Transcript Study types

Medical Discoveries
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2600 BC Imhotep describes 200 illnesses
420 BC Hippocrates Oath
1249 Glasses to correct eye vision
1736 Operation of appendix
1796 Vaccination against smallpox1976 eradication of smallpox
1895 Röntgen
1928 Penicillin
1954 First kidney transplant
1965 Ultrasound
1971 CT
1981 Discovery of HIV
1987 Separation of conjoined twins
2000
 2003
 2006
 2007
Human Genome sequenced
SARS
HPV vaccine
Stem cells created from skin
cells
 2012 HIV Pre-exposure
prophylaxis
 2013 First created kidney
transplanted in mice
 2015 CRISPR interference
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describe new things
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determine causes of diseases
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determine which medication/procedure is
better
Original research article
new knowledge
for the first time
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Clinical observation
Case report
Case series
Observational studies
Cross-sectional
Case-control
Cohort
Experimental studies
(Randomized) controlled clinical trial
N of 1 trial
Qualitative studies
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detailed report of the symptoms, signs,
diagnosis, treatment, or a follow-up of an
individual patient.
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anecdotal evidence – lack of generalizability
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CARE (i.e. CAse REport) guidelines
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Include patient’s perspective and informed
consent
A 42-year-old male electrician presented to
the eye clinic with decreasing vision 4 weeks
after an electrical burn of 14,000 V to the left
shoulder. His vision in both eyes was limited
to perception of hand motions, with an
intraocular pressure of 14 mm Hg in each
eye. Slit-lamp examination showed bilateral
stellate anterior subcapsular opacities of the
lens.
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Four months after the injury, the patient underwent
cataract extraction and implantation of an
intraocular lens, which was followed by
improvement in visual acuity to 20/70 in the right
eye and 20/400 in the left eye. Two years after the
injury, a retinal detachment developed in the left
eye, and the patient underwent repair. At a 10-year
follow-up visit, the patient's visual acuity was
20/100 in the right eye, but in the left eye he could
only count fingers
Although the patient was legally blind, he was able
to read with the use of low-vision aids and was
able to independently commute on public
transportation. When lenticular opacities are the
sole manifestations of electrical injury, cataract
extraction is expected to produce a functional
outcome. However, with concurrent damage to the
optic nerve and retina, complete visual
rehabilitation may be limited.
A strike of lightning left
Winston Kemp, a 24-yearold electrician, with a skin
discoloration. Known as a
"Lichtenberg figure," for the
German physicist who first
described seeing a similar
pattern while experimenting
with static electricity, these
reddish fern-leaf patterns
are a skin reaction to a
lightning strike.
They are sometimes referred
to as "lightning flowers" or
"lightning trees." and tend
to occur on the arms, back,
neck, chest, or shoulders of
lightning strike victims.
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number of subjects with a known exposure,
treatment, or outcome
informed consent and patients’ perspective
should also be included
statistical procedures justified
In the period October 1980-May 1981, 5 young men were
treated for biopsy-confirmed Pneumocystis carinii
pneumonia at 3 different hospitals in Los Angeles,
California. Two of the patients died. All 5 patients had
laboratory-confirmed previous or current
cytomegalovirus (CMV) infection and candidal mucosal
infection. The patients did not know each other and had
no known common contacts or knowledge of sexual
partners who had had similar illnesses. Two of the 5
reported having frequent homosexual contacts with
various partners. All 5 reported using inhalant drugs,
and 1 reported parenteral drug abuse. Patients had
profoundly depressed in vitro proliferative responses to
mitogens and antigens.
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Pneumocystis pneumonia in the United States is
almost exclusively limited to severely
immunosuppressed patients (1). The occurrence
of pneumocystosis in these 5 previously healthy
individuals without a clinically apparent
underlying immunodeficiency is unusual. The fact
that these patients were homosexuals suggests
an association between some aspect of a
homosexual lifestyle or disease acquired through
sexual contact and Pneumocystis pneumonia in
this population. It also suggests the possibility
of a cellular-immune dysfunction related to a
common exposure that predisposes individuals
to opportunistic infections such as
pneumocystosis and candidiasis.
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a snapshot of a population (sample)
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survey conducted at one point in time
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determines prevalence
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association not casuation
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Reporting guidelines – STROBE (Strengthening
- % of characteristic (disease) found
the Reporting of Observational Studies in
Epidemiology)
Students at the Karolinska Institute Medical
University, Stockholm, Sweden were asked to
complete a Higher Education Stress Inventory
(HESI) and the Major Depression Inventory (MDI).
