Effects of BDNF Val66Met genotype and schizophrenia familial risk on a neural functional network for cognitive control in humans.

Cognitive control represents an essential neuropsychological characteristic that allows for the rapid adaption of a changing environment by constant re-allocation of cognitive resources. This finely tuned mechanism is impaired in psychiatric disorders such as schizophrenia and contributes to cognitive deficits. Neuroimaging has highlighted the contribution of the anterior cingulate cortex (ACC) and prefrontal regions (PFC) on cognitive control and demonstrated the impact of genetic variation, as well as genetic liability for schizophrenia. In this study, we aimed to examine the influence of the functional single-nucleotide polymorphism (SNP) rs6265 of a plasticity-related neurotrophic factor gene, BDNF (Val66Met), on cognitive control. Strong evidence implicates BDNF Val66Met in neural plasticity in humans. Furthermore, several studies suggest that although the variant is not convincingly associated with schizophrenia risk, it seems to be a modifier of the clinical presentation and course of the disease. In order to clarify the underlying mechanisms using functional magnetic resonance imaging (fMRI), we studied the effects of this SNP on ACC and PFC activation, and the connectivity between these regions in a discovery sample of 85 healthy individuals and sought to replicate this effect in an independent sample of 253 individuals. Additionally, we tested the identified imaging phenotype in relation to schizophrenia familial risk in a sample of 58 unaffected first-degree relatives of schizophrenia patients. We found a significant increase in interregional connectivity between ACC and PFC in the risk-associated BDNF 66Met allele carriers. Furthermore, we replicated this effect in an independent sample and demonstrated its independence of structural confounds, as well as task specificity. A similar coupling increase was detectable in individuals with increased familial risk for schizophrenia. Our results show that a key neural circuit for cognitive control is influenced by a plasticity-related genetic variant, which may render this circuit particular susceptible to genetic and environmental risk factors for schizophrenia.

[Intramedullary injection with tethered cord : Case report of a rare complication during spinal anesthesia]. / Intramedulläre Injektion bei "tethered cord" : Fallbericht einer seltenen Komplikation bei Spinalanästhesie.

Although very rare, severe neurological complications can occur when undergoing spinal anesthesia. This report describes and analyses a case of spinal injury due to an undiagnosed tethered cord (TC) during spinal anesthesia for a cesarean section of a 31-year-old woman expecting twins. As a consequence of spinal dysraphism during embryogenesis, an atypically low conus level can occur and increase the risk of injury during neuraxial anesthesia, especially in the absence of symptoms. Injuries can be caused by mechanical trauma from direct needle injury, hematoma or neurotoxicity from local anesthetics. Special attention should therefore be paid to frequent symptoms, such as a hairy nevus on the back, deformities of the feet or bladder and bowels, voiding and micturition dysfunction in order to reduce the risk of complications.

Systematic review and meta-analysis of the volume-outcome relationship in pancreatic surgery.

BACKGROUND: Many studies have shown lower mortality and higher survival rates after pancreatic surgery with high-volume providers, suggesting that centralization of pancreatic surgery can improve outcomes. The methodological quality of these studies is open to question. This study involves a systematic review of the volume-outcome relationship for pancreatic surgery with a meta-analysis of studies considered to be of good quality. METHODS: A systematic search of electronic databases up to February 2010 was performed to identify all primary studies examining the effects of hospital or surgeon volume on postoperative mortality and survival after pancreatic surgery. All articles were critically appraised with regard to methodological quality and risk of bias. After strict inclusion, meta-analysis assuming a random-effects model was done to estimate the effect of higher surgeon or hospital volume on patient outcome. RESULTS: Fourteen studies were included in the meta-analysis. The results showed a significant association between hospital volume and postoperative mortality (odds ratio 0.32, 95 per cent confidence interval 0.16 to 0.64), and between hospital volume and survival (hazard ratio 0.79, 0.70 to 0.89).The effect of surgeon volume on postoperative mortality was not significant (odds ratio 0.46, 0.17 to 1.26). Significant heterogeneity was seen in the analysis of hospital volume and mortality. Sensitivity analysis showed no correlation with the extent of risk adjustment or study country; after removing one outlier study, the result was homogeneous. The data did not suggest publication bias. CONCLUSION: There was a consistent association between high hospital volume and lower postoperative mortality rates with improved long-term survival.

