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Asfour et al. (2006): Effect of high-dose sodium selenite therapy on polymorphonuclear leukocyte apoptosis in non-Hodgkin's lymphoma patients

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Reference ↗
Title Effect of high-dose sodium selenite therapy on polymorphonuclear leukocyte apoptosis in non-Hodgkin's lymphoma patients
Topic Selenium
Author Asfour, IA, El Shazly, S, Fayek, MH, Hegab, HM, Raouf, S, Moussa, MAR
Year 2006
Journal Biological trace element research
DOI https://link.springer.com/article/10.1385/BTER:110:1:19

Study Note

Brief summary

In this study, 30 subjects with non-Hodgkin's lymphoma were randomly divided into two arms. One arm received selenium during chemotherapy and the other arm received nothing in addition. The infection rate and the performance of the heart muscle were examined. Both were significantly better at the end of the study in the arm that had received selenium compared to the simple control arm. The focus of the study is on laboratory parameters that are not relevant to this guideline. This is noticeable in the description of the other two endpoints, which are only briefly touched on and described very little. Overall, the study lacks a lot of individual information such as the age of the test subjects, the randomization process, the time period of the survey or the exact number of side effects that occurred. It should also be noted that the analysis carried out is very simplified and does not take into account the possible influence of other factors such as age etc. in any way. This may distort the results, particularly in view of the very small sample size, which could cast doubt on a direct influence of selenium on the change in the endpoints.


In dieser Studie wurden 30 Probanden mit Non-Hodgkin-Lymphom zufällig in zwei Gruppen eingeteilt. Eine Gruppe bekam während der Chemotherapie Selen und die andere Gruppe bekam nichts Zusätzliches. Untersucht wurden die Infektionsrate und die Leistungsfähigkeit des Herzmuskels. Beides war zum Ende der Studie bedeutsam besser in der Gruppe, welche Selen erhalten hatte im Vergleich zur einfachen Kontrollgruppe. Der Schwerpunkt der Studie liegt auf Laborparametern, welche für diese Leitlinie nicht relevant sind. Dies merkt man in der Beschreibung der beiden anderen Endpunkte, welche nur kurz angerissen und wenig beschrieben werden. Insgesamt fehlen in der Studie viele einzelne Informationen wie das Alter der Probanden, der Ablauf des Randomisierungsprozesses, der Zeitraum der Erhebung oder die genaue Anzahl der aufgetretenen Nebenwirkungen. Es ist zudem anzumerken, dass die durchgeführte Analyse sehr vereinfacht ist und in keinerlei Richtung einen möglichen Einfluss von anderen Faktoren wie Alter etc. berücksichtigt. Dies kann insbesondere in Anbetracht der sehr geringen Stichprobenanzahl das Ergebnis verzerren, wodurch ein direkter Einfluss von Selen auf die Veränderung der Endpunkte angezweifelt werden könnte.

Study Design

Prospective / Retrospective Prospective: forward-looking, examples include clinical trials, cohort studies, and long-term observational studies;</br>Retrospective: backward-looking, relying on existing data, examples include case-control studies and retrospective cohort studies Prospective
Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals Monocentric
Blinding No: Open, all parties are aware of group assignments;</br>Single: one party is unaware of group assignments (generally participants);</br>Double: two parties are unaware of group assignments (generally the participants and the researchers); </br>Triple: concealing group assignment from additional parties No
Is randomized Yes
Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control No
Number of arms 2

Study characteristics

Inclusion criteria Newly diagnosed non-Hodgkin’s lymphoma (NHL) of intermediate and high grade
Exclusion criteria NI
N randomized 30
Analysis PP: Per Protocol analysis, i.e. only participants included who adhered to the study protocol.</br>ITT: Intention-to-treat analysis, i.e. all randomized participants included regardless of any drop-outs or changes in assignment.</br>mITT: modified Intention-to-treat analysis can refer to analyses in which participants with missing outcome data are excluded or it can refer to analyses in which only participants who received at least one treatment dose are included. In this case, participants dropped out of the study prematurely for reasons unrelated to the treatment. ITT Analysis
Specifications on analyses No ITT analysis specified, but no drop-out occured
Countries of data collection Egypt
LoE Level of evidence 2b Oxford 2009
Outcome timeline Data collection times T0: Baseline