The prevalence of depressive symptoms among
students was 12.9%, significantly higher than in
the general population, and was 16.1% among
female students versus 8.1% among males. A
total of 2.7% of students had made suicide
attempts, but none during the previous year. A
gender difference regarding stress levels was
also seen, where women reported higher levels of
stress than men.
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identify factors that may contribute to a
medical condition by comparing subjects who
have that condition/disease (the "cases") with
patients who do not have the
condition/disease but are otherwise similar
(the "controls")
rare diseases – hard to find large samples
odds ratio - how strongly the presence or
absence of a factor is associated with the
disease
vrijeme
past
Measurem
ent - now
exposed
not-exposed
Disease
cases
(cases)
exposed
not-exsposed
Healthy
controls
(controls)
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B: Pancreatic neuroendocrine tumors (PNETs) are
uncommon, and little is known about their risk factors
and association with other cancers. We evaluated
whether the following risk factors known to be
associated with pancreatic adenocarcinoma are also
associated with PNETs: smoking, alcohol use, family
history of PNET, other cancers, and personal history of
diabetes.
M: Patients with PNETs seen at Mayo Clinic Rochester
between 2000 and 2011 were compared with controls
seen for a general medical evaluation. Patients and
controls completed the same questionnaires, 309
patients were matched to 602 controls (2:1) on age,
sex, and region of residence.
RESULTS:
Personal smoking history was not associated with
PNETs. Alcohol use was less common among
cases (54% vs 67%, P < 0.001). Cases were more
likely to report a family member with sarcoma (P
= 0.02), PNET (P = 0.02), gallbladder cancer (P =
0.02), ovarian cancer (P = 0.04), and gastric
cancer (P = 0.01). There was no association with
other cancers in family members. Diabetes was
more commonly reported by cases than controls
(19% vs 11%, P < 0.001).
CONCLUSIONS:
With the exception of diabetes, risk factors that are
associated with pancreatic adenocarcinoma are
not risk factors for PNETs.
cohort – basic tactical unit of a Roman legion (480 soldiers)
Does a certain factor increase the likelihood of a disease?
Step 1 - form a cohort – individuals without a certain characteristic –
(without the disease)
Step 2 - form two groups 1) exposed to a factor and 2) non-exposed
Step 3 – follow them over time (months, years, decades)
Incidence (a number of new cases during a time period, usually a year)
can determine causality
Relative risk: ratio of the probability of an event occurring in an
exposed group to the probability of the event occurring in the nonexposed group
Cohort studies are used to determine the causes of disease and to
follow effectiveness of treatment
The researchers in 1948 recruited 5,209 men and women between
the ages of 30 and 62 from the town of Framingham,
Massachusetts, and began the first round of extensive physical
examinations and lifestyle interviews that they would later
analyze for common patterns related to cardio vascular diseases
for the next 30 years.
1961 Cholesterol level, blood pressure, and electrocardiogram
abnormalities found to increase the risk of heart disease
1967 Physical activity found to reduce the risk of heart disease and
obesity to increase the risk of heart disease
1988 High levels of HDL cholesterol found to reduce risk of death
1999 Lifetime risk at age 40 years of developing coronary heart
disease is one in two for men and one in three for women
2002 Lifetime risk of developing high blood pressure in middleaged adults is 9 in 10.
2005 Lifetime risk of becoming overweight exceeds 70 percent,
that for obesity approximates 1 in 2
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In the present - researchers pick a cohort from
the past (e.g. those born in 1960, or those living
in a certain city, working at a specific factory) and
collect data from existing medical records
They are also divided into two groups – exposed
and non-exposed
The time to complete a retrospective study is
only as long as it takes to collect and interpret
the data.
Retrospective cohort study was conducted in 233 benzene
factories and 83 control factories in 12 cities in China in
1982. The benzene cohort and the control cohort consisted
of 28,460 benzene exposed workers and 28,257 control
workers. Medical records were checked from 1972.
Thirty cases of leukaemia (25 dead and 5 alive) were detected
in the former and four cases (all dead) in the latter.
Most (76.6%) cases of benzene leukaemia were of the acute
type. The mortality due to benzene leukaemia was high in
organic synthesis plants followed by painting and rubber
synthesis industries.). Of the 25 cases of leukaemia, seven
had a histThe concentration of benzene to which patients
with a leukaemia were exposed ranged from 10 to 1000
mg/m3 (mostly from 50 to 500 mg/m3ory of chronic
benzene poisoning before the leukaemia developed. The
relative risk of leukaemia for the benzene workers was 6.97.