Cardiac magnetic resonance imaging in daily practice in a peripheral medical centre: description of the first 383 patients.

BACKGROUND: Cardiac magnetic resonance (CMR) imaging has evolved over the last decade into an indispensable diagnostic instrument. CMR imaging noninvasively provides structural, functional and morphological information with high spatial resolution and an unlimited field of view. Since October 2006 the VieCuri Medical Centre in Venlo has a CMR scanner at its disposal. OBJECTIVES: The goal of this study was to analyse the impact of CMR imaging on diagnosis and treatment in daily practice in the setting of a medium-volume peripheral hospital. METHODS: All patients who underwent CMR imaging between October 2006 and November 2008 were included in this analysis. The medical history before and after the CMR scan, the application form for CMR imaging and the outcome of the scans were reviewed. CMR images, obtained using a 1.5-T magnetic resonance imaging system, were reviewed by a multidisciplinary team. RESULTS: In 235 patients CMR imaging demonstrated one or more abnormalities, whereas CMR imaging did not identify any abnormalities in 148 patients. CMR imaging confirmed an expected finding in 166 cases, identified an unexpected condition in 69 cases, ruled out an expected finding in 59 cases and ruled out a suspected condition in 89 cases. Due to better insight into diagnosis, CMR imaging resulted in a change of treatment in 166 of the total of 383 CMR scans (43%). CONCLUSION: In a relevant number of cases CMR imaging leads to a change in the treatment of a patient, proving the value of CMR imaging as a diagnostic modality. Therefore, CMR imaging is an excellent opportunity for peripheral medical centres to improve efficiency and the standard of patient care. (Neth Heart J 2010;18:524-30.).

A systematic review and meta-analysis of the volume-outcome relationship in the surgical treatment of breast cancer. Are breast cancer patients better of with a high volume provider?

AIMS: To conduct a systematic review of the literature on the volume-outcome relationship for the surgical treatment of breast cancer with consideration of the methodological quality of the available evidence and to perform a meta-analysis on the studies of considered good quality. METHODS: A systematic search was done to identify all articles examining the effects of hospital or surgeon volume on clinical outcome of the surgical treatment of breast cancer. Reviews, opinion articles and surveys were excluded. All articles were critically appraised on methodological quality and risk of bias. After strict inclusion, meta-analysis assuming a random effects model was done to estimate the effect of higher hospital or surgeon volume on patient outcome. RESULTS: We found 12 studies of good methodological quality which could be included for meta-analysis. The results showed a significant association between high volume providers and an improved survival. The association is the most robust for surgeon volume (HR 0.80 (0.71-0.90) and RR 0.85 (0.80-0.90). In addition there is an effect of hospital volume on the in-hospital mortality, although the mortality was very low (0.1-0.2%). Results of meta-analysis were heterogeneous. Sensitivity analysis showed a larger effect size for studies also adjusting for comorbidity for both studies on hospital and surgeon volume. The data were not suggestive for publication bias. CONCLUSIONS: The results show that survival after breast cancer surgery is significantly associated with high volume providers.

Volume and outcome in colorectal cancer surgery.

AIMS: There is a growing consensus to concentrate high-risk surgical procedures to high volume surgeons in high volume hospitals. However, there is fierce debate about centralizing more common malignancies such as colorectal cancer. The objective of this review is to conduct a meta-analysis using the best evidence available on the volume-outcome relationship for colorectal cancer treatment. METHODS: A systematic search was performed to identify all relevant articles studying the relation between hospital and/or surgeon volume and clinical outcomes for colorectal cancer. Using strict inclusion criteria, 23 articles were selected concerning colon cancer, rectal cancer or both diseases together as 'colorectal cancer'. Pooled estimated effect sizes were calculated using the casemix adjusted outcomes of the highest volume group opposed to the lowest volume group. RESULTS: High volume hospitals have a significantly lower postoperative mortality in half of the pooled results. Non significant results show a trend in favour of high volume hospitals. All results showed a significantly better long term survival in high volume hospitals. High volume surgeons have a lower postoperative mortality, although evidence is sparse. All analyses showed a significantly better long term survival in favour of high volume surgeons. CONCLUSIONS: The results show a clear and consistent relation between high volume providers and improved long term survival. This applies to both high volume hospitals and high volume surgeons. Most results show a relation between high volume providers and a reduced postoperative mortality, but evidence is less convincing. In the ideal world, extensive population based audit registrations with casemix adjusted feedback should make rigid minimal volume standards obsolete. Until then, using volume criteria for hospitals and surgeons treating colorectal cancer can improve mortality and especially long term survival.

