Torn between two lovers: Lokaal volksgezondheidsbeleid tussen politiek en wetenschap

Alcoholverslaving en angststoornissen zouden in Nederland topprioriteit zijn, als we ons zouden baseren op de wetenschappelijke gegevens over de ziektelast in de bevolking. Vele honderdduizenden mensen lijden aan deze ziekten. Dat is meestal langdurig en tast de kwaliteit van leven ernstig aan. Angststoornissen en alcoholafhankelijkheid staan dan ook in de top vijf van ziekten die de meeste ellende in Nederland veroorzaken (gemeten in DALY’s; dat is een combinatie van het aantal mensen dat aan een ziekte lijdt, hoe lang ze eraan lijden, hoe erg ze er last van hebben, en hoeveel mensen er uiteindelijk aan overlijden). Top vijf ziektelast in de bevolking (DALY’s) 1. coronaire hartziekten 2. angststoornissen 3. beroerte 4. COPD 5. alcoholafhankelijkheidInaugurele rede in verkorte vorm uitgesproken ter gelegenheid van het aanvaarden van het ambt van hoogleraar Volksgezondheidsbeleid aan het Erasmus MC te Rotterdam op 4 april 200

Personality traits and health-related quality of life in patients with mood and anxiety disorders

Background: Health-related quality of life (HRQL) is an accepted outcome measure in patients with mood and anxiety disorders. Yet, surprisingly little attention has been paid to the determinants. In this paper we test the hypothesis that it is associated with personality traits while controlling for mental disorders. Methods: A large sample of outpatients (n=640) with mood and anxiety disorders was studied. The empirically supported five factor model of normal personality traits was assessed using the NEO-FFI and includes: neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness. Mental disorders were assessed with the CIDI, and HRQL with the SF-36. Results: Regression analyses revealed that the NEO-FFI scores, with the exception of conscientiousness, were significantly associated with SF-36 subscales and summary scores, independently from the mental disorders. The percentage of explained variance due to the personality traits was highest for the subscales Vitality (10.0%), Mental Health (13.3%) and the Mental Health Summary Score (9.5%). Furthermore, specific personality traits were related to specific SF-36 subscales. Conclusions: A low HRQL of patients with mood or anxiety disorders is not only determined by the disease or the current health but is also shaped by personality traits that are relatively stable throughout an individual’s life time. Key words: Anxiety disorders, Depressive disorder, Health-related quality of life, Personalit

Childhood Characteristics of Adolescent Inpatients with Early-Onset and Adolescent-Onset Disruptive Behavior

Childhood characteristics are associated with life-course-persistent antisocial behavior in epidemiological studies in general population samples. The present study examines this association in an inpatient sample. The purpose is to identify easily measurable childhood characteristics that may guide choice of treatment for adolescent psychiatric inpatients with severe disruptive behavior. Patients (N = 203) were divided into two groups with either early-onset (EO) or adolescent-onset (AO) disruptive behavior, based on ages at which professional care was used for disruptive behavior, referral to special education, and criminal offences. Both groups differed on several childhood characteristics. No gender differences in these characteristics were found. Logistic regression analysis indicated that individuals with grade retention in primary school, childhood impulsive behavior, and a history of physical abuse, had the highest probability of being member of the EO group. These characteristics are reasonably easy to identify, likely apply to other clinical samples as well, and may help clinicians to target their treatment

Gene therapy for insulin dependent diabetes mellitus using IL-12p40- producing islet grafts

