Research Methods and Critical Appraisal

This document provides an overview of research methods and critical appraisal in the field of study. It includes a detailed analysis of various articles and their findings. The topics covered include the effects of levothyroxine therapy on bone mineral density, different formulations of levothyroxine for treating hypothyroidism, the impact of excess iodine on metabolic patterns, and the thyroid hormone profile in patients ingesting different formulations of levothyroxine. The document also includes a retrospective analysis of levothyroxine treatment in pregnant women with hypothyroidism.

RESEARCH METHODS AND
CRITICAL APPRAISAL

Table of Contents
Introduction........................................................................................................................1
Research Question........................................................................................................1
Research methods and critical appraisal of articles..........................................................1
Effects of levothyroxine therapy on bone mineral density and bone turnover markers
in premenopausal women with thyroid cancer after thyroidectomy...............................1
Different Formulations of Levothyroxine for Treating Hypothyroidism: A Real-Life
Study..............................................................................................................................2
Iodine in excess in the alterations of carbohydrate and lipid metabolic pattern as well
as histomorphometric changes in associated organs....................................................3
Thyroid Hormone Profile in Patients Ingesting Soft Gel Capsule or Liquid
Levothyroxine Formulations with Breakfast...................................................................4
Levothyroxine Treatment of Pregnant Women with Hypothyroidism: Retrospective
Analysis of a US Claims Database................................................................................5
Management of fetal goitre due to hypothyroidism by levothyroxine tablet installation
into amniotic fluid...........................................................................................................6
REREFENCES..................................................................................................................7

INTRODUCTION
Research Question
Is the Levothyroxine more effective than Potassium Iodide in the treatment of
hypothyroidism in young adults (25-40) in UK?
RESEARCH METHODS AND CRITICAL APPRAISAL OF ARTICLES
Effects of levothyroxine therapy on bone mineral density and bone turnover markers in
premenopausal women with thyroid cancer after thyroidectomy
In this article long-term levothyroxine treatment impact upon BMD and BMT with
premenopausal women with differentiated thyroid cancer have been investigated. It was
a primary research in which 65 premenopausal women were chosen as subjects who
has received LT4 therapy at least once in a year. All the women were of age group 32
to 45 years of age and were receiving treatment from Heilongjiang Provincial Hospital of
China. Selecting 65 women as subject helped in analysing levothyroxine treatment
effect upon their bone turnover markers and bone mineral density (Bin-Hong and et. al.,
2020). All the 65 subjects were chosen on the basis of some set exclusion and inclusion
criteria. One of the main inclusion criteria was to select women who did not had history
of thyroid disease as this study was for studying effect of levothyroxine on thyroid
cancer. Women with any other disease history were excluded like asthma, heart
disease and many more. Other than these there were various other kinds of criteria on
the basis of which 65 subjects were selected. All the selected women had normal
menstrual cycle and were diagnosed as per the diagnosis criteria defined by World
health organization. All kinds of important ethical considerations were also considered
for this research. For example, before selecting the participants ethical approval from
Medical Ethics Committee of Heilongjiang Provincial Hospital was taken. Written
consent from all the participants were taken and subjects those who agreed to
participate and signed to participate were enrolled for the study.
With the help of primary data collection methods all the important information
was collected. As it was a quantitative research, quantitative data analysis method was
chosen in which with the help of statistical analysis method desired results and
hypothesis were analysed in order to answer the research question and reach to a
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defined conclusion. In order to perform statistical analysis IBM SPSS version 20.0 was
used. All the collected data information or data were categorized into groups in order to
be evaluated in terms of percentage and frequency. For further analysis Chi-square test
method was used so that comparison between two prevailing groups can be done.
Various kinds of test were performed upon subjects in order to measure their Z score of
lumbar, FT3, FT4, TSH, iPTH, P1NP, CTX-1, calcium, vitamin D3, phosphorus and
alkaline phosphatase in all the participants were measured. So that on the basis of
these categories p-value can be calculated using multivariate logistic regression. Within
this analysis p hose value were < 0.05 were considered as statistically significant.
These methods helped the researcher to evaluate that most of the subjects had low
BMD who had received d long-term LT4 therapy especially for their DTC after
thyroidectomy. Choice of statistical methods also helped in analysing that TSH
suppression therapy was one of the main significant factors because of which risk of
decreasing bone strength was prevailing and bone turnover was increasing.
