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ABSTRACT: Sporadic ALS is a multifactorial disease for which there are probably multiple genetic risk factors. An association with increased parental age might suggest there is a role for specific (epi)genetic changes. Previous studies have shown conflicting results on the association between parental age and the risk of ALS. A large, population based study might help in the search for specific (epi)genetic risk factors. We performed a population based, case-control study in the Netherlands. Date of birth of both mother and father was retrieved from the National Register. Multivariate logistic regression analysis was performed in 769 patients with sporadic ALS, 49 patients with a hexanucleotide repeat expansion in C9orf72, and 1929 age-, gender- and geographically-matched controls. Multivariate analyses showed no difference in either paternal or maternal age at delivery (adjusted for age of subject, age of other parent at delivery, and level of education) in patients with sporadic ALS, nor in patients with a hexanucleotide repeat expansion in C9orf72 compared to controls. In conclusion, parental age was not associated with an increased risk of ALS in our study. (Epi)genetic alterations that are associated with increased parental age are not, therefore, likely to contribute to the aetiology of sporadic ALS.
Amyotrophic Lateral Sclerosis 11/2012; · 3.40 Impact Factor
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ABSTRACT: Smoking has been posited as a possible risk factor for amyotrophic lateral sclerosis (ALS), but large population-based studies of patients with incident disease are still needed. The authors performed a population-based case-control study in the Netherlands between 2006 and 2009, including 494 patients with incident ALS and 1,599 controls. To prove the relevance of population-based incidence cohorts in case-control studies, the authors compared results with those from cohorts including patients with prevalent ALS and referral patients. Subjects were sent a questionnaire. Multivariate analyses showed an increased risk of ALS among current smokers (odds ratio = 1.38, 95% confidence interval (CI): 1.02, 1.88) in the incident patient group only. Cox regression models showed that current smoking was also independently associated with shorter survival (hazard ratio = 1.51, 95% CI: 1.07, 2.15), explaining the lack of association in the prevalent and referral patient groups. Current alcohol consumption was associated with a reduced risk of ALS (incident patient group: odds ratio = 0.52, 95% CI: 0.40, 0.75). These findings indicate that current smoking is associated with an increased risk of ALS, as well as a worse prognosis, and alcohol consumption is associated with a reduced risk of ALS, further corroborating the role of lifestyle factors in the pathogenesis of ALS. The importance of population-based incident patient cohorts in identifying risk factors is highlighted by this study.
American journal of epidemiology 07/2012; 176(3):233-9. · 5.59 Impact Factor
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ABSTRACT: Cardiovascular disease (CVD) mortality is reported to be lower in haemophilia patients than in the general population, but information on the occurrence of non-fatal CVD is lacking. The aim of our study was to assess CVD history in a cohort of living haemophilia patients.
Retrospective data on the occurrence of myocardial infarction, angina pectoris, ischaemic stroke and intracranial bleeding in 709 living Dutch and British haemophilia patients aged 30 yr or older were analysed and compared with the general age-matched male population.
There was a trend towards a lower cumulative incidence of myocardial infarction (1.7% vs. 4.0%) and ischaemic stroke (0% vs. 1.5%) in patients with severe haemophilia than in the general population, while the occurrence of angina pectoris was similar (3.2 vs. 3.7%). As expected, the cumulative incidence of intracranial bleeding was, on the other hand, significantly increased in haemophilia patients (1.6% vs. 0.4% in the general population).
Our results suggest a protective effect of severe haemophilia against acute ischaemic CVD.
European Journal Of Haematology 07/2012; 89(4):336-9. · 2.61 Impact Factor
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ABSTRACT: With increasing life expectancy, more haemophilia patients will be confronted with age-related problems. To ensure optimal care, it is important to know the occurrence of both fatal and non-fatal cardiovascular disease, malignancies and other types of co-morbidity in these patients. Our aim was to retrospectively assess the occurrence of co-morbidity and causes of death in a substantial birth-cohort of haemophilia patients.
Data on all types of co-morbidity were collected from medical records of 408 haemophilia patients (204 severe, 204 non-severe) born before 1971, and compared with the Dutch age-matched general male population.
