Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Individual, family and offence characteristics of high risk childhood offenders: comparing non-offending, one-time offending and re-offending Dutch-Moroccan migrant children in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Childhood offenders are at an increased risk for developing mental health, social and educational problems later in life. An early onset of offending is a strong predictor for future persistent offending. Childhood offenders from ethnic minority groups are a vulnerable at-risk group. However, up until now, no studies have focused on them.</p> <p>Aims</p> <p>To investigate which risk factors are associated with (re-)offending of childhood offenders from an ethnic minority.</p> <p>Method</p> <p>Dutch-Moroccan boys, who were registered by the police in the year 2006-2007, and their parents as well as a control group (n = 40) were interviewed regarding their individual and family characteristics. Two years later a follow-up analysis of police data was conducted to identify one-time offenders (n = 65) and re-offenders (n = 35).</p> <p>Results</p> <p>All groups, including the controls, showed substantial problems. Single parenthood (OR 6.0) and financial problems (OR 3.9) distinguished one-time offenders from controls. Reading problems (OR 3.8), having an older brother (OR 5.5) and a parent having Dutch friends (OR 4.3) distinguished re-offenders from one-time offenders. First offence characteristics were not predictive for re-offending. The control group reported high levels of emotional problems (33.3%). Parents reported not needing help for their children but half of the re-offender's families were known to the Child Welfare Agency, mostly in a juridical framework.</p> <p>Conclusion</p> <p>The Moroccan subgroup of childhood offenders has substantial problems that might hamper healthy development. Interventions should focus on reaching these families tailored to their needs and expectations using a multi-system approach.</p

Pathogenesis, diagnosis and management of pneumorrhachis

Pneumorrhachis (PR), the presence of intraspinal air, is an exceptional but eminent radiographic finding, accompanied by different aetiologies and possible pathways of air entry into the spinal canal. By reviewing the literature and analysing a personal case of traumatic cervical PR after head injury, we present current data regarding the pathoanatomy, clinical and radiological presentation, diagnosis and differential diagnosis and treatment modalities of patients with PR and associated pathologies to highlight this uncommon phenomenon and outline aetiology-based guidelines for the practical management of PR. Air within the spinal canal can be divided into primary and secondary PR, descriptively classified into extra- or intradural PR and aetiologically subsumed into iatrogenic, traumatic and nontraumatic PR. Intraspinal air is usually found isolated not only in the cervical, thoracic and, less frequently, the lumbosacral regions but can also be located in the entire spinal canal. PR is almost exceptional associated with further air distributions in the body. The pathogenesis and aetiologies of PR are multifold and can be a diagnostic challenge. The diagnostic procedure should include spinal CT, the imaging tool of choice. PR has to be differentiated from free intraspinal gas collections and the coexistence of air and gas within the spinal canal has to be considered differential diagnostically. PR usually represents an asymptomatic epiphenomenon but can also be symptomatic by itself as well as by its underlying pathology. The latter, although often severe, might be concealed and has to be examined carefully to enable adequate patient treatment. The management of PR has to be individualized and frequently requires a multidisciplinary regime

Single domain antibodies: promising experimental and therapeutic tools in infection and immunity

Antibodies are important tools for experimental research and medical applications. Most antibodies are composed of two heavy and two light chains. Both chains contribute to the antigen-binding site which is usually flat or concave. In addition to these conventional antibodies, llamas, other camelids, and sharks also produce antibodies composed only of heavy chains. The antigen-binding site of these unusual heavy chain antibodies (hcAbs) is formed only by a single domain, designated VHH in camelid hcAbs and VNAR in shark hcAbs. VHH and VNAR are easily produced as recombinant proteins, designated single domain antibodies (sdAbs) or nanobodies. The CDR3 region of these sdAbs possesses the extraordinary capacity to form long fingerlike extensions that can extend into cavities on antigens, e.g., the active site crevice of enzymes. Other advantageous features of nanobodies include their small size, high solubility, thermal stability, refolding capacity, and good tissue penetration in vivo. Here we review the results of several recent proof-of-principle studies that open the exciting perspective of using sdAbs for modulating immune functions and for targeting toxins and microbes

Bijwerkingen na vaccinatie tegen humaan papillomavirus : Resultaten van de 2010 campagne in Nederland

