Adherence to guideline recommendations for Barrett's esophagus (BE) surveillance endoscopies: Effects of dedicated BE endoscopy lists.

Background and study aims For non-dysplastic Barrett's Esophagus (BE) patients, guidelines recommend endoscopic surveillance every 3 to 5 years with four-quadrant random biopsies every 2 cm of BE length. Adherence to these guidelines is low in clinical practice. Pooling BE surveillance endoscopies on dedicated endoscopy lists performed by dedicated endoscopists could possibly enhance guideline adherence, detection of visible lesions, and dysplasia detection rates (DDRs). Patients and methods Data were used from the ACID-study (Netherlands Trial Registry NL8214), a prospective trial of BE surveillance in the Netherlands. BE patients with known or previously treated dysplasia were excluded. Guideline adherence, detection of visible lesions, and DDRs were compared for patients on dedicated and general endoscopy lists. Results A total of 1,244 patients were included, 318 on dedicated lists and 926 on general lists. Endoscopies on dedicated lists showed significantly higher adherence to the random biopsy protocol (85% vs. 66%, P <0.01) and recommended surveillance intervals (60% vs. 47%, P <0.01) compared to general lists. Detection of visible lesions (8.8% vs. 8.1%, P =0.79) and DDRs were not significantly different (6.9% and 6.6%, P =0.94). None (0.0%) of the patients scheduled on dedicated lists and 10 (1.1%) on general lists were diagnosed with esophageal adenocarcinoma ( P =0.07). In multivariable analysis, dedicated lists were significantly associated with biopsy protocol adherence and adherence to surveillance interval recommendations with odds ratios of 4.45 (95% confidence interval [CI] 2.07-9.57) and 1.64 (95% CI 1.03-2.61), respectively. Conclusions Dedicated endoscopy lists are associated with better adherence to the random biopsy protocol and surveillance interval recommendations.

Effects of structured involvement of the primary care team versus standard care after a cancer diagnosis on patient satisfaction and healthcare use: the GRIP randomised controlled trial.

BACKGROUND: The growing number of cancer survivors and treatment possibilities call for more personalised and integrated cancer care. Primary care seems well positioned to support this. We aimed to assess the effects of structured follow-up of a primary care team after a cancer diagnosis. METHODS: We performed a multicentre randomised controlled trial enrolling patients curatively treated for breast, lung, colorectal, gynaecologic cancer or melanoma. In addition to usual cancer care in the control group, patients randomized to intervention were offered a "Time Out consultation" (TOC) with the general practitioner (GP) after diagnosis, and subsequent follow-up during and after treatment by a home care oncology nurse (HON). Primary outcomes were patient satisfaction with care (questionnaire: EORTC-INPATSAT-32) and healthcare utilisation. Intention-to-treat linear mixed regression analyses were used for satisfaction with care and other continuous outcome variables. The difference in healthcare utilisation for categorical data was calculated with a Pearson Chi-Square or a Fisher exact test and count data (none versus any) with a log-binomial regression. RESULTS: We included 154 patients (control n = 77, intervention n = 77) who were mostly female (75%), mainly diagnosed with breast cancer (51%), and had a mean age of 61 (SD ± 11.9) years. 81% of the intervention patients had a TOC and 68% had HON contact. Satisfaction with care was high (8 out of 10) in both study groups. At 3 months after treatment, GP satisfaction was significantly lower in the intervention group on 3 of 6 subscales, i.e., quality (- 14.2 (95%CI -27.0;-1.3)), availability (- 15,9 (- 29.1;-2.6)) and information provision (- 15.2 (- 29.1;-1.4)). Patients in the intervention group visited the GP practice and the emergency department more often ((RR 1.3 (1.0;1.7) and 1.70 (1.0;2.8)), respectively). CONCLUSIONS: In conclusion, the GRIP intervention, which was designed to involve the primary care team during and after cancer treatment, increased the number of primary healthcare contacts. However, it did not improve patient satisfaction with care and it increased emergency department visits. As the high uptake of the intervention suggests a need of patients, future research should focus on optimizing the design and implementation of the intervention. TRIAL REGISTRATION: GRIP is retrospectively (21/06/2016) registered in the 'Netherlands Trial Register' (NTR5909).