Ten patients had 11 myocardial infarctions, none of which were fatal. The cumulative incidence of non-fatal myocardial infarction was significantly lower in patients with severe haemophilia than in the general population (0.5% versus 4.8%), but was not decreased in patients with non-severe haemophilia (4.4%). Intracranial bleeding occurred significantly more often in haemophilia patients. The occurrence of non-virus related malignancies, and other non-virus related co-morbidities was similar in haemophilia patients and the general population. HIV infection was present in 12% of patients, and hepatitis C infection in 56%. Seventy-eight patients (19%) were deceased. Main causes of death were malignancies, AIDS, hepatitis C, and intracranial bleeding.
Our results showed a decreased occurrence of myocardial infarction in patients with severe haemophilia, suggesting a protective effect of very low clotting factor levels on thrombotic cardiac events. No differences were found between haemophilia patients and the general population in the occurrence of any other type of non-virus related co-morbidity.
Thrombosis Research 12/2011; 130(2):157-62. · 2.44 Impact Factor
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ABSTRACT: Few studies have reported on Barrett's esophagus (BE) in children. Moreover, information on the age at diagnosis and the duration between reflux-symptoms and diagnosis is lacking.
A review of the literature was performed in PubMed, EMBASE and the Cochrane database.
Fourteen articles were included, of which 4 cohort studies and 10 studies investigating patients already diagnosed with BE. The cohort studies showed 37 patients diagnosed with BE (0.3-4.8%), mean age 12.4 years. Time between onset of reflux-symptoms and BE was 2.8 years. All 14 studies together showed 176 patients with BE (mean age 9.5 years). Time between onset of reflux-symptoms and BE was 5.3 years. During endoscopic follow-up of 45 patients, 26 still had BE, 17 no longer had evidence of BE, and two had developed esophageal-adenocarcinoma.
This review shows that BE and esophageal-adenocarcinoma occur in children. However, criteria used to define BE by the included studies were not comparable to the current criteria and data on GERD symptoms may have been inaccurate. Therefore, we recommend performing a long-term prospective study on the relationship between (duration of) GERD and the development of BE in children in order to define screening guidelines.
Digestive and Liver Disease 03/2011; 43(9):682-7. · 3.05 Impact Factor
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ABSTRACT: Epilepsy has a significant impact on health-related quality of life (HRQOL) of patients and personal coping style is an important determinant. Less is known about home caregivers. This study investigates HRQOL and coping style of both patients and caregivers and their interaction. Epilepsy patients attending the outpatient clinic of the University Medical Centre in Utrecht and their caregivers were sent EQ5D and RAND-36 questionnaires. The Utrecht Coping List was used to chart personal coping styles. HRQOL scores of patients and caregivers were compared to the general Dutch population. The association between patient and caregiver HRQOL scores was calculated. A stepwise backward multivariate linear regression analysis was used to explain variances in caregiver HRQOL. Eighty-six couples (49%) returned all questionnaires. Caregiver HRQOL scores were comparable to the general Dutch population (EQ5D: 0.88-0.88; p = 0.90, RAND-36 MCS: -2 points; p = 0.16), while patients HRQOL scores were lower (EQ5D: 0.79; p < 0.01, RAND-36 MCS -10 points; p < 0.01). However, on several specific domains, associations between patient and caregiver HRQOL scores within couples were found. Passive coping style explained 50% of variation in HRQOL scores of caregivers. As a group, caregivers of epilepsy patients have normal HRQOL, but there are significant associations between patient and caregiver HRQOL scores. Improving caregiver HRQOL through interventions on coping style might benefit patients as well. Recognizing personal coping styles of both patient and caregiver should be part of a patient-oriented approach in treatment.
Journal of Neurology 03/2011; 258(10):1788-94. · 3.47 Impact Factor
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ABSTRACT: Having epilepsy has a large impact on one's well-being, but often seizure frequency and severity do not explain self-reported quality of life. We hypothesized that one's personal coping style is more important. In this study, 105 patients attending the outpatient neurological clinic at the University Medical Centre in Utrecht, the Netherlands, with a diagnosis of partial epilepsy, aged 17-80 years, completed questionnaires. Demographic information, disease characteristics, health-related quality of life (HRQoL), and coping styles were obtained by postal-validated HRQoL questionnaires: the EQ5D and RAND-36 and the Utrecht Coping List. A passive coping style explained 45% of the variance in the mental component of HRQoL and was more important than 'objective' seizure-related measures. Confounders such as employment, gender, and side-effects of treatment explained another 6%. Passive coping style also influenced the physical component of the HRQoL, but here seizure-related factors predominated. Overall, epilepsy patients showed a more avoiding coping style, and female patients a less active coping style and more reassuring thoughts, compared to the Dutch population. The personal coping style of patients appears to be more important than seizure-related measures in predicting mental aspects of quality of life. Coping style characteristics rather than disease characteristics should guide clinical decision-making in patients with epilepsy. Further studies should investigate the effect on HRQoL of behavioral interventions to improve coping.
