For getting help during the practical activities access: Instructions and Interpretations.   

Introduction

Case-control studies are an important category of clinical studies which evaluates the link between one or more prognostic factors and various pathological conditions.

In these studies, the relationship between the factor (s) and the occurrence of a disease is assessed, or whether a particular factor changes the progression of a disease (amelioration or healing). Prognostic factors can be: risk factors (favoring the occurrence of a disease) or protective factors (prevent the disease or help the process of healing). Investigating the relationship between possible prognostic factors and disease can be achieved through all types of data collection without the researcher intervening.
In the case-control study, it starts from the fact that the disease is rare and the cases are first identified ( subjects who have a certain disease) and then the controls are chose: subjects with similar characteristics, (gender, age, socio-economic status) they do not have the disease. Only after that, with retrospective or transversal methods, the researcher is looking for prognostic factors in these groups. There are several methods for identifying prognostic factors, some of them are: laboratory determinations, standardized questionnaire, interview with the subject / family members, or consultation of medical records of subjects enrolled in the study.
Strengths of the case-control study:·Efficacy in case of rare diseases or high period of latency diseases·  Relatively easy to achieve (not expensive, it takes a short period of time)· Allows analysis of several prognostic factors Weaknesses of the case-control study:can bring false information (eg. subjects forget some of previous exposures, or sick subjects tend to remember even non-significant exposures in comparison to healthy people) the time between the onset of exposure and the onset of the illness may be difficult to determine         

Example of a case-control study:

               An example of case-control study is the one led by the authors  Destaalem Gebremedhin, Haftu Berh and Kahsu Gebrekirstos, a study entitled „Risk Factors for Neonatal Sepsis in Public Hospitals of Mekelle City, North Ethiopia,2015: Unmatched Case Control Study”,published in 2016,in the journal Plos One (ISI, IF:2.80, Q1).Article source:

http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0154798&type=printable

Definitions used in the study:Neonatal sepsis  - Systemic inflammatory response  in the presence, or as a result of a proven or suspected infection in a newborn. The infection can be bacterial, viral or fungal.  

Scenario-example

               Gebremedhin D et al. have conducted a study on newborns registered at public hospitals in Mekelle, North Ethiopia, from December 2014 to June 2015, to identify risk factors for neonatal sepsis. The data needed for the study were collected from the infant's medical records and questionnaire applied to the mothers.  Two groups of subjects were compiled in the study: a sample of 78( newborns diagnosed with neonatal sepsis) and a control group of 156 (newborns without sepsis).
The inclusion criteria for cases were:·         newborns registered in pediatric or neonatal intensive care in public hospitals in Mekelle City, North Ethiopia during the study period with at least one of the following IMNCI (Integrated Management of Neonatal and Childhood Illness) clinical features: fever (≥37.5 ° C) or hypothermia (≤ 35.5 ° C), increased breathing (≥ 60 breaths per minute), severe chest retraction, movements only when stimulated, seizures, lethargy or unconsciousness ·         at least 2 haematological criteria: total white blood cells (12000 cells/m³⁾, absolute neutrophil number (1500 cells/mm³ or >7500 cells/mm³), erythrocyte sedimentation rate (>15/1h),  number of platelets( > 440 cells/m³) .
The inclusion criteria for the control group were:·         newborns who did not meet the sepsis criteria and who were enrolled in neonatal pediatric or intensive care units of public hospitals in Mekelle, North Ethiopia during the study period 

Reaserch protocol

Aim and objectives

The aim of this study was to evaluate the association between the mother's history of urinary tract infection(UTI)  or sexually transmitted infection(STI)  and neonatal sepsis.

 Objectives: testing for the link between the factor (prolonged rupture of the membrane) and the disease (neonatal sepsis)·         quantifying the importance of this link : estimation of the odds ratio indicator (OR) 2. Domain of research: risk factors or/and prognostic factors 3. Study type:·         Based on study objectives: analytical study·         Based on the results of the researchers: observational study·         Based on the matching technique that was used in choosing the groups: without matching Note:analytical study = groups of patients are compared, associations between different clinical characteristics are testeddescriptive study=it describes a number of cases or a single group of patients and do not search for possible associations / linksobservational study = the type of study that does not involve the researcher intervention on the progression of the disease.matching in studies = for each subject in the case group/exposed group there is a subject with similar characteristics for the control /unexposed group.  For ex. Matching by: same sex, similar age (identical or +/- 2 years), same risk factors (eg diabetics). The match can be made 1: 1 or 1: 2, 1: 3, 1: 4 (one case at 1/2/3/4 controls). 4. Target population and study sample: Target population: Newborn babies arriving in the world in the section of obstetrics in public hospitals in Mekelle, North Ethiopia, December 2014 - June 2015. Study sample:Inclusion criteria: Babies born between December 2014 and June 2015 in the Mekelle, Northern Ethiopia hospitals' public hospitals.Exclusion criteria :Note: In this scenario, the exclusion criteria are not mentioned.Sample size:The authors mention in the article that the size of the sample was estimated at 234 subjects for a type II error of 0,20 (a 80% study power), a proportion of  UTI/STI with neonates without sepsis of 13% (determined in another study per similar population), control/cases (ratio) = 2: 1, and an OR = 2,87. We believe that the size of the sample was sufficient. 5. Data collection method·         based on the studied population: systematic random sampling-see the Method section of the article·         based on the duration of data collection: longitudinal retrospective·         based on the grouping method: Case – control (the two groups were defined according to the presence/absence of neonatal sepsis).
!Note: Types of probabilistic samplingRandom simple sampling: Each element within the population has the same chance of     being included in the sampleRandom systematic sampling: assumes random choice of a start number (step), from which, adding a fixed size will result in a unit (element) of the sampleRandom layered sampling: consists of dividing the research population into layers according to certain characteristics (genes, age groups) to randomly subtract sub-samples (groups) proportional to the size of the layer from each layer, groups that are then combined to obtain a single sampleRandom cluster sampling: The research population is divided into clusters and a number of groups are randomly selected with all the units included. 
6. Statistical analysis Demographic and clinical characteristics of the mother:Age: continuous quantitative variableCivil status, religion, ethnicity, occupation: nominal qualitative variablesEducational level (primary school, secondary school, college or faculty): ordinal qualitative variableHistory of urinary tract infection or sexually transmitted infection (TUI/STI), hypertension disorders, the birth environment, prolonged membrane rupture, intrapartum fever: dichotomial qualitative variables Demographic and clinical features of the newborn:Newborn gender (M/F), Apgar score at 1minute (7 coded with 1 versus  ≥7 coded with 0), Apgar score at 5 minutes (7 coded with 1 versus ≥7 coded with 0), birth resuscitation (yes/no),  sepsis (yes/no): dichotomial qualitative variables

