Critique of Research Statistics

Biostatistics

Submitted by:
Naoe, Jemavel T.
Pacheco, Mia Lariza S.
Saquilayan, Sophia Anne V.
Sibug, Joshua Gabriel B.
3GMT

Iron Deficiency: a Nutritional Gap

Jane Symons

Iron deficiency is one of the most common nutritional gaps in England, United
Kingdom. It is widespread in the world. Iron deficiency anemia (IDA) is caused by poor
diet, blood loss and poor oxygen supply. When one does not consume foods rich in iron
such as meat, poultry, and fish, he or she is more likely to develop iron-deficiency
anemia. The blood loss is caused by long or heavy menstrual periods and internal
bleeding, etc.

The Correlation between Sleep Duration and Iron Levels of Teenagers

Symons (2015) presented in her study entitled, Iron Deficiency: a Nutritional

Gap. This shows the effect of sleep duration and iron levels in the body of teenagers
aged 13 to 19. Thirteen randomly selected teenagers from United Kingdom were made
to sleep for a specific time. Iron was then measured by conducting hemoglobin and
hematocrit test. The individual who slept for 12 hours was said to have an iron
production of 15.8 mg/day. Eleven-hour sleep was the sleep duration the next teenager
had which caused him or her to have an iron production of 14.1 mg/day, 10 hours for
14.0 mg/day and 9 hours for 12.9 mg/day. However, an outlier from the trend was set to
the teenager who slept for 8 hours who was said to have an iron production of 13.5
mg/day. This situation might have occurred because of several reasons like high iron
intake. Moreover, the individual who slept for 7 hours had iron production of 11.3
mg/day, 6 hours for 10.2, 5 hours for 9.6 mg/day, 4 hours for 8.9 mg/day, three hours for
8.6 mg/day, two hours for 7.4 mg/day and the individual who slept for an hour had 6.4
mg/day iron production. Lastly, a sleep-deprived teenager who was randomly selected
and did not sleep had 6.1 mg/day iron production which was measured the next day.
The slope computed was 1. The r value is 0.998 which depicts correlation of sleep
duration and iron production of the body.

Critique of Iron Deficiency: a Nutritional Gap

By: Mia Lariza S. Pacheco

In the research paper entitled Iron Deficiency: a Nutritional Gap by Jane Symons,
the relationship of iron production and sleep duration is presented. An experiment was
conducted in order to gather data that were plotted in a graph.

The researcher did not show the measure of central tendencies (i.e. mean,
median, mode. However, she used data organization that put system to the data
regarding the correlation between sleep durations and iron levels among teenagers.
The researcher did not also utilize measures of variability and reliability and validity, the
spread or dispersion. The only statistical measurements shown were slope and r-value.
The researcher did not use or show the test made, which was probably a t-test, in order
to determine if the relationship of the two variables, sleep duration and iron production,
is significant. The slope computed was 1. The correlation coefficient, the r-value, was
shown to be 0.998. It portrays that 99.8% of the values of y or the iron production of
teenagers measured in mg/dl will change if the value of x, the sleep duration of
teenagers measured in hours is changed. The correlation coefficient measured is close
to 1. Therefore, there is a very high correlation between iron production among
teenagers and sleep duration.

Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders

Eduardo Oda

Introduction
Primary sleep disorders are those not associated with a medical condition,
substance use or concurrent psychological disorder. In order to be diagnosed with a
primary sleep disorder, the sleep disturbance must cause significant distress or
impairment in social, occupational, or other areas of functioning [1]. Nine percent of
Americans report having insomnia [2]. Thirty-five to forty percent of Americans report
having problems falling asleep or excessive daytime sleepiness [3]. Primary sleep
disorders are often comorbid with psychiatric disorders, neurological and cardiovascular
diseases [4]. Average medical expenses of individuals with insomnia in the United
States is nearly $2000 greater annual than those without sleep problems [5]. Poor sleep
is also associated with an increased risk of mortality, hospitalization and traffic
accidents [6][8].
First line treatment options for primary sleep disorders often include
psychological or behavioral therapies [9]. Sleep hygiene, sleep restriction, stimulus
control, relaxation training and cognitive therapy are examples of such nonpharmacological therapies, all of which have shown some evidence of efficacy [10]
[12]. Pharmacological treatments for primary sleep disorders, like insomnia, include
benzodiazepine receptor agonists, benzodiazepines, sedating antidepressants and
other drugs with sedating feature (anxiolytics, antipsychotics, antihistamines). Sideeffects vary between these medications and can range from residual daytime