Journal of Neurology 01/2011; 258(1):37-43. · 3.47 Impact Factor
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ABSTRACT: Severe hemophilia requires life-long treatment with expensive clotting factor concentrates; studies comparing effects of different therapeutic strategies over decades are very difficult to perform. A simulation model was developed to evaluate the long-term outcome of on demand, prophylactic and mixed treatment strategies for patients with severe hemophilia A.
A computer model was developed based on individual patients' data from a Dutch cohort study in which intermediate dose prophylaxis was used and a French cohort study in which on demand treatment was used, and multivariate regression analyses. This model simulated individual patients' life expectancy, onset of bleeding, life-time joint bleeds, radiological outcome and concentrate use according to the different treatment strategies.
According to the model, life-time on demand treatment would result in an average of 1,494 joint bleeds during the hemophiliac's life, and consumption of 4.9 million IU of factor VIII concentrate. In contrast, life-time intermediate dose prophylaxis resulted in a mean of 357 joint bleeds and factor consumption of 8.3 million IU. A multiple switch strategy (between prophylactic and on demand treatment based on bleeding pattern) resulted in a mean number of 395 joint bleeds and factor consumption of 6.6 million IU. The estimated proportion of patients with Pettersson scores over 28 points was 32% for both the prophylactic and the multiple switching strategies, compared to 76% for continuous on demand treatment.
The present model allows evaluation of the impact of various treatment strategies on patients' joint bleeds and clotting factor consumption. It may be expanded with additional data to allow more precise estimates and include economic evaluations of treatment strategies.
Haematologica 01/2011; 96(5):738-43. · 6.42 Impact Factor
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ABSTRACT: Detection of absolute and relative lymphocytosis in otherwise asymptomatic elderly patients is very common in the primary care setting and frequently results in referral for screening of lymphoproliferative disorders. Since many B-cell chronic lymphoproliferative disorders (B-CLPD) are indeed asymptomatic at diagnosis in most patients with lymphocytosis, no sign of such a disorder is usually detected. Currently, specific guidelines for screening of patients with lymphocytosis are lacking. We investigated the practicability and clinical value of a single colour CD19 count performed by a primary care laboratory in order to improve the diagnostic follow-up of patients with lymphocytosis in a primary care laboratory.
The capability of detecting monoclonal B-cell lymphocytosis and B-CLPD by CD19, was first confirmed in patient samples with known B-CLPD. Next, in a previously defined geographic area, a CD19 count was performed on all samples for patients aged ≥40 years with relative or absolute lymphocytosis but without neutropenia. Clinical follow-up, with a median of 4 years, was performed using both a survey among the requesting general practitioners and by analysis of the records of the referral hospitals within the borders of the defined area.
A total of 520 cases with asymptomatic lymphocytosis were identified. In all cases, the CD19 count was performed; 207 (40%) showed increased values and 313 (60%) showed normal values. An increase in CD19 proved highly sensitive for detection of B-CLPD (98%, 95% CI; 94%-100%) with a high positive predictive value (57%, 95% CI; 50%-63%). The area under curve, the receiver-operating characteristic curve of the CD19 count (0.93, 95% CI; 0.91-0.96), was significantly higher compared to the absolute lymphocyte count (0.86, 95% CI; 0.83-0.89), especially in patients with moderate lymphocytosis.
This study indicates that the CD19 count, performed by a primary care laboratory, is feasible and a promising tool for initial screening of lymphocytosis to discriminate B-CLPD from benign causes of lymphocytosis.