Contrast-enhanced ultrasound for multiple liver lesions after bone marrow transplant in a child with leukaemia: Multifocal focal nodular hyperplasia.

We present a case of a two-year-old girl in which liver lesions were characterised on contrast-enhanced ultrasound as multifocal focal nodular hyperplasia. This child had previously undergone haematopoietic stem cell transplantation for juvenile myelomonocytic leukaemia and was suspected to have hepatobiliary graft versus host disease. Liver biopsy was performed to confirm the unexpected focal nodular hyperplasia and look for concurrent graft versus host disease. Focal nodular hyperplasia was histologically confirmed on a background of diffuse liver damage in keeping with polypharmacotherapy, steatosis and sepsis. An element of graft versus host disease was not excluded but was not confidently shown in the sample of the lesion. This case report describes and illustrates how contrast-enhanced ultrasound may be of use to further assess hepatic lesions in a complex case of multifactorial hepatic pathology. Radiologists, haematologists and pathologists should be aware that multifocal focal nodular hyperplasia is part of the differential diagnosis of liver lesions in a child with liver damage due to complex disease and treatment. Biopsy remains the gold standard, if there is a concurrent clinical suspicion of graft versus host disease.

Adherence to surveillance guidelines for colorectal adenomatous polyps in the elderly.

OBJECTIVE: Determining adherence to recommended surveillance intervals after polypectomy in elderly patients. DESIGN: A retrospective cohort study including 531 patients aged above 70 years undergoing polypectomy between 2009-2011 in a large Dutch teaching hospital, identified using the hospital's pathology registry. Outcomes of the index colonoscopy were reviewed. The interval until the next colonoscopy was assessed and compared both to the advised interval according to the Dutch guidelines and the gastroenterologist's recommendation. Reasons for deviating from the guideline were assessed. RESULTS: The initial recommendation of the gastroenterologist for the surveillance interval was in accordance to the guideline in 59.1% of the patients. In 21.8% the gastroenterologist's advice was not documented. In 15.8% of the patients the gastroenterologist recommended to perform surveillance endoscopy earlier than the guideline, mainly based on polyp characteristics. The gastroenterologist advised endoscopy when the guideline advised no surveillance at all in 1.0%, later than the guideline recommendation in 1.2%, or did not recommend surveillance when the guideline advised to continue in 1.0%. Actual surveillance intervals were in accordance to the guideline in 54.4% and in accordance to the initial advice of the gastroenterologist in 58.4% of the patients. CONCLUSION: Only in 41% of patients was the gastroenterologist's recommendation regarding surveillance after polypectomy either absent (21.8%) or not in accordance to the guideline (19.2%). Future research should focus on developing an evidence-based decision algorithm for elderly patients to support gastroenterologists and patients in the choices regarding cessation of surveillance at a certain level of frailty, comorbidity or remaining life-expectancy.

Effectiveness of an intensive treatment programme combining prolonged exposure and eye movement desensitization and reprocessing for severe post-traumatic stress disorder.

Background: There is room for improvement regarding the treatment of severe post-traumatic stress disorder (PTSD). Intensifying treatment to increase patient retention is a promising development. Objective: The aim of this study was to determine the effectiveness of an intensive trauma-focused treatment programme over 8 days for individuals suffering from severe PTSD. Method: Treatment was provided for 347 PTSD patients (70% women; mean age = 38.32 years, SD = 11.69) and consisted of daily sessions of prolonged exposure and eye movement desensitization and reprocessing (EMDR) therapy (16 sessions in total), physical activity, and psycho-education. All participants had experienced multiple traumas, including sexual abuse (74.4%), and suffered from multiple comorbidities (e.g. 87.5% had a mood disorder). Suicidal ideation was frequent (73.9%). PTSD symptom severity was assessed by both clinician-rated [Clinician Administered PTSD Scale (CAPS)] and self-report [PTSD Symptom Scale Self Report (PSS-SR) and Impact of Event Scale (IES)] inventories. For a subsample (n = 109), follow-up data at 6 months were available. Results: A significant decline in symptom severity was found (e.g. CAPS intention-to-treat sample Cohen's d = 1.64). At post-treatment, 82.9% showed a clinically meaningful response and 54.9% a loss of diagnosis. Dropout was very low (2.3%). Conclusions: Intensive trauma-focused treatment programmes including prolonged exposure, EMDR therapy, and physical activity can be effective for patients suffering from severe PTSD and are associated with low dropout rates.