Weight at birth (1500-2500 grams,  ≥2500 grams), gestational age ( 42 weeks): ordinal qualitative variables

Data description: It can be done either through a frequency table, contingency table, or vertical or horizontal column chart.

The bivariate association between the exposer factor and the disease can be demonstrated trough statistical Chi-square test or Fisher's exact test (the latter applies if expected frequencies in the contingency table are   20% of cells)

Multivariate association between the exposure factor and the disease: through multivariate logistic regression.

To quantify the importance of the association between the risk factor and the disease, the chances of having sepsis (OR) and the associated 95% confidence interval (CI) will be calculated.·         If the estimated odds ratio  OR> 1 and both ends (lower limit and upper limit) of the confidence interval are greater than >1 then it can be stated that the exposure factor is a risk factor·         If the estimated odds ratio  OR 1 and both ends (lower limit and upper limit) of the confidence interval are less than 1 then we can assume that the exposure factor can be a protective factor.·         If the odds ratio OR = 1 or the confidence interval contains 1 then we can say that we do not have enough evidence to demonstrate that the exposure factor is a risk or a protective factor. !Note: The odds ratio can be determined in the unadjusted form (also referred to as the "crude odds ratio") representing the chance of disease in exposed versus non-exposed patients and / or in the adjusted form (also called the "adjusted odds ratio") representing the chance of disease in exposed versus non-exposed patients adjusted after the presence of other covariates. 

Expected results. Data analysis and presentation

1. Sample description

In the present study, the description of the characteristics measured on the sample was made using the contingency tables presented in a condensed form in the Results section of the article.

Table 1. Description of the socio-demographic characteristics of the study groups

Source: imagine preluată din articolul Gebremedhin D, Berhe H, Gebrekirstos K. Risk Factors for Neonatal Sepsis in Public Hospitals of Mekelle City, North Ethiopia, 2015: Unmatched Case Control Study. PLoS One. 2016 May 10;11(5):e0154798.

2. 2. Bivariate and multivariate association between a history of urinary tract infection or a sexually transmitted infection and neonatal sepsis.

The contingency of risk factor (TUI / STI) and disease (sepsis):

TUI / STI= the history of the mother of urinary infection or sexually transmitted infection

Table 2. Bivariate and multivariate association between TUI /STI and neonatal sepsis

Source: preluat din articolul Gebremedhin D, Berhe H, Gebrekirstos K. Risk Factors for Neonatal Sepsis in Public Hospitals of Mekelle City, North Ethiopia, 2015: Unmatched Case Control Study. PLoS One. 2016 May 10;11(5):e0154798.

Column Chart for the relationship between risk factor and disease (made in Excel):

Figure 1. Relationship between the TUI(AIU) /STI( AIS) mother's history and neonatal sepsis

The odds ratio (unadjusted OR) and the associated confidence interval (Table 2)( to calculate the point estimator and associated confidence interval the EpiInfo program can be used) the result writing format: point estimator (95% CI: superior limit-inferior limit); OR = 6,8 (95% CI: 3,6-12,8)

The value of p (made in EpiInfo is reported as p = value - the name of the test used, with a maximum of 3 decimal places, if p 0.001 then "p 0.001"): p 0.001-Chi-square test

Note: In the present study, the authors also estimated the rate of chance adjusted for different associations such as maternal age, background, type of birth, prolonged rupture of the membrane, etc.