Different Formulations of Levothyroxine for Treating Hypothyroidism: A
Real-Life Study
Most of the Hypothyroid patients are treated with LT4. This tablet is mostly used
for formulation of LT4 and also helps in fastening regimen which is required for
absorption of active principle. This study has focused on assessing LT4 performance in
coherence of Hypothyroid patients without causing any kind of potential malabsorption
of LT4 tablet as well as providing restored euthyroidism (Scappaticcio and et. al., 2019).
As this was a primary research, primary data collection method was used. For this two
main institutes participated within this research. One institute was of Switzerland
(Thyroid Centre of Ente Ospedaliero Cantonale in Lugano/Bellinzona) and another
institute is of Italy (Unit of Endocrinology mainly and Metabolic Diseases of University of
Campania). Overall design of the study was conducted into two main phases. At first
phase hypothyroid patients were first scanned in order to check whether they were
eligible to participate within the study or not. In which both inclusion and exclusion
criteria were checked. One of the main inclusion criteria on the basis of which patients
were selected was adults with hypothyroidism who were on LT4 therapy for less than
six months. Other than this there are four other inclusion criteria were: having
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TSH, commercialized LT4 preparations without changing dose over time and having a
stable body weight within last six months.
Exclusion criteria on the basis of which patients were excluded were: suspecting
intestinal malabsorption, using drugs that have interference on absorption of LT4,
identified cardiovascular symptoms, patients with health failure history, affect by any
kind of recent infection and women who were pregnant. All the selected patient’s data
was observed and LT4 injection time and time interval between breakfast and LT4
injection. Second phase was re-evaluation phase at this point again inclusion and
exclusion were checked and patients were excluded from the study if: their LT4
formulation or doses were changed, change in body weight was found, suffered from
infection, report any kind of clinical news. Various kinds of laboratory measurements
were conducted on selected patients in order to measure their sensitivity of TSH, serum
level of free-T4, free-T3 were measured in the presence of skewed TSH value and from
these results baseline diagnostic thyroid results were extracted. Ethical consideration
from both the institutes were taken for participation of selected patients and other than
this all the selected patients were asked of their written consent and those who had
signed the consent form were asked to participated within the study. In order to analyse
all the collected primary data from the selected final patient’s quantitative analysis
method was used i.e. statistical analysis was performed were different parameters were
expressed as IQR range and median. Further for this statistical analysis Chi-squared
test method was used for comparison of frequencies. P value less than 0.5 was set as
statistical significance. For performance of this quantitative analysis GraphPad version 7
was used. Usage of these primary and quantitative analysis methods helped the
researcher to identify that nonsolid LT4 formulations performance remain uninfluenced
by correct or incorrect use of therapy. It also helped in identifying that LT4 tablets does
not guarantee euthyroidism when it is ingested when gap between breakfast and LT4
tablet is less than 30 minutes.
Iodine in excess in the alterations of carbohydrate and lipid metabolic
pattern as well as histomorphometric changes in associated organs
This study majorly focuses on exploring influence of exposure of excess iodine
on lipid metabolism and carbohydrate with histoarchitecture on few organs such as liver,
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kidney, pancreas, cardiac muscles and skeletal. In order to reach defined conclusion for
this primary research was conducted. In order to collect primary data for the study 12
rats were taken for collection of required data (Sarkar and et., al, 2018.). All the selected
12 rats were selected. Out of which six of them were fed iodine with the help of gavage
at a dose of 3.5 mg potassium iodide (KI)/100-g body weight, with correspondence of
500 times daily psychological daily dose of iodine for first 30 days then for 60 days.
Other rest of the six rats formed a control group. All the primary data was collected with
the help of laboratory measurement in which few tests were done and measured in
order to calculated few parameters on the basis of which test can be completed.
For further analysis set parameters were observed so that results of both the rats
can be analysed in an appropriate manner. Parameters set for this analysis that were
measured were, urinary iodine, serum T3 and Serum T4, Thyroidal iodine concentration
and testicular iodine concentration. In order to analyse collected data quantitative
methodologies were used and with the help of statistical data analysis method
Epididymal Sperm count was analysed for all the 12 rats of 30 days treatment and of 60
days treatment. Statistical analysis methods also helped in analysing change in body
weight of rats both before treatment and after treatment of 30 days and 60 days. All the
data analysed with the help of this method was expressed as mean ± standard
deviation (SD). For this one- way analysis of variance of ANOVA with Tukey’s post hoc
test was conducted. Like above two research studies in this as well p value lower than
0.5 was considered as statistically significant. For this statistical analysis Microsoft
Excel 2007 and Origin 8 software packages were used. This statistical analysis helped
the researcher in analysing both numerically and graphically that all the rats who were
provided with KI treatment showed growth in their body weight and urinary iodine with
low TH level. It also helped in reaching to a conclusion that excess exposure of iodine
for longer duration caused development of biochemical state of hypothyroidism. This
clearly explains that methods chosen by the researcher were quite appropriate as with
the help of this primary quantitative analysis methods, researcher was able to analyse
development of hypothyroidism with the rats that further responsible for the
hyperglycaemic and hypercholestromic status.
