Evidence
From REF 1 .
Observational studies fall under the category of analytic study designs and are further sub-classified as observational or experimental study designs ( Figure 1 ). The goal of analytic studies is to identify and evaluate causes or risk factors of diseases or health-related events. The differentiating characteristic between observational and experimental study designs is that in the latter, the presence or absence of undergoing an intervention defines the groups. By contrast, in an observational study, the investigator does not intervene and rather simply “observes” and assesses the strength of the relationship between an exposure and disease variable. 6 Three types of observational studies include cohort studies, case-control studies, and cross-sectional studies ( Figure 1 ). Case-control and cohort studies offer specific advantages by measuring disease occurrence and its association with an exposure by offering a temporal dimension (i.e. prospective or retrospective study design). Cross-sectional studies, also known as prevalence studies, examine the data on disease and exposure at one particular time point ( Figure 2 ). 6 Because the temporal relationship between disease occurrence and exposure cannot be established, cross-sectional studies cannot assess the cause and effect relationship. In this review, we will primarily discuss cohort and case-control study designs and related methodologic issues.
Analytic Study Designs. Adapted with permission from Joseph Eisenberg, Ph.D.
Temporal Design of Observational Studies: Cross-sectional studies are known as prevalence studies and do not have an inherent temporal dimension. These studies evaluate subjects at one point in time, the present time. By contrast, cohort studies can be either retrospective (latin derived prefix, “retro” meaning “back, behind”) or prospective (greek derived prefix, “pro” meaning “before, in front of”). Retrospective studies “look back” in time contrasting with prospective studies, which “look ahead” to examine causal associations. Case-control study designs are also retrospective and assess the history of the subject for the presence or absence of an exposure.
The term “cohort” is derived from the Latin word cohors . Roman legions were composed of ten cohorts. During battle each cohort, or military unit, consisting of a specific number of warriors and commanding centurions, were traceable. The word “cohort” has been adopted into epidemiology to define a set of people followed over a period of time. W.H. Frost, an epidemiologist from the early 1900s, was the first to use the word “cohort” in his 1935 publication assessing age-specific mortality rates and tuberculosis. 7 The modern epidemiological definition of the word now means a “group of people with defined characteristics who are followed up to determine incidence of, or mortality from, some specific disease, all causes of death, or some other outcome.” 7
A well-designed cohort study can provide powerful results. In a cohort study, an outcome or disease-free study population is first identified by the exposure or event of interest and followed in time until the disease or outcome of interest occurs ( Figure 3A ). Because exposure is identified before the outcome, cohort studies have a temporal framework to assess causality and thus have the potential to provide the strongest scientific evidence. 8 Advantages and disadvantages of a cohort study are listed in Table 2 . 2 , 9 Cohort studies are particularly advantageous for examining rare exposures because subjects are selected by their exposure status. Additionally, the investigator can examine multiple outcomes simultaneously. Disadvantages include the need for a large sample size and the potentially long follow-up duration of the study design resulting in a costly endeavor.
Cohort and Case-Control Study Designs
Advantages and Disadvantages of the Cohort Study
Gather data regarding sequence of events; can assess causality |
Examine multiple outcomes for a given exposure |
Good for investigating rare exposures |
Can calculate rates of disease in exposed and unexposed individuals over time (e.g. incidence, relative risk) |
Large numbers of subjects are required to study rare exposures |
Susceptible to selection bias |
May be expensive to conduct |
May require long durations for follow-up |
Maintaining follow-up may be difficult |
Susceptible to loss to follow-up or withdrawals |
Susceptible to recall bias or information bias |
Less control over variables |
Cohort studies can be prospective or retrospective ( Figure 2 ). Prospective studies are carried out from the present time into the future. Because prospective studies are designed with specific data collection methods, it has the advantage of being tailored to collect specific exposure data and may be more complete. The disadvantage of a prospective cohort study may be the long follow-up period while waiting for events or diseases to occur. Thus, this study design is inefficient for investigating diseases with long latency periods and is vulnerable to a high loss to follow-up rate. Although prospective cohort studies are invaluable as exemplified by the landmark Framingham Heart Study, started in 1948 and still ongoing, 10 in the plastic surgery literature this study design is generally seen to be inefficient and impractical. Instead, retrospective cohort studies are better indicated given the timeliness and inexpensive nature of the study design.