Interpretation of data. Discussions

1. Interpreting the results from a statistical point o view: The aim of the study was to test and quantify the association between the mother's history of  UTI /STI and neonatal sepsis.From a statistical point of view, association testing was made by formulating two hypotheses (the null hypothesis and the alternative hypothesis), the null hypothesis being the one tested. In the case of its rejection, we affirm that we are in favor of the alternative hypothesis.Null Hypothesis: There is no significant association between the mother's history of UTI /STI and neonatal sepsis.Alternative hypothesis: There is a significant association between the mother's history of UTI /STI and neonatal sepsis.Because p 0.05, there is significant association between the mother's history of UTI /STI and neonatal sepsis.From a statistical point of view, the quantification of the association was achieved by punctual estimation of the OR indicator (unadjusted and adjusted) and the 95% confidence interval associated with it. Point estimate:OR = 6,8;  newborns whose mothers had a history of UTI/STI during pregnancy had a 6,8-times higher chance of developing sepsis compared to neonates whose mothers did not have UTI/STI.Reliable interval for OR: 95% CI: 3,6-12,8 - we are 95% sure that the odds ratio for the study population will be between 3,6 and 12,8 (if we extract samples of the same size from the study population, 95% of CI will contain the chance rate in the target population of newborns).In addition, OR> 1 and both ends of the confidence interval were greater than 1, so the history of the UTI/STI mother is a risk factor for neonatal sepsis. !Note: In the study presented, the authors also analyzed the association between UTI/STI in the context of presence of other covariates (maternal and neonatal factors) such as hypertension in pregnancy, intrapartum fever, birth complications, low score at 5 minutes, etc. - and an adjusted OR = 5.23, 95% IC: 1,8-15,04. Since the results were statistically significant, it can be argued that the history of UTI / STI of the mother remains an independent risk factor for neonatal sepsis.
2. Interpreting the results from a clinical point of view: The size of the OR indicator in clinical context:• Very important / moderate / not importantOR = 6,8 shows a moderate magnitude in the context of similar studies performed on the same population as having an OR = 12,9 (see section Discussion of the article)
Accuracy of result (see confidence interval): • Relatively accurate / imprecise (broad range - imprecise results, narrow range - accurate results)The confidence interval of 95%: 3,6-12,8 can be considered as a relatively accurate interval • Relatively important clinical connection (both ends with significant clinical value) The link between the maternal factors (UTI / STI history during pregnancy) can be considered as clinically relevant and relatively important (in the simulation of the size of the sample, the authors considering an OR = 2,87 effect size to be of interest). 

Conclusions of the study

The history of the mother`s urinary tract infection or sexually transmitted infection as a maternal factor contributes to the risk of neonatal sepsis, being even an independent risk factor.

On Infomed server, in your own folder make a new LAB02 folder. Download the following file in this folder and answer inside to all practical activities requiered. Save the file.

LAB 02 - Practical Activity

Data file - EXCEL

Results obtained with EpiInfo - for those who cannot install it

For getting help during the practical activities access: Instructions and Interpretations.   

The Bibliographic Study & Citing References Using the Vancouver Style

Practical activity

The bibliographic study is the study of the specialized literature by consulting scientific articles, papers, specialized books and treatises on the subject that you intend to research. It is an essential stage in the preparation and construction of a research, as well as in the communication of its results.

Once the research idea has been established, the following step is bibliographic documentation. The identification data of scientific articles, papers, specialized books and treatises (authors, title ...) together with the notes and / or the summary of the article constitute a bibliographic record. This helps you easily retrieve information from articles or books that you find of interest when documenting your future research. The bibliographic records will later be used to justify the information presented in your work, by quoting the corresponding scientific works, as well as to build the reference list that you will write in the "References" section, arranged in the order in which they have been quoted in your work.
Bibliographic documentation is performed by accessing various sources such as: the personal library, the University Library, the Electronic Library of UMF Cluj (http://www.umfcluj.ro/educatie-ro/reurseedu-ro/biblioteca-ro), specialty journals (PubMed: www.pubmed.gov, SpringerLink: www.springerlink.com, ScienceDirect: www.sciencedirect.com, ProQuest, Oxford Journals, BMJ Journals, Thieme, Medline, Thomson Micromedex, The Cochrane Collaboration: http://www.cochranelibrary.com, Dentistry and Oral Sciences (DOSS): https://health.ebsco.com/products/dentistry-oral-sciences-source, EMBASE: www.embase.com, etc.).
PubMed (https://www.ncbi.nlm.nih.gov/pubmed), the database of the National Medicine Library of the United States of America, is a free resource that provides access to MEDLINE, quotes and abstracts in the fields of medicine (general, dental, veterinary), nursing, and life sciences. PubMed allows searching for specialized articles by providing access to their abstracts. For some of these articles it also provides access to their full-text or links to the publishing journal. The search terms used by PubMed are those of the MeSH (Medical Subject Headings), a standard dictionary of medical terms. For more details regarding MeSH, you can access the following resource: https://www.nlm.nih.gov/bsd/disted/video.

A PubMed search allows you to identify the following pieces of information:

• Title of the article
• Authors' names
• Abbreviation of the journal, year of publication, volume, issue, extreme pages
• Language in which the article was published (if not English)
• Searching with PubMed also allows certain restrictions to be imposed, regarding the:
  • Article type (review, editorial, original article, clinical trial, etc.)
  • Type of access (abstract / full text - link to the journal where the article was published / free full text - access to Open Access articles)
  • Publication period
  • Species (human / animal subjects)
  • Other additional filters (the language in which the article was published, demographic criteria: age, gender).

Quoting references in Vancouver style

If you use information from published sources in your texts, or cite a full or partial text, you must clearly state this. By using a reference, you credit the authors of that source and defend yourself from possible accusations of plagiarism or pertaining to the truthfulness and accuracy of the respective information. A reference links your text to the original source of the information.
The reference citation style in the medical field uses the Vancouver system.

Its use implies:
signaling the use of a reference in the text by inserting numbers between straight brackets. These numbers will be in ascending order, starting from the beginning of the document.
the existence of a numbered references list at the end of the document, containing the details of the sources quoted in the text. These details will be written in a standard format, specific to each type of quoted document (article published in a printed magazine, article published on the internet, book, book chapter, etc.)

Example of Vancouver style citations

Formatting the reference list - punctuation marks, separators between entities, etc. - depends on the type of quoted document.

