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Cancer Epidemiology, Biomarkers &... Feb 2014Several observational studies have investigated autoimmune disease and subsequent risk of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several observational studies have investigated autoimmune disease and subsequent risk of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Findings have been largely inconsistent and hindered by the rarity and heterogeneity of the autoimmune disorders investigated. A systematic review of the literature was undertaken to evaluate the strength of the evidence linking prior autoimmune disease and risk of MGUS/multiple myeloma.
METHODS
A broad search strategy using key terms for MGUS, multiple myeloma, and 50 autoimmune diseases was used to search four electronic databases (PubMed, Medline, Embase, and Web of Science) from inception through November 2011.
RESULTS
A total of 52 studies met the inclusion criteria, of which 32 were suitably comparable to perform a meta-analysis. "Any autoimmune disorder" was associated with an increased risk of both MGUS [n = 760 patients; pooled relative risk (RR) 1.42; 95% confidence interval (CI), 1.14-1.75] and multiple myeloma (n>2,530 patients; RR 1.13, 95% CI, 1.04-1.22). This risk was disease dependent with only pernicious anemia showing an increased risk of both MGUS (RR 1.67; 95% CI, 1.21-2.31) and multiple myeloma (RR 1.50; 95% CI, 1.25-1.80).
CONCLUSIONS
Our findings, based on the largest number of autoimmune disorders and patients with MGUS/multiple myeloma reported to date, suggest that autoimmune diseases and/or their treatment may be important in the etiology of MGUS/multiple myeloma. The strong associations observed for pernicious anemia suggest that anemia seen in plasma cell dyscrasias may be of autoimmune origin.
IMPACT
Underlying mechanisms of autoimmune diseases, general immune dysfunction, and/or treatment of autoimmune diseases may be important in the pathogenesis of MGUS/multiple myeloma.
Topics: Autoimmune Diseases; Case-Control Studies; Cohort Studies; Humans; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Observational Studies as Topic; Risk Factors
PubMed: 24451437
DOI: 10.1158/1055-9965.EPI-13-0695 -
Alimentary Pharmacology & Therapeutics Feb 2013Pernicious anaemia (PA) has an increased risk for gastric cancer (GC). It is not established whether PA patients need to undergo endoscopic/histological follow-up. (Review)
Review
BACKGROUND
Pernicious anaemia (PA) has an increased risk for gastric cancer (GC). It is not established whether PA patients need to undergo endoscopic/histological follow-up.
AIM
To provide a systematic overview of the literature on PA and the development of gastric cancer, to estimate the gastric cancer incidence-rate.
METHODS
According to PRISMA, we identified studies on PA patients reporting the incidence of gastric cancer. Quality of studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Meta-analysis on annual gastric cancer incidence rates was performed.
RESULTS
Twenty-seven studies met eligibility criteria. 7 studies were of high, 6 of medium, 10 of low and 4 of very low quality. Gastric cancer incidence-rates ranged from 0% to 0.2% per person-years in 7 American, from 0% to 0.5% in 2 Asiatic, from 0% to 1.2% in 11 Northern European studies and from 0% to 0.9% in 7 studies from other European countries. The incidence-rates of gastric cancer ranged from 0% to 1.2% per person-years in studies which used gastroscopy, from 0.1% to 0.9% in those based on International Classification of Disease. Heterogeneity between studies was not statistically significant at the 5% level (Chi-squared test = 17.9, P = 0.08). The calculated pooled gastric cancer incidence-rate was 0.27% per person-years. Meta-analysis showed overall gastric cancer relative risk in PA as 6.8 (95% CI: 2.6-18.1).
CONCLUSIONS
This systematic review shows a pooled gastric cancer incidence-rate in pernicious anaemia of 0.27% per person-years and an estimated nearly sevenfold relative risk of gastric cancer in pernicious anaemia patients. Further high quality studies are needed to confirm this higher risk.
