Informative value of referral letters from general practice for child and adolescent mental healthcare.

Although referral letters (RLs) form a nodal point in a patient's care journey, little is known about their informative value in child and adolescent mental healthcare. To determine the informative value of RLs to child and adolescent psychiatry, we conducted a chart review in medical records of minors registered at specialized mental healthcare between January 2015 and December 2017 (The Netherlands). Symptoms indicated in RLs originating from general practice (N = 723) were coded and cross-tabulated with the best estimate clinical classifications made in psychiatry. Results revealed that over half of the minors in the sample were classified in concordance with at least one reason for referral. We found fair to excellent discriminative ability for indications made in RLs concerning the most common psychiatric classifications (95% CI AUC: 60.9-70.6 for anxiety disorders to 90.5-100.0 for eating disorders). Logistic regression analyses suggested no statistically significant effects of gender, age, severity or mental healthcare history, with the exception of age and attention deficit hyperactivity disorders (ADHD), as RLs better predicted ADHD with increasing age (OR = 1.14, 95% CI 1.03-1.27). Contextual problems, such as difficulties studying, problems with parents or being bullied were indicated frequently and associated with classifications in various disorder groups. To conclude, general practitioners' RLs showed informative value, contrary to common beliefs. Replication studies are needed to reliably incorporate RLs into the diagnostic work-up.

The Canadian Neuromuscular Disease Registry 2010-2019: A Decade of Facilitating Clinical Research Througha Nationwide, Pan-NeuromuscularDisease Registry.

We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.

A validated photonumeric scale for infraorbital dark circles and its application in evaluating the efficacy of a cosmetic treatment product in a split-face randomized clinical trial.

OBJECTIVE: As a result of their complex aetiology and periodicity, dark circles are difficult to characterize and measure, with current assessment techniques relying on specialist equipment, image analysis or proprietary grading scales. There is therefore a need to develop and validate a photonumeric scale for assessing infraorbital dark circles, which can provide an objective and consumer relevant tool for evaluating this condition and the efficacy of treatment products and procedures. METHODS: A panel of expert clinical evaluators reviewed approximately three thousand facial photographs collected over a 5-year period and selected images representing a dynamic range of dark circles. A 10-point photonumeric scale was created, with corresponding descriptors and images for each grade of the scale. To rigorously validate the scale, linearity, sensitivity and precision were assessed by colorimetry and in-clinic evaluation. Reproducibility was assessed photographically with both experienced and inexperienced clinical evaluators, whereas intragrader repeatability was assessed live in-clinic. The scale was then employed in a split-face randomized clinical trial on 58 subjects to evaluate the efficacy of a cosmetic treatment product over 8 weeks. RESULTS: Colour analysis of the images showed the scale was linear, with statistically significant correlations observed when colour data (CIElab; Individual Typology Angle) were plotted against the corresponding grades (r > 0.9, P < 0.001). Colour difference (Delta E) was calculated between the infraorbital zone and the surrounding skin, and when data were plotted against the grades, a statistically significant correlation was observed (r = 0.99, P < 0.01). The magnitude of the Delta E suggested that changes in grade are visibly perceptible to the human eye, and therefore, the scale is sensitive and clinically relevant. Intergrader reproducibility showed strong correlation (0.96) and >90% agreement between experienced evaluators, whereas intragrader repeatability assessment showed >90% perfect agreement between grades. Use of this scale in a clinical trial demonstrated the efficacy of a cosmetic product, with a mean statistically significant (P < 0.001) decrease in grade of 0.74 compared to baseline, and 0.59 versus the untreated control, after 8 weeks of treatment. CONCLUSION: Our photonumeric scale for infraorbital dark circles is sensitive and robust and provides an objective and easy-to-use tool to evaluate dark circles and their treatment.

