Trends in treatment, incidence and survival of hypopharynx cancer: a 20-year population-based study in the Netherlands

Hypopharynx cancer has the worst prognosis of all head and neck squamous cell cancers. Since the 1990s, a treatment shift has appeared from a total laryngectomy towards organ preservation therapies. Large randomized trials evaluating treatment strategies for hypopharynx cancer, however, remain scarce, and frequently this malignancy is evaluated together with larynx cancer. Therefore, our aim was to determine trends in incidence, treatment and survival of hypopharynx cancer. We performed a population-based cohort study including all patients diagnosed with T1-T4 hypopharynx cancer between 1991 and 2010 in the Netherlands. Patients were recorded by the national cancer registry database and verified by a national pathology database. 2999 patients were identified. The incidence increased significantly with 4.1% per year until 1997 and decreased non-significantly afterwards. For women, the incidence increased with 1.7% per year during the entire study period. Total laryngectomy as primary treatment significantly decreased, whereas radiotherapy and chemoradiation increased. The 5-year overall survival significantly increased from 28% in 1991-2000 to 34% in 2001-2010. Overall survival for T3 was equal for total laryngectomy and (chemo)radiotherapy, but for T4-patients the survival was significantly better after primary total laryngectomy (+/- adjuvant radiotherapy). This large population-based study demonstrates a shift in treatment preference towards organ preservation therapies. The 5-year overall survival increased significantly in the second decade. The assumed equivalence of organ preservation and laryngectomy may require reconsideration for T4 diseas

Simulating an integrated critiquing system

OBJECTIVE: To investigate factors that determine the feasibility and effectiveness of a critiquing system for asthma/COPD that will be integrated with a general practitioner's (GP's) information system. DESIGN: A simulation study. Four reviewers, playing the role of the computer, generated critiquing comments and requests for additional information on six electronic medical records of patients with asthma/COPD. Three GPs who treated the patients, playing users, assessed the comments and provided missing information when requested. The GPs were asked why requested missing information was unavailable. The reviewers reevaluated their comments after receiving requested missing information. MEASUREMENTS: Descriptions of the number and nature of critiquing comments and requests for missing information. Assessment by the GPs of the critiquing comments in terms of agreement with each comment and judgment of its relevance, both on a five-point scale. Analysis of causes for the (un-)availability of requested missing information. Assessment of the impact of missing information on the generation of critiquing comments. RESULTS: Four reviewers provided 74 critiquing comments on 87 visits in six medical records. Most were about prescriptions (n = 28) and the GPs' workplans (n = 27). The GPs valued comments about diagnostics the most. The correlation between the GPs' agreement and relevance scores was 0.65. However, the GPs' agreements with prescription comments (complete disagreement, 31.3%; disagreement, 20.0%; neutral, 13.8%; agreement, 17.5%; complete agreement, 17.5%) differed from their judgments of these comments' relevance (completely irrelevant, 9.0%; irrelevant, 24.4%; neutral, 24.4%; relevant, 32.1%; completely relevant, 10.3%). The GPs were able to provide answers to 64% of the 90 requests for missing information. Reasons available information had not been recorded were: the GPs had not recorded the information explicitly; they had assumed it to be common knowledge; it was available elsewhere in the record. Reasons information was unavailable were: the decision had been made by another; the GP had not recorded the information. The reviewers left 74% of the comments unchanged after receiving requested missing information. CONCLUSION: Human reviewers can generate comments based on information currently available in electronic medical records of patients with asthma/COPD. The GPs valued comments regarding the diagnostic process the most. Although they judged prescription comments relevant, they often strongly disagreed with them, a discrepancy that poses a challenge for the presentation of critiquing comments for the future critiquing system. Requested additional information that was provided by the GPs led to few changes. Therefore, as system developers faced with the decision to build an integrated, non-inquisitive or an inquisitive critiquing system, the authors choose the former

Annual Research Review: interparental conflict and youth psychopathology: an evidence review and practice focused update

The quality of the interparental relationship is recognized as an important influence on child and adolescent psychopathology. Historically, clinically-oriented research on this topic has focused on the impacts of parental divorce and domestic violence as primary interparental relationship influences on child outcomes, to the relative neglect of dimensional or qualitative features of the couple/interparental relationship for youth (child and adolescent) psychopathology. Recent research has highlighted that children are affected by attributes of interparental conflict, specifically how parents express and manage conflicts in their relationship, across a continuum of expressed severity and negativity – ranging from silence to violence. Further, new evidence highlights that children’s emotional, behavioral, social, academic outcomes and future interpersonal relationships are adversely affected by conflict between parents/carers whether adults are living together or not (i.e. married or separated), or where children are or are not genetically related to their rearing parents (e.g. adoption). We review evidence and present an integrated theoretical model, highlighting how children are affected by interparental conflict and what this evidence base means for effective intervention and prevention program development, as well as the development of possible cost-benefit models. Additionally, we review policy implications of this research and highlight some very recent examples of UK-based policy focusing on addressing the interparental relationship and its impact on youth psychopathology

Pregnancy, time to pregnancy and obstetric outcomes among female childhood cancer survivors: results of the DCOG LATER-VEVO study