Hb A1c in relation to intrauterine growth among male adolescents in southern Brazil.

The fetal origins hypothesis states that nutritional deprivation in utero affects fetal development and contributes to the incidence of diseases associated with the metabolic syndrome in later life. This study investigated whether haemoglobin (Hb) A(1c), an indicator of blood glucose, varied among healthy male adolescents according to their fetal growth rate, in a middle-income setting. Participants were men aged 18 years, belonging to the 1982 Pelotas birth cohort. Complete data, including gestational age and Hb A(1c) at age 18 years, were available for 197 individuals. There was an inverse association between mean Hb A(1c) and birthweight for the gestational age, but not birthweight alone. The association remained significant after adjustment for family income and mother's education, as well as for body mass index at 18 years (P for trend=0.01 and 0.03, respectively).

Declining incidence of peptic ulcer but not of its complications: a nation-wide study in The Netherlands.

BACKGROUND: Despite reports of decreasing hospitalizations and mortality due to peptic ulcer, it is unclear whether the incidence has truly declined over time. AIM: To investigate time trends in the incidence of and in hospital admission rates for peptic ulcer in the Netherlands. METHODS: The nationwide registry of pathology reports (PALGA) and the national registry of hospital admissions (Landelijke Medische Registratie) were used. Standardized morbidity ratios were calculated to assess the magnitude of the changes. RESULTS: The age-adjusted incidence of gastric ulcer halved for both men (standardized morbidity ratio 0.48; CI 0.46-0.49) and women (standardized morbidity ratio 0.49; CI 0.47-0.51). Although the number of gastric biopsies obtained at endoscopy increased, the proportion with a diagnosis of peptic ulcer decreased by more than 50% (standardized morbidity ratio 0.47; CI 0.46-0.49). The admission rate for peptic ulcer more than halved between 1980 and 2003. In contrast, admission rates for complicated ulcers barely changed and slightly increased among women. CONCLUSIONS: The incidence of histopathologically confirmed gastric ulcer halved between 1992 and 2003 in the Netherlands. As the number of gastric biopsies increased in this period, a true decrease is likely. Hospital admissions for peptic ulcer declined dramatically between 1980 and 2003, but remained unchanged or slightly increased for complicated ulcers.

Optimal follow-up strategies after aorto-iliac prosthetic reconstruction: a decision analysis and cost-effectiveness analysis.

OBJECTIVE: The primary aim of ultrasound follow-up after aorto-iliac prosthetic reconstruction is to correct false aneurysms before rupture occurs. We investigated whether follow-up improves the life expectancy of patients and sought to identify the most cost-effective follow-up strategy. DESIGN OF THE STUDY: A Monte Carlo Markov decision model was constructed. The occurrence of false aneurysms was modelled as a time-dependent process for each anastomotic site, based on published series. Using this model, the impact of various follow-up strategies was investigated for three types of prostheses, aorto-distal tube, aorto-bi-iliac, and aorto-bi-femoral prostheses. Main outcome measures were discounted quality adjusted life years (dQALYs), discounted costs, and (discounted) cost-effectiveness (CE) ratios. RESULTS: Follow-up of patients with aorto-distal tube and aorto-bifemoral prostheses did not result in an improvement life expectancy and was not cost-effective, QALYs 7.53 and 7.62 years, respectively. The results for aorto-distal tube and aorto-bifemoral prostheses were not sensitive to any variation in the model parameters. In the base case analysis, the life expectancy of patients with aorto-bi-iliac prostheses was 7.50 QALYs (95% confidence interval 7.46-7.54) whether or not they underwent routine follow-up. However, patients aged 54 years or younger gained 0.11 QALYs with annual follow-up (p<0.05). The most cost-effective strategy was annual follow-up that starts 10 years after the initial operation, and continues up to 30 years after surgery (4600 Euro; CE ratio 21,000 Euro per QALY). When perioperative mortality of elective reconstruction of false aneurysms is 2% or lower (e.g. when endovascular treatment is used), a small improvement is observed (7.56 vs. 7.50 QALYs; p<0.05; CE ratio 35,000 Euro per QALY). CONCLUSIONS: Annual follow-up of aorto-bi-iliac prostheses should be restricted to patients aged 54 or younger and not start before 10 years after surgery. The same strategy can only be considered for older patients if mortality for secondary intervention is lower than 2%. Since patients with aorto-distal tube and aorto-bi-femoral prostheses do not benefit from follow-up for the detection of false aneurysms, this practice should be discouraged in these patient groups.