References for original articles published in printed journals

General structure:
Name of author(s) followed by first name(s) initial(s)¹. Article title. Abbreviated name of the journal². year of publication;volume number(issue number)³:extreme pages⁴.
1 For the initial / initials of the surname, no spaces or punctuation marks are used between the initials, the authors are separated by commas (,) and if there are 7 or more authors, only the first 6 authors are mentioned, followed by the expression: , et al.
2 To find the abbreviation of a journal, you can use the following link: https://www.ncbi.nlm.nih.gov/nlmcatalog/journals
3 the volume number usually corresponds to the number of appearances of the journal since its launch and is followed, between round brackets, by the issue number inside that volume
4 The first and last pages of the article, while omitting all repeating digits in the last page.

Example:

The Reference: Pompili M, Riccardi L, Covino M, Barbaro B, Di Stasi C, Orefice R, et al. Contrastenhanced gray-scale harmonic ultrasound in the efficacy assessment of ablation treatments for hepatocellular carcinoma. Liver Int. 2005;25(5):954-61.

References for original articles published in on-line journals, only in electronic format

General structure:
Author(s)¹. Article title. Abbreviated name of the journal [Internet] year of publication [cited citation date²]; volume number(issue number):article identifier. Available from: web page address.
1 For the initial / initials of the surname, no spaces or punctuation marks are used between the initials, the authors are separated by commas (,) and if there are 7 or more authors, only the first 6 authors are mentioned, followed by the expression: , et al.
2 The current date, when you have consulted and cited the article
Optionally, if available, you can add electronic identification information: Digital Object Identifier (DOI) - useful for easy Internet search, PubMed ID - unique ID number in the Medline / Pubmed database, or PubMed Central PMCID: doi: zzzzzzz. PubMed PMID: zzzzzzz; PubMed Central PMCID: PMC zzzzzzz.
Example of a reference to an original article from a journal published in electronic format:

The reference: Dudea D, Lasserre JF, Alb C, Culic B, Pop Ciutrila IS, Colosi H. Patients' perspective on dental aesthetics in a South-Eastern European community. J Dent [Internet] 2012 [cited 2018 Mar 2];40 Suppl 1:e72-81. DOI: 10.1016/j.jdent.2012.01.016. Available from: https://www.sciencedirect.com/science/article/pii/S0300571212000255?via%3Dihub

References for books

General structure:

Author(s)¹. Book title. Edition². Publication place³: Publisher; year of publication.
1 For the initial / initials of the surname, no spaces or punctuation marks are used between the initials, the authors are separated by commas (,) and if there are 7 or more authors, only the first 6 authors are mentioned, followed by the expression: , et al.
2 If the book is at its first edition, this piece of information is omitted
3 The city in which the publisher is based
As a rule, all the information required to build the reference is contained on the cover and on the first pages of the book.

Example:

Eisen HN. Immunology: an introduction to molecular and cellular principles of the immune response. 5th ed. New York: Harper and Row; 1974.

More details on the Vancouver citation system can be found at: https://www.nlm.nih.gov/bsd/uniform_requirements.html

Practical activity

Aims and benefits of this practical activit:

• Performing a scenario based search using the PICO method.
• Creating a search strategy to identify a manageable number of articles on a certain research topic.
• Using Clinical Queries and search restrictions by certain criteria offered in PubMed (e.g. by article type, year of publication, etc.).
• Acquiring the skills for writing references in the Vancouver style standard.
• Creating a bibliographic record file with a table of contents, to easily retrieve items of interest by title.
• Aquiring bibliographic documentation skills for research and current practice.

Clinical Queries allows the search for clinical studies according to their type: therapy, diagnostic, prognostic (risk factors).

On Infomed server, in your own folder make a new LAB01 folder. Download the following file in this folder and answer inside to all practical activities requiered. Save the file.

LAB 01 - Practical Activity

Ussefull web links:

• PICO Query: https://pubmedhh.nlm.nih.gov/nlmd/pico/piconew.php
• Pubmed Clinical Query: https://www.ncbi.nlm.nih.gov/pubmed/clinical

For getting help during the practical activities access: Instructions and Interpretations.   

The Bibliographic Study & Citing References Using the Vancouver Style

Practical activity

The bibliographic study is the study of the specialized literature by consulting scientific articles, papers, specialized books and treatises on the subject that you intend to research. It is an essential stage in the preparation and construction of a research, as well as in the communication of its results.

Once the research idea has been established, the following step is bibliographic documentation. The identification data of scientific articles, papers, specialized books and treatises (authors, title ...) together with the notes and / or the summary of the article constitute a bibliographic record. This helps you easily retrieve information from articles or books that you find of interest when documenting your future research. The bibliographic records will later be used to justify the information presented in your work, by quoting the corresponding scientific works, as well as to build the reference list that you will write in the "References" section, arranged in the order in which they have been quoted in your work.
Bibliographic documentation is performed by accessing various sources such as: the personal library, the University Library, the Electronic Library of UMF Cluj (http://www.umfcluj.ro/educatie-ro/reurseedu-ro/biblioteca-ro), specialty journals (PubMed: www.pubmed.gov, SpringerLink: www.springerlink.com, ScienceDirect: www.sciencedirect.com, ProQuest, Oxford Journals, BMJ Journals, Thieme, Medline, Thomson Micromedex, The Cochrane Collaboration: http://www.cochranelibrary.com, Dentistry and Oral Sciences (DOSS): https://health.ebsco.com/products/dentistry-oral-sciences-source, EMBASE: www.embase.com, etc.).
PubMed (https://www.ncbi.nlm.nih.gov/pubmed), the database of the National Medicine Library of the United States of America, is a free resource that provides access to MEDLINE, quotes and abstracts in the fields of medicine (general, dental, veterinary), nursing, and life sciences. PubMed allows searching for specialized articles by providing access to their abstracts. For some of these articles it also provides access to their full-text or links to the publishing journal. The search terms used by PubMed are those of the MeSH (Medical Subject Headings), a standard dictionary of medical terms. For more details regarding MeSH, you can access the following resource: https://www.nlm.nih.gov/bsd/disted/video.

