The observation of early childhood physical aggression: A psychometric study of the system for coding early physical aggression (SCEPA)

We investigated the reliability and (convergent and discriminant) validity of an observational measure of physical aggression in toddlers and preschoolers, originally developed by Keenan and Shaw [1994]. The observation instrument is based on a developmental definition of aggression. Physical aggression was observed twice in a laboratory setting, the first time when children were 1-3 years old, and again 1 year later. Observed physical aggression was significantly related to concurrent mother-rated physical aggression for 2- to 4-year-olds, but not to maternal ratings of nonaggressive externalizing problems, indicating the measure's discriminant validity. However, we did not find significant 1-year stability of observed physical aggression in any of the age groups, whereas mother-rated physical aggression was significantly stable for all ages. The observational measure shows promise, but may have assessed state rather than trait aggression in our studv. © 2008 Wiley-Liss, Inc

Infections after auxiliary partial liver transplantation. Experiences in the first ten patients

Summary In ten auxiliary partial liver transplant recipients selective bowel decontamination (SBD) was used to reduce infections due to gram-negative microorganisms and fungi. During SBD no gram-negative infections occurred. Candida peritonitis was observed in one patient. After discontinuation of SBD serious infections of gram-negative origin did occur and three fungal infections were seen. SBD seems to have a favourable effect in reducing infections by gram-negative microorganisms and fungi. Most striking was the number of enterococcal infections that occurred. Five out of ten patients developed enterococcal infections which in two cases contributed to a fatal outcome. These infections occurred after increase of the number of enterococci in faeces and concomitant positive cultures of bile, ascites or wound drains. This increase could be due to the use of SBD. Also, the kind of biliary anastomosis may play an important role in the relatively high incidence of enterococcal infections. In the postoperative period, recurrence of hepatitis B infection in the liver graft was observed in all patients with cirrhosis due to this virus. Problems caused by other viral infections or protozoal infections remained limited in these ten patients. Zusammenfassung Bei Patienten, bei denen eine auxiliäre, partielle Lebertransplantation durchgeführt wurde, wurde die selektive Darmdekontamination (SBD) eingesetzt, um Infektionen durch gramnegative Mikroorganismen und Pilze zu vermindern. Während SBD traten keine Infektionen durch gramnegative Bakterien auf. Bei einem Patienten wurde eine Candida-Peritonitis beobachtet. Nach Beendigung der SBD kam es zu schweren Infektionen durch gramnegative Bakterien, außerdem zu drei Pilzinfektionen. SBD hat offensichtlich einen günstigen Einfluß im Hinblick auf eine Verminderung von Infektionen durch gramnegative Erreger und Pilze. Bemerkenswert hoch war die Zahl der aufgetretenen Enterokokkeninfektionen. Bei fünf der zehn Patienten traten Enterokokkeninfektionen auf, die in zwei Fällen den letalen Ausgang mitbestimmten. Diesen Infektionen gingen ein Anstieg der Enterokokkenzahlen im Stuhl und zugleich positive Kulturen in Galle, Aszites und Wunddrainagen voraus. Es ist möglich, daß die SBD die Zunahme von Enterokokkeninfektionen begünstigte. Auch die Art der Gallengangsanastomose kann hierzu wesentlich beigetragen haben. Bei allen Patienten, bei denen die Zirrhose durch Hepatitis B Virus verursacht war, kam es postoperativ zu einem Rezidiv durch dieses Virus im Lebertransplantat. Probleme durch andere virale oder Protozoeninfektionen hielten sich bei diesen zehn Patienten in Grenzen

Long-term consequences of juvenile vulvar lichen sclerosus:A cohort study of adults with a histologically confirmed diagnosis in childhood or adolescence