In 2010 werden er minder bijwerkingen gemeld na vaccinatie tegen HPV dan in 2009. Ook zijn er in 2010, net als in 2009, geen onverwachte of volgens de criteria ernstige bijwerkingen (Serious Adverse Events) gemeld die door het vaccin zijn veroorzaakt. In 2010 zijn meisjes die geboren zijn in 1997 gevaccineerd tegen HPV. Ook zijn meisjes geboren in 1993-1996, die niet (volledig) waren gevaccineerd in 2009, nogmaals uitgenodigd. Tijdens deze campagne is onderzoek gedaan naar de mogelijke bijwerkingen van het vaccin. De mogelijke bijwerkingen die optraden op de vaccinatielocaties werden geregistreerd. Verder werden spontane meldingen in het reguliere systeem voor meldingen van mogelijke bijwerkingen verzameld en is er een onderzoek gedaan naar de verdraagbaarheid van het vaccin. Verschijnselen die kort na de vaccinatie optraden kwamen 7,7 keer voor per 10.000 toegediende doses. Hierbij kwam (bijna)flauwvallen het meest voor. Spontane meldingen van mogelijke bijwerkingen werden in 5,4 keer per 10.000 toegediende doses gemeld. De meldgraad van zowel verschijnselen die kort na de vaccinatie optraden als van spontane meldingen was lager dan tijdens de campagne in 2009. Bij de spontane meldingen ging het in 23% om een heftige gebeurtenis zoals flauwvallen, migraine en stuipen. Van alle meldingen van mogelijke bijwerkingen van het vaccin werd in 67,4% een oorzakelijk verband met de vaccinatie vastgesteld. In de studie naar de verdraagbaarheid is door 2308 meisjes (65%) tenminste één vragenlijst teruggestuurd. Een reactie rond de prikplaats werd gerapporteerd door 82,4% van de meisjes, voornamelijk pijn en verminderd gebruik van de arm. Hiervan classificeerde 14,8% van de meisjes de reactie als heftig. Algemene verschijnselen waaronder spierpijn, moeheid of hoofdpijn werd gerapporteerd door 78,7% van de meisjes. Het percentage gerapporteerde lokale reacties en algemene bijwerkingen was lager dan in 2009. Het voorkomen van sommige mogelijke bijwerkingen steeg met de leeftijd en was meestal lager na de tweede en derde dosis dan na de eerste dosis. Zeventien meisjes (0,4%) hebben de huisarts bezocht in de week na de vaccinatie, maar niemand heeft het ziekenhuis bezocht. De resultaten worden gebruikt om het publiek en de professionals te informeren over het veiligheidsprofiel van het HPV vaccin in de periode na introductie van massa vaccinatie.In 2010, less AEs were reported after vaccination against HPV compared with 2009. Furthermore, as in 2009, no unexpected or Serious Adverse Events were reported after vaccination against HPV that were considered causally related to the vaccination. During 2010, girls born in 1997 were vaccinated against HPV. Furthermore, girls born in 1993-1996, who were not or not fully vaccinated in 2009, were invited again. Intensified surveillance of AEs was performed. Immediate AEs on mass vaccination locations were registered. Spontaneous reports through the enhanced passive surveillance system were collected and a study on the tolerability of the vaccine was performed. Immediate AEs on locations of mass vaccination occurred in 7.7/10,000 administered doses. Presyncope or syncope was most frequently reported. The reporting rate of spontaneous reports was 5.4/10,000 administered doses overall. The reporting rates of both immediate AEs and spontaneous reports were lower compared with the 2009 campaign. No differences in reporting rates of spontaneous reports were found between the girls born in 1997 (regular NIP) and girls born in 1993-1996 (catch-up campaign). Twenty-three percent of the reports concerned a major AE, including fainting, migraine and convulsions. Of all reports, 67.4% was assessed to be causally related to the vaccination. In the study on tolerability, at least one questionnaire was returned by 2308 girls (65%). Local reactions were reported in 82.4%, mostly pain at the injection site and/or reduced use of the arm. Of all local reactions, 14.8% was classified as pronounced. In 78.7% any systemic AE was reported, in which myalgia was reported the most often. The reported proportions of local reactions and systemic AEs were lower than in the 2009 campaign. Some local reactions and systemic AEs increasing with age, and most incidences were lower after the second and third dose than after the first dose. The GP was visited by 17 girls (0.4%) within one week after the vaccination, but none visited the hospital. Results are used to inform public and professionals on the safety profile of the HPV vaccine observed in the period post introduction of mass vaccination.VW

Early Lactate-Guided Therapy in Intensive Care Unit Patients A Multicenter, Open-Label, Randomized Controlled Trial

Rationale: It is unknown whether lactate monitoring aimed to decrease levels during initial treatment in critically ill patients improves outcome. Objectives: To assess the effect of lactate monitoring and resuscitation directed at decreasing lactate levels in intensive care unit (ICU) patients admitted with a lactate level of greater than or equal to 3.0 mEq/L. Methods: Patients were randomly allocated to two groups. In the lactate group, treatment was guided by lactate levels with the objective to decrease lactate by 20% or more per 2 hours for the initial 8 hours of ICU stay. In the control group, the treatment team had no knowledge of lactate levels (except for the admission value) during this period. The primary outcome measure was hospital mortality. Measurements and Main Results: The lactate group received more fluids and vasodilators. However, there were no significant differences in lactate levels between the groups. In the intention-to-treat population (348 patients), hospital mortality in the control group was 43.5% (77/177) compared with 33.9% (58/171) in the lactate group (P = 0.067). When adjusted for predefined risk factors, hospital mortality was lower in the lactate group (hazard ratio, 0.61; 95% confidence interval, 0.43-0.87; P = 0.006). In the lactate group, Sequential Organ Failure Assessment scores were lower between 9 and 72 hours, inotropes could be stopped earlier, and patients could be weaned from mechanical ventilation and discharged from the ICU earlier. Conclusions: In patients with hyperlactatemia on ICU admission, lactate-guided therapy significantly reduced hospital mortality when adjusting for predefined risk factors. As this was consistent with important secondary endpoints, this study suggests that initial lactate monitoring has clinical benefit