sleepiness to dependence [13]. There are many over-the-counter medications and

herbal therapies that are used by individuals to treat insomnia. However the efficacy
and side-effect profile of these substances are not as well known or studied as
prescription medications [14].
Many trials have been performed to assess the efficacy of exogenous melatonin
in treating primary sleep disorders. Melatonin is a hormone secreted primarily by the
pineal gland in response to variations in the circadian cycle and has been used for the
last two decades for the treatment of sleep disorders in adults and children [15]. In
contrast to most available sleep medications, melatonin has little dependence potential,
is not associated with habituation and typically produces no hangover. Given its
reported hypnotic effects, relatively benign side-effect profile and over-the-counter
availability, melatonin has been widely utilized in the United States [16].
A previous meta-analysis demonstrated that melatonin was beneficial in treating
most primary sleep disorders over the short-term (4 weeks or less) [17]. However, since
this meta-analysis, 7 trials have been published with an additional 1258 subjects. These
additional trials nearly triple the sample size of previous meta-analyses. The additional
power provided by these new trials will (1) allow us to more precisely estimate
measures of treatment effects and (2) examine moderators of melatonin efficacy.
Specifically, we will examine melatonins effects on sleep latency, total sleep time and
sleep quality. We will also examine the moderating effects of measure type, dose and
duration of melatonin treatment.

Methods
Selection of Studies
PubMed was searched by two reviewers (AQ and EFO) using the terms
Melatonin and Sleep Disorder. The search was further limited to include only
randomized controlled trials and meta-analyses. The bibliographies of related reviews,
meta-analyses and included articles were searched for additional eligible citations. All
studies included were published before or on March 2012.
Inclusion Criteria
Trials were included if they (1) analyzed primary sleep disorders as defined by
the DSM-IV, (2) examined the effects of melatonin, (3) were randomized placebo
controlled trials, (4) had at least 10 participants for parallel designs or 5 participants for
crossover designs and (5) were published in English. Disagreements regarding the
inclusion of studies were discussed between the two reviewers (AQ and EFO) and
ultimately decided by the third reviewer (MHB) when necessary.
Publication bias was assessed by plotting the effect size against standard error
for each trial (funnel plot) [18]. In addition, publication bias was statistically tested by the
Eggers test and by determining the association between sample size and effect size in
meta-regression [18]. Heterogeneity between trials was determined by means of two
separate statistical estimates using Comprehensive Meta-Analysis. First, a Q-statistic
was employed to provide a test of statistical significance indicating whether the
differences in effect sizes are due to subject-level sampling error alone or other sources.

In addition, we estimated heterogeneity using I-square statistic, which estimates the

proportion of total variance that is attributable to between-study variance.
For secondary analyses we performed several subgroup analyses and metaregressions. Stratified subgroup analysis was used to assess the effects of type of
measure (subjective/objective). We used the test for subgroup differences in
Comprehensive Meta-Analysis to determine whether subgroups reduced overall
heterogeneity [19]. We initially intended to examine the effects of age group (children
younger than 18 years old vs. adults older than 18 years old) on melatonins effects.
However, there were not enough trials in children to conduct this analysis. Metaregression was performed to examine the association between melatonin efficacy in
trials and continuous variables such as (1) dose and (2) duration. Our threshold for
statistical significance was selected to be p<.05 for the primary analysis, as well as for
all subgroups analyses and meta-regression. Forest plots were generated separately on
Microsoft Excel using previously published methods to aid in presentation of the
results [20]. All data including information on the inclusion/exclusion of studies and
extraction of data for meta-analysis is available from the corresponding author by
request.
Results
Included Studies
We included nineteen studies involving a total of 1683 subjects in this metaanalysis [21][39]. From the search on Pubmed and related bibliography above
described 268 studies were selected. A total of 249 manuscripts were excluded for the