OBJECTIF: En raison de leur étiologie et de leur périodicité complexes, les cernes sont difficiles à caractériser et à mesurer, les techniques d'évaluation actuelles reposant sur des équipements spécialisés, l'analyse d'images ou des échelles de notation exclusives. Il est donc nécessaire de développer et de valider une échelle photonumérique pour évaluer les cernes infraorbitaires, laquelle peut fournir un outil objectif et pertinent pour le consommateur et tester l'efficacité des produits et des procédures de traitement. MÉTHODES: Un panel d'évaluateurs cliniques experts a examiné environ trois mille photographies du visage recueillies sur une période de 5 ans, ainsi que des images sélectionnées représentant une plage dynamique de cernes. Une échelle photonumérique à 10 points a été créée, avec des descripteurs et des images correspondants à chaque grade de l'échelle. Afin de valider rigoureusement l'échelle, la linéarité, la sensibilité et la précision ont été évaluées par colorimétrie et en clinique. La reproductibilité a été évaluée sur le plan photographique par des évaluateurs cliniques expérimentés et inexpérimentés, tandis que la répétabilité intragrade a été évaluée en direct en clinique. L'échelle a ensuite été utilisée dans un essai clinique randomisé à deux parties sur 58 sujets, afin d'évaluer l'efficacité d'un produit de traitement cosmétique sur 8 semaines. RÉSULTATS: L'analyse des couleurs des images a montré que l'échelle était linéaire, avec des corrélations statistiquement significatives observées lorsque les données de couleurs (CIElab ; angle de typologie individuel) ont été tracées par rapport aux grades correspondants (r > 0,9, P < 0,001). La différence de couleur (Delta E) a été calculée entre la zone infraorbitaire et la peau environnante, et lorsque les données ont été tracées par rapport aux grades, une corrélation statistiquement significative a été observée (r = 0,99, P < 0,01). L'ampleur du delta E a suggéré que les changements de grade sont visiblement perceptibles à l'œil humain, l'échelle étant par conséquent sensible et cliniquement pertinente. La reproductibilité intergrade a montré une forte corrélation (0,96) et une concordance > 90 % entre les évaluateurs expérimentés, tandis que l'évaluation de la répétabilité intragrade a montré une concordance parfaite > 90 % entre les grades. L'utilisation de cette échelle lors d'un essai clinique a démontré l'efficacité d'un produit cosmétique, avec une diminution moyenne statistiquement significative (P < 0,001) du grade de 0,74 par rapport à la référence, et de 0,59 par rapport au témoin non traité, après 8 semaines de traitement. CONCLUSION: Notre échelle photonumérique pour les cernes infraorbitaires est sensible et robuste, fournissant un outil objectif et facile à utiliser afin d'évaluer les cernes et leur traitement.

SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes.

OBJECTIVES: To understand SARS-Co-V-2 infection and transmission in UK nursing homes in order to develop preventive strategies for protecting the frail elderly residents. METHODS: An outbreak investigation involving 394 residents and 70 staff, was carried out in 4 nursing homes affected by COVID-19 outbreaks in central London. Two point-prevalence surveys were performed one week apart where residents underwent SARS-CoV-2 testing and had relevant symptoms documented. Asymptomatic staff from three of the four homes were also offered SARS-CoV-2 testing. RESULTS: Overall, 26% (95% CI 22-31) of residents died over the two-month period. All-cause mortality increased by 203% (95% CI 70-336) compared with previous years. Systematic testing identified 40% (95% CI 35-46) of residents as positive for SARS-CoV-2, and of these 43% (95% CI 34-52) were asymptomatic and 18% (95% CI 11-24) had only atypical symptoms; 4% (95% CI -1 to 9) of asymptomatic staff also tested positive. CONCLUSIONS: The SARS-CoV-2 outbreak in four UK nursing homes was associated with very high infection and mortality rates. Many residents developed either atypical or had no discernible symptoms. A number of asymptomatic staff members also tested positive, suggesting a role for regular screening of both residents and staff in mitigating future outbreaks.

Pregnant women at increased risk of adverse perinatal outcomes: A combination of less healthy behaviors and adverse psychosocial and socio-economic circumstances.