Humaan papillomavirus vaccinatiecampagne voor 13-16-jarige meisjes in 2009 in Nederland : Resultaten van de postmarketing veiligheidsbewaking

In 2009 zijn over de humaan papillomavirus (HPV) vaccinatie inhaalcampagne geen ernstige verschijnselen na vaccinatie gemeld die door het vaccin zijn veroorzaakt. Het vaccin kan daardoor op de korte termijn als veilig worden beoordeeld. Dit blijkt uit onderzoek naar de mogelijke bijwerkingen van het HPV vaccin van dat jaar. De meisjes hebben veelvuldig verschijnselen als pijn in de arm en spierpijn gemeld, maar deze bleken over het algemeen mild en kortdurend. In Nederland is in 2009 de vaccinatie tegen het HPV geïntroduceerd, het virus dat baarmoederhalskanker kan veroorzaken. In 2009 zijn de 13- tot en met 16-jarige meisjes ingeënt. Vanaf 2010 worden jaarlijks 12-jarige meisjes gevaccineerd. Het schema bestaat uit drie prikken, die de meisjes op grootschalige locaties krijgen toegediend. In 2009 zijn in totaal 558.226 doses van dit vaccin toegediend. In het onderzoek zijn de mogelijke bijwerkingen geregistreerd die op de vaccinatielocatie optraden. Daarnaast zijn de zogeheten spontane meldingen voor dit vaccin verzameld vanuit het reguliere systeem voor meldingen van mogelijke bijwerkingen van vaccinaties. Tot slot is onderzocht hoe de meisjes het vaccin verdroegen door hen een vragenlijst over mogelijke bijwerkingen te laten invullen. Bij 27 per 10.000 toegediende doses zijn kort na de vaccinatie verschijnselen opgetreden. (Bijna) Flauwvallen kwam hierbij het vaakst voor (62,1%). Spontane meldingen zijn in 11,6 keer per 10.000 toegediende doses gemeld. In 13,4% ging het om een heftige gebeurtenis, zoals flauwvallen, migraine en stuipen, als mogelijke bijwerking van het vaccin. Hiervan werd bij 75,6% een oorzakelijk verband met de vaccinatie vastgesteld. In het onderzoek naar verdraagbaarheid rapporteerde 85% van de meisjes over de drie prikken gemiddeld een reactie rond de prikplaats, zoals pijn of verminderd gebruik van de arm. Hiervan classificeerde gemiddeld 16% van de melders de reactie als heftig. Verschijnselen als spierpijn, moeheid of hoofdpijn, kwamen voor bij gemiddeld 83% van de deelnemers.In 2009, no serious adverse events were reported after vaccination against human papillomavirus (HPV) that were considered causally related to the vaccination. Research on adverse events in this year implies that the HPV vaccination catch-up campaign has been a safe intervention on the short-term. Girls experienced frequently pain at the injection site and myalgia, but mostly mild and all were transient. Vaccination against HPV, the virus that can cause cervical cancer, was newly introduced in 2009 in the Netherlands. In 2009, girls born in 1993 to 1996 were invited for vaccination. From 2010, yearly 12-year-old girls were invited. Vaccination includes three doses, administered on mass vaccination locations. In total 558,226 doses were administered in 2009. In intensified safety surveillance, all immediate occurring adverse events on locations of mass vaccination were registered. Besides that, spontaneous reports were collected through the enhanced passive surveillance system. Furthermore, a questionnaire study was performed on the tolerability of the vaccine. The reporting rate of immediate occurring adverse events on locations of mass vaccination was 27.1/10,000 administered doses. Most frequently reported was presyncope and syncope (62.1%). The reporting rate of spontaneous reports was 11.6/10,000 administered doses. In 13.4% it concerned major adverse events, for instance fainting, migraine, and convulsions. Of these major adverse events, 75.6% were assessed causally related to the vaccination. In the survey on tolerability, 85% of the girls, on average after the three successive doses, reported local reactions, such as pain at the injection site or reduced use of the arm. Of these reactions 16% were classified as pronounced. Systemic adverse events, for instance myalgia, fatigue, or headache, were experienced by 83% of the girls on average.VW