[The epidemiology of tumors of the testes in the Netherlands: accurate rendering by the Registry of Histopathology and Cytopathology (PALGA)]. / Epidemiologie van testistumoren in Nederland: accurate weergave in de PALGA-registratie.

OBJECTIVE: To investigate recent trends in the incidence of testicular cancer and to describe epidemiological characteristics of various subtypes of testicular cancer. DESIGN: Descriptive. METHOD: Using the nationwide registry of pathology reports (PALGA), the incidence of all newly-diagnosed cases of testicular cancer between the years 1991 and 2002 was analyzed according to age and subtype. To test the accuracy of the PALGA figures, a comparison was made with incidence figures (1991-1998) produced by the Netherlands Cancer Registry. RESULTS: 5856 cases of testicular cancer were diagnosed. The age-adjusted incidence increased from 4.8 to 6.6 per 100,000. The incidence of non-seminoma increased to a larger extent than that of seminoma. The incidence of malignant lymphoma of testicular origin did not increase, but it remained the most frequent testicular tumour beyond the age of 65. Non-seminoma was the most common tumour below the age of 30, while seminoma was the most commonly found tumour between the ages of 30 and 65. When PALGA began recording statistics, the incidence figures showed a difference of up to 10% with the figures produced by the cancer registry, but this has decreased to 1-2% in more recent years. CONCLUSION: The incidence of testicular cancer increased from the 1990s up to 2002. The incidence figures of histopathologically confirmed cases of cancer in the PALGA registry were timely and accurate.

Saphenous vein versus PTFE for above-knee femoropopliteal bypass. A review of the literature.

The autogenous saphenous vein is considered the best bypass graft material for arterial bypasses below the inguinal ligament. However, a synthetic graft or prosthesis is considered an acceptable alternative, especially when the distal anastomosis is situated above the knee. Some studies even suggest that patency rates for vein and synthetic grafts are comparable, whereas others indicate that a vein graft is superior to a prosthetic graft, even above the knee. To test the hypothesis that both vein grafts and synthetic prostheses are equally beneficial in the above-knee position, we performed a systematic review of available studies comparing the patency of saphenous vein and polytetrafluoroethylene (PTFE) as bypass material. English and German medical literature from 1966 to 2002 was searched using Medline, and 25 articles meeting our inclusion and exclusion criteria were selected. The patency of venous bypasses was superior to that of PTFE bypasses at all time intervals studied. After 2 years, the primary patency rate of venous bypasses was 81% as compared to 67% for PTFE bypasses, and after 5 years it was 69 and 49%, respectively. After 5 years, the secondary patency of PTFE bypasses reached 60%. When only randomized trials were considered, venous bypasses were again superior to PTFE bypasses at all intervals studied. After 2 years, the primary patency rate of venous and PTFE bypasses was 80 and 69%, respectively, and after 5 years it was 74 and 39%, respectively. Since both randomized and retrospective studies comparing venous with PTFE bypasses showed that vein grafts were 'better' than PTFE prostheses, the null hypothesis that there is no difference between the two types of graft material was rejected (p=0.008). We conclude from this systematic review that if a saphenous vein is available, a venous bypass should be chosen at all times, even if patients have an anticipated short life expectancy (<2 years). If the saphenous vein is absent or not suitable for bypass grafting, PTFE is a good alternative as bypass material.