following reasons: 123 were not randomized placebo controlled trials, 61 did not
examine sleep disorders, 40 did not examine primary sleep disorders, thirteen did not
examine the effects of melatonin, four did not have sample size fitting the inclusion
criteria, five manuscripts were follow-up studies, two manuscripts were not in a peerreviewed journal, and one study was retracted. Nineteen studies were included in the
analysis, fourteen studies on the efficacy of melatonin for the treatment of insomnia,
four studies on delayed sleep phase syndrome and one study on REM sleep behavior
disorder.
Discussion and Conclusion
Our meta-analysis demonstrates that melatonin significantly improves sleep in
subjects with primary sleep disorders compared to placebo. Melatonin reduces sleeponset latency, increases total sleep time and improves overall sleep quality compared to
placebo to a statistically significant degree. It should be noted that the improvements in
sleep parameters in absolute terms were smaller than previous meta-analyses of
benzodiazepines and newer non-benzodiazepine sleep medications. For instance, the
reduction in sleep latency observed with melatonin in this meta-analysis, slightly less
than 7 minutes, was less than sleep-latency reduction observed in previous metaanalyses of other available sleep medications. A previous meta-analysis demonstrated a
significant benefit of benzodiazepines (10.0 to 19.6 minutes) and non-benzodiazepine
sleep medicines (12.8 to 17 minutes) in reducing sleep-onset latency for primary sleep
disorders [21]. Thus prescription sleep medications are quite likely more effective than
melatonin, although head-to-head trials could definitely alleviate any doubts regarding
the relative efficacy of these agents.

Meta-regressions were performed to assess the relationship between effect,

duration and dose. Higher melatonin doses and longer duration trials were related to
significant greater effect sizes on sleep latency and total sleep time. These findings
suggest that there is no evidence of the development of tolerance with melatonin use.
This

stands

in

contrast

to

other

commonly

used

hypnotics

such

as

benzodiazepines [13]. No greater effects in sleep quality were observed with melatonin
dose or trial duration, suggesting that melatonin effects on sleep quality are constant for
any duration or dose.
Given our findings, it is important to note some limitations of this meta-analysis.
Due to the relatively small number of trials that met our inclusion criteria, our metaregression analysis had limited power. This problem was exacerbated by one trial that
contributed a very large weight to our overall findings [22]. The relatively small number
of trials also limits the ability of the Eggers Test to demonstrate publication bias.
However there was no evidence of publication bias for all outcome measures on funnel
plot as well. There were relatively few studies examining the efficacy of melatonin in
children with primary sleep disorders and this precluded any stratified subgroup analysis
based on age. The presence of mostly trials examining primary insomnia limited our
ability to perform an analysis based on diagnoses.
Despite these limitations, this meta-analysis demonstrated that exogenous
melatonin administered to subjects with primary sleep disorders modestly improved
sleep parameters including sleep latency, total sleep time and sleep quality. This finding
corroborates the results of a previous meta-analysis conducted in the area several

years ago that also demonstrated a significant benefit of melatonin [17]. The benefits of
melatonin compared to placebo appear smaller than that of available prescription sleep
medications. However, melatonin should be considered in clinical practice due to its
benign side-effect profile, cost and limited evidence of habituation and tolerance.
Further research is needed to examine the long-term benefits of sleep medications
including the comparative efficacy of melatonin to common prescription sleep
medication