Antecedentes: Hay un margen de mejora con respecto al tratamiento del trastorno de estrés postraumático severo (TEPT). Intensificar el tratamiento para aumentar la retención de paciente es un desarrollo prometedor.Objetivo: Determinar la efectividad de un programa de tratamiento intensivo centrado en trauma durante 8 días para personas que presentan TEPT severo.Método: Se proporcionó tratamiento a 347 pacientes con TEPT (70,0% mujeres, edad media = 38,32 años, DE = 11,69) y consistió en sesiones diarias de exposición prolongada y terapia EMDR (16 sesiones en total), actividad física, y psico-educación. Todos los participantes habían experimentado múltiples traumas, incluido abuso sexual (74,4%), y padecían múltiples comorbilidades (por ejemplo, 87,5% trastorno anímico). La ideación suicida fue frecuente (73,9%). La gravedad de los síntomas de TEPT fue evaluada tanto por el clínico con inventarios calificados (CAPS) como por auto-reporte (PSS-SR y IES). Para una submuestra (N=109) se dispuso de datos de seguimiento a los seis meses.Resultados: Se encontró una disminución significativa en la gravedad de los síntomas (por ejemplo, en la muestra CAPS ITT d = 1,64 de Cohen). En el post tratamiento, el 82,9% mostró una respuesta clínicamente significativa y el 54,9% una pérdida del diagnóstico. El abandono fue muy bajo (2,3%).Conclusiones: Los programas intensivos de tratamientos centrados en trauma, incluido la terapia de exposición prolongada, la terapia EMDR y la actividad física, pueden ser efectivos para los pacientes que sufren de trastorno de estrés postraumático severo y se asocian con bajas tasas de abandono.

The Longitudinal Association between Self-esteem and Depressive Symptoms in Adolescents: Separating between-person effects from within-person effects.

Many longitudinal studies have investigated whether self-esteem predicts depressive symptoms (vulnerability model) or the other way around (scar model) in adolescents. The most common method of analysis has been the Cross-lagged Panel Model (CLPM). The CLPM does not separate between-person effects from within-person effects, making it unclear whether the results from previous studies actually reflect the within-person effects, or whether they reflect differences between people. We investigated the associations between self-esteem and depressive symptoms at the within-person level, using Random Intercept Cross-Lagged Panel Models (RI-CLPM). To get an impression of the magnitude of possible differences between the RI-CLPM and CLPM, we compared the results of both models. We used data from three longitudinal adolescent samples (age range 7-18; Study 1: N=1,948; Study 2: N=1,455; Study 3: N=316). Intervals between the measurements were 1-1.5 years. Single-paper meta-analyses showed support for small within-person associations from self-esteem to depressive symptoms, but not the other way around, thus only providing some support for the vulnerability model. The cross-lagged associations in the aggregated RI-CLPM and CLPM showed similar effect sizes. Overall, our results show that over 1-1.5 year time intervals, low self-esteem may negatively influence depressive symptoms over time within adolescents, but only weakly so.

Management of eosinophilic esophagitis in daily clinical practice.