A PubMed search allows you to identify the following pieces of information:

• Title of the article
• Authors' names
• Abbreviation of the journal, year of publication, volume, issue, extreme pages
• Language in which the article was published (if not English)
• Searching with PubMed also allows certain restrictions to be imposed, regarding the:
  • Article type (review, editorial, original article, clinical trial, etc.)
  • Type of access (abstract / full text - link to the journal where the article was published / free full text - access to Open Access articles)
  • Publication period
  • Species (human / animal subjects)
  • Other additional filters (the language in which the article was published, demographic criteria: age, gender).

Quoting references in Vancouver style

If you use information from published sources in your texts, or cite a full or partial text, you must clearly state this. By using a reference, you credit the authors of that source and defend yourself from possible accusations of plagiarism or pertaining to the truthfulness and accuracy of the respective information. A reference links your text to the original source of the information.
The reference citation style in the medical field uses the Vancouver system.

Its use implies:
signaling the use of a reference in the text by inserting numbers between straight brackets. These numbers will be in ascending order, starting from the beginning of the document.
the existence of a numbered references list at the end of the document, containing the details of the sources quoted in the text. These details will be written in a standard format, specific to each type of quoted document (article published in a printed magazine, article published on the internet, book, book chapter, etc.)

Example of Vancouver style citations

Formatting the reference list - punctuation marks, separators between entities, etc. - depends on the type of quoted document.

References for original articles published in printed journals

General structure:
Name of author(s) followed by first name(s) initial(s)¹. Article title. Abbreviated name of the journal². year of publication;volume number(issue number)³:extreme pages⁴.
1 For the initial / initials of the surname, no spaces or punctuation marks are used between the initials, the authors are separated by commas (,) and if there are 7 or more authors, only the first 6 authors are mentioned, followed by the expression: , et al.
2 To find the abbreviation of a journal, you can use the following link: https://www.ncbi.nlm.nih.gov/nlmcatalog/journals
3 the volume number usually corresponds to the number of appearances of the journal since its launch and is followed, between round brackets, by the issue number inside that volume
4 The first and last pages of the article, while omitting all repeating digits in the last page.

Example:

The Reference: Pompili M, Riccardi L, Covino M, Barbaro B, Di Stasi C, Orefice R, et al. Contrastenhanced gray-scale harmonic ultrasound in the efficacy assessment of ablation treatments for hepatocellular carcinoma. Liver Int. 2005;25(5):954-61.

References for original articles published in on-line journals, only in electronic format

General structure:
Author(s)¹. Article title. Abbreviated name of the journal [Internet] year of publication [cited citation date²]; volume number(issue number):article identifier. Available from: web page address.
1 For the initial / initials of the surname, no spaces or punctuation marks are used between the initials, the authors are separated by commas (,) and if there are 7 or more authors, only the first 6 authors are mentioned, followed by the expression: , et al.
2 The current date, when you have consulted and cited the article
Optionally, if available, you can add electronic identification information: Digital Object Identifier (DOI) - useful for easy Internet search, PubMed ID - unique ID number in the Medline / Pubmed database, or PubMed Central PMCID: doi: zzzzzzz. PubMed PMID: zzzzzzz; PubMed Central PMCID: PMC zzzzzzz.
Example of a reference to an original article from a journal published in electronic format:

The reference: Dudea D, Lasserre JF, Alb C, Culic B, Pop Ciutrila IS, Colosi H. Patients' perspective on dental aesthetics in a South-Eastern European community. J Dent [Internet] 2012 [cited 2018 Mar 2];40 Suppl 1:e72-81. DOI: 10.1016/j.jdent.2012.01.016. Available from: https://www.sciencedirect.com/science/article/pii/S0300571212000255?via%3Dihub

References for books

General structure:

Author(s)¹. Book title. Edition². Publication place³: Publisher; year of publication.
1 For the initial / initials of the surname, no spaces or punctuation marks are used between the initials, the authors are separated by commas (,) and if there are 7 or more authors, only the first 6 authors are mentioned, followed by the expression: , et al.
2 If the book is at its first edition, this piece of information is omitted
3 The city in which the publisher is based
As a rule, all the information required to build the reference is contained on the cover and on the first pages of the book.

Example:

Eisen HN. Immunology: an introduction to molecular and cellular principles of the immune response. 5th ed. New York: Harper and Row; 1974.

More details on the Vancouver citation system can be found at: https://www.nlm.nih.gov/bsd/uniform_requirements.html

Practical activity

Aims and benefits of this practical activit:

• Performing a scenario based search using the PICO method.
• Creating a search strategy to identify a manageable number of articles on a certain research topic.
• Using Clinical Queries and search restrictions by certain criteria offered in PubMed (e.g. by article type, year of publication, etc.).
• Acquiring the skills for writing references in the Vancouver style standard.
• Creating a bibliographic record file with a table of contents, to easily retrieve items of interest by title.
• Aquiring bibliographic documentation skills for research and current practice.

Clinical Queries allows the search for clinical studies according to their type: therapy, diagnostic, prognostic (risk factors).

On Infomed server, in your own folder make a new LAB01 folder. Download the following file in this folder and answer inside to all practical activities requiered. Save the file.