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Thyroid Hormone Profile in Patients Ingesting Soft Gel Capsule or Liquid
Levothyroxine Formulations with Breakfast
This study majorly focuses on investigating whether soft gel capsule formulation
of L-T4 could be ingested at breakfast time or not. For this study, 2371 patients were
assessed with hypothyroidism and on the basis of selection criteria 60 patients between
age group of 18 to 65 years were selected (51 females and 9 males). All the patients
with stable euthyroidism who were receiving liquid L-T4 therapy ingested with
breakfast, were enrolled in this study (Cappelli and et. al., 2016). All the eligible patients
were searched in database of Thyroid Unit of the Department of Clinical and
Experimental Sciences, University of Brescia, Italy. There were certain criteria’s set- in
order to select participants: first was that patients were provided with treatment of
hypothyroidism with liquid L-T4 ingested during each patient’s normal breakfast,
have stable levothyroxine replacement in last 6 months, have complete medical history
and have details of current drug therapy and any previous therapy. It was important for
all the participants to maintain same breakfast habits with their ongoing therapy for
entire duration of the study. All the selected participants had to undergo laboratory
measurements for THS, fT4, fT3 levels, liquid L-T4 to the soft gel capsule formulation at
the same dose of liquid L-T4. All the primary data collected from all the 60 selected
participants was analysed using quantitative analytical method. For this study
researcher has used statistical analysis method for quantitative analysis using SPSS
17.0 software.
While performing this analysis normal distribution was checked with the help of
Shapiro-Wilk test. All the results were presented as median with minimum and
maximum values. All the Continuous variables were compared with the help of two test
t- test and Wilcoxon signed rank test. P value less than 0.5 were all considered as
statistically significant.
Levothyroxine Treatment of Pregnant Women with Hypothyroidism:
Retrospective Analysis of a US Claims Database
This study majorly focused on pregnant women with hypothyroidism and also
examines whether all the guidelines during pregnancy are being adhered or not. In
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order to achieve desired aim and reach to a defined and appropriate conclusion
retrospective study was conducted. It is a kind of study in which two group of people are
compared those who have required disease or comes under defined condition and
second group of people are those individuals who are quite similar but do not have
desired disease or condition. For this study women of age group 18 to 49 years of age
were considered (Lage and et. al., 2020). Even in this all the women who were pregnant
in 2014 and came within the defined age group with hypothyroidism criteria were
selected and included in this retrospective study. In order to select participants, step by
step exclusion process was done. This helped the researcher to categorize women in
three categories: first was of all pregnant women, second was of women who were
treated with levothyroxine and rest who were untreated. All the women who were
selected to participate within the study were asked for their written consent. For this
study quantitative analysis methods were used and samples were analysed with the
help of descriptive statistics that includes mean, median, standard deviation, continuous
variables with interquartile range, and percentage and frequency for categorial
variables. In order to obtain results Kolmogorov-Smirnov test was conducted with
relevant continuous variables (THS and age). Differences within these variables were
performed using Mann-Whitney U tests and differences within two categories was done
using Kruskal-Wallis tests. Lastly examination of differences in categorial variables was
analysed using chi-square tests. All the above specified analysis and examination were
done using SAS, version 9.4 tool.
All the selected women were categorized on the basis of their obesity,
depression, type 2 diabetes, Dyslipidaemia, migraine, hypertension and Type 1
diabetes. With the help of Statistical analysis methods all the collected data were
analysed on the basis of few parameters such as primary results, alternative THS,
stricter monitoring requirements, earlier pregnancy start date and later pregnancy start
date and were categorised as approximately treated with levothyroxine, under treated
with levothyroxine, over treated with levothyroxine and not monitored. This helped the
researcher to analyse that whether all the specified guidelines were adhered or not by
measuring thyroid-stimulating hormone (TSH) target achievement for all the women
who were treated with levothyroxine. This primary quantitative analysis methods helped
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the researcher to identify that large number of women who were provided with treatment
of levothyroxine were not treated in a proper manner and clinical guidelines many cases
were not adhered as well. It was also observed by the researcher that there was a huge
difference between general health of women who were treated with levothyroxine and
those who were left untreated.