Clinical Chemistry and Laboratory Medicine 11/2010; 49(1):115-20. · 2.15 Impact Factor
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ABSTRACT: Occupational and environmental exposures may contribute to the risk of developing sporadic amyotrophic lateral sclerosis (ALS). To summarize the available evidence, a systematic review of the literature on occupation as a potential determinant of ALS was performed according to the MOOSE guidelines. From MEDLINE, EMBASE, CINAHL, and Cochrane databases, selected studies were methodologically appraised according to Armon's classification system for ALS risk factor studies. Each occupation studied was reclassified according to the International Standard Classification of Occupations (ISCO-88). The vote-counting method was applied to summarize the data. Of 3773 potentially relevant studies, 51 were initially included. Of these, 12 studies provided risk estimates for individual occupations – one case-control, two register-based case-control, and nine register-based cohort studies. All studies fell into Armon's level of evidence class IV, indicating methodological limitations. Due to the heterogeneity of study methodology, data could not be pooled. The vote-counting method revealed several candidate occupations: veterinarians and other health workers, athletes, hairdressers, power-production plant, electrical and military workers. However, well designed studies with standardized assessment of occupation are needed to provide a more definitive answer about exogenous risk factors of ALS.
11/2009; 10(5-6):295-301.
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Blood 11/2009; 114(23):4907; author reply 4907-8. · 9.90 Impact Factor
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Marc G Besselink,
Hjalmar C van Santvoort,
Willem Renooij,
Martin B de Smet,
Marja A Boermeester, Kathelijn Fischer,
Harro M Timmerman,
Usama Ahmed Ali,
Geert A Cirkel,
Thomas L Bollen, [......],
Cornelis J van Laarhoven,
Adriaan C Tan,
Menno A Brink,
Erwin van der Harst,
Peter J Wahab,
Casper H van Eijck,
Cornelis H Dejong,
Karel J van Erpecum,
Louis M Akkermans,
Hein G Gooszen
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ABSTRACT: To determine the relation between intestinal barrier dysfunction, bacterial translocation, and clinical outcome in patients with predicted severe acute pancreatitis and the influence of probiotics on these processes.
Randomized, placebo-controlled, multicenter trial on probiotic prophylaxis (Ecologic 641) in patients with predicted severe acute pancreatitis (PROPATRIA).
Excretion of intestinal fatty acid binding protein (IFABP, a parameter for enterocyte damage), recovery of polyethylene glycols (PEGs, a parameter for intestinal permeability), and excretion of nitric oxide (NOx, a parameter for bacterial translocation) were assessed in urine of 141 patients collected 24 to 48 h after start of probiotic or placebo treatment and 7 days thereafter.
IFABP concentrations in the first 72 hours were higher in patients who developed bacteremia (P = 0.03), infected necrosis (P = 0.01), and organ failure (P = 0.008). PEG recovery was higher in patients who developed bacteremia (PEG 4000, P = 0.001), organ failure (PEG 4000, P < 0.0001), or died (PEG 4000, P = 0.009). Probiotic prophylaxis was associated with an increase in IFABP (median 362 vs. 199 pg/mL; P = 0.02), most evidently in patients with organ failure (P = 0.001), and did not influence intestinal permeability. Overall, probiotics decreased NOx (P = 0.05) but, in patients with organ failure, increased NOx (P = 0.001).
Bacteremia, infected necrosis, organ failure, and mortality were all associated with intestinal barrier dysfunction early in the course of acute pancreatitis. Overall, prophylaxis with this specific combination of probiotic strains reduced bacterial translocation, but was associated with increased bacterial translocation and enterocyte damage in patients with organ failure.
Annals of surgery 10/2009; 250(5):712-9. · 7.90 Impact Factor
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ABSTRACT: Background
Von Willebrand factor (VWF) is critical for the in vivo survival of factor VIII (FVIII). Since FVIII half-life correlates with VWF-antigen pre-infusion levels, we hypothesized that VWF levels are useful to predict FVIII half-life.
Methodology
Standardized half-life studies and analysis of pre-infusion VWF and VWF-propeptide levels were performed in a cohort of 38 patients with severe haemophilia A (FVIII
PLoS ONE 08/2009; 4(8). · 4.09 Impact Factor
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ABSTRACT: To determine the natural course of sporadic adult-onset lower motor neuron syndrome in a long-term prospective study of patients with the syndrome.
Inception cohort with a follow-up of 72 months.
Three university hospitals in the Netherlands (referral centers for neuromuscular diseases).
Thirty-two patients were classified as having the following phenotypes according to previously defined criteria: progressive muscular atrophy (PMA; 10 patients), segmental distal muscular atrophy (8 patients), and segmental proximal muscular atrophy (14 patients). A disease duration of at least 4 years was chosen to exclude most patients with amyotrophic lateral sclerosis (ALS).
