Participants also completed three surveys containing questions regarding upper respiratory symptoms WURSS and quality of life SF at baseline, just before travel and at 4-days after travel. Most cold episodes occurred in the placebo group 17 vs. Placebo group participants had a significantly longer duration of cold episode days vs. These data suggest a significant reduction of cold duration and severity in air travelers.
Fatigue, impairment of immunity as well as increased stress and mental changes has been reported during and after long-distance flights [ 4 , 5 , 6 ].
A recent review of medical in-flight events lists respiratory symptoms among the most common medical complaints reported [ 7 ]. Not surprisingly, many studies have investigated the occurrence of nasal dryness and the increased risk of developing upper respiratory disorders such as allergic rhinitis and attracting virus or bacteria induced respiratory infections during long-haul air travel [ 8 , 9 ]. Moreover, an added risk of spreading respiratory diseases, including influenza, aboard commercial flights exists [ 10 ].
Recently, for the first time a herbal medicine, echinacea, was trialled in travellers and showed protective effect against the development of respiratory symptoms during travel involving long-haul flights [ 11 ].
Following travellers return from overseas, participants using echinacea displayed a lower respiratory symptom score and the overall percentage of participants affected by respiratory disease symptoms was marginally lower in the Echinacea group compared to placebo.
However, there are other herbs that have traditionally been used to treat respiratory symptoms and aid in the recuperation from a cold. Black elderberries for example, are well known to be supportive agents against common cold and flu like symptoms and have been used for centuries [ 12 ].
Interestingly, a non-travel related clinical trial just revealed that a combination of echinacea herb and root extract supplemented with elderberry Sambucus nigra L. Elderberries have shown antibacterial [ 14 ] and antiviral activities in in vitro [ 15 ]. A pilot trial with elderberry extract lozenges HerbalScience, Singapore also confirmed a beneficial effect on severity and duration of cold and flu like symptoms [ 17 ].
In recent times, elderberry has gained popularity in research and the wider community due to its reported antioxidant [ 18 ], antidiabetic [ 19 ], anti-inflammatory and immune-modulating [ 20 ], as well as antidepressant [ 21 ] properties. The berries are dark violet-black drupes which grow in clusters and owe their colour to the anthocyanins; a group of phenolic compounds which, amongst flavonoids, are abundant in elderberries and considered the active constituents of the fruits [ 22 ].
However, elderberries also contain a variety of nutrients ranging from various vitamins A, B 1 , B 2 , B 6 , B 9 , C and E , trace elements such as Cu, Zn, Fe and minerals such as K, Ca and Mg to phytochemicals such as carotenoids, phytosterols and polyphenols. Given that elderberry supplementation has never been investigated so far for its possible beneficial effects in air-travelers, we conducted a randomized controlled trial aimed at identifying whether capsules containing a proprietary membrane filtered Elderberry extract Iprona, Italy , standardized to polyphenols, are effective in preventing respiratory symptoms, but also if they positively impact on the overall physical and mental health of travelers when using long-haul, commercial flights as means of transport.
Participants were recruited through travel agencies; radio, newspaper and TV advertisements, and emails circulated to all staff and students at a university on the Gold Coast, Australia. All participants gave written informed consent before participating in the study. Volunteers were included if they were a minimum of 18 years of age and in good general health. Volunteers were excluded if they were currently in another clinical trial or were in one less than 30 days ago, had a known plant allergy, were suffering from respiratory diseases e.
Three hundred and twenty five volunteers met the inclusion criteria and were randomly assigned to trial capsules. The random allocation sequence provided by an independent consultant was computer generated using a randomisation plan from www. A list of consecutive study numbers was generated. Treatment groups were allocated by trial staff, but the allocation was concealed by assigning each participant with a unique number.
Participants, chief investigators and trial staff were blinded to group allocation. A randomised, double-blind placebo controlled clinical trial was conducted between April and December in Australia with economy class passengers travelling to an overseas destination, on a minimum of 7 h flight, i.
Figure 1 outlines the study design. For all participants treatment would commence 10 days before flying overseas and would be completed five days after arriving at the travel destination. The actual treatment time varied between participants depending on their actual travel duration ranging from 15 to 16 days. Cold diagnosis was assessed by measuring the Jackson Score. The elderberry extract used in this trial is a proprietary membrane filtered elderberry Sambucus nigra L.