本研究では, インスリン依存型糖尿病 (IDDM) のモデル動物である NOD (nonobese diabetic) マウスに, 抑制性サイトカイン遺伝子をアデノウイルスベクターを用いて導入した膵ラ島移植を行ない自己免疫機序による拒絶反応の阻止を試みた。糖尿病発症NODマウスに, IL-12p40およびIL-10遺伝子をアデノウイルスベクターを用いて導入したNODマウス膵ラ島を移植した。IL-12p40産生膵ラ島移植では4週間以上の移植片の生着を認めたが, IL-10産生膵ラ島移植では移植片の長期の生着は得られなかった。組織学的検討では, IL-12p40産生膵ラ島移植では移植7日および60日後で正常膵ラ島構造を維持し軽度の単核球浸潤のみ認めたが, IL-10産生膵ラ島移植では移植7日後ですでに著明な単核球浸潤を伴い膵ラ島構造も破壊されていた。また, RT-PCR法での移植片局所のサイトカインの解析より, 移植片の長期生着のメカニズムとして, IL-12p40産生膵ラ島移植ではIFN-γ産生細胞の減少とTGF-β産生細胞の誘導により免疫寛容が成立した可能性が示唆された。以上より, IL-12p40産生膵ラ島移植では移植片の長期生着が可能であり, 今後のIDDM発症後の治療法として膵ラ島移植を用いた遺伝子療法の確立への第一歩と考えられた。 / Insulin dependent diabetes mellitus (IDDM) is considered to be a T cell-mediated autoimmune disease. It has been demonstrated that T helper (Th) 1 cells would play an important role in destruction of pancreatic β cells. It has recently been reported that systemic administration of IL-12 accelerates diabetes onset and that IL-12p40, an antagonist of IL-12, prevents diabetes development. From these results, we considered to establish gene therapy for IDDM with the islet grafts producing immunosuppressive cytokine such as IL-12p40. The syngeneic islet transplantation into diabetic nonobese diabetic (NOD) mice was performed using the recombinant adenoviral vector with inserted mlL-12p40 (Ad. IL-12p40) or mlL-10 (Ad. IL-10). Ad. IL-12p40-transfected islet grafts could significantly prevent autoimmune diabetes recurrence for over 4wk after transplantation (Tx). In contrast, Ad.IL-10 could not prolong syngeneic islet graft survival. Histological study revealed that IL-12p40-producing islet grafts remained normal in configulation with a small amount of lymphoid infiltration on day 60 after Tx, in contrast to IL-10-producing islet grafts with massive infiltration on day 7 after Tx. Reverse transcription (RT)-PCR analysis demonstrated that IL-12p40 gene transfer into islet grafts led to the significant decrease of IFN- 7 and the augmentation of TGF-β. These results suggest that IL-12 plays a key role in the autoimmune diabetes and that locally-produced IL-12p40 protects syngeneic islet grafts from recurrent autoimmune destruction of β cells by reducing IFN- γ and increasing TGF-β. This novel gene therapy would be clinically applicable to human IDDM

Influenza A(H1N1) Oseltamivir Resistant Viruses in the Netherlands During the Winter 2007/2008

Background: Antiviral susceptibility surveillance in the Netherlands was intensified after the first reports about the emergence of influenza A(H1N1) oseltamivir resistant viruses in Norway in January, 2008. Methods: Within the existing influenza surveillance an additional questionnaire study was performed to retrospectively assess possible risk factors and establish clinical outcome of all patients with influenza virus A(H1N1) positive specimens. To discriminate resistant and sensitive viruses, fifty percent inhibitory concentrations for the neuramidase inhibitors oseltamivir and zanamivir were determined in a neuraminidase inhibition assay. Mutations previously associated with resistance to neuramidase inhibitors and M2 blockers (amantadine and rimantadine) were searched for by nucleotide sequencing of neuraminidase and M2 genes respectively. Results: Among 171 patients infected with A(H1N1) viruses an overall prevalence of oseltamivi resistance of 27% (95% CI: 20-34%) was found. None of influenza A(H1N1) oseltamivir resistant viruses tested was resistant against amantadine or zanamivir. Patient characteristics, underlying conditions, influenza vaccination, symptoms, complications, and exposure to oseltamivir and other antivirals did not differ significantly between patients infected with resistant and sensitive A(H1N1) viruses. Conclusion: In 2007/2008 a large proportion of influenza A(H1N1) viruses resistant to oseltamivir was detected. There were no clinical differences between patients infected with resistant and sensitive A(H1N1) viruses. Continuous monitoring of the antiviral drug sensitivity profile of influenza viruses is justified, preferably using the existing sentinel surveillance, however, complemented with data from the more severe end of the clinical spectrum. In order to act timely on emergencies of public health importance we suggest setting up a surveillance system that can guarantee rapid access to the latter. (aut. ref.