LAB 01 - Practical Activity

Ussefull web links:

• PICO Query: https://pubmedhh.nlm.nih.gov/nlmd/pico/piconew.php
• Pubmed Clinical Query: https://www.ncbi.nlm.nih.gov/pubmed/clinical

For getting help during the practical activities access: Instructions and Interpretations.   

Introduction

Case-control studies are an important category of clinical studies which evaluates the link between one or more prognostic factors and various pathological conditions.

In these studies, the relationship between the factor (s) and the occurrence of a disease is assessed, or whether a particular factor changes the progression of a disease (amelioration or healing). Prognostic factors can be: risk factors (favoring the occurrence of a disease) or protective factors (prevent the disease or help the process of healing). Investigating the relationship between possible prognostic factors and disease can be achieved through all types of data collection without the researcher intervening.
In the case-control study, it starts from the fact that the disease is rare and the cases are first identified ( subjects who have a certain disease) and then the controls are chose: subjects with similar characteristics, (gender, age, socio-economic status) they do not have the disease. Only after that, with retrospective or transversal methods, the researcher is looking for prognostic factors in these groups. There are several methods for identifying prognostic factors, some of them are: laboratory determinations, standardized questionnaire, interview with the subject / family members, or consultation of medical records of subjects enrolled in the study.
Strengths of the case-control study:·Efficacy in case of rare diseases or high period of latency diseases·  Relatively easy to achieve (not expensive, it takes a short period of time)· Allows analysis of several prognostic factors Weaknesses of the case-control study:can bring false information (eg. subjects forget some of previous exposures, or sick subjects tend to remember even non-significant exposures in comparison to healthy people) the time between the onset of exposure and the onset of the illness may be difficult to determine         

Example of a case-control study:

               An example of case-control study is the one led by the authors  Destaalem Gebremedhin, Haftu Berh and Kahsu Gebrekirstos, a study entitled „Risk Factors for Neonatal Sepsis in Public Hospitals of Mekelle City, North Ethiopia,2015: Unmatched Case Control Study”,published in 2016,in the journal Plos One (ISI, IF:2.80, Q1).Article source:

http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0154798&type=printable

Definitions used in the study:Neonatal sepsis  - Systemic inflammatory response  in the presence, or as a result of a proven or suspected infection in a newborn. The infection can be bacterial, viral or fungal.  

Scenario-example

               Gebremedhin D et al. have conducted a study on newborns registered at public hospitals in Mekelle, North Ethiopia, from December 2014 to June 2015, to identify risk factors for neonatal sepsis. The data needed for the study were collected from the infant's medical records and questionnaire applied to the mothers.  Two groups of subjects were compiled in the study: a sample of 78( newborns diagnosed with neonatal sepsis) and a control group of 156 (newborns without sepsis).
The inclusion criteria for cases were:·         newborns registered in pediatric or neonatal intensive care in public hospitals in Mekelle City, North Ethiopia during the study period with at least one of the following IMNCI (Integrated Management of Neonatal and Childhood Illness) clinical features: fever (≥37.5 ° C) or hypothermia (≤ 35.5 ° C), increased breathing (≥ 60 breaths per minute), severe chest retraction, movements only when stimulated, seizures, lethargy or unconsciousness ·         at least 2 haematological criteria: total white blood cells (12000 cells/m³⁾, absolute neutrophil number (1500 cells/mm³ or >7500 cells/mm³), erythrocyte sedimentation rate (>15/1h),  number of platelets( > 440 cells/m³) .
The inclusion criteria for the control group were:·         newborns who did not meet the sepsis criteria and who were enrolled in neonatal pediatric or intensive care units of public hospitals in Mekelle, North Ethiopia during the study period 

Reaserch protocol

Aim and objectives

The aim of this study was to evaluate the association between the mother's history of urinary tract infection(UTI)  or sexually transmitted infection(STI)  and neonatal sepsis.

 Objectives: testing for the link between the factor (prolonged rupture of the membrane) and the disease (neonatal sepsis)·         quantifying the importance of this link : estimation of the odds ratio indicator (OR) 2. Domain of research: risk factors or/and prognostic factors 3. Study type:·         Based on study objectives: analytical study·         Based on the results of the researchers: observational study·         Based on the matching technique that was used in choosing the groups: without matching Note:analytical study = groups of patients are compared, associations between different clinical characteristics are testeddescriptive study=it describes a number of cases or a single group of patients and do not search for possible associations / linksobservational study = the type of study that does not involve the researcher intervention on the progression of the disease.matching in studies = for each subject in the case group/exposed group there is a subject with similar characteristics for the control /unexposed group.  For ex. Matching by: same sex, similar age (identical or +/- 2 years), same risk factors (eg diabetics). The match can be made 1: 1 or 1: 2, 1: 3, 1: 4 (one case at 1/2/3/4 controls). 4. Target population and study sample: Target population: Newborn babies arriving in the world in the section of obstetrics in public hospitals in Mekelle, North Ethiopia, December 2014 - June 2015. Study sample:Inclusion criteria: Babies born between December 2014 and June 2015 in the Mekelle, Northern Ethiopia hospitals' public hospitals.Exclusion criteria :Note: In this scenario, the exclusion criteria are not mentioned.Sample size:The authors mention in the article that the size of the sample was estimated at 234 subjects for a type II error of 0,20 (a 80% study power), a proportion of  UTI/STI with neonates without sepsis of 13% (determined in another study per similar population), control/cases (ratio) = 2: 1, and an OR = 2,87. We believe that the size of the sample was sufficient. 5. Data collection method·         based on the studied population: systematic random sampling-see the Method section of the article·         based on the duration of data collection: longitudinal retrospective·         based on the grouping method: Case – control (the two groups were defined according to the presence/absence of neonatal sepsis).
!Note: Types of probabilistic samplingRandom simple sampling: Each element within the population has the same chance of     being included in the sampleRandom systematic sampling: assumes random choice of a start number (step), from which, adding a fixed size will result in a unit (element) of the sampleRandom layered sampling: consists of dividing the research population into layers according to certain characteristics (genes, age groups) to randomly subtract sub-samples (groups) proportional to the size of the layer from each layer, groups that are then combined to obtain a single sampleRandom cluster sampling: The research population is divided into clusters and a number of groups are randomly selected with all the units included. 
6. Statistical analysis Demographic and clinical characteristics of the mother:Age: continuous quantitative variableCivil status, religion, ethnicity, occupation: nominal qualitative variablesEducational level (primary school, secondary school, college or faculty): ordinal qualitative variableHistory of urinary tract infection or sexually transmitted infection (TUI/STI), hypertension disorders, the birth environment, prolonged membrane rupture, intrapartum fever: dichotomial qualitative variables Demographic and clinical features of the newborn:Newborn gender (M/F), Apgar score at 1minute (7 coded with 1 versus  ≥7 coded with 0), Apgar score at 5 minutes (7 coded with 1 versus ≥7 coded with 0), birth resuscitation (yes/no),  sepsis (yes/no): dichotomial qualitative variables