This extract is currently used in the production of various products marketed in Asia, the US and Europe. The elderberry capsules used in this trial were produced by Plantafood in Germany in accordance with the principles and guidelines of Good Manufacturing Practice.
The mg elderberry extract also contain several mineral, trace elements and vitamins including relatively high levels of magnesium 1. Placebo capsules were manufactured to match the elderberry capsules in size, excipients and appearance.
Capsules were supplied in identical blister packs with identical labelling. Labelling only identified the participant number. The dose selection was based on dosages used by popular elderberry products which range from mg to mg per day.
Compliance was assessed by calculating the percentage of capsules taken against total capsules expected to be taken during the treatment period. Jackson Score: Over the entire study period, all participants maintained a diary. This was to record cold symptoms, as well as additional health issues or disease symptoms and additional medication taken.
The diary helped participants with recalling information when completing the surveys and allowed researchers to identify possible inconsistencies in data documentation. This matrix was based on the work by Jackson and colleagues, who described the clinical features and symptoms of a virally induced common cold [ 23 ]. Their definition is currently accepted as the most valid method for differentiating a cold from isolated symptoms like hay fever or allergies that do not develop into the clinical picture of a cold.
A set of three predefined prophylactic variables were analyzed in a confirmatory manner: i the total number of cold episodes; ii cumulative episode days; and iii co-medicated cold episodes.
The WURSS is a responsive, reliable and valid instrument for evaluating QoL outcomes related to respiratory illness, measuring all significant health-related dimensions that are negatively affected by the common cold [ 24 , 25 ].
It includes 10 items assessing symptoms, nine items assessing functional impairments and one item each assessing global severity and global change over the last 24 h, all of which are based on 7-point Likert-type severity scales. A previous validation of the instrument showed that a cumulative score should be calculated by summing the severity scores of the first 20 items with high severity scores indicating high symptom load.
The MID is the term generally used to quantify the minimum amount of positive change that patients perceive, and would accept an associated treatment as being beneficial or worth taking—a clinically significant effect [ 26 ]. Therefore, individuals that presented with a respiratory disorder symptom score of We analyzed observed data only, i.
The SF is a generic measure and has been developed to provide a shorter, yet valid alternative to the SF, which has been seen by many health researchers as too long to administer [ 28 ]. The SF is weighted and summed to provide easily interpretable scales for physical and mental health. Physical and Mental Health Composite Scores PCS and MCS are computed using the scores of twelve questions and range from 0 to , where a zero score indicates the lowest level of health measured by the scales and indicates the highest level of health.
It has been validated to correlate with cold episodes [ 29 ]. It will be used to identify a possible sub-group of heightened stress participants and help analysing a possible correlation between increased stress and the effects of elderberry for this sub-group as opposed to the overall participant group. The primary outcome measure for this study is the total number of cold episode days measured for the previous six days. This estimate is based on similar previous studies conducted by Jawad et al.
The flow of participants through the trial between April and December is summarised in Figure 2. Six hundred and twelve people were screened, with a number deemed ineligible by inclusion criteria i.
Reasons for declining participation included not wanting to be on placebo, travel cancellation and personal circumstances. Of the trial participants, 13 participants did not receive the trial medication due to various reasons e.
However, completed the first survey. Thus Intention to treat ITT analysis was performed on participants. Of the participants analysed, were assigned elderberry capsules and were assigned placebo. The majority of the participants were women, non-smoker, on average 50 years old, travelled for holiday with a travel time of over 16 h Table 1.
About half of the participants received the flu vaccination. Participants in the placebo and active groups did not differ significantly at baseline. Thus, the two treatment groups can be considered reasonably well balanced at baseline. To confirm that blinding was effective, all participants were asked to speculate whether they were taking elderberry or placebo. Moreover, the symptom score in the placebo group over these days was , whereas in the elderberry group it was Figure 3 B.
Cold episode days A and cold symptom score B of participants with a well-defined cold established from the Jackson Score. This indicates that a participant suffering from a cold episode while taking elderberry would on average experience a 2-day shorter duration of the cold 4. In both groups half the participants with a defined cold used co-medication to relieve symptoms.