Smoking during pregnancy is associated with a multitude of health behaviors and with the psychosocial and socio-economic circumstances of pregnant women. Limited research has so far been conducted on the clustering of these characteristics and on their effect on pregnancy outcomes. This study aimed to identify different groups of pregnant women based on their behavioral, psychosocial and socio-economic characteristics and their pregnancy outcomes. In total, 2455 women who were 12 weeks pregnant completed a questionnaire on smoking behavior, health behaviors and psychosocial and socio-economic characteristics. Neonatal and maternal outcomes were extracted from the Dutch perinatal registration. Subgroups were identified with latent class analysis and adverse pregnancy outcomes were compared between subgroups with logistic regression. Women were classified into four latent classes. Two classes represented the healthy higher-educated pregnant women who did not smoke: one group of multigravida women and one of primigravida women, also characterized by less pregnancy-specific knowledge and more pregnancy-related stress. The remaining women were grouped into two less healthy groups. One group frequently quit smoking, reported less healthy eating, less physical activity and comparable stress levels as the healthy higher-educated groups. The last group contained the most smokers, had the highest scores on psychosocial and pregnancy-related stress and the most adverse socio-economic circumstances. This group had an increased risk of adverse maternal outcomes, in particular developing diabetes during pregnancy. A comprehensive and integrated approach is needed to improve outcomes in pregnancies with a combination of adverse health, psychosocial, and socio-economic conditions.

Parent Training Programs for Ethnic Minorities: a Meta-analysis of Adaptations and Effect.

This meta-analysis focuses on parent training programs for ethnic minority families and reports on (i) the adaptation of program content and (ii) the process that informs these adaptations. Relevant studies are reviewed to determine the adaptations made and the impact of the adaptations on parenting and child outcomes. Studies were eligible for inclusion if they enrolled predominantly ethnic minority parents with children aged 0-12 years, used a randomized controlled trial design with post-intervention assessments, focused on group-based parent training programs and on prevention of parenting problems, and reported parenting behavior outcomes. A total of 18 studies were included in the analysis. The results show that parent training programs targeting ethnic minority parents have a small but significant effect on improving parenting behavior (k = 18, Cohen's d = 0.30), child outcomes (k = 16, Cohen's d = 0.13), and parental perspectives (k = 8, Cohen's d = 0.19). Most of the programs made adaptations related to surface and deep structure sensitivity. Programs with cultural adaptations, especially deep structure sensitivity (k = 7, Cohen's d = 0.54), are more effective in improving parenting behavior. Because only a third of the included studies provided details on the processes that guided the adaptations made, additional studies are needed to provide information on the process of adaptation; this will enable others to learn from the procedures that can be undertaken to culturally adapt interventions.

Critical stakeholder determinants to the implementation of intersectoral community approaches targeting childhood obesity.

Several intersectoral community approaches targeting childhood obesity (IACOs) have been launched in the Netherlands. Translation of these approaches into practice is however arduous and implementation. We therefore studied the implementation of five IACOs in the Netherlands for one-and-a-half years. IACO implementation was evaluated via an adapted version of the MIDI questionnaire, consisting of 18 theory-based constructs. A response rate of 62% was obtained. A hierarchical multivariate linear regression model was used to analyse our data; the final regression model predicted 65% of the variance in adherence. Higher levels of self-efficacy, being an implementer embedded in community B, and having more than 1 year of experience with IACO implementation were associated with higher degrees of adherence. Formal ratification of implementation by management and being prescribed a higher number of activities were related to lower degrees of adherence. We advise that, when designing implementation strategies, emphasis should be placed on the enhancement of professionals' self-efficacy, limitation of the number of activities prescribed and allocation of sufficient time to get acquainted and experienced with IACO implementation. Longitudinal studies are needed to further evaluate interaction between and change within critical determinants while progressing through the innovation process.

Determinants of participation in a cardiometabolic health check among underserved groups.