The early use of yellow fever virus strain 17D for vaccine production in Brazil--a review.

The use of yellow fever (YF) virus 17D strain for vaccine production adapted in Brazil since its introduction in 1937 was reviewed. This was possible due to the availability of official records of vaccine production. The retrieved data highlight the simultaneous use of several serially passaged 17D substrain viruses for both inocula and vaccine preparation that allowed uninterrupted production. Substitution of these substrain viruses became possible with the experience gained during quality control and human vaccination. Post-vaccinal complications in humans and the failure of some viruses in quality control tests (neurovirulence for monkeys) indicated that variables needed to be reduced during vaccine production, leading to the development of the seed lot system. The 17DD substrain, still used today, was the most frequently used substrain and the most reliable in terms of safety and efficacy. For this reason, it is possible to derive an infectious cDNA clone of this substrain combined with production in cell culture that could be used to direct the expression of heterologous antigens and lead to the development of new live vaccines.

The utility of health states after stroke: a systematic review of the literature.

BACKGROUND: To perform decision analyses that include stroke as one of the possible health states, the utilities of stroke states must be determined. We reviewed the literature to obtain estimates of the utility of stroke and explored the impact of the study population and the elicitation method. SUMMARY OF REVIEW: We searched various databases for articles reporting empirical assessment of utilities. Mean utilities of major stroke (Rankin Scale 4 to 5) and minor stroke (Rankin Scale 2 to 3) were calculated, stratified by study population and elicitation method. Additionally, the modified Rankin Scale was mapped onto the EuroQol classification system. Utilities were obtained from 23 articles. Patients at risk for stroke assigned utilities of 0.26 and 0.55 to major and minor stroke, respectively. Stroke survivors assigned higher utilities to both major (0.41) and minor stroke (0.72). The EuroQol completed by stroke survivors revealed a utility of 0.32 and 0.71 for major and minor stroke, respectively. Utilities elicited by the Standard Gamble were generally higher, while those obtained by the Visual Analogue Scale were lower than the Time Trade Off values. Remaining variation between utilities may be caused by differences in definitions of the health states. The mapped EuroQol indicated a utility of 0.64 for minor stroke and a value just below zero for major stroke. CONCLUSIONS: For minor stroke, a utility between 0.50 and 0.70 seems to be reasonable for both decision analyses and cost-effectiveness studies. The utility of major stroke may range between 0 and 0.30 and may possibly be negative.

The independent prognostic value of comorbidity among men aged < 75 years with localized prostate cancer: a population-based study.

OBJECTIVE: To investigate which prognostic factors apply in patients with localized prostate cancer diagnosed after the introduction of prostate-specific antigen (PSA) testing, as comorbidity has significant prognostic value for patients who were diagnosed with localized prostate cancer in the 1970s. Patients and methods Using the Eindhoven Cancer Registry, we assessed a population-based cohort of patients aged < 75 years with localized (T1-T3M0) prostate cancer diagnosed between 1993 and 1995 in a defined area with 2 million inhabitants in the southern Netherlands (n = 894). After a mean follow-up of 2.9 years, overall survival was modelled by Cox regression analyses. RESULTS: Comorbidity was the most important prognostic factor, especially for those aged < 70 years; at 60 years old, patients with one concomitant disease were twice as likely to die than those with no comorbidity (95% confidence interval, CI, 1.0-4.3), whereas the hazard ratio (HR) was 7.2 (3.1-16.6) for two or more diseases. This was not caused by a reduced use of curative treatment for these patients. At the age of 74 years, comorbidity was no longer a significant prognostic factor. Poor differentiation of the tumour was also an important prognostic factor at all ages; this became increasingly apparent 2 years after diagnosis (HR 3.4, CI 1.5-7.7). Conclusion Comorbidity had a decisive influence on the prognosis for patients with localized prostate cancer. Because this effect was stronger in younger patients the assessment of comorbidity seems most important when evaluating the risk of early death.

Ritanserin as add-on medication to neuroleptic therapy for patients with chronic or subchronic schizophrenia.