Weight at birth (1500-2500 grams,  ≥2500 grams), gestational age ( 42 weeks): ordinal qualitative variables

Data description: It can be done either through a frequency table, contingency table, or vertical or horizontal column chart.

The bivariate association between the exposer factor and the disease can be demonstrated trough statistical Chi-square test or Fisher's exact test (the latter applies if expected frequencies in the contingency table are   20% of cells)

Multivariate association between the exposure factor and the disease: through multivariate logistic regression.

To quantify the importance of the association between the risk factor and the disease, the chances of having sepsis (OR) and the associated 95% confidence interval (CI) will be calculated.·         If the estimated odds ratio  OR> 1 and both ends (lower limit and upper limit) of the confidence interval are greater than >1 then it can be stated that the exposure factor is a risk factor·         If the estimated odds ratio  OR 1 and both ends (lower limit and upper limit) of the confidence interval are less than 1 then we can assume that the exposure factor can be a protective factor.·         If the odds ratio OR = 1 or the confidence interval contains 1 then we can say that we do not have enough evidence to demonstrate that the exposure factor is a risk or a protective factor. !Note: The odds ratio can be determined in the unadjusted form (also referred to as the "crude odds ratio") representing the chance of disease in exposed versus non-exposed patients and / or in the adjusted form (also called the "adjusted odds ratio") representing the chance of disease in exposed versus non-exposed patients adjusted after the presence of other covariates. 

Expected results. Data analysis and presentation

1. Sample description

In the present study, the description of the characteristics measured on the sample was made using the contingency tables presented in a condensed form in the Results section of the article.

Table 1. Description of the socio-demographic characteristics of the study groups

Source: imagine preluată din articolul Gebremedhin D, Berhe H, Gebrekirstos K. Risk Factors for Neonatal Sepsis in Public Hospitals of Mekelle City, North Ethiopia, 2015: Unmatched Case Control Study. PLoS One. 2016 May 10;11(5):e0154798.

2. 2. Bivariate and multivariate association between a history of urinary tract infection or a sexually transmitted infection and neonatal sepsis.

The contingency of risk factor (TUI / STI) and disease (sepsis):

TUI / STI= the history of the mother of urinary infection or sexually transmitted infection

Table 2. Bivariate and multivariate association between TUI /STI and neonatal sepsis

Source: preluat din articolul Gebremedhin D, Berhe H, Gebrekirstos K. Risk Factors for Neonatal Sepsis in Public Hospitals of Mekelle City, North Ethiopia, 2015: Unmatched Case Control Study. PLoS One. 2016 May 10;11(5):e0154798.

Column Chart for the relationship between risk factor and disease (made in Excel):

Figure 1. Relationship between the TUI(AIU) /STI( AIS) mother's history and neonatal sepsis

The odds ratio (unadjusted OR) and the associated confidence interval (Table 2)( to calculate the point estimator and associated confidence interval the EpiInfo program can be used) the result writing format: point estimator (95% CI: superior limit-inferior limit); OR = 6,8 (95% CI: 3,6-12,8)

The value of p (made in EpiInfo is reported as p = value - the name of the test used, with a maximum of 3 decimal places, if p 0.001 then "p 0.001"): p 0.001-Chi-square test

Note: In the present study, the authors also estimated the rate of chance adjusted for different associations such as maternal age, background, type of birth, prolonged rupture of the membrane, etc.