INTRODUCTION: Vulvar lichen sclerosus (VLS) occurs in at least one in 900 girls. There is limited knowledge as to what extent the disease persists in adulthood and what the repercussions in adulthood may be. The aim of this study is to evaluate the long-term consequences of VLS diagnosed in childhood or adolescence. MATERIAL AND METHODS: The population of females histologically diagnosed with VLS in childhood or adolescence in the Netherlands between 1991 and 2015 was identified through the national pathology database. Histological specimens were retrieved and re-evaluated. Potential participants for whom the diagnosis was reconfirmed and who are now adults, were then traced and surveyed. Descriptive statistics were calculated and compared with the literature. Main outcome measures are the demographics of the cohort, their scores on standardized quality of life (QoL) and sexuality questionnaires and answers to additional questions regarding patients' experience with the disease. The questionnaires used were the Dermatology Life Quality Index (DLQI), the Skindex-29, the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). Secondary outcome measures include obstetric history and histological features found in the original tissue specimens. RESULTS: A total of 81 women participated, median age 29.0 years, median follow-up from childhood diagnosis 19.5 years. Both QoL and sexuality were somewhat affected in 51.9% of cases. Less than half (45%) reported having regular check-ups. Forty-five (56%) reported symptoms within the past year; of those with symptoms, 14 (31%) were not under surveillance. Cesarean section rate (14.5%) was comparable to the general population, and there were more high-grade obstetric anal sphincter injuries with vaginal deliveries than expected. Sixteen respondents (20%) were not aware of the childhood diagnosis prior to this study. CONCLUSIONS: Symptoms due to VLS are reported by most adults diagnosed as juveniles. QoL and sexuality are affected and correlate to recent symptoms. VLS as a juvenile does not preclude a vaginal delivery. Women diagnosed with VLS in childhood or adolescence are often lost to follow-up.</p

Discontinuation of anti-PD-1 monotherapy in advanced melanoma:Outcomes of daily clinical practice

There is no consensus on the optimal treatment duration of anti-PD-1 for advanced melanoma. The aim of our study was to gain insight into the outcomes of anti-PD-1 discontinuation, the association of treatment duration with progression and anti-PD-1 re-treatment in relapsing patients. Analyses were performed on advanced melanoma patients in the Netherlands who discontinued first-line anti-PD-1 monotherapy in the absence of progressive disease (n = 324). Survival was estimated after anti-PD-1 discontinuation and with a Cox model the association of treatment duration with progression was assessed. At the time of anti-PD-1 discontinuation, 90 (28%) patients had a complete response (CR), 190 (59%) a partial response (PR) and 44 (14%) stable disease (SD). Median treatment duration for patients with CR, PR and SD was 11.2, 11.5 and 7.2 months, respectively. The 24-month progression-free survival and overall survival probabilities for patients with a CR, PR and SD were, respectively, 64% and 88%, 53% and 82%, 31% and 64%. Survival outcomes of patients with a PR and CR were similar when anti-PD-1 discontinuation was not due to adverse events. Having a PR at anti-PD-1 discontinuation and longer time to first response were associated with progression [hazard ratio (HR) = 1.81 (95% confidence interval, CI = 1.11-2.97) and HR = 1.10 (95% CI = 1.02-1.19; per month increase)]. In 17 of the 27 anti-PD-1 re-treated patients (63%), a response was observed. Advanced melanoma patients can have durable remissions after (elective) anti-PD-1 discontinuation

Early diagnosis and follow-up of acute schistosomiasis in a cluster of infected Belgian travellers by detection of antibodies and circulating anodic antigen (CAA): a diagnostic evaluation study