Cardiometabolic diseases affect underserved groups disparately. Participation in health checks is also lower, widening health inequalities in society. Two-stage screening (non-invasive health risk assessment (HRA) and GP consultations for high-risk individuals) seems cost-effective, provided that drop-out rates are low in both steps. We aimed to explore the process of decision-making regarding HRA participation among underserved groups (45-70 y): native Dutch with a lower socioeconomic status (SES), Turkish, Moroccan, and Surinamese participants. We conducted a cross-sectional questionnaire study. The questionnaire comprised the following determinants: a self-formulated first reaction, a structured set of predefined determinants, and the most important barrier(s) and facilitator(s) for HRA completion. We used univariable and (stepwise) multivariate logistic regression analyses to assess which determinants were associated with HRA completion. Of the 892 participants in the questionnaire, 78% (n = 696) also completed the HRA. Moroccans and patients from GP practices with a predominantly non-Western population less often completed the HRA. A lower SES score, wanting to know one's risk, not remembering receiving the invitation (thus requiring a phone call), fear of the test result and/or adjusting lifestyle, perceived control of staying healthy, wanting to participate, and perceiving no barriers were associated with completing the HRA. We conclude that our 'hard-to-reach' population may not be unwilling to participate in the HRA. A more comprehensive approach, involving key figures within a community informing people about and providing help completing the HRA, would possibly be more suitable. Efforts should be particularly targeted at the less acculturated immigrants with an external locus of control.

Implementation of intersectoral community approaches targeting childhood obesity: a systematic review.

The implementation of intersectoral community approaches targeting childhood obesity (IACO) is considered challenging. To help overcome these challenges, an overview of the evidence to date is needed. We searched four databases to identify papers that reported on the determinants of successful implementation of IACOs, resulting in the inclusion of 25 studies. We appraised study quality with the Crowe Critical Appraisal Tool and the Quality Framework; reported implementation outcome indicators were reviewed via narrative synthesis. Quality of included studies varied. The most frequently reported indicators of implementation success were fidelity and coverage. Determinants related to the social-political context and the organization were most often cited as influencing implementation, in particular, 'collaboration between community partners', 'the availability of (human) resources' and 'time available for implementation'. The association between determinants and implementation variability was never explicated. We conclude that although some insights into the effective implementation of IACOs are present, more research is needed. Emphasis should be placed on elucidating the relationship between determinants and implementation success. Research should further focus on developing a 'golden standard' for evaluating and reporting on implementation research. These actions will improve the comparison of study outcomes and may constitute the cumulative development of knowledge about the conditions for designing evidence-based implementation strategies.

The effectiveness of school-based smoking prevention interventions among low- and high-SES European teenagers.

Preventing smoking initiation among adolescents of lower socio-economic groups is crucial for the reduction of socio-economic inequalities in health. The aim of the present study was to examine whether effective smoking prevention interventions in Europe are equally effective among adolescents of low- and high-socio-economic status (SES). As part of the European Union-funded TEENAGE project, three school-based smoking prevention intervention studies in Europe were selected for secondary analyses: (i) a Dutch class competition intervention, (ii) the European Smoking Prevention Framework (ESFA) study and (iii) the A Stop Smoking in Schools Trial (ASSIST) intervention. All three studies differed in effectiveness by SES. The Dutch class competition study only had a significant effect among higher SES adolescents. The results for the ESFA study and ASSIST study were mixed and depended on which SES indicator was used. The conclusion of the study is that stratified analyses provide important insights in differential intervention effects for higher and lower socio-economic groups. Although findings from the different studies were mixed, interventions that use a social network approach in which youngsters are allowed to deliver the intervention themselves may be a successful strategy in targeting adolescents from lower socio-economic groups.

Does a smoking prevention program in elementary schools prepare children for secondary school?

INTRODUCTION: A smoking prevention program was developed to prepare children in elementary school for secondary school. This study assessed the effects on smoking in secondary school. METHODS: In 2002, 121 schools in The Netherlands were randomly assigned to the intervention or control group. The intervention group received 3 lessons in 5th grade of elementary school and a second 3 lessons in 6th grade. The control group received "usual care". Students completed 5 questionnaires: before and after the lessons in 5th and 6th grade and in the first class of secondary school. At baseline, 3173 students completed the questionnaire; 57% completed all questionnaires. RESULTS: The program had limited effect at the end of elementary school. One year later in secondary school significant effects on behavioral determinants and smoking were found. The intervention group had a higher intention not to smoke (ß=0.13, 95% confidence interval=0.01-0.24) and started to smoke less often than the control group (odds ratio=0.59, 95% confidence interval=0.35-0.99): smoking increased from 2.5% to 3.6% in the intervention group and from 3.2% to 6.5% in the control group. Girls showed the largest differences in smoking between intervention and control condition. CONCLUSIONS: A prevention program in elementary school seems to be effective in preventing smoking.