Retrospective cohort studies, also known as historical cohort studies, are carried out at the present time and look to the past to examine medical events or outcomes. In other words, a cohort of subjects selected based on exposure status is chosen at the present time, and outcome data (i.e. disease status, event status), which was measured in the past, are reconstructed for analysis. The primary disadvantage of this study design is the limited control the investigator has over data collection. The existing data may be incomplete, inaccurate, or inconsistently measured between subjects. 2 However, because of the immediate availability of the data, this study design is comparatively less costly and shorter than prospective cohort studies. For example, Spear and colleagues examined the effect of obesity and complication rates after undergoing the pedicled TRAM flap reconstruction by retrospectively reviewing 224 pedicled TRAM flaps in 200 patients over a 10-year period. 11 In this example, subjects who underwent the pedicled TRAM flap reconstruction were selected and categorized into cohorts by their exposure status: normal/underweight, overweight, or obese. The outcomes of interest were various flap and donor site complications. The findings revealed that obese patients had a significantly higher incidence of donor site complications, multiple flap complications, and partial flap necrosis than normal or overweight patients. An advantage of the retrospective study design analysis is the immediate access to the data. A disadvantage is the limited control over the data collection because data was gathered retrospectively over 10-years; for example, a limitation reported by the authors is that mastectomy flap necrosis was not uniformly recorded for all subjects. 11
An important distinction lies between cohort studies and case-series. The distinguishing feature between these two types of studies is the presence of a control, or unexposed, group. Contrasting with epidemiological cohort studies, case-series are descriptive studies following one small group of subjects. In essence, they are extensions of case reports. Usually the cases are obtained from the authors' experiences, generally involve a small number of patients, and more importantly, lack a control group. 12 There is often confusion in designating studies as “cohort studies” when only one group of subjects is examined. Yet, unless a second comparative group serving as a control is present, these studies are defined as case-series. The next step in strengthening an observation from a case-series is selecting appropriate control groups to conduct a cohort or case-control study, the latter which is discussed in the following section about case-control studies. 9
Selection of subjects in cohort studies.
The hallmark of a cohort study is defining the selected group of subjects by exposure status at the start of the investigation. A critical characteristic of subject selection is to have both the exposed and unexposed groups be selected from the same source population ( Figure 4 ). 9 Subjects who are not at risk for developing the outcome should be excluded from the study. The source population is determined by practical considerations, such as sampling. Subjects may be effectively sampled from the hospital, be members of a community, or from a doctor's individual practice. A subset of these subjects will be eligible for the study.
Levels of Subject Selection. Adapted from Ref 9 .
Because prospective cohort studies may require long follow-up periods, it is important to minimize loss to follow-up. Loss to follow-up is a situation in which the investigator loses contact with the subject, resulting in missing data. If too many subjects are loss to follow-up, the internal validity of the study is reduced. A general rule of thumb requires that the loss to follow-up rate not exceed 20% of the sample. 6 Any systematic differences related to the outcome or exposure of risk factors between those who drop out and those who stay in the study must be examined, if possible, by comparing individuals who remain in the study and those who were loss to follow-up or dropped out. It is therefore important to select subjects who can be followed for the entire duration of the cohort study. Methods to minimize loss to follow-up are listed in Table 3 .
Methods to Minimize Loss to Follow-Up
Exclude subjects likely to be lost |
Planning to move |
Non-committal |
Obtain information to allow future tracking |
Collect subject's contact information (e.g. mailing addresses, telephone numbers, and email addresses) |
Collect social security and/or Medicare numbers |
Maintain periodic contact |
By telephone: may require calls during the weekends and/or evenings |
By mail: repeated mailings by e-mail or with stamped, self-addressed return envelopes |
Other: newsletters or token gifts with study logo |
Adapted from REF 2 .