Background: In order to evaluate the diagnostic value of schistosome circulating anodic antigen (CAA) detection, serum and urine CAA-levels were determined in a single cluster of 34 Belgian tourists at three timepoints within a period of 14 weeks following proven Schistosoma exposure in South Africa and compared with two in-house antibody assays. Methods: Samples were collected 4-5 and 7-8 weeks post-exposure and subsequently 5-6 weeks following praziquantel treatment. Schistosoma antibodies were detected by an adult worm antigen-immunofluorescence assay (AWA-IFA) and a soluble egg antigen-enzyme-linked immunosorbent assay (SEA-ELISA), while CAA concentrations were determined by the Up-Converting reporter Particle labelled Lateral Flow (UCP-LF) test. Results: Antibodies were detected in 25/34 (73%) travellers pre-treatment and in 27/34 (79%) post-treatment, with the AWA-IFA showing better performance than the SEA-ELISA. Pre-treatment, CAA was detected in 13/ 34 (38%) and 33/34 (97%) of the travellers in urine and serum, respectively. Post-treatment, all except one traveller became serum CAA negative. This in contrast to the detected antibodies, as well as the previously reported diagnostic results of this cluster. Conclusions: The UCP-LF CAA serum assay has been demonstrated as the most sensitive method for the diagnosis of early Schistosoma infections and post-treatment monitoring in travellers.Medical Microbiolog

Safety and Efficacy of Checkpoint Inhibition in Patients With Melanoma and Preexisting Autoimmune Disease:A Cohort Study

BACKGROUND: Because immune checkpoint inhibition (ICI) can cause immune-related adverse events (irAEs) mimicking immunologic diseases, patients with preexisting autoimmune disease (AID) have been excluded from clinical trials. OBJECTIVE: To evaluate the safety and efficacy of ICI in patients with advanced melanoma with and without AID. DESIGN: Nationwide cohort study. SETTING: The Netherlands. PATIENTS: 4367 patients with advanced melanoma enrolled in the Dutch Melanoma Treatment Registry (DMTR) between July 2013 and July 2018 and followed through February 2019. MEASUREMENTS: Patient, clinical, and treatment characteristics; irAEs of grade 3 or higher; treatment response; and survival. RESULTS: A total of 415 patients (9.5%) had AID, categorized as rheumatologic AID (n = 227), endocrine AID (n = 143), inflammatory bowel disease (IBD) (n = 55), or "other" (n = 8). Of these, 228 patients (55%) were treated with ICI (vs. 2546 [58%] without AID); 87 were treated with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), 187 with anti-programmed cell death 1 (PD-1), and 34 with the combination. The incidences of irAEs of grade 3 or higher in patients with AID were 30% (95% CI, 21% to 41%) with anti-CTLA-4, 17% (CI, 12% to 23%) with anti-PD-1, and 44% (CI, 27% to 62%) with combination therapy; for patients without AID, the incidences were 30% (CI, 27% to 33%) (n = 916), 13% (CI, 12% to 15%) (n = 1540), and 48% (CI, 43% to 53%) (n = 388), respectively. Patients with AID more often discontinued anti-PD-1 treatment because of toxicity than patients without AID (17% [CI, 12% to 23%] vs. 9% [CI, 8% to 11%]). Patients with IBD were more prone to anti-PD-1-induced colitis (6 / 31 = 19% [CI, 7% to 37%]) than patients with other AIDs (3% [CI, 0% to 6%]) and patients without AID (2% [CI, 2% to 3%]). The objective response rate was similar in patients with versus without AID who were treated with anti-CTLA-4 (10% [CI, 5% to 19%] vs. 16% [CI, 14% to 19%]), anti-PD-1 (40% [CI, 33% to 47%] vs. 44% [CI, 41% to 46%]), or the combination (39% [CI, 20% to 59%] vs. 43% [CI, 38% to 49%]). Survival did not differ between patients with and those without AID (median, 13 months [CI, 10 to 16 months] vs. 14 months [CI, 13 to 15 months]). LIMITATION: Information was limited on AID severity and immunosuppressive treatment. CONCLUSION: Response to ICI with anti-CTLA-4, anti-PD-1, or their combination for advanced melanoma and overall incidence of any irAEs of grade 3 or higher were similar in patients with and without preexisting AID. However, severe colitis and toxicity requiring early discontinuation of treatment occurred more frequently among patients with preexisting IBD, warranting close follow-up. PRIMARY FUNDING SOURCE: The Netherlands Organization for Health Research and Development