The relationship of the orientation of the transverse acetabular ligament and acetabular labrum to the suggested safe zones of cup positioning in total hip arthroplasty.

BACKGROUND: There is a need to develop and validate a method for establishing cup orientation that is patient specific and independent of the anterior pelvic plane. It is our hypothesis that the transverse acetabular ligament and acetabular labrum can be used to do this. The objective of this study is to define the orientation of the plane formed by the transverse acetabular ligament and acetabular labrum and to examine whether these local landmarks lie within the limits of acceptance for cup positioning. METHODS: Twenty-five consecutive patients, who were being investigated for labral tears with a MRI arthrogram of the hip, were enrolled in this prospective study. The orientation of the transverse acetabular ligament-labrum plane was determined by manually selecting points on the transverse acetabular ligament and labrum. The best-fit plane through these points was determined and its operative orientation expressed with respect to a constructed pelvic coordinate system. RESULTS: The operative anteversion of the transverse acetabular ligament-labrum plane ranged from 5.3-36.1 inverted exclamation mark (mean 23.0 inverted exclamation mark + or - 7.4 inverted exclamation mark standard deviation). The inclination ranged from 38.4-50.3 inverted exclamation mark (mean 45.6 inverted exclamation mark + or - 3.2 inverted exclamation mark standard deviation). CONCLUSIONS: The transverse acetabular ligament and acetabular labrum offer a possible solution to the many difficulties involved in cup placement during total hip arthroplasty. This paper highlights the variation in the orientation of these local acetabular landmarks and questions the logic of a set target for cup positioning.

A case of pseudoarthrosis of the lateral talar process and distal fibula in a professional athlete.

We report a case of osteoarthritis of a pseudoarthrosis between the tip of the fibula and the lateral process of the talus. This was treated by excision of pseudoarthrosis with lateral ligament reconstruction.

[Slight decrease in the prevalence of smoking around pregnancy]. / Licht dalende prevalentie van roken rondom de zwangerschap.

OBJECTIVE: To establish smoking prevalence of fertile-aged women; before and during pregnancy, and 6 months after delivery. DESIGN: Cross-sectional. METHOD: Yearly surveys by questionnaires handed out during 2001-2003 to mothers visiting a Well Baby Clinic with infants aged 0-6 months. RESULTS: Out ofa total of 14,540 questionnaires, 9133 (63%) were completed and returned. Before pregnancy 25% of all the women concerned smoked, 6% stopped 6 months before getting pregnant; this percentage rose between 2001 (5%) and 2003 (7%). During pregnancy, 14% of the women smoked. This percentage was significantly lower in 2002 and 2003 (13%) compared to 16% in 2001. 11% smoked while pregnant (average 5 cigarettes daily), and 3% stopped some time during pregnancy. Of the mothers who quitted smoking before or during pregnancy, two thirds did so permanently. Nevertheless 15% of all women smoked during the first half year after delivery. This percentage was lowest in 2003 (14%) and highest in 2001 (17%). 28% of all mothers with infants aged 0-6 months had partners who smoked (daily 10 cigarettes average), these women were more likely to start smoking again (RR: 2). CONCLUSION: Minor positive changes were observed within the study period. A smoking partner contributed to smoking relapse after delivery.

Sustainability of the prevention of passive infant smoking within well-baby clinics.

This study assessed the antecedents of continued use of an education program to prevent passive smoking in infants. It consists of a booklet for parents and a manual for health professionals describing a five-step procedure for discussing passive smoking. A questionnaire was sent to 67 managers, 670 nurses, and 335 physicians working in well-baby clinics (response rate: 70%, 53%, 47% respectively). Questions concerned the completeness of use, level of institutionalization, and characteristics of the organization, the user, and the dissemination strategy. Seventy-one percent of nurses and 42% of physicians worked with the program. They foremost provided the first three steps of the five-step procedure. Physicians' completeness of use was related to their perceived responsibility in providing this education, and nurses' use was related to their perceived self-efficacy, responsibility, training attendance, participation in the adoption decision, and level of institutionalization. Diffusion efforts should focus on improving the completeness of use and level of institutionalization.