Management of fetal goitre due to hypothyroidism by levothyroxine tablet
installation into amniotic fluid
This article discusses about management of fatel goitre because of
hypothyroidism using levothyroxine tablet which are installed into amniotic fluid. Major
focus of the study is whether levothyroxine tablet installed in amoitic fluid can be used
for treatment in fetal goitre. This article includes research about 3 people who
developed fetal goitre and hypothyroidism these were confirmed by cordocentesis. The
research conducted was primary research as this included study of these 3 people with
specific disease and later they were treated with levothyroxine tablet by installing it into
amniotic fluid. The research included all three cases with polyhydramnios between 26-
29 weeks of gestation (Yadav and Pradhan, 2019). Enlarged fetal thyroid was revealed
through ultrasound. The enalarged fetal thyroid was with increased vascularity and
polyhydamnios. This research included that the cord blood was also found with high
TSH and free triiodothyronine and free thyroxine were low. Later they were treated with
installation of levothyroxine tablet into amniotic fluid for 7/seven days and they resulted
in decrease in thyroid volume. The primary reaserch conducted in this researcher
observed all these cases and later after gestation babies were given thyroid
replacement therapy. Primary research and observation helps researchers in such case
to understand all the positive aspects of the treatment which was being given to the
patient. Researcher can identify is there is any negative or side effect of this and along
with suitability in different type of health of the patients.
Goitre is a condition caused by hypothyroidism mainly and rarely the patient may be
euthyroid or even hyperthyroid. In goitre, thyroid gland enlarges in order to restore the
body need of thyroxine hormone(T3, T4) which may cause some obstruction of the
trachea or oesophagus which are present behind the Thyroid gland. The enlarged
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thyroid has high vascularity which is seen on USG and even in antenatal ultrasound if
this occurs in developing fetus.
Fetal hypothyroidism is a very critical situation which may cause multiple defects in the
fetus such as cleft palate, short stature, multiple bony defects and multiple organ
defects as well since thyroxine is the Chief hormone responsible for intraembryonic
development of fetus along with insulin (Yadav and Pradhan, 2019). Screening of this is
mainly done by antenatal ultrasound but the diagnostic test of this is cord blood TSH
level obtained by cordocentesis. In India we don't have the injectable thyroxine so in this
case we performed intra-amniotic instillation of levothyroxine (10mcg/kg fetal weight). A
7 day dose of it was dissolved in aspirated amniotic fluid and injected back into the
amniotic sac. Serial instillation of levothyroxine similarly resulted in the delivery of the
baby near term (37weeka) and all the babies were put on the thyroid replacement
therapy. This resulted in the normal development of the babies in terms of milestones
achievements.
So from such study we can conclude that intra-amniotic instillation of levothyroxine can
be used in treatment of fetal goitre.
Analysis of research method helped in analysing that in all the selected articles
primary research was conducted and for analysis quantitative statistical methods were
used.
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REREFENCES
Books and Journals
Bin-Hong, D., and et. al., 2020. Effects of levothyroxine therapy on bone mineral density
and bone turnover markers in premenopausal women with thyroid cancer after
thyroidectomy. Endokrynologia Polska, 70(1), pp.15-20.
Lage, M.J., and et. al., 2020. Levothyroxine Treatment of Pregnant Women with
Hypothyroidism: Retrospective Analysis of a US Claims Database. Advances in
Therapy, 37(2), pp.933-945.
Online
Cappelli, C., and et. al., 2016. [Online]. Available through: <
https://www.hindawi.com/journals/ije/2016/9043450/ >.
Sarkar, D., and et., al, 2018. [Online]. Available through:
<https://www.degruyter.com/view/journals/jbcpp/29/6/article-p631.xml>
Scappaticcio, L., and et. al., 2019. [Online]. Available through: <
https://www.hindawi.com/journals/ije/2020/4524759/#abstract>
Yadav, S., and Pradhan, M., 2019. [Online]. Available through:<
https://obgyn.onlinelibrary.wiley.com/doi/full/10.1002/uog.21635>
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