Time of study group formation
Time of data collection
Cross-sectional study
Case control study
Experimental research
Historical cohort study
Cohort study
sadašnjost
prošlost
Past
Present
budućnost
Future
RCT - Randomized controlled
trial
The researchers recruited 5,209 men and women between the ages
of 30 and 62 from the town of Framingham, Massachusetts, and
began the first round of extensive physical examinations and
lifestyle interviews that they would later analyze for common
patterns related to cardio vascular diseases.
1961 Cholesterol level, blood pressure, and electrocardiogram
abnormalities found to increase the risk of heart disease
1967 Physical activity found to reduce the risk of heart disease and
obesity to increase the risk of heart disease
1988 High levels of HDL cholesterol found to reduce risk of death
1999 Lifetime risk at age 40 years of developing coronary heart
disease is one in two for men and one in three for women
2002 Lifetime risk of developing high blood pressure in middleaged adults is 9 in 10.
2005 Lifetime risk of becoming overweight exceeds 70 percent,
that for obesity approximates 1 in 2
Antibiotic streptomycin had been discovered two years
previously by Waksman (Schatz, Bugie, and Waksman,
1944); in the intervening period its power of inhibiting
tubercle bacilli in vitro, and the results of treatment in
experimental tuberculous infection in guinea-pigs, had
been reported; these results were strikingly better than
those with any previous chemotherapeutic agent in
tuberculosis.
In 1946 no controlled trial of streptomycin in pulmonary
tuberculosis had been undertaken in the U.S.A. The
Committee of the Medical Research Council decided then
that a part of the small supply of streptomycin allocated to
it for research purposes would be best employed in a
rigorously planned investigation with concurrent controls.
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By September, 1947, 109 patients had been accepted,
and no more were admitted to this trial. Two patients
had died within the Preliminary observation week; these
are excluded from the analysis. Of the remaining 107
patients 55 had been allocated to the streptomycin
group and 52 to the control group.
Determination of whether a patient would be treated by
streptomycin and bed-rest (S case) or by bed-rest alone
(C case) was made by reference to a statistical series
based on random sampling numbers drawn up for each
sex at each centre by Professor Bradford Hill.
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Four of the 55 S patients (7%) and 14 of the 52 C
patients (27%) died before the end of six months. The
difference between the two series is statistically
significant; the probability of it occurring by chance is
less than one in a hundred.
At four months after admission the general condition
had improved in 40 (73%) of the 55 S patients,
compared with 26 (50%) of 52 C patients.
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Analysis of the results at the end of the first six-month
period has shown that the course of bilateral acute
progressive disease can be halted by streptomycin
therapy; 51% of the streptomycin-treated patients
showed considerable improvement radiologically when
comparison was made with their chest radiographs
taken on admission. That streptomycin was the agent
responsible for this result is attested by the presence in
this trial of the control group of patients, among whom
considerable improvement was noted in only four (8%),
and two of these four patients had improved only after
collapse therapy. In other words streptomycin therapy
was effecting what the patient's tissues alone could not
do-checking the spread of the tubercle bacillus in one
of its most favorable milieiux.
Crosssectional
study
Case-control
Cohort
Experimental
prevalence
-
incidence
incidence
Outcome
>1
1
>1
>1
Causality
No
No
Yes
Yes
big/small
small
big
small/big
Duration
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Price
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Incidence/
Prevalence
Sample (N)
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a single patient is the entire trial
It is used to choose optimal choice of
treatment (drug) for a patient (personalized
medicine)
random allocation can be used to determine
the order in which an experimental and a
control intervention are given to a patient
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ABA design – most common
A – no treatment or placebo or golden standard
B – experimental drug
Variants:
ABAB
ABABAB
ABBA
concerns about the carryover effects of the
interventions - interventions may linger in the
system after administration
it is important to ensure that the treatment
periods are sufficiently long (washout and
crossover periods) and that statistical methods
appropriately accommodate or consider
carryover effects when data is analyzed
Ornithine transcarbamylase deficiency (OTCD) is an X-linked
disorder of the urea cycle. It is often fatal in affected males.