Survival outcomes of patients with advanced mucosal melanoma diagnosed from 2013 to 2017 in the Netherlands - A nationwide population-based study

Background: Mucosal melanoma (MM) is rare and has a poor prognosis. Since 2011, new effective treatments are available for advanced melanoma. It is unclear whether patients with mucosal melanoma equally benefit from these new treatments compared with patients with cutaneous melanoma (CM). Methods: Patients with advanced MM and CM diagnosed between 2013 and 2017 were included from a nationwide population-based registry – the Dutch Melanoma Treatment Registry. Overall survival (OS) was estimated with the Kaplan-Meier method (also for a propensity score-matched cohort). A Cox model was used to analyse the association of possible prognostic factors with OS. Results: In total, 120 patients with MM and 2960 patients with CM were included. Median OS was 8.7 months and 14.5 months, respectively. Patients with MM were older (median age 70 versus 65 years) and more often female (60% versus 41%), compared with CM. In total, 77% and 2% of the MM patients were treated with first-line immunotherapy and targeted therapy, respectively, compared with 49% and 33% of the CM patients. In contrast to CM, OS for MM did not improve for patients diagnosed in 2015–2017, compared with 2013–2014. ECOG performance score ≥1 (HR = 1.99 [1.26–3.15; p = 0.003]) and elevated LDH level (HR = 1.63 [0.96–2.76]; p = 0.069) in MM were associated with worse survival. Conclusions: Within the era of immune and targeted therapies, prognosis for patients with advanced MM has not improved as much as for CM. Collaboration is necessary to enlarge sample size for research to improve immunotherapeutic strategies and identify targetable mutations

Early parenting intervention: Family risk and first-time parenting related to intervention effectiveness

The effects of cumulative risk and parity on the effectiveness of a home based parenting intervention were tested in a randomized controlled trial with 237 families with 1- to 3-year-old children screened for high levels of externalizing behavior. The intervention was aimed at enhancing positive parenting and decreasing externalizing behaviors. The results showed that cumulative risk was not associated with either change in child externalizing behaviors or change in positive parenting. When intervention effectiveness was compared for primiparas (i.e., first-time mothers) versus multiparas (i.e., mothers with more than one child), we found that intervention mothers of first-born children displayed an increase in their use of positive discipline strategies as compared to first-time mothers in the control group, whereas a similar effect for multiparas was absent. Among multiparas we found an intervention effect on sensitivity, with control group mothers showing an increase in sensitivity, whereas the intervention group showed a constant level of sensitivity over time. These results suggest that parity may be a moderator of intervention effectiveness. Implications for investigating moderators of intervention effectiveness are discussed. © 2007 Springer Science+Business Media, LLC

Predicting growth curves of early childhood externalizing problems: Differential susceptibility of children with difficult temperament

Using an accelerated longitudinal design, the development of externalizing problems from age 2 to 5 years was investigated in relation to maternal psychopathology, maternal parenting, gender, child temperament, and the presence of siblings. The sample consisted of 150 children selected at age 2-3 years for having high levels of externalizing problems. Parenting was measured using observational methods, and maternal reports were used for the other variables. Overall, mean levels of externalizing problems decreased over time, and higher initial levels (intercept) were related to a stronger decrease (negative slope) in externalizing problems. Results showed that higher levels of maternal psychopathology were related to less decrease in early childhood externalizing problems. Parental sensitive behavior predicted a stronger decrease in externalizing problems, but only for children with difficult temperaments. A stronger decrease of externalizing problems in children with older siblings also pertained only to children with difficult temperaments. Thus, temperamentally difficult children appear to be more susceptible to environmental influences on the development of externalizing behaviors. Our results indicate that the role of siblings in early childhood externalizing problems deserves more research attention, and that intervention efforts need to take into account temperamental differences in children's susceptibility to environmental influences. © 2009 Springer Science+Business Media, LLC