The effect of ritanserin, a potent 5HT 2A/2C receptor antagonist, used as an add-on medication to neuroleptic treatment in patients with schizophrenia, was compared with that of placebo, in an international, double-blind, parallel-group study. Previously established neuroleptic therapy was maintained, and ritanserin 10 mg or placebo was given once daily for 8 weeks. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression (CGI) cale. Safety assessments included the Extrapyramidal Symptom Rating Scale (ESRS), and the requirement for antiparkinsonian medication was monitored. About 70 per cent of patients completed the treatment. There was no difference between the two groups in the numbers of patients with clinical improvement at endpoint on the PANSS negative subscale and total PANSS. The CGIs of overall severity of schizophrenia were better under placebo. The overall prevalence of side effects and the requirements for antiparkinsonism medication were comparable in the two groups. Copyright 2000 John Wiley & Sons, Ltd.

Long-term survival of prostate cancer in southeastern Netherlands.

With the increase in detection at an early stage, only a few and conflicting results have been reported on the long-term outcome for prostate cancer beyond 10 years. The vast majority of prostate cancer patients diagnosed between 1955 and 1984 in southeastern Netherlands, with a population of almost one million inhabitants, did not receive any curative treatment. We calculated the prognosis for 10-year survivors of prostate cancer diagnosed in the era preceding prostate-specific antigen (PSA) testing to determine how long these patients exhibited excess mortality. All patients under age 70 diagnosed with prostate cancer and registered in the population-based Eindhoven Cancer Registry between 1955 and 1984 were included in the study. Relative survival was calculated for those who survived for at least 10 years (n = 174). Initially, these patients still exhibited an almost 25% excess mortality risk, but this decreased with time and no excess mortality was found after 15 years.

Serious co-morbidity among unselected cancer patients newly diagnosed in the southeastern part of The Netherlands in 1993-1996.

The purpose of this study was to determine the prevalence of serious concomitant conditions at diagnosis among unselected patients with cancer, increasingly older in industrialized countries. About 34,000 newly diagnosed cancer patients were recorded in the Eindhoven Cancer Registry between 1993 and 1996; subsequently data on serious co-morbidity, classified according to the Charlson scheme (J Chron Dis 1987; 40: 373-383), were collected from the clinical records by registry personnel. Co-morbid conditions were present in 12% of adult patients below 45 years of age, 28% of those 45-59 years, 53% of those 60-74 years, and 63% of patients over 75 years of age, the prevalence being highest for patients with lung (58%), kidney (54%), stomach (53%), bladder (53%), and prostate cancer (51%). Males exhibited a 10% higher prevalence than females with similar tumors. Among patients over 60 years the most frequent conditions were heart and vascular diseases (ranging across the various tumors from 10% to 30%), hypertension (11-25%), another cancer (10-20%), COPD (chronic obstructive pulmonary disease) (3-25%), and diabetes mellitus (5-25%). Inclusion of frequent co-morbid conditions in prognostic research as well as the development of specific guidelines for patient care seems warranted.

Comorbidity in patients with prostate cancer and its relevance to treatment choice.

OBJECTIVE: To evaluate the prevalence of comorbidity among patients with prostate cancer in relation to tumour and patient characteristics and to assess if comorbidity was a determining factor in the treatment choice for patients with localized prostate cancer. PATIENTS AND METHODS: Serious comorbidity was recorded in the Eindhoven Cancer Registry (according to a published list of such diseases) for all patients (2941) with prostate cancer newly diagnosed between 1993 and 1996 in the southern part of The Netherlands. Logistic regression was then used to assess which factors determined the treatment choice. RESULTS: The prevalence of at least one serious comorbid condition was 38% for patients aged 60-69 years, 48% when aged 70-74 years and 53% for those aged >/=75 years, the cardiovascular and chronic obstructive lung diseases being most frequent. Patients aged 60-69 years were more likely to be treated with radical prostatectomy for moderately differentiated tumour confined to the prostate, or when younger and diagnosed in a hospital with a high case-load. The presence of comorbidity had little influence of this choice. CONCLUSION: Comorbidity was common in patients with prostate cancer, but the decision of urologists in the southern Netherlands to use radical prostatectomy was determined largely by the patient's age and the urologist's experience.