On average participants co-medicated for 1. The participants suffering from a cold took in total 25 conventional medicines, belonging to 10 different categories, and one complementary medicine. Some took one medicine, others up to four. The complementary medicine used was an Indonesian product called Tolak angin.
However, when comparing both groups with each other at each individual time point baseline, just before travel and four days after travel , the WURSS scores did not differ significantly at any time point, i. However, the survey completed immediately before travel and overseas showed a trend for more placebo participants reporting significant symptoms than elderberry participants, a trend that approaches significance at least for the before travel survey.
With regards to the secondary outcome measures, Quality of Life QoL measures, the individual scales of SF12 and their component summaries physical and mental were analyzed. However, the change was not significant for any of the subdomains data not shown. This indicates that mental health is strongly positively affected by travel whether people take elderberry or not. Overall, treatment was well tolerated.
Five participants reported adverse events such as i itchy throat and cold-like symptoms 2 participants ; ii fatigue 2 participants and iii kidney pain 1 participant , however, a causal relationship between elderberry and the events could not be established. The two participants who reported itchy throat and cold-like symptoms were later unblinded as taking placebo and elderberry capsules, respectively.
The two participants who reported fatigue were also later un-blinded as taking placebo and elderberry capsules, respectively. And, the participant who reported kidney pain was unblinded as taking placebo. Individual sub-group analysis for participants that had no flu vaccination, travelled for more than 16 h, were more than 50 years old, fully complied with study medication schedule and were stressed, showed no significant differences between placebo and elderberry for any of the QoL indices for any of the survey time points data not shown.
In this study, participants in both, the placebo and elderberry group tended to experience an increase in respiratory symptoms from the time the trial started baseline to four days after arriving overseas. Double-blind experiments are simply not possible in some scenarios. For example, in an experiment looking at which type of psychotherapy is the most effective, it would be impossible to keep participants in the dark about whether or not they actually received therapy.
So why would researchers opt for such a procedure? There are a couple of important reasons. The double-blind procedure helps minimize the possible effects of experimenter bias.
Researchers sometimes have subjective feelings and biases that might have an influence on how the subjects respond or how the data is collected. In one research article, randomized double-blind placebo studies were identified as the "gold standard" when it comes to intervention-based studies. Imagine that researchers want to determine if consuming energy bars before a demanding athletic event leads to an improvement in performance.
The researchers might begin by forming a pool of participants that are fairly equivalent regarding athletic ability. Some participants are randomly assigned to a control group while others are randomly assigned to the experimental group. Participants are then be asked to eat an energy bar. All of the bars are packaged the same, but some are sports bars while others are simply bar-shaped brownies. The real energy bars contain high levels of protein and vitamins, while the placebo bars do not.
Because this is a double-blind study, neither the participants nor the experimenters know who is consuming the real energy bars and who is consuming the placebo bars. The participants then complete a predetermined athletic task, and researchers collect data performance.
Once all the data has been obtained, researchers can then compare the results of each group and determine if the independent variable had any impact on the dependent variable.
A double-blind study can be a useful research tool in psychology and other scientific areas. By keeping both the experimenters and the participants blind, bias is less likely to influence the results of the experiment. A double-blind experiment can be set up when the lead experimenter sets up the study but then has a colleague such as a graduate student collect the data from participants. The type of study that researchers decide to use, however, may depend upon a variety of factors, including characteristics of the situation, the participants, and the nature of the hypothesis under examination.
Ever wonder what your personality type means? Sign up to find out more in our Healthy Mind newsletter. National Institutes of Health. Misra S. Randomized double blind placebo control studies, the "Gold Standard" in intervention based studies. Goodwin, CJ. The validity of the RCT rests not just on theoretical arguments, but also on the discrepancy between the RCT and less rigorous evidence the difference is sometimes considered an objective measure of bias.
A brief overview of historical and recent developments in "the discrepancy argument" is presented. The article then examines the possibility that some of this "deviation from truth" may be the result of artifacts introduced by the masked RCT itself. Can an "unbiased" method produce bias?
0コメント