In recent years, new guidelines and recommendations have been published regarding the diagnostic criteria and therapeutic management of eosinophilic esophagitis (EoE). The aim of this study is to assess the diagnostic and therapeutic management of patients diagnosed with EoE in daily clinical practice and whether this was performed according to current guidelines and recommendations. A population-based, multicenter retrospective cohort study was conducted using data from the national pathology registry (PALGA), medical records, and telephone interviews of patients diagnosed with EoE in two academic and two nonacademic hospitals in the period 2004 to 2014. The study was approved by all involved ethical committees. Data regarding demographics, clinical manifestations, endoscopic results, histologic samples, and therapeutic strategies were collected. Standard statistical analyses were performed to summarize patient characteristics. We included 119 patients diagnosed with EoE in this study. The median age at onset of symptoms was 29 years (IQR: 15-42) and the median age at diagnosis was 38 years (IQR: 23-51 years), leading to a median diagnostic patients' delay of 6.5 years (IQR: 2-14 years). The median physicians' delay in diagnosis between first contact in the hospital and diagnosis was 1.0 year (IQR: 1-7 years). The incidence of newly diagnosed patients with EoE increased steadily over a period of 11 years. Criteria for the microscopic diagnosis of EoE varied between pathologists in each hospital. Initial treatment included topical corticosteroids (TCS) (30.3%), proton pump inhibitors (PPI) (29.4%), or a combination (10.1%). A follow-up endoscopy was performed in 40.3% of patients. During follow-up, treatment included PPIs (76.0%), TCS (59.6%), a combination of PPIs and TCS (45.4%), and endoscopic dilations (6.7%). Diagnostic and therapeutic discrepancies between daily clinical practice and recommendations from current and past guidelines were observed. Apart from developing guidelines, efforts should be undertaken to implement these in daily clinical practice.

[Functional abdominal symptoms in children: the role of the abdominal X-ray and measurement of colon transit time]. / Functionele buikklachten bij kinderen.

Functional constipation and functional non-retentive faecal incontinence are common problems in childhood; these functional defaecation disorders are diagnosed according to the Rome IV criteria. Here we describe the role of an abdominal X-ray in diagnosing functional defaecation disorders, and address the limited additional value of a plain abdominal X-ray. In limited cases it may be helpful to determine colonic transit time using an abdominal X-ray to differentiate between functional constipation and functional non-retentive faecal incontinence. The diagnostic value of abdominal X-rays in children with functional abdominal pain will be discussed. The aims of this article are to explore ways of reducing unnecessary use of abdominal X-rays and reducing unnecessary radiation exposure in children with functional defaecation disorders and functional abdominal pain.

Positional therapy in patients with residual positional obstructive sleep apnea after upper airway surgery.

PURPOSE/BACKGROUND: A considerable portion of patients has residual positional obstructive sleep apnea (POSA) after upper airway surgery. Those patients could benefit from additional treatment with positional therapy (PT). The objective of this prospective study was to assess the additional effect of PT in patients with residual POSA after upper airway surgery for sleep apnea. METHODS: A polysomnography (PSG) was used to diagnose a patient with residual POSA after surgery. After informed consent, patients were treated with PT for 3 months and underwent a follow-up PSG while using the sleep position trainer (SPT). Changes in apnea-hypopnea index (AHI) and sleep position parameters were analyzed. Compliance rates and mean disease alleviation (MDA) were determined. RESULTS: Thirty-three patients with a median postoperative AHI of 18.3/h sleep were included. With the SPT median AHI dropped to 12.5/h sleep and the Epworth Sleepiness Scale (ESS) improved from 10.0 to 7.0. After 3 months, 37.5 % patients were considered responders of whom 31.3 % had treatment success. The compliance rate with SPT was 89.0 %. MDA was 44.7 % for SPT alone. With the combination of both surgery and SPT, MDA was 65.6 %. CONCLUSIONS: The results of this study indicate that additional PT in a complex OSA patient population with residual POSA after surgery can increase overall therapeutic effectiveness by improving the median MDA from 39.5 % (effect of surgery alone) to 65.6 % (effect of combining surgery and PT).

How the concept of biochemical response influenced the management of primary biliary cholangitis over time.