Purpose: To evaluate pregnancy rates, time to pregnancy (TTP) and obstetric outcomes in female childhood cancer survivors (CCSs) and to identify specific diagnosis- and treatment-related factors associated with these outcomes. Methods: The study is part of the DCOG LATER-VEVO study, a nationwide multicenter cohort study evaluating fertility among long-term Dutch female CCSs. Data were collected by questionnaire. The current study included 1095 CCSs and 812 controls, consisting of sisters of CCSs and a random sample of women from the general population. Results: Among the subgroup of women who ever had the desire to become pregnant, the chance of becoming pregnant was significantly lower for CCSs than controls (OR 0.5, 95%CI 0.4–0.8). Moreover, TTP was 1.1 times longer for CCSs compared to controls (p = 0.09) and was significantly longer in survivors of CNS and renal tumours. Overall, no differences were found between CCSs and controls regarding the probability of ever having had a miscarriage, still birth, or induced abortion. However, CCSs had a significantly increased risk of delivering preterm (OR 2.2, 95%CI 1.3–3.7) and delivering via caesarean section (OR 1.8, 95%CI 1.2–2.6). Treatment with lower abdominal/pelvic radiotherapy was strongly associated with several adverse obstetric outcomes. Conclusion: CCSs are less likely to have ever been pregnant. Among those who do become pregnant, certain subgroups of CCSs are at increased risk of longer TTP. Moreover, as pregnant CCSs, especially those treated with lower abdominal/pelvic radiotherapy, are more likely to develop various adverse obstetric outcomes, appropriate obstetric care is highly advocated

Lung function, exercise tolerance, and physical growth of children with congenital lung malformations at 8 years of age

Objective: To improve counseling on congenital lung malformations (CLM) by describing long-term outcomes of children either operated on or managed by observation. Study design: We analyzed lung function (spirometry), exercise tolerance (Bruce treadmill), and physical growth of 8-year-old children with CLM who participated in our longitudinal prospective follow-up program. The data are shown as median standard deviation scores (SDS) with IQR, or estimated marginal means (95% CI) on the basis of general linear models. Results: Twenty-nine (48%) of the 61 children had required surgery at a median age of 108 (IQR: 8-828) days, and 32 (52%) were managed by observation. In the surgery group, all lung function measurements (except for forced vital capacity [FVC]) were significantly below 0 SDS, with median FEV1 −1.07 (IQR: −1.70 to −0.56), FEV1/FVC −1.49 (−2.62 to −0.33), and FEF25%-75% −1.95 (−2.57 to −0.63) (all P < 0.001). Children in the observation group had normal FEV1 and FVC, whereas FEV1/FVC (−0.81 (−1.65 to −0.14)) and FEF25%-75% (−1.14 (−1.71 to −0.22)) were significantly below 0 SDS (both P < 0.001). Mean exercise tolerance was significantly below 0 SDS in both groups (observation: −0.85 (95% CI: −1.30 to −0.41); surgery: −1.25 (−1.69 to −0.80)); eight (28%) children in the observation group and ten (40%) in the surgery group scored <−1 SDS. Physical growth was normal in both groups. Conclusion: Children with CLM may be at risk for reduced lung function and exercise tolerance, especially those who required surgery. As little pulmonary morbidity was found in children with asymptomatic CLM, this study supports a watchful waiting approach in this group

Ultrasound markers for prediction of complex gastroschisis and adverse outcome: longitudinal prospective nationwide cohort study

Objectives: To identify antenatal ultrasound markers that can differentiate between simple and complex gastroschisis and assess their predictive value. Methods: This was a prospective nationwide study of pregnancies with isolated fetal gastroschisis that underwent serial longitudinal ultrasound examination at regular specified intervals between 20 and 37 weeks' gestation. The primary outcome was simple or complex (i.e. involving bowel atresia, volvulus, perforation or necrosis) gastroschisis at birth. Fetal biometry (abdominal circumference and estimated fetal weight), the occurrence of polyhydramnios, intra- and extra-abdominal bowel diameters and the pulsatility index (PI) of the superior mesenteric artery (SMA) were assessed. Linear mixed modeling was used to compare the individual trajectories of cases with simple and those with complex gastroschisis, and logistic regression analysis was used to estimate the strength of association between the ultrasound parameters and outcome. Results: Of 104 pregnancies with isolated fetal gastroschisis included, four ended in intrauterine death. Eighty-one (81%) liveborn infants with simple and 19 (19%) with complex gastroschisis were included in the analysis. We found no relationship between fetal biometric variables and complex gastroschisis. The SMA-PI was significantly lower in fetuses with gastroschisis than in healthy controls, but did not differentiate between simple and complex gastroschisis. Both intra- and extra-abdominal bowel diameters were larger in cases with complex, compared to those with simple, gastroschisis (P < 0.001 and P < 0.005, respectively). The presence of intra-abdominal bowel diameter ≥ 97.7th percentile on at least three occasions, not necessarily on successive examinations, was associated with an increased risk of the fetus having complex gastroschisis (relative risk, 1.56 (95% CI, 1.02–2.10); P = 0.006; positive predictive value, 50.0%; negative predictive value, 81.4%). Conclusions: This large prospective longitudinal study found that intra-abdominal bowel dilatation when present repeatedly during fetal development can differentiate between simple and complex gastroschisis; however, the positive predictive value is low, and therefore the clinical usefulness of this marker is limited

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

The LHCb upgrade I

The LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software