Validity and Reliability of the Strengths and Difficulties Questionnaire in 5–6 Year Olds: Differences by Gender or by Parental Education?

Introduction: The Strengths and Difficulties Questionnaire (SDQ) is a relatively short instrument developed to detect psychosocial problems in children aged 3-16 years. It addresses four dimensions: emotional problems, conduct problems, hyperactivity/inattention problems, peer problems that count up to the total difficulties score, and a fifth dimension; prosocial behaviour. The validity and reliability of the SDQ has not been fully investigated in younger age groups. Therefore, this study assesses the validity and reliability of the parent and teacher versions of the SDQ in children aged 5-6 years in the total sample, and in subgroups according to child gender and parental education level. Methods: The SDQ was administered as part of the Dutch regularly provided preventive health check for children aged 5-6 years. Parents provided information on 4750 children and teachers on 4516 children. Results: Factor analyses of the parent and teacher SDQ confirmed that the original five scales were present (parent RMSEA = 0.05; teacher RMSEA = 0.07). Interrater correlations between parents and teachers were small (ICCs of 0.21-0.44) but comparable to what is generally found for psychosocial problem assessments in children. These correlations were larger for males than for females. Cronbach's alphas for the total difficulties score were 0.77 for the parent SDQ and 0.81 for the teacher SDQ. Four of the subscales on the parent SDQ and two of the subscales on the teacher SDQ had an alpha <0.70. Alphas were generally higher for male children and for low parental education level. Discussion: The validity and reliability of the total difficulties score of the parent and teacher SDQ are satisfactory in all groups by informant, child gender, and parental education level. Our results support the use of the SDQ in younger age groups. However, some subscales are less reliable and we recommend only to use the total difficulties score for screening purposes

Comparing Pandemic to Seasonal Influenza Mortality: Moderate Impact Overall but High Mortality in Young Children

Background: We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed - and thus an underestimation - whereas seasonal influenza mortality is often more inclusively estimated. For a valid comparison, our study used the same statistical methodology and data types to estimate pandemic and seasonal influenza mortality. Methods and Findings: We used data on all-cause mortality (1999-2010, 100% coverage, 16.5 million Dutch population) and influenza-like-illness (ILI) incidence (0.8% coverage). Data was aggregated by week and age category. Using generalized estimating equation regression models, we attributed mortality to influenza by associating mortality with ILI-incidence, while adjusting for annual shifts in association. We also adjusted for respiratory syncytial virus, hot/cold weather, other seasonal factors and autocorrelation. For the 2009 pandemic season, we estimated 612 (range 266-958) influenza-attributed deaths; for seasonal influen

Transmission of Novel Influenza A(H1N1) in Households with Post-Exposure Antiviral Prophylaxis

BACKGROUND: Despite impressive advances in our understanding of the biology of novel influenza A(H1N1) virus, little is as yet known about its transmission efficiency in close contact places such as households, schools, and workplaces. These are widely believed to be key in supporting propagating spread, and it is therefore of importance to assess the transmission levels of the virus in such settings. METHODOLOGY/PRINCIPAL FINDINGS: We estimate the transmissibility of novel influenza A(H1N1) in 47 households in the Netherlands using stochastic epidemic models. All households contained a laboratory confirmed index case, and antiviral drugs (oseltamivir) were given to both the index case and other households members within 24 hours after detection of the index case. Among the 109 household contacts there were 9 secondary infections in 7 households. The overall estimated secondary attack rate is low (0.075, 95%CI: 0.037-0.13). There is statistical evidence indicating that older persons are less susceptible to infection than younger persons (relative susceptibility of older persons: 0.11, 95%CI: 0.024-0.43. Notably, the secondary attack rate from an older to a younger person is 0.35 (95%CI: 0.14-0.61) when using an age classification of <or=12 versus >12 years, and 0.28 (95%CI: 0.12-0.50) when using an age classification of <or=18 versus >18 years. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the overall household transmission levels of novel influenza A(H1N1) in antiviral-treated households were low in the early stage of the epidemic. The relatively high rate of adult-to-child transmission indicates that control measures focused on this transmission route will be most effective in minimizing the total number of infections