BACKGROUND: Criteria assessing biochemical response to ursodeoxycholic acid (UDCA) are established risk stratification tools in primary biliary cholangitis (PBC). We aimed to evaluate to what extent liver tests influenced patient management during a three decade period, and whether this changed over time. METHODS: 851 Dutch PBC patients diagnosed between 1988 and 2012 were reviewed to assess patient management in relation to liver test results during UDCA treatment. To do so, biochemical response at one year was analysed retrospectively according to Paris-1 criteria. RESULTS: Response was assessable for 687/851 (81%) patients; 157/687 non-responders. During a follow-up of 8.8 years (IQR 4.8-13.9), 141 died and 30 underwent liver transplantation. Transplant-free survival of non-responders (60%) was significantly worse compared with responders (87%) (p < 0.0001). Management was modified in 46/157 (29%) non-responders. The most frequent change observed, noted in 26/46 patients, was an increase in UDCA dosage. Subsequently, 9/26 (35%) non-responders became responders within the next two years. Steroid treatment was started in one patient; 19 patients were referred to a tertiary centre. No trend towards more frequent changes in management over time was observed (p = 0.10). CONCLUSION: Changes in medical management occurred in a minority of non-responders. This can largely be explained by the lack of accepted response criteria and of established second-line treatments for PBC. Nevertheless, the observation that response-guided management did not increase over time suggests that awareness of the concept of biochemical response requires further attention,particularly since new treatment options for PBC will soon become available.

Adolescent Loneliness and Social Skills: Agreement and Discrepancies Between Self-, Meta-, and Peer-Evaluations.

Lonely adolescents report that they have poor social skills, but it is unknown whether this is due to an accurate perception of a social skills deficit, or a biased negative perception. This is an important distinction, as actual social skills deficits require different treatments than biased negative perceptions. In this study, we compared self-reported social skills evaluations with peer-reported social skills and meta-evaluations of social skills (i.e., adolescents' perceptions of how they believe their classmates evaluate them). Based on the social skills view, we expected negative relations between loneliness and these three forms of social skills evaluations. Based on the bias view, we expected lonely adolescents to have more negative self- and meta-evaluations compared to peer-evaluations of social skills. Participants were 1342 adolescents (48.64 % male, M age = 13.95, SD = .54). All classmates rated each other in a round-robin design to obtain peer-evaluations. Self- and meta-evaluations were obtained using self-reports. Data were analyzed using polynomial regression analyses and response surface modeling. The results indicated that, when self-, peer- and meta-evaluations were similar, a greater sense of loneliness was related to poorer social skills. Loneliness was also related to larger discrepancies between self- and peer-evaluations of loneliness, but not related to the direction of these discrepancies. Thus, for some lonely adolescents, loneliness may be related to an actual social skills deficit, whereas for others a biased negative perception of one's own social skills or a mismatch with the environment may be related to their loneliness. This implies that different mechanisms may underlie loneliness, which has implications for interventions.

Picture Your Nursing Home: Exploring the Sense of Home of Older Residents through Photography.

The quality of the built environment can impact the quality of life and the sense of home of nursing home residents. This study investigated (1) which factors in the physical and social environment correlate with the sense of home of the residents and (2) which environmental factors are most meaningful. Twelve participants engaged in a qualitative study, in which photography was as a supportive tool for subsequent interviews. The data were analysed based on the six phases by Braun and Clarke. The four themes identified are (1) the physical view; (2) mobility and accessibility; (3) space, place, and personal belongings; and (4) the social environment and activities. A holistic understanding of which features of the built environment are appreciated by the residents can lead to the design and retrofitting of nursing homes that are more in line with personal wishes.

Reexpansion pulmonary edema after chest drainage for pneumothorax: A case report and literature overview.

BACKGROUND: Reexpansion pulmonary edema (RPE) is a rare complication that may occur after treatment of lung collapse caused by pneumothorax, atelectasis or pleural effusion and can be fatal in 20% of cases. The pathogenesis of RPE is probably related to histological changes of the lung parenchyma and reperfusion-damage by free radicals leading to an increased vascular permeability. RPE is often self-limiting and treatment is supportive. CASE REPORT: A 76-year-old patient was treated by intercostal drainage for a traumatic pneumothorax. Shortly afterwards he developed reexpansion pulmonary edema and was transferred to the intensive care unit for ventilatory support. Gradually, the edema and dyspnea diminished and the patient could be discharged in good clinical condition. CONCLUSION: RPE is characterized by rapidly progressive respiratory failure and tachycardia after intercostal chest drainage. Early recognition of signs and symptoms of RPE is important to initiate early management and allow for a favorable outcome.