Muscle strength, functional impairment, and respiratory function were assessed at 0, 6, 12, 18, and approximately 72 months.
The diagnosis had to be changed to ALS in 3 patients (classified at inclusion as PMA in 2 patients and segmental proximal muscular atrophy in 1) owing to the development of upper motor neuron signs in 2 patients and familial ALS in 1. The remaining 8 patients with PMA showed further deterioration, and the other 24 patients remained more or less stable during long-term follow-up. Respiratory insufficiency developed in 6 of the 11 patients with ALS or PMA, 5 of whom died.
Patients with lower motor neuron syndromes and a disease duration of at least 4 years usually have a favorable prognosis if muscle involvement has a segmental distribution. In patients with a generalized phenotype, progression is relentlessly progressive and eventually leads to death due to respiratory insufficiency.
Archives of neurology 07/2009; 66(6):751-7. · 6.31 Impact Factor
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Hjalmar C van Santvoort,
Marc G Besselink,
Annemarie C de Vries,
Marja A Boermeester, Kathelijn Fischer,
Thomas L Bollen,
Geert A Cirkel,
Alexander F Schaapherder,
Vincent B Nieuwenhuijs,
Harry van Goor, [......],
Bas L Weusten,
Cees J van Laarhoven,
Peter J Wahab,
Adriaan C Tan,
Matthijs P Schwartz,
Erwin van der Harst,
Miguel A Cuesta,
Peter D Siersema,
Hein G Gooszen,
Karel J van Erpecum
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ABSTRACT: The role of early endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis (ABP) remains controversial. Previous studies have included only a relatively small number of patients with predicted severe ABP. We investigated the clinical effects of early ERCP in these patients.
We performed a prospective, observational multicenter study in 8 university medical centers and 7 major teaching hospitals. One hundred fifty-three patients with predicted severe ABP without cholangitis enrolled in a randomized multicenter trial on probiotic prophylaxis in acute pancreatitis were prospectively followed. Conservative treatment or ERCP within 72 hours after symptom onset (at discretion of the treating physician) were compared for complications and mortality. Patients without and with cholestasis (bilirubin: >2.3 mg/dL [40 mumol/L] and/or dilated common bile duct) were analyzed separately.
Of the 153 patients, 81 (53%) underwent ERCP and 72 (47%) conservative treatment. Groups were highly comparable at baseline. Seventy-eight patients (51%) had cholestasis. In patients with cholestasis, ERCP (52/78 patients: 67%), as compared with conservative treatment, was associated with fewer complications (25% vs. 54%, P = 0.020, multivariate adjusted odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.13-0.99, P= 0.049). This included fewer patients with >30% pancreatic necrosis (8% vs. 31%, P = 0.010). Mortality was nonsignificantly lower after ERCP (6% vs. 15%, P = 0.213, multivariate adjusted OR: 0.44, 95% CI: 0.08-2.28, P = 0.330). In patients without cholestasis, ERCP (29/75 patients: 39%) was not associated with reduced complications (45% vs. 41%, P = 0.814, multivariate adjusted OR: 1.36; 95% CI: 0.49-3.76; P = 0.554) or mortality (14% vs. 17%, P = 0.754, multivariate adjusted OR: 0.78; 95% CI: 0.19-3.12, P = 0.734).
Early ERCP is associated with fewer complications in predicted severe ABP if cholestasis is present.
Annals of surgery 07/2009; 250(1):68-75. · 7.90 Impact Factor
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Epilepsia 06/2009; 50(5):1294-6. · 3.96 Impact Factor
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ABSTRACT: Von Willebrand factor (VWF) is critical for the in vivo survival of factor VIII (FVIII). Since FVIII half-life correlates with VWF-antigen pre-infusion levels, we hypothesized that VWF levels are useful to predict FVIII half-life.
Standardized half-life studies and analysis of pre-infusion VWF and VWF-propeptide levels were performed in a cohort of 38 patients with severe haemophilia A (FVIII <1 IU/ml), aged 15-44 years. Nineteen patients had blood-group O. Using multivariate linear regression-analysis (MVLR-analysis), the association of VWF-antigen, VWF-propeptide, age and body-weight with FVIII half-life was evaluated.
