq m(-2)) or 241Am (160-1220 Bq m(-2)). Among all sampling sites, the bank of the Romashka channel exhibits the highest radioisotope concentrations. At this site, some short half-life gamma emitters were detected as well indicating recent aquatic discharge in the channel. In comparison, soils that underwent atmospheric depositions like peat and forest soils exhibit lower activities of actinides and 137Cs. Soil activities are too high to be related solely to global fallout and thus the source of plutonium must be discharges from the Siberian Chemical Combine (SCC) plant. This is confirmed by plutonium isotopic ratios measured by ICP-MS; the low 241Pu/239Pu and 240Pu/239Pu atomic ratios with respect to global fallout ratio or civil nuclear fuel are consistent with weapons grade signatures. Up to now, the influence of Tomsk-Seversk plutonium discharges was speculated in the Ob River and its estuary. Isotopic data from the present study show that plutonium measured in SCC probably constitutes a significant source of plutonium in the aquatic environment, together with plutonium from global fallout and other contaminated sites including Tomsk, Mayak (Russia) and Semipalatinsk (Republic of Kazakhstan). It is estimated that the proportion of plutonium from SCC source can reach 45% for 239Pu and 60% for 241Pu in the sediments.

The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing.

The autoinflammatory disorders Muckle-Wells syndrome, familial cold urtecaria and chronic infantile neurological cutaneous and articular syndrome are associated with mutations in the NALP3 (Cryopyrin) gene, which is the central platform of the proinflammatory caspase-1 activating complex, named the inflammasome. In patients with another autoinflammatory disorder, familial Mediterranean fever (FMF), mutations in the SPRY domain of the Pyrin protein are frequently found. Recent evidence suggests that Pyrin associates with ASC, an inflammasome component, via its Pyrin domain, thereby halting the inflammatory response. This interaction, however, does not explain the effects of mutations of the SPRY domain found in FMF patients. Here we show that the Pyrin SPRY domain not only interacts with NALP3, but also with caspase-1 and its substrate pro-interleukin(IL)-1beta. Whereas a Pyrin knockdown results in increased caspase-1 activation and IL-1beta secretion, overexpression of the SPRY domain alone blocks these processes. Thus Pyrin binds to several inflammasome components thereby modulating their activity.

Two-view mammography at the incident round has improved the rate of screen-detected breast cancer in Wales.

AIM: To investigate whether pre-invasive and invasive cancer detection rates were improved in Wales after the introduction of two views at incident screens. METHODS: The records of women attending follow-up screening for 2 years before and 2 years after the introduction of two-view incident screening were analysed. Cancer detection rates were compared before and after introduction of two view screening. RESULTS: At the incident round 98,752 women had one and 95,464 had two views. Five hundred and fifty-five cancers were detected with one view and 744 with two, an increased detection rate from 5.6 to 7.8 cancers per 1000 women screened (p=0.01). Two hundred and thirty-nine small cancers were detected with one view and 323 with two, increasing the detection rate from 2.4 to 3.4 per 1000 women screened (p=0.05). CONCLUSIONS: Two-view mammography at incident rounds detects more cancers and more favourable prognosis small cancers than single-view mammograms.

The estrogen-responsive B box protein: a novel enhancer of interleukin-1beta secretion.

The estrogen-responsive B box protein (EBBP) and Pyrin belong to a family of structurally related proteins. While mutations in the pyrin gene cause an autoinflammatory disease, the biological function of EBBP is unknown. In this study, we identified the proinflammatory cytokine interleukin-1beta (IL-1beta) as an EBBP-binding partner. Furthermore, caspase-1 and NACHT, LRR and Pyrin domain containing protein (NALP) 1, two components of the recently identified inflammasome, a platform for the activation of caspase-1, also interact with EBBP. These proteins bind to the RFP domain of EBBP, suggesting that this domain of so far unknown function is an important protein-binding domain. EBBP was secreted in a caspase-1-dependent manner from cultured cells, and its secretion was enhanced by IL-1beta. Vice versa, endogenous and overerexpressed EBBP increased IL-1beta secretion. These results provide evidence for a role of EBBP in innate immunity by enhancing the alternative secretion pathway of IL-1beta.