Interpretation of data. Discussions

1. Interpreting the results from a statistical point o view: The aim of the study was to test and quantify the association between the mother's history of  UTI /STI and neonatal sepsis.From a statistical point of view, association testing was made by formulating two hypotheses (the null hypothesis and the alternative hypothesis), the null hypothesis being the one tested. In the case of its rejection, we affirm that we are in favor of the alternative hypothesis.Null Hypothesis: There is no significant association between the mother's history of UTI /STI and neonatal sepsis.Alternative hypothesis: There is a significant association between the mother's history of UTI /STI and neonatal sepsis.Because p 0.05, there is significant association between the mother's history of UTI /STI and neonatal sepsis.From a statistical point of view, the quantification of the association was achieved by punctual estimation of the OR indicator (unadjusted and adjusted) and the 95% confidence interval associated with it. Point estimate:OR = 6,8;  newborns whose mothers had a history of UTI/STI during pregnancy had a 6,8-times higher chance of developing sepsis compared to neonates whose mothers did not have UTI/STI.Reliable interval for OR: 95% CI: 3,6-12,8 - we are 95% sure that the odds ratio for the study population will be between 3,6 and 12,8 (if we extract samples of the same size from the study population, 95% of CI will contain the chance rate in the target population of newborns).In addition, OR> 1 and both ends of the confidence interval were greater than 1, so the history of the UTI/STI mother is a risk factor for neonatal sepsis. !Note: In the study presented, the authors also analyzed the association between UTI/STI in the context of presence of other covariates (maternal and neonatal factors) such as hypertension in pregnancy, intrapartum fever, birth complications, low score at 5 minutes, etc. - and an adjusted OR = 5.23, 95% IC: 1,8-15,04. Since the results were statistically significant, it can be argued that the history of UTI / STI of the mother remains an independent risk factor for neonatal sepsis.
2. Interpreting the results from a clinical point of view: The size of the OR indicator in clinical context:• Very important / moderate / not importantOR = 6,8 shows a moderate magnitude in the context of similar studies performed on the same population as having an OR = 12,9 (see section Discussion of the article)
Accuracy of result (see confidence interval): • Relatively accurate / imprecise (broad range - imprecise results, narrow range - accurate results)The confidence interval of 95%: 3,6-12,8 can be considered as a relatively accurate interval • Relatively important clinical connection (both ends with significant clinical value) The link between the maternal factors (UTI / STI history during pregnancy) can be considered as clinically relevant and relatively important (in the simulation of the size of the sample, the authors considering an OR = 2,87 effect size to be of interest). 

Conclusions of the study

The history of the mother`s urinary tract infection or sexually transmitted infection as a maternal factor contributes to the risk of neonatal sepsis, being even an independent risk factor.

On Infomed server, in your own folder make a new LAB02 folder. Download the following file in this folder and answer inside to all practical activities requiered. Save the file.

LAB 02 - Practical Activity

Data file - EXCEL

Results obtained with EpiInfo - for those who cannot install it

Clinical Skills Book - VARIANT 1 (NEW BOOK)

10. Critical appraisal (Evidence Based Medicine - EBM) / Efficient use of resources

10.1. Knows the systematic search methods in bibliographic databases

(Metodologia cercetării ştiinţifice)

10.2. Critically evaluates data, information, and scientific evidence in medical and academic situations (Metodologia cercetării ştiinţifice)

10.3.1 Critically evaluates data found in literature in order to assess the benefits and risks of current and proposed methods of investigation, treatment and prevention of illness (Metodologia cercetării ştiinţifice)

10.4. Uses the computer for information, patient data recording and communication

(Metodologia cercetării ştiinţifice)

10.5. Prepares oral presentations for scientific symposia

(Metodologia cercetării ştiinţifice)

10.6. Prepares presentations for health education of the general public

(Metodologia cercetării ştiinţifice)

Clinical Skills Book - VARIANT 2 (OLD BOOK)

8. Managerial Skills

8.1. Carries out a critical evaluation of diagnostic and screening tests

10. Critical appraisal (EBM)

10.1. Performs a critical assessment of data, information, and documents

10.2. Performs a critical evaluation of literature data to assess the benefits and risks of prophylactic, diagnostic and therapeutic measures

10.3. Uses the computer for bibliographic documentation, to record patient data and to communicate

10.6. Applies  EBM principles in fundamental research and clinical practice

Exam validation and bonuses

In order to validate the exam, the marks obtained in both the practical and theoretical examinations need to be higher or at least equal to 5.

The practical examination has a weight of 30% in calculating the final mark.

If the practical score is less than 10 but higher than 5, the group tutor may award up to 1 bonus point for the student’s activity during the semester.

During both exams, students are allowed to consult a personal single page with hand-written notes, in order to encourage comprehension and discourage learning by heart. Example questions or questionnaires from previous years, printed or copied material, as well as books, are NOT allowed and will be considered exam fraud.

The written exam consists of 40 multiple choice questions to be solved in 80 minutes.

The multiple choice questions are weighted based on their difficulty, hence, the test will be scored out of 100 points.

The written exam has a weight of 70% towards the final mark.

Up to 1 bonus point may be awarded to students who interact constructively and repeatedly during lectures. The bonus may be added to the final mark of the written examination, but only if that mark is already above 5.

Correction method of the written exam:

• Question with one correct answer:
  • 5 concordances = 1 point
  • less than 5 concordances = 0 points
• Question with 2 correct answers:
  • 5 concordances = 1 point
  • 4 concordances = 0.8 points
  • less than 4 concordances = 0 points
• Question with 3 or more correct answers:
  • 5 concordances = 1 point
  • 4 concordances = 0.8 points
  • 3 concordances = 0.5 points
  • less than 3 concordances = 0 points

Mandatory Bibliography

• Lecture presentations
• Learning material distributed during lectures
• All practical activities and their explanatory files, accessible on www.info.umfcluj.ro

Optional Bibliography

• Hulley SB, Cummings SR, Browner WS, Grady DG, Newman TB. Designing Clinical Research. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013.
• Drugan T, Berghe AS, Bolboaca SD, Bondor C, Calinici C, Colosi H, Cutas A, Iancu M, Istrate D, Leucuta DC, Valeanu M. Metodologia Cercetării Științifice Medicale. Cluj-Napoca: Editura Medicală Universitară „Iuliu Haţieganu”, 2017.

.

.

.

.