Treatment for affected individuals includes dietary protein
restriction, activation of alternative pathways of nitrogen
excretion and L-arginine supplementation. Depending on the
amount of X chromosome inactivation skewing, females show
variable clinical manifestations, and sometimes the need for
treatment, including medications, is unclear. We conducted
an n of 1 randomized controlled trial on an obligate OTC
carrier. The treating physician and patient were blinded to
treatment. Either placebo capsules or L-arginine capsules
were given for weekly periods. Weekly efficacy indicators
included plasma arginine and glutamine levels and a quality
of life/mood assessment questionnaire scale. Clear evidence
of benefit with L-arginine compared to placebo was shown.
This is the first time an n of 1 randomized controlled trial has
been reported for an X-linked metabolic condition.
in-depth understanding of a phenomena
Main question is - Why?
“when little is known about a topic, when the
research context is poorly understood, when the
boundaries of the domain are ill defined, when the
phenomenon is not quantifiable, when the nature
of the problem is murky, or when the investigator
suspects that the status quo is poorly conceived
and the topic needs to be re-examined”
Brief overview of
qualitative research
Methods:
• Participant observation
• In-depth interviews
• Focus groups
• Text/discourse analysis
Designs:
• Ethnography
• Grounded theory
• Phenomenology
Why use qualitative
research:
• New/emergent topics
• “Lived experience”
• Meanings and motives
under the numbers
• Develop hypotheses
for further quantitative
testing (“mixed
methods”)
AIM: The aim of this study was to describe Norwegian healthcare staffs' experiences of
participating in care of patients with Ebola virus disease in Sierra Leone.
BACKGROUND: Ebola is one of the most feared viruses known. Ebola virus disease is highly
contagious with high mortality.
DESIGN: Descriptive study with qualitative approach.
METHOD: Individual narrative and focus group interviews were obtained during 2015 with
eight nurses and one physician who had worked in Ebola care in Sierra Leone. The
interviews were analysed using qualitative content analysis.
RESULT: The analysis resulted in the two themes: 'Experiencing security by learning to
manage risks'; and 'Developing courage and growth by facing personal fears'.
Subthemes were: 'Relying on safeguard actions', 'Managing risk of contagion',
'Developing strategies for care despite risks', 'Constantly reminded of death',
'Successively defeating fears' and last, 'Increasing motivation through meaningfulness'.
The participants described the reliance on training, organized effort, strict guidelines
and equipment. They were respectful of the risk of transmission, made risk
assessments, took responsibility, handled risky situations and were reminded of
suffering and death.
CONCLUSION: Despite challenges, the hazardous work with Ebola virus disease patients
was experienced as meaningful which was an important motivator. Safe care was central
in working with Ebola patients, but the care relation was challenged.
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Systematic reviews with/without a metaanalysis
Systematic review - exhaustive review of
current literature relevant to a research
question (very detailed search strategy)
Meta-analysis is “the statistical analysis of a
large collection of analysis results from
individual studies for the purpose of
integrating the findings”
BACKGROUND: Mumps, measles and rubella (MMR) are serious diseases that can
lead to potentially fatal illness, disability and death. However, public debate over
the safety of the trivalent MMR vaccine and the resultant drop in vaccination
coverage in several countries persists, despite its almost universal use and
accepted effectiveness.
OBJECTIVES: To assess the effectiveness and adverse effects associated with the
MMR vaccine in children up to 15 years of age.
SEARCH METHODS: For this update we searched the Cochrane Central Register of
Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), which includes
the Cochrane Acute Respiratory Infections Group's Specialised Register, PubMed
(July 2004 to May week 2, 2011) and Embase.com (July 2004 to May 2011).
MAIN RESULTS: We included five randomised controlled trials (RCTs), one controlled
clinical trial (CCT), 27 cohort studies, 17 case-control studies, five time-series
trials, one case cross-over trial, two ecological studies, six self controlled case
series studies involving in all about 14,700,000 children and assessing
effectiveness and safety of MMR vaccine. Based on the available evidence, one
MMR vaccine dose is at least 95% effective in preventing clinical measles and 92%
effective in preventing secondary cases among household contacts.
Exposure to the MMR vaccine was unlikely to be associated with autism, asthma,
leukaemia, hay fever, type 1 diabetes, gait disturbance, Crohn's disease,
demyelinating diseases, bacterial or viral infections.
Hierarchy of evidence
1.
2.
3.
4.
N of 1 randomized control trial
Systematic reviews of randomized control trials
Single randomized control trial
Systematic review of observational (cross-sectional, cohort,
or case-control) studies
5. Single observational (cross-sectional, cohort, or case-control)
study
6. Physiologic studies (studies of blood pressure, cardiac
output, exercise capacity, bone density, etc)
7. Unsystematic clinical observations (case series, case report)