T1: Day 3

T2: Day 8

Characteristics of participants

Setting Refers to cancer therapy setting.</br>- Curative therapy: aims to completely eradicate a disease and achieve a full recovery; </br>- Neo-adjuvant therapy: form of curative therapy, given before the primary treatment for cancer (usually surgery); </br>- Adjuvant therapy: form of curative therapy, given after the primary treatment for cancer (usually surgery); </br>- Palliative therapy: focuses on providing relief from symptoms and improving the quality of life for patients, without necessarily targeting the underlying disease; </br>- Active surveillance: involves close monitoring of disease progression without any intervention (typically used for prostate cancer);</br>- No therapy setting: Patients who completed therapy/are currently not in cancer treatment, cancer survivors. Curative
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included Hematologic Cancers - Lymphoma (Hodgkin and Non-Hodgkin)
Cancer stages Early Stage: generally refers to cancer that is localized to the area where it started, mostly stages I and II;</br>Advanced Stage: cancer that has spread beyond its original site, mostly stages III and IV, with stage IV indicating distant metastasis Early Stage, Advanced Stage
Specifications on cancer stages Non-Hodgkin intermediate and high grade
Comorbidities NI
Current cancer therapies Chemotherapy
Specifications on cancer therapies Combination chemotherapy composed of cyclophosphamide doxorubicin, oncovine, and prednisone (CHOP), treatment consisted of sisted of 750 mg/m2 on first day of the treatment cycle intravenously (IV) cyclophosphamide, 50 mg/m2 IV doxorubicin, 1.4 mg/m2 IV vincristine, and 100 mg po days 1 to 5 prednisone; chemotherapy cycles were repeated every 28 days
Previous cancer therapies NI
Gender Mixed
Gender specifications 30 participants, n=14 female and n=16 male
Age groups NI
Age groups specification NI

Arms

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment Intervention
Number of participants (arm) N randomized 15
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date 0
Drop-out reasons NA
Intervention Sodium selenite

+ unclear treatment with antiemetic medication

Dosage and regime Sodium selenite was administered on days 3–7 of the chemotherapy
One-time application No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information. 8
Side effects / Interactions Gastrointestinal complaints with dizziness and occasional vomiting (was controlled with antiemetic medication) - no numbers given
Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment Passive control
Number of participants (arm) N randomized 15
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date 0
Drop-out reasons NA
Intervention None

+ unclear treatment with antiemetic medication

Dosage and regime NA
One-time application No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information. 8
Side effects / Interactions NA

Outcomes

Toxicity

Outcome type As specificed by the authors Primary
Outcome specification Infectionrate after chemotherapy
Type of measurement NI
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". After chemotherapy (8 days): significant less infections in sodium selenite arm (20%) compared to control arm (67%); p<0.05
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". NA
Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process some concerns
Bias due to deviation from intended intervention (assignment to intervention) low risk
Bias due to deviation from intended intervention (adhering to intervention) NA
Bias due to missing outcome data low risk
Bias in measurement of the outcome some concerns
Bias in selection of the reported result some concerns
Other sources of bias some concerns
Overall RoB judgment high risk

Ejection fraction

Outcome type As specificed by the authors Primary
Outcome specification Cardiac ejection fraction
Type of measurement NI
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". After chemotherapy (8 days): significantly better cardiac ejection fraction in sodium selenite arm (mean(SD)= 63(6%)) vs. control arm (69(6%)); p <0.05
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall". NA
Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process some concerns
Bias due to deviation from intended intervention (assignment to intervention) low risk
Bias due to deviation from intended intervention (adhering to intervention) NA
Bias due to missing outcome data low risk
Bias in measurement of the outcome some concerns
Bias in selection of the reported result some concerns
Other sources of bias some concerns
Overall RoB judgment high risk

Funding and Conflicts of Interest

Funding NI
Conflicts of Interest NI

Further points for assessing the study

Sample

Power analysis performed No
- Sample size corresponds to power analysis NA
- Reasons for insufficient sample size based on power analysis No
If no power analysis performed: at least moderate sample size (n >= 30 per arm) No
Ethnicity mentioned No

Alternative Explanation

Other explanations for an effect besides the investigated intervention Yes
- Possibility of attention effects NA
- Possibility of placebo effects Yes
- Other reasons
  • No inclusion or balancing according to baseline values of the test subjects (very simple statistical calculation, with high risk of bias)
  • No information on the randomization process or possible drop-outs
  • No indication of when follow-up on cardiac ejection fraction took place

Statistics

Correct use of parametric and non-parametric tests Testing for normal distribution only necessary if parametric tests are used, NI: use of parametric tests without report of normal distribution testing Yes
Correction for multiple testing NA
Measurement of compliance NI
Consistent reporting in numbers (figures, flowchart, abstract, results) No
Comprehensive and coherent reporting No
Cross-over No
- Sufficient washout period NA
- Tested for carry-over effects NA
- Tested for sequence effects NA

Interpretation of results

Effect sizes reported (clinical vs. statistical significance) No
Side effects systematically recorded NI
Side effects considered in result interpretation Yes
Ethics votum NI


Additional Notes

PRO:

  • Detailed medical examination.
  • Comparability of values for measured endpoints given.


CONTRA:

  • Very small sample size and no power analysis.
  • No blinding or placebo arm.
  • No mention of ethics approval.
  • Discrepancies between ejection fraction data in the abstract and table.
  • No inclusion or balancing based on participants' baseline values (very simple statistical calculation with high risk of bias).
  • Infection rate is significant in text but not indicated as significant in the table (p>0.05 but marked as "S" for significant).
  • Very superficial presentation of results.
  • Imprecise and insufficient description of side effects.
  • No statistical proof of arm comparability at baseline regarding demographic variables.
  • No information on the randomization process or possible drop-outs.
  • No indication of when follow-up on cardiac ejection fraction took place.
  • No age specification.
  • Although selenium serum measurement is mentioned, no data is provided.
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