Follow-up of implantable cardioverter-defibrillator therapy: comparison of coronary artery disease and dilated cardiomyopathy.

PURPOSE: Since several large trials have proven the effectiveness of implantable cardioverter-defibrillators (ICDs) in patients with left ventricular dysfunction, disadvantages have become more apparent. As the prognosis of patients with cardiovascular diseases is improving, assessment of ICD patients and re-evaluation of the current guidelines is mandatory. We aimed to evaluate differences in mortality and occurrence of (in)appropriate shocks in ICD patients with coronary artery disease (CAD) or dilated cardiomyopathy (DCM). METHODS: In a large teaching hospital, all consecutive patients with systolic dysfunction due to CAD or DCM who received an ICD with and without resynchronisation therapy, were collected in a database. RESULTS: A total of 320 consecutive patients (age 67 ± 10 years) were classified as CAD patients and 178 (63 ± 11 years) as DCM patients. Median follow-up was 40 months (interquartile range [IQR] 23─57 months). All-cause mortality was 14 % (CAD 15 % vs DCM 13 %). Appropriate shocks occurred in 13 % of all patients (CAD 15 % vs DCM 11 %, p = 0.12) and inappropriate shocks occurred in 10 % (CAD 8 % vs DCM 12 %, p = 0.27). Multivariate analysis demonstrated impaired left ventricular ejection fraction, QRS >120, age ≥75 years and low estimated glomerular filtration rate as predictors for all-cause mortality. Predictors for inappropriate shocks were permanent and paroxysmal atrial fibrillation. CONCLUSION: Mortality rates were similar in patients with CAD and DCM who received an ICD. Furthermore, no differences were found in the occurrence of appropriate and inappropriate ICD interventions between these patient groups.

Cutaneous granulomas in ataxia telangiectasia and other primary immunodeficiencies: reflection of inappropriate immune regulation?

BACKGROUND: Non-infective cutaneous granulomas with unknown pathogenesis occur in various primary immunodeficiencies (PIDs) including ataxia telangiectasia (A-T). OBJECTIVE: To find a common immunological denominator in these cutaneous granulomas. METHODS: The dermatological and immunological features of 4 patients with A-T and cutaneous granulomas were described. The literature on skin granulomas in A-T and in other PIDs is reviewed. RESULTS: All 4 A-T patients had progressive granulomas on their limbs and showed decreased IgG and IgA concentrations with normal IgM levels. They had a marked decrease in B cells and naïve T cells coinciding with the appearance of the cutaneous granulomas. Similar B- and T-cell abnormalities were described in patients with other PIDs with skin granulomas. CONCLUSIONS: We hypothesize that the pathogenesis of these skin granulomas is related to immune dysregulation of macrophages due to the absence of naïve T cells with an appropriate T-cell receptor repertoire and the unopposed activity of γδ T cells and/or natural killer cells.

Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours.

BACKGROUND: Immunodeficiency in ataxia telangiectasia (A-T) is less severe in patients expressing some mutant or normal ATM kinase activity. We, therefore, determined whether expression of residual ATM kinase activity also protected against tumour development in A-T. METHODS: From a total of 296 consecutive genetically confirmed A-T patients from the British Isles and the Netherlands, we identified 66 patients who developed a malignant tumour; 47 lymphoid tumours and 19 non-lymphoid tumours were diagnosed. We determined their ATM mutations, and whether cells from these patients expressed any ATM with residual ATM kinase activity. RESULTS: In childhood, total absence of ATM kinase activity was associated, almost exclusively, with development of lymphoid tumours. There was an overwhelming preponderance of tumours in patients <16 years without kinase activity compared with those with some residual activity, consistent with a substantial protective effect of residual ATM kinase activity against tumour development in childhood. In addition, the presence of eight breast cancers in A-T patients, a 30-fold increased risk, establishes breast cancer as part of the A-T phenotype. CONCLUSION: Overall, a spectrum of tumour types is associated with A-T, consistent with involvement of ATM in different mechanisms of tumour formation. Tumour type was influenced by ATM allelic heterogeneity, residual ATM kinase activity and age.

Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity.

Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animals and may be implicated in the etiology of mood-related phenotypes. However, genetic association studies of the BDNF Val66Met polymorphism (single nucleotide polymorphism rs6265) in major depressive disorder (MDD) have produced inconsistent results. We conducted a meta-analysis of studies comparing the frequency of the BDNF Val66Met-coding variant in depressed cases (MDD) and nondepressed controls. A total of 14 studies involving 2812 cases with DSM-III or -IV defined MDD and 10 843 nondepressed controls met the inclusion criteria. Analyses were stratified either by gender or ethnicity (Asian and Caucasian) because MDD is more prevalent in women and in Caucasians and because BDNF allele frequencies differ by ethnicity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were provided for allelic analyses (Met versus Val), as well as for genotypic analyses (Met/Met and Val/Met versus Val/Val). In the total sample, the BDNF Val66Met polymorphism was not significantly associated with depression. However, the gender stratified analyses revealed significant effects in both the allelic and genotypic analyses in men (OR(MET), 95% CI; 1.27 (1.10-1.47); OR(MET/MET), 95% CI; 1.67 (1.19-2.36)). Stratification according to ethnicity did not show significant effects of the Val66Met polymorphism on MDD. Our results suggest that the BDNF Val66Met polymorphism is of greater importance in the development of MDD in men than in women. Future research into gender issues will be of interest.

Clinical spectrum of ataxia-telangiectasia in adulthood.

OBJECTIVE: To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene. METHODS: Retrospective analysis of the clinical characteristics and course of disease in 13 adult patients with variant A-T of 9 families and 6 unrelated adults with classic A-T and mutation analysis of the ATM gene and measurements of ATM protein expression and kinase activity. RESULTS: Patients with variant A-T were only correctly diagnosed in adulthood. They often presented with extrapyramidal symptoms in childhood, whereas cerebellar ataxia appeared later. Four patients with variant A-T developed a malignancy. Patients with classic and variant A-T had elevated serum alpha-fetoprotein levels and chromosome 7/14 rearrangements. The mildest variant A-T phenotype was associated with missense mutations in the ATM gene that resulted in expression of some residual ATM protein with kinase activity. Two splicing mutations, c.331 + 5G>A and c.496 + 5G>A, caused a more severe variant A-T phenotype. The splicing mutation c.331 + 5G>A resulted in less ATM protein and kinase activity than the missense mutations. CONCLUSIONS: Ataxia-telangiectasia (A-T) should be considered in patients with unexplained extrapyramidal symptoms. Early diagnosis is important given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment. Measurement of serum alpha-fetoprotein and chromosomal instability precipitates the correct diagnosis. There is a clear genotype-phenotype relation for A-T, since the severity of the phenotype depends on the amount of residual kinase activity as determined by the genotype.

Familiality of depression in the community; associations with gender and phenotype of major depressive disorder.

INTRODUCTION: Although associations between family history and depression have been shown in clinical patients, it is unknown if they also apply to subjects living in the community. The present study considers the relationship between family loading and depression phenotype characteristics in a large community-based sample. METHOD: In a Dutch representative population sample of 7,076 individuals, lifetime diagnosis of depression was classified according to severity, course and age of onset. A family loading score of depression (FLSD) was computed by taking the proportion of the first-degree relatives for whom a history of depression was reported. RESULTS: There was a strong association between FLSD and lifetime diagnosis of MDD. Severity, recurrence and early onset of depression were the specific phenotypic characteristics associated with familiality. The effects of FLSD and gender were independent. CONCLUSION: Associations between family history and risk for depression in the community confirm those reported from clinical-based studies using direct interviewing of relatives. A stronger degree of familiality is associated with specific phenotypic characteristics of depression.