FVIII half-life was shorter in blood-group O-patients compared to non-O-patients (11.5+/-2.6 h versus 14.3+/-3.0 h; p = 0.004). VWF-antigen levels correlated with FVIII half-life considerably better in patients with blood-group non-O than O (Pearson-rank = 0.70 and 0.47, respectively). Separate prediction models evolved from MVLR-analysis for blood-group O and non-O patients, based on VWF-antigen and VWF/propeptide ratio. Predicted half-lives deviated less than 3 h of observed half-life in 34/38 patients (89%) or less than 20% in 31/38 patients (82%).
Our approach may identify patients with shorter FVIII half-lives, and adapt treatment protocols when half-life studies are unavailable. In addition, our data indicate that survival of FVIII is determined by survival of endogenous VWF rather than VWF levels per se.
PLoS ONE 02/2009; 4(8):e6745. · 4.09 Impact Factor
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ABSTRACT: Occupational and environmental exposures may contribute to the risk of developing sporadic amyotrophic lateral sclerosis (ALS). To summarize the available evidence, a systematic review of the literature on occupation as a potential determinant of ALS was performed according to the MOOSE guidelines. From MEDLINE, EMBASE, CINAHL, and Cochrane databases, selected studies were methodologically appraised according to Armon's classification system for ALS risk factor studies. Each occupation studied was reclassified according to the International Standard Classification of Occupations (ISCO-88). The vote-counting method was applied to summarize the data. Of 3773 potentially relevant studies, 51 were initially included. Of these, 12 studies provided risk estimates for individual occupations--one case-control, two register-based case-control, and nine register-based cohort studies. All studies fell into Armon's level of evidence class IV, indicating methodological limitations. Due to the heterogeneity of study methodology, data could not be pooled. The vote-counting method revealed several candidate occupations: veterinarians and other health workers, athletes, hairdressers, power-production plant, electrical and military workers. However, well designed studies with standardized assessment of occupation are needed to provide a more definitive answer about exogenous risk factors of ALS.
Amyotrophic Lateral Sclerosis 01/2009; 10(5-6):295-301. · 3.40 Impact Factor
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ABSTRACT: Environmental exposure to chemicals and metals may contribute to the risk of sporadic amyotrophic lateral sclerosis (ALS). Two systematic reviews of the literature on these topics performed according to the well-established MOOSE guidelines are presented. Literature cited in MEDLINE, EMBASE, CINAHL, and Cochrane databases (up to March 2007) as well as references of relevant articles were screened for case-control or cohort studies investigating the associations between sporadic ALS and exposure to chemical agents or metals. Methodology of selected studies was appraised according to Armon's classification system for ALS risk factor studies as well as a newly developed classification system for quality of exposure assessment. Seven of the 38 studies concerning exposure to chemicals and three of the 50 studies concerning exposure to metals fulfilled the validity criteria. In two independent studies meeting the validity criteria, a significant association with increased ALS risk was reported for exposure to pesticides. This systematic review demonstrated the difficulty in attaining a high level of evidence due to lack of high quality of methodological and exposure assessment components. Although pesticide exposure was identified as candidate risk factor, more well-designed studies are needed to provide a definitive answer about exogenous factors of ALS.
Amyotrophic Lateral Sclerosis 01/2009; 10(5-6):302-9. · 3.40 Impact Factor
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ABSTRACT: Environmental exposure to chemicals and metals may contribute to the risk of sporadic amyotrophic lateral sclerosis (ALS). Two systematic reviews of the literature on these topics performed according to the well-established MOOSE guidelines are presented. Literature cited in MEDLINE, EMBASE, CINAHL, and Cochrane databases (up to March 2007) as well as references of relevant articles were screened for case-control or cohort studies investigating the associations between sporadic ALS and exposure to chemical agents or metals. Methodology of selected studies was appraised according to Armon's classification system for ALS risk factor studies as well as a newly developed classification system for quality of exposure assessment. Seven of the 38 studies concerning exposure to chemicals and three of the 50 studies concerning exposure to metals fulfilled the validity criteria. In two independent studies meeting the validity criteria, a significant association with increased ALS risk was reported for exposure to pesticides. This systematic review demonstrated the difficulty in attaining a high level of evidence due to lack of high quality of methodological and exposure assessment components. Although pesticide exposure was identified as candidate risk factor, more well-designed studies are needed to provide a definitive answer about exogenous factors of ALS.
Amyotrophic Lateral Sclerosis 12/2008; · 3.40 Impact Factor
