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NSUP: Vitamin B12 (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To present data on clinical manifestations of food-cobalamin malabsorption in elderly patients.

Inclusion Criteria:
  • Established cobalamin deficiency related to food-cobalamin malabsorption (FCM). FCM was defined according to the criteria of Carmel:
    • Low serum vitamin B12 level
    • Normal Schilling test result using free 58Co-cyancobalamin and intrinsic factor-bound 57Co-cyanocobalamin
    • Lack of serum antibodies to intrinsic factor
    • Daily intake of vitamin B12 of at least five mcg.
  • Age 65 years and older
  • Serum cobalamin level less than 200pg per dL confirmed in two serum samples or in association with a total homocysteine level greater than 13umol per L.
Exclusion Criteria:

None.

Description of Study Protocol:
  • Recruitment: 92 elderly patients with confirmed cobalamin deficiency related to FCM were identified from the original cohort study of 172 consecutive elderly patients with documented cobalamin deficiency
  • Design: 28 (30.4%) were treated with crystalline oral cyanocobalamin (daily dose between 125mcg and 1,000mcg) and the remaining patients were treated with intramuscular cyanocobalamin (monthly dose between 500mcg and 1,000mcg).
     
Data Collection Summary:
  • Timing of measurements: All data were obtained retrospectively from medical records, including history of drugs or alcohol intake, clinical status, relevant biochemical data (e.g., serum vitamin B12 and total homocysteine levels), blood cell count and bone marrow examination
  • Before treatment and after three months: Mean hemoglobin (g per dL), mean erythrocyte cell volume (fL), mean serum vitamin B12 (pg per dL), mean serum homocysteine (umol per L)
  • Dependent variables:
    • Mean hemoglobin
    • Mean erythrocyte cell volume
    • Mean serum vitamin B12
    • Mean serum homocysteine
    • Clinical manifestations.

 


 


 

Description of Actual Data Sample:
  • Initial N: 92 (60 women, 32 men)
  • Attrition (final N): 92
  • Age: 76±8 years (range, 65 to 91 years)
  • Ethnicity: White.

Other Relevant Demographics

Clinical manifestations:

  • 41 patients (44.5%) had mild sensory polyneuropathy
  • 36 patients (39.1%) had decreased or absent reflexes (i.e., knee jerk, Achilles tendon reflex)
  • Nine patients (9.8%) had subjective complaints of paresthesia of the legs (i.e., tingling and burning sensations)
  • 21 patients (22.8%) had confusion or impaired mental functioning as determined by the Folstein test
  • 10 patients (10.9%) had features suggestive of an ischemic stroke
  • All patients had high blood pressure, diabetes mellitus or atrial fibrillation
  • One patient had a combined medullary sclerosis
  • 19 patients (20.7%) had physical asthenia (i.e., profound weakness)
  • 12 patients (13%) had bilateral edema of the legs related to severe anemia
  • Two patients had jaundice from ineffective erythropoiesis.

Location

Universitaires de Strasbourg, France.

Summary of Results:
  • In all cases, correction of the serum vitamin B12 levels (greater than 200pg per ml) occurred within the first month of therapy
  • In all patients, improvement of blood count parameters (hemoglobin levels, erythrocyte cell volume and number of leukocytes and platelets) occurred within the first three months of therapy
  • Correction of blood count abnormalities was observed in two-thirds of the patients (N=58 patients)
  • Symptom recovery was observed in 33 patients (35.9%) i.e., 18 patients with peripheral neuropathy, 14 patients with asthenia, two patients with jaundice-related to ineffective erythropoiesis and one patient with combined medullary sclerosis
  • For patients with dementia, a nonsignificant mild improvement on the Folstein test score was described (from 21.5±4.2 to 22.7±3.8, P<.07)
  • Long-term outcome (mean follow up of one year (range: one month to 2.4 years) data was available for only 26 patients treated with intramuscular (N=13) or oral cobalamin (N=13). All of these patients including those on oral treatment had normal serum vitamin B12 levels and improvement of total homocysteine levels and blood count parameters. No hematologic abnormalities were found in 11 of the 13 patients (84.6%) treated with oral cobalamin therapy.
  • Mean serum vitamin B12 was 131±38pg per ml
  • Mean total serum homocysteine was 22.1±9.3umol per L
  • Mean hemoglobin level was 10.9±2.5g per dL
  • Mean erythrocyte cell volume was 95.7±12.7fL.
Author Conclusion:

The results of this study suggest that the syndrome of FCM may be the leading cause of vitamin B12 deficiency in the elderly in a casual relationship with atrophic gastritis. These results also suggest that this disorder may be associated with significant neurologic, psychologic and hematologic abnormalities which appear to respond equally well to either oral or parenteral B12 therapy.

Funding Source:
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:

All data was obtained retrospectively from medical records.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
  1. Was the research question clearly stated? Yes
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? N/A
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? N/A
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
  1.3. Were the target population and setting specified? Yes
  2. Was the selection of study subjects/patients free from bias? No
2. Was the selection of study subjects/patients free from bias? No
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? N/A
  2.2. Were criteria applied equally to all study groups? N/A
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? No
  2.4. Were the subjects/patients a representative sample of the relevant population? No
  3. Were study groups comparable? N/A
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
  4. Was method of handling withdrawals described? N/A
4. Was method of handling withdrawals described? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) N/A
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
  5. Was blinding used to prevent introduction of bias? N/A
5. Was blinding used to prevent introduction of bias? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
  6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? ???
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? ???
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? ???
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? ???
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? ???
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? ???
  6.6. Were extra or unplanned treatments described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
  7. Were outcomes clearly defined and the measurements valid and reliable? ???
7. Were outcomes clearly defined and the measurements valid and reliable? ???
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? ???
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? ???
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? ???
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? ???
  7.5. Was the measurement of effect at an appropriate level of precision? ???
  7.5. Was the measurement of effect at an appropriate level of precision? ???
  7.6. Were other factors accounted for (measured) that could affect outcomes? ???
  7.6. Were other factors accounted for (measured) that could affect outcomes? ???
  7.7. Were the measurements conducted consistently across groups? N/A
  7.7. Were the measurements conducted consistently across groups? N/A
  8. Was the statistical analysis appropriate for the study design and type of outcome indicators? ???
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? ???
  8.1. Were statistical analyses adequately described and the results reported appropriately? ???
  8.1. Were statistical analyses adequately described and the results reported appropriately? ???
  8.2. Were correct statistical tests used and assumptions of test not violated? ???
  8.2. Were correct statistical tests used and assumptions of test not violated? ???
  8.3. Were statistics reported with levels of significance and/or confidence intervals? ???
  8.3. Were statistics reported with levels of significance and/or confidence intervals? ???
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? ???
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? ???
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? ???
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? ???
  8.6. Was clinical significance as well as statistical significance reported? ???
  8.6. Was clinical significance as well as statistical significance reported? ???
  8.7. If negative findings, was a power calculation reported to address type 2 error? ???
  8.7. If negative findings, was a power calculation reported to address type 2 error? ???
  9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
  10. Is bias due to study's funding or sponsorship unlikely? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes
  10.2. Was the study free from apparent conflict of interest? Yes