Salihah et al. (2016): The effectiveness of inhaled ginger essential oil in improving dietary intake in breast-cancer patients experiencing chemotherapy-induced nausea and vomiting

Reference ↗
Title	The effectiveness of inhaled ginger essential oil in improving dietary intake in breast-cancer patients experiencing chemotherapy-induced nausea and vomiting
Topic	Ginger
Author	Salihah, N, Mazlan, N, Lua, P
Year	2016
Journal	Focus on Alternative and Complementary Therapies
DOI	https://doi.org/10.1111/fct.12236

Study Note

This study includes further endpoints to the study Lua et al. (2015): Effects of inhaled ginger aromatherapy on chemotherapy-induced nausea and vomiting and health-related quality of life in women with breast cancer

Brief summary

This study is a so-called cross-over study, i.e. the groups are swapped. 60 breast cancer patients who received chemotherapy with a strong emetic effect were divided into two groups (random selection). All received a glass bottle in the shape of a pendant. Two drops of ginger oil or placebo were placed in the bottle. The bottle was hung approx. 20 cm below the nose and was then held directly under the nose at least 3 times a day. It was to be worn for 5 days during the chemo cycle, including at night. After one cycle, the groups were swapped. The ginger aroma did not influence the frequency of vomiting. However, the patients in the respective ginger group suffered significantly less fatigue, pain, loss of appetite and severity of nausea/vomiting. The participants also reportedly did not notice the difference between the ginger oil and the placebo oil. The participants in the ginger group suffered significantly more often from constipation than those taking the placebo. The study is not well reported, so it is reasonable to assume that the study was not methodologically well conducted and the results must be interpreted with caution.

Diese Studie ist ein sog. Cross-over Studie, i.e. die Gruppen werden getauscht. 60 Brustkrebspatientinnen, die eine stark brechreizauslösende Chemotherapie erhielten, wurden in zwei Gruppen (zufällige Auswahl) geteilt. Alle erhielten einen Glasflakon in Form eines Anhängers. In den Flakon wurden zwei Tropfen Ingweröl oder Plazebo hineingetan. Der Flakon hing ca. 20 cm unterhalb der Nase, wurde dann mind. 3x am Tag direkt unter die Nase gehalten. Er sollte 5 Tage während des Chemozyklus, auch nachts, getragen werden. Nach einem Zyklus wurden die Gruppen getauscht. Das Ingweraroma hat die Häufigkeit des Erbrechens nicht beeinflusst. Allerdings litten die Patientinnen in der jeweiligen Ingwergruppe bedeutsam weniger unter Fatigue, Schmerz, Appetitlosigkeit und Stärke der Übelkeit/Erbrechen. Die Teilnehmerinnen haben angeblich auch den Unterschied zwischen dem Ingwer- und dem Plazeboöl nicht gemerkt. In der jeweiligen Ingwergruppe litten die Teilnehmerinnen bedeutsam häufiger unter Verstopfung als unter Plazebo. Die Studie ist nicht gut berichtet, so dass die Vermutung naheliegt, dass die Studie methodisch nicht gut durchgeführt worden ist und die Ergebnisse mit Vorsicht interpretiert werden müssen.

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	Multicentric
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	Single
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	Yes
Number of arms	2

Study characteristics

Inclusion criteria	Women with a normal sense of smell; had a diagnosis of breast cancer; were receiving chemotherapy and experiencing nausea and/or vomiting of any severity (previously described in our earlier article13); were due to receive at least two further chemotherapy courses using similar chemotherapeutic agents
Exclusion criteria	Women with other malignancies, allergies to ginger, perfumes or cosmetics or who were undergoing concurrent radiotherapy
N randomized	75
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.	NI
Specifications on analyses	ANOVA
Countries of data collection	Malaysia
LoE Level of evidence	2b Oxford 2009
Outcome timeline Data collection times	NI

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	Breast Cancer
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	Breast cancer: Stage I: n=5; Stage II: n=35; Stage III: n=15; Stage IV: n=5
Comorbidities	NI
Current cancer therapies	Chemotherapy
Specifications on cancer therapies	In all patients: High (>90%) emetic risk 5-Flouracil + epirubicin + cyclophosphamide (FEC): 45% (SD 75.0) Docetaxel + doxorubicin and cyclophosphamide (TAC): 7% (SD 11.7) Low (10—30%) emetic risk Docetaxel: 8% (SD 13.3)
Previous cancer therapies	Chemotherapy
Gender	Female
Gender specifications	100 % female
Age groups	Adults (18+)
Age groups specification	Mean(SD): 47.3(9.26) years

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	38
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	8
Drop-out reasons	Reasons: delayed chemotherapy > 2 weeks: n = 3 very mild dizziness: n = 1 decline further study participation: n = 4
Intervention	Ginger essential oils
Dosage and regime	Antiemetics + bottle with 2 drops of ginger oil Glass pendant (in the form of a small flask), to be hung approx. 20 cm from the nose, the bottle was held directly under the nose and inhaled deeply at least 3 times a day for 2 minutes each time Start: Day 1 of 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.	5
Side effects / Interactions	Very mild dizziness or light-headedness on day-5 of aromatherapy treatment n= 1

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Placebo
Number of participants (arm) N randomized	37
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	7
Drop-out reasons	Reasons: delayed chemotherapy > 2 weeks: n = 3 time problem: n = 1 decline further study participation: n = 3
Intervention	Ginger fragrance oil (placebo)
Dosage and regime	Antiemetics + bottle Glass pendant (in the form of a small flask), to be hung approx. 20 cm from the nose, the bottle was held directly under the nose and inhaled deeply at least 3 times a day for 2 minutes each time Start: Day 1 of 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.	5
Side effects / Interactions	No side effects were reported

Outcomes

Nutrition status

Outcome type As specificed by the authors	Primary
Outcome specification	Nutrition (calorie intake, energy requirements met, proportion of fat, carbohydrates, protein and fiber)
Type of measurement	Observation
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".	Calorie intake: sign. main effect time and arm; p's< 0.001, no sign. placebo-arm x Time (p=0.638) kcal (Mean(SD)) intervention-arm vs. placebo-arm sign. difference at day 3 (1262.5(239.6) vs. 1237.8(251.9); p=0.015) and day 5 of chemotherapy (1424.9(233.4) vs. (1392.5(235.0); p=0.002) Covered energy requirement: Sign. Main effect time and arm; p's< 0.001, no sign. interaction arm x time (p=0.604) In % (Mean±SD) intervention-arm vs. placebo-arm sign. difference at day 3 (77.9(14.3) vs. 76.3(14.5); p=0.010) and day 5 of chemotherapy (87.8(13.7) vs. 85.9(13.9); p=0.002) Proportions of fat, carbohydrates, protein and fiber: No significant arm difference
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	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

Funding and Conflicts of Interest

Funding	Public funding
Conflicts of Interest	No significant arm differences in the assessment: odor, applicability, helpful therapy

Further points for assessing the study

Sample

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

Alternative Explanation

Other explanations for an effect besides the investigated intervention	?
- Possibility of attention effects	?
- Possibility of placebo effects	?
- Other reasons	?

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	?
Correction for multiple testing	?
Measurement of compliance	?
Consistent reporting in numbers (figures, flowchart, abstract, results)	?
Comprehensive and coherent reporting	?
Cross-over	?
- Sufficient washout period	?
- Tested for carry-over effects	?
- Tested for sequence effects	?

Interpretation of results

Effect sizes reported (clinical vs. statistical significance)	?
Side effects systematically recorded	?
Side effects considered in result interpretation	?
Ethics votum	?

Additional Notes

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