Case-control studies were historically borne out of interest in disease etiology. The conceptual basis of the case-control study is similar to taking a history and physical; the diseased patient is questioned and examined, and elements from this history taking are knitted together to reveal characteristics or factors that predisposed the patient to the disease. In fact, the practice of interviewing patients about behaviors and conditions preceding illness dates back to the Hippocratic writings of the 4 th century B.C. 7
Reasons of practicality and feasibility inherent in the study design typically dictate whether a cohort study or case-control study is appropriate. This study design was first recognized in Janet Lane-Claypon's study of breast cancer in 1926, revealing the finding that low fertility rate raises the risk of breast cancer. 13 , 14 In the ensuing decades, case-control study methodology crystallized with the landmark publication linking smoking and lung cancer in the 1950s. 15 Since that time, retrospective case-control studies have become more prominent in the biomedical literature with more rigorous methodological advances in design, execution, and analysis.
Case-control studies identify subjects by outcome status at the outset of the investigation. Outcomes of interest may be whether the subject has undergone a specific type of surgery, experienced a complication, or is diagnosed with a disease ( Figure 3B ). Once outcome status is identified and subjects are categorized as cases, controls (subjects without the outcome but from the same source population) are selected. Data about exposure to a risk factor or several risk factors are then collected retrospectively, typically by interview, abstraction from records, or survey. Case-control studies are well suited to investigate rare outcomes or outcomes with a long latency period because subjects are selected from the outset by their outcome status. Thus in comparison to cohort studies, case-control studies are quick, relatively inexpensive to implement, require comparatively fewer subjects, and allow for multiple exposures or risk factors to be assessed for one outcome ( Table 4 ). 2 , 9
Advantages and Disadvantages of the Case-Control Study
Good for examining rare outcomes or outcomes with long latency |
Relatively quick to conduct |
Relatively inexpensive |
Requires comparatively few subjects |
Existing records can be used |
Multiple exposures or risk factors can be examined |
Susceptible to recall bias or information bias |
Difficult to validate information |
Control of extraneous variables may be incomplete |
Selection of an appropriate comparison group may be difficult |
Rates of disease in exposed and unexposed individuals cannot be determined |
An example of a case-control investigation is by Zhang and colleagues who examined the association of environmental and genetic factors associated with rare congenital microtia, 16 which has an estimated prevalence of 0.83 to 17.4 in 10,000. 17 They selected 121 congenital microtia cases based on clinical phenotype, and 152 unaffected controls, matched by age and sex in the same hospital and same period. Controls were of Hans Chinese origin from Jiangsu, China, the same area from where the cases were selected. This allowed both the controls and cases to have the same genetic background, important to note given the investigated association between genetic factors and congenital microtia. To examine environmental factors, a questionnaire was administered to the mothers of both cases and controls. The authors concluded that adverse maternal health was among the main risk factors for congenital microtia, specifically maternal disease during pregnancy (OR 5.89, 95% CI 2.36-14.72), maternal toxicity exposure during pregnancy (OR 4.76, 95% CI 1.66-13.68), and resident area, such as living near industries associated with air pollution (OR 7.00, 95% CI 2.09-23.47). 16 A case-control study design is most efficient for this investigation, given the rarity of the disease outcome. Because congenital microtia is thought to have multifactorial causes, an additional advantage of the case-control study design in this example is the ability to examine multiple exposures and risk factors.
Sampling in a case-control study design begins with selecting the cases. In a case-control study, it is imperative that the investigator has explicitly defined inclusion and exclusion criteria prior to the selection of cases. For example, if the outcome is having a disease, specific diagnostic criteria, disease subtype, stage of disease, or degree of severity should be defined. Such criteria ensure that all the cases are homogenous. Second, cases may be selected from a variety of sources, including hospital patients, clinic patients, or community subjects. Many communities maintain registries of patients with certain diseases and can serve as a valuable source of cases. However, despite the methodologic convenience of this method, validity issues may arise. For example, if cases are selected from one hospital, identified risk factors may be unique to that single hospital. This methodological choice may weaken the generalizability of the study findings. Another example is choosing cases from the hospital versus the community; most likely cases from the hospital sample will represent a more severe form of the disease than those in the community. 2 Finally, it is also important to select cases that are representative of cases in the target population to strengthen the study's external validity ( Figure 4 ). Potential reasons why cases from the original target population eventually filter through and are available as cases (study participants) for a case-control study are illustrated in Figure 5 .
Levels of Case Selection. Adapted from Ref 2 .
Selecting the appropriate group of controls can be one of the most demanding aspects of a case-control study. An important principle is that the distribution of exposure should be the same among cases and controls; in other words, both cases and controls should stem from the same source population. The investigator may also consider the control group to be an at-risk population, with the potential to develop the outcome. Because the validity of the study depends upon the comparability of these two groups, cases and controls should otherwise meet the same inclusion criteria in the study.