Critique of Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders

By: Mia Lariza S. Pacheco

In the study entitled Meta-Analysis: Melatonin for the Treatment of Primary Sleep
Disorders, data were obtained using Microsoft Excel spreadsheets, as aforementioned
in the research. Extricated data were said to be sleep onset latency, total sleep time,
sleep quality, age of sample, dose, duration, drug formulation. Sleep onset latency, total
sleep time and sleep quality data were also classified in objective measures, (i.e.
polysomnography or actigraphy) and subjective measures (i.e. scales, questionnaires,
sleep logs).
By inducing 19 studies involving a total of 1683 subjects, primary outcome
measure was mean improvement in sleep onset latency, total sleep time and sleep
quality. Due to the relatively small number of trials that met the inclusion criteria of the
meta-analysis, regression analysis had limited power because of the relatively small
number of trials that limited the ability of the Eggers Test, which is used to test for
funnel plot asymmetry, to demonstrate publication bias. Nevertheless, there was no
evidence of publication bias for all outcome measures on funnel plot.

Signs & Symptoms of Iron Deficiency in Teens

Beth Greenwood

Iron deficiency and anemia are two pieces of a condition that often affects
teenagers: fatigue. Teens may be tired for other reasons, such as staying up late to do
homework or to study for tests, extracurricular activities or trying to manage a job plus
school, but anemia from iron deficiency can make things worse. Signs and symptoms of
iron deficiency can be subtle and easy to overlook.
Iron Deficiency
Iron deficiency can result when you have increased iron needs. Blood loss from
heavy menstrual periods may cause iron deficiency, as can frequent blood donations or
food sensitivity. Iron may also become deficient if you dont eat enough iron-containing
foods or cant absorb what you do eat. Vegetarians are at increased risk for iron
deficiency because iron from plant foods is not as well absorbed as iron from animal
sources.
Anemia
The symptoms of anemia are primarily related to oxygen transport. Red blood
cells contain hemoglobin, a protein that transports oxygen from the lungs to all cells in
the body. Iron is an integral component of hemoglobin. Iron deficiency anemia -- the
most common cause of anemia in American teenagers, according to KidsHealth.org -causes a drop in red blood cells and hemoglobin. As the hemoglobin levels drop below
normal, symptoms begin to appear.

Fatigue, Pallor, Rapid Heartbeat

The most common symptom of iron deficiency in teenagers is fatigue. The
decrease in available oxygen because of inadequate hemoglobin means the bodys
cells cannot carry out their metabolic functions. Red blood cells provide the normal pink
color to the skin, so a person with anemia may be pale. Your heart will beat faster
because its trying to get the required amount of oxygen to the body by speeding up the
circulation.
Other Symptoms
Even before anemia develops, iron deficiency can affect your mental functions.
You may have difficulty concentrating, remembering things or learning something new.
As iron deficiency anemia progresses, you may feel tired all the time and short of
breath. Climbing stairs or exercising can become a major effort, because your body
cannot respond to the extra demand for oxygen. Headaches are another symptom of
iron deficiency anemia. You may feel cold all the time, have an inflamed tongue or be
more susceptible to infections.
Diagnosis and Treatment
Symptoms like fatigue and pallor indicate possible Iron deficiency and the
resulting anemia. Blood tests can determine iron levels in the body, the number of red
blood cells you have and the level of your hemoglobin. Iron deficiency may be corrected
by dietary changes, but you may also need iron supplements. Since iron deficiency can

be caused by factors other than diet, the correct diagnosis is important. If you have
questions or concerns, consult a health-care professional.
Critique of Signs & Symptoms of Iron Deficiency in Teens
By: Mia Lariza S. Pacheco

The article Signs & Symptoms of Iron Deficiency in Teens by Beth Greenwood is
a mere summary of a research published online. The main conclusion of the
summarized report is that the most common symptom of iron deficiency in teenagers is
fatigue. The occurrence of the fatigue incidence in teenagers could have been
statistically proven. There were no statistical data shown that made the researcher
wrote about the affectivity of fatigue in teenagers having iron deficiency condition. The
researcher emphasized the correlation between fatigue and deficiency of iron in teens.
However, it would be better to use statistical measures to show the relationship. The
researcher could have shown the logical regression analysis by obtaining the slope and
the r-value from an experiment. T-test could have also been made to know if the
variables have significant differences.