Topics: Anemia, Pernicious; Gastroscopy; Humans; Incidence; Risk Factors; Stomach Neoplasms
PubMed: 23216458
DOI: 10.1111/apt.12177 -
BMC Geriatrics Jun 2010Pernicious anaemia is undeniably associated with vitamin B12 deficiency, but the association between subnormal vitamin B12 concentrations and anaemia in older people is... (Comparative Study)
Comparative Study Review
BACKGROUND
Pernicious anaemia is undeniably associated with vitamin B12 deficiency, but the association between subnormal vitamin B12 concentrations and anaemia in older people is unclear. The aim of this systematic review was to evaluate the association between subnormal vitamin B12 concentrations and anaemia in older people.
METHODS
Clinical queries for aetiology and treatment in bibliographic databases (PubMed [01/1949-10/2009]; EMBASE [01/1980-10/2009]) were used. Reference lists were checked for additional relevant studies. Observational studies (> or =50 participants) and randomized placebo-controlled intervention trials (RCTs) were considered.
RESULTS
25 studies met the inclusion criteria. Twenty-one observational cross-sectional studies (total number of participants n = 16185) showed inconsistent results. In one longitudinal observational study, low vitamin B12 concentrations were not associated with an increased risk of anaemia (total n = 423). The 3 RCTs (total n = 210) were well-designed and showed no effect of vitamin B12 supplementation on haemoglobin concentrations during follow-up in subjects with subnormal vitamin B12 concentrations at the start of the study. Due to large clinical and methodological heterogeneity, statistical pooling of data was not performed.
CONCLUSIONS
Evidence of a positive association between a subnormal serum vitamin B12 concentration and anaemia in older people is limited and inconclusive. Further well-designed studies are needed to determine whether subnormal vitamin B12 is a risk factor for anaemia in older people.
Topics: Age Factors; Aged; Cross-Sectional Studies; Dementia; Humans; Longitudinal Studies; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 20573208
DOI: 10.1186/1471-2318-10-42 -
International Journal of Laboratory... Feb 2009The objective of this review was to evaluate oral cobalamin (vitamin B(12)) therapy in adult and elderly patients, from the perspective of a hematologist. PubMed was... (Review)
Review
The objective of this review was to evaluate oral cobalamin (vitamin B(12)) therapy in adult and elderly patients, from the perspective of a hematologist. PubMed was systematically searched for English and French articles published from January 1990 to January 2007. Data from our working group, the 'Groupe d'étude des carences en vitamine B(12)des Hôpitaux Universitaires de Strasbourg', have also been included. Several prospective studies in well-determined population (n = 4), prospective randomized studies (n = 3) and a systematic review by the Cochrane group (n = 1) provide evidence that oral cobalamin therapy may adequately treat cobalamin deficiency, particularly hematological abnormalities or manifestations. These studies suggest that at least 1000 microg/day of oral cyanocobalmin are needed for pernicious anemia and a mean daily dose of 250 microg for food-cobalamin malabsorption. This present review confirms the previously reported efficacy of oral cobalamin treatment in adult and elderly patients.
Topics: Clinical Trials as Topic; Humans; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 19032377
DOI: 10.1111/j.1751-553X.2008.01115.x -
Family Practice Jun 2006Vitamin B(12) deficiency is common, increasing with age. Most people are treated in primary care with intramuscular vitamin B(12). Several studies have reported equal... (Comparative Study)
Comparative Study Review
BACKGROUND
Vitamin B(12) deficiency is common, increasing with age. Most people are treated in primary care with intramuscular vitamin B(12). Several studies have reported equal efficacy of oral administration of vitamin B(12).
OBJECTIVES
We set out to identify randomized controlled trial (RCT) evidence for the effectiveness of oral versus intramuscular vitamin B(12) to treat vitamin B(12) deficiency.
METHODS
We conducted a systematic review searching databases for relevant RCTs. Outcomes included levels of serum vitamin B(12), total serum homocysteine and methylmalonic acid, haemoglobin and signs and symptoms of vitamin B(12) deficiency.