Rupture of the tibialis posterior tendon: an important differential in the assessment of ankle injuries.

Rupture of the tibialis posterior tendon can be missed. We report a case of posterior tibialis tendon rupture that, owing to misdiagnosis, resulted in a significant foot deformity requiring arthrodesis for chronic pain.

Behavioural factors related to metabolic control in patients with phenylketonuria.

BACKGROUND: The objective of this study was to determine the importance of parental factors possibly related to dietary control in early and continuously treated patients with phenylketonuria (PKU). METHODS: A questionnaire was disseminated among parents of 238 patients with PKU born after the nationwide introduction of newborn screening for PKU (1 September 1974) until 31 December 1995. The questionnaire was based on a behavioural model measuring people's attitudes, subjective norms, and self-efficacy. Dietary control was defined on the basis of mean phenylalanine (Phe) concentration of the PKU patients measured between 1 January 1994 and 31 December 1996. RESULTS: Response rate was 71%. Attitudes: children of parents who believed that their child adheres well to the diet, even if his or her Phe concentrations are sometimes too high, had lower Phe concentrations than children of parents who disagree with this statement (adjusted difference -103 micromol/L, p < 0.001). Subjective norm: Phe concentrations were higher when parents answered that their relatives did not approve when their child deviates from the diet (p = 0.004). Self-efficacy: children of parents who reported difficulties in having their child eat the synthetic protein substitute three times a day had higher Phe concentrations than those of parents who did not have such difficulties (adjusted difference 156 micromol/L, p = 0.007). CONCLUSION: More attention should be given to parents having their child eat the synthetic protein substitute at least three times a day and to teaching parents to keep strictly to the diet without being too rigid. These factors were strongly associated to dietary control and may be amenable to change.

Parental education on passive smoking in infancy does work.

BACKGROUND: Passive smoking is harmful to young children. A protocol has been developed to allow health care workers to communicate with parents about preventing passive smoking. The main message was to refrain from smoking in the presence of the child. The aim of the study was to assess the effectiveness of this education programme. METHOD: The prevalence of smoking in the presence of infants aged 0-10 months was compared before and after the implementation of the education programme. National samples of mothers completed questionnaires in 1996 (n = 1,129) and in 1999 (n = 2,534). Questions were asked about smoking in the living room in the presence of infants, and about parental smoking, and background characteristics. RESULTS: The prevalence of passive infant smoking decreased from 41% to 18%. The adjusted odds ratio for passive infant smoking in 1999 compared to 1996 was 0.34 (0.26-0.44) when none of the parents smoked, 0.19 (0.14-0.27) when one of the parents smoked, and 0.30 (0.20-0.44) when both parents smoked. CONCLUSION: The implementation of this health education programme seems to have been very successful in reducing passive smoking in children. Implementation of similar health education programmes in other countries is recommended.

Prevention of smoking in adolescents with lower education: a school based intervention study.

OBJECTIVE: To assess the effect of an antismoking intervention focusing on adolescents in lower education. Students with lower education smoke more often and perceive more positive norms, and social pressure to smoke, than higher educated students. An intervention based on peer group pressure and social influence may therefore be useful to prevent smoking among these students. DESIGN: Group randomised controlled trial. SETTING: 26 Dutch schools that provided junior secondary education. SUBJECTS: 1444 students in the intervention and 1118 students in the control group, all in the first grade, average age 13 years. INTERVENTION: Three lessons on knowledge, attitudes, and social influence, followed by a class agreement not to start or to stop smoking for five months and a class based competition. MAIN OUTCOME MEASURES: Comparison of smoking status before and immediately after and one year after the intervention, using multilevel analysis. RESULTS: In the intervention group, 9.6% of non-smokers started to smoke, in the control group 14.2%. This leads to an odds ratio of 0.61 (95% CI= 0.41 to 0.90) to uptake smoking in the intervention group compared with the control group. One year after the intervention, the effect was no longer significant. CONCLUSIONS: In the short-term, an intervention based on peer pressure decreases the proportion of adolescents with lower education who start smoking. Influencing social norms and peer pressure would therefore be a promising strategy in terms of preventing smoking among adolescents. The results also suggest that additional interventions in later years are needed to maintain the effect.

Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.