A case-control study design that exemplifies this methodological feature is by Chung and colleagues, who examined maternal cigarette smoking during pregnancy and the risk of newborns developing cleft lip/palate. 18 A salient feature of this study is the use of the 1996 U.S. Natality database, a population database, from which both cases and controls were selected. This database provides a large sample size to assess newborn development of cleft lip/palate (outcome), which has a reported incidence of 1 in 1000 live births, 19 and also enabled the investigators to choose controls (i.e., healthy newborns) that were generalizable to the general population to strengthen the study's external validity. A significant relationship with maternal cigarette smoking and cleft lip/palate in the newborn was reported in this study (adjusted OR 1.34, 95% CI 1.36-1.76). 18
Matching is a method used in an attempt to ensure comparability between cases and controls and reduces variability and systematic differences due to background variables that are not of interest to the investigator. 8 Each case is typically individually paired with a control subject with respect to the background variables. The exposure to the risk factor of interest is then compared between the cases and the controls. This matching strategy is called individual matching. Age, sex, and race are often used to match cases and controls because they are typically strong confounders of disease. 20 Confounders are variables associated with the risk factor and may potentially be a cause of the outcome. 8 Table 5 lists several advantages and disadvantages with a matching design.
Advantages and Disadvantages for Using a Matching Strategy
Advantages | Disadvantages |
---|---|
Eliminate influence of measurable confounders (e.g. age, sex) | May be time-consuming and expensive |
Eliminate influence of confounders that are difficult to measure | Decision to match and confounding variables to match upon are decided at the outset of the study |
May be a sampling convenience, making it easier to select the controls in a case-control study | Matched variables cannot be examined in the study |
May improve study efficiency (i.e. smaller sample size) | Requires a matched analysis |
Vulnerable to overmatching: when matching variable has some relationship with the outcome |
Investigations examining rare outcomes may have a limited number of cases to select from, whereas the source population from which controls can be selected is much larger. In such scenarios, the study may be able to provide more information if multiple controls per case are selected. This method increases the “statistical power” of the investigation by increasing the sample size. The precision of the findings may improve by having up to about three or four controls per case. 21 - 23
Evaluating exposure status can be the Achilles heel of case-control studies. Because information about exposure is typically collected by self-report, interview, or from recorded information, it is susceptible to recall bias, interviewer bias, or will rely on the completeness or accuracy of recorded information, respectively. These biases decrease the internal validity of the investigation and should be carefully addressed and reduced in the study design. Recall bias occurs when a differential response between cases and controls occurs. The common scenario is when a subject with disease (case) will unconsciously recall and report an exposure with better clarity due to the disease experience. Interviewer bias occurs when the interviewer asks leading questions or has an inconsistent interview approach between cases and controls. A good study design will implement a standardized interview in a non-judgemental atmosphere with well-trained interviewers to reduce interviewer bias. 9
In 2004, the first meeting of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) group took place in Bristol, UK. 24 The aim of the group was to establish guidelines on reporting observational research to improve the transparency of the methods, thereby facilitating the critical appraisal of a study's findings. A well-designed but poorly reported study is disadvantaged in contributing to the literature because the results and generalizability of the findings may be difficult to assess. Thus a 22-item checklist was generated to enhance the reporting of observational studies across disciplines. 25 , 26 This checklist is also located at the following website: www.strobe-statement.org . This statement is applicable to cohort studies, case-control studies, and cross-sectional studies. In fact, 18 of the checklist items are common to all three types of observational studies, and 4 items are specific to each of the 3 specific study designs. In an effort to provide specific guidance to go along with this checklist, an “explanation and elaboration” article was published for users to better appreciate each item on the checklist. 27 Plastic surgery investigators should peruse this checklist prior to designing their study and when they are writing up the report for publication. In fact, some journals now require authors to follow the STROBE Statement. A list of participating journals can be found on this website: http://www.strobe-statement.org./index.php?id=strobe-endorsement .
Due to the limitations in carrying out RCTs in surgical investigations, observational studies are becoming more popular to investigate the relationship between exposures, such as risk factors or surgical interventions