RESULTS
Two RCTs comparing oral with intramuscular administration of vitamin B(12) met our inclusion criteria. The trials recruited a total of 108 participants and followed up 93 of these from 90 days to 4 months. In one of the studies, mean serum vitamin B(12) levels were significantly higher in the oral (643 +/- 328 pg/ml; n = 18) compared with the intramuscular group (306 +/- 118 pg/ml; n = 15) at 2 months (P < 0.001) and 4 months (1005 +/- 595 versus 325 +/- 165 pg/ml; P < 0.0005) and both groups had neurological responses. In the other study, serum vitamin B(12) levels increased significantly in those receiving oral vitamin B(12) and intramuscular vitamin B(12) (P < 0.001).
CONCLUSIONS
The evidence derived from these limited studies suggests that 2000 microg doses of oral vitamin B(12) daily and 1000 microg doses initially daily and thereafter weekly and then monthly may be as effective as intramuscular administration in obtaining short-term haematological and neurological responses in vitamin B(12)-deficient patients.
Topics: Administration, Oral; Anemia, Pernicious; Humans; Injections, Intramuscular; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex
PubMed: 16585128
DOI: 10.1093/fampra/cml008 -
The Cochrane Database of Systematic... 2003An association between neuropsychiatric disorders and vitamin B12 deficiency has been recognized since 1849 when pernicious anaemia was first described. It has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
An association between neuropsychiatric disorders and vitamin B12 deficiency has been recognized since 1849 when pernicious anaemia was first described. It has been suggested that deficiency of vitamin B12 might contribute to age-associated cognitive impairment. Low serum vitamin B12 concentrations are found in more than 10% of older people. A high prevalence of low serum vitamin B12 levels, and other indicators of vitamin B12 deficiency have been reported among people with Alzheimer's disease. A review is needed of trials assessing effects of vitamin B12 supplementation on cognitive function in later life.
OBJECTIVES
To examine the effect of B12 supplementation on cognitive function of demented and elderly healthy people in terms of preventing the onset or progression of cognitive impairment or dementia.
SEARCH STRATEGY
The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 12 September 2002 using the terms listed in additional table 1. In addition MEDLINE 1966 to 2002/09 and EMBASE 1980-2002/08 were searched using the same terms and cognit* to pick up studies with healthy volunteers.
SELECTION CRITERIA
All randomized double-blind trials in which vitamin B12 at any dose was compared with placebo.
DATA COLLECTION AND ANALYSIS
Both reviewers applied the selection criteria to assess the quality of the studies. One reviewer collated and analysed the data. For each outcome measure data were sought on every patient randomized.
MAIN RESULTS
From the two included studies (Seal 2002; Fourniere 1997) of people with dementia and low serum vitamin B12 levels, there was no statistically significant evidence of treatment effect, vitamin B12 supplementation compared with placebo, on cognitive function.
REVIEWER'S CONCLUSIONS
Evidence of any efficacy of vitamin B12 in improving the cognitive function of people with dementia and low serum B12 levels is insufficient. The two trials of acceptable methodology (Fourniere 1997; Seal 2002) were restricted to a small number of patients with Alzheimer's disease and other types of cognitive impairment. No trials involving people without dementia or using other definitions of vitamin B12 deficiency were found.
Topics: Aged; Cognition; Cognition Disorders; Dementia; Humans; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 12918012
DOI: 10.1002/14651858.CD004326 -
Osteoporosis International : a Journal... 2001Available evidence suggests that fracture prediction with bone densitometry may improve when used on people at high risk of osteoporotic fractures. The objectives of... (Review)
Review
Available evidence suggests that fracture prediction with bone densitometry may improve when used on people at high risk of osteoporotic fractures. The objectives of this literature review were: (1) to identify risk factors for fracture that are associated with the development of a low bone mass for both men and women; (2) to describe and assess the relationship between these factors and the risk of fracture; and (3) to classify them according to the strength of their association with fracture incidence. Studies were identified from MEDLINE (1982-1997), HealthSTAR (1975-1997) and The Cochrane Library (1997) databases. Pre-stated inclusion criteria (original analytic studies assessing risk factors for osteoporotic fractures in men and women) and methodologic quality were assessed by two independent investigators. Information on the study design and analysis, characteristics of participants, exposure (risk factor) and outcome measures (relative risk and odds ratios for fracture incidence), control for potential confounding factors and risk estimates was extracted using a standardized protocol. Qualitative and meta-analytic techniques were used for data synthesis. As a result, risk factors were classified into three groups according to their strength of association with fracture: high risk (RR > or = 2), moderate risk (1 < RR < 2) and no risk or protective (RR < or = 1). Of approximately 80 risk factors identified from 94 cohort and 72 case-control studies, 15% were classified in the high-risk group, including low body weight, loss of weight, physical inactivity, the consumption of corticosteroids or anticonvulsants, primary hyperparathyroidism, diabetes mellitus type 1, anorexia nervosa, gastrectomy, pernicious anemia, and aging (> 70-80 years). Eighteen percent and 8% of risk factors were classified in the moderate and no risk group respectively, whereas 60% showed either a lack of scientific evidence confirming their association with fracture or contradictory results. An efficient strategy for bone densitometry provision may thus be its selective use in those individuals who present with several strong or moderate risk factors for fracture related to bone mass loss.
Topics: Adrenal Cortex Hormones; Age Factors; Anemia, Pernicious; Anorexia Nervosa; Anticonvulsants; Body Weight; Bone Density; Densitometry; Diabetes Mellitus, Type 1; Exercise; Female; Fractures, Bone; Humans; Hyperparathyroidism; Male; Osteoporosis; Risk Assessment; Risk Factors; Sensitivity and Specificity
PubMed: 11716183
DOI: 10.1007/s001980170031 -
Scandinavian Journal of Clinical and... Feb 2000In clinical practice, the finding of an elevated mean corpuscular volume (MCV), macrocytic anaemia or specific neurological symptoms is often the reason to test for... (Review)
Review
In clinical practice, the finding of an elevated mean corpuscular volume (MCV), macrocytic anaemia or specific neurological symptoms is often the reason to test for vitamin B12 (B12) deficiency. Use of the MCV as a test for the detection or exclusion of B12 deficiency is only justified if the diagnostic accuracy is sufficiently high. However, the sensitivity and specificity are not well known. We performed a systematic review of the diagnostic value of an elevated MCV for B12 deficiency in both anaemic and non-anaemic patients. Of approximately 3500 titles and/or abstracts that were screened, 37 original papers contained usable data. The population under study proved to be the characteristic of major influence on the study outcome. Pooling of data from different studies was performed in subsets of the data corresponding to the different populations studied. The cut-off levels of both MCV and serum B12 had a significant influence on the study outcomes. The data, however, were pooled without taking these cut-off levels into account. The pooled estimates should be interpreted with this limitation in mind. The reference standards were (1) a low serum B12 concentration and (2) a B12 deficiency confirmed by low serum B12 combined with additional diagnostic investigations. In the population that was randomly screened for low serum B12, the sensitivity of the MCV for B12 deficiency was 17%, whereas the sensitivity was 30% for B12 deficiency in patients with anaemia. When measurement of serum B12 was ordered to exclude B12 deficiency as part of the patients' treatment, the sensitivity was 30% for low serum B12 concentration, 58% for B12 deficiency and 75% for B12 deficiency in patients with anaemia. In the population with pernicious anaemia, the sensitivity was far from perfect (77%). In the five studies that reported data on the positive predictive value of the MCV for B12 deficiency, this ranged from 0% (0/6) to 55% (11/20). This systematic review shows that a considerable number of B12-deficient patients will remain unnoticed when the MCV is used to rule in patients for further evaluation. Depending on the population studied, up to 84% of cases will than be missed. The MCV can be used to make the diagnosis of B12 deficiency more--or less--probable. An elevated MCV justifies the measurement of serum B12. The MCV should not be used as the only parameter ruling out the diagnosis of B12 deficiency.
Topics: Erythrocyte Indices; Erythrocytes; Humans; Predictive Value of Tests; Vitamin B 12 Deficiency
PubMed: 10757449
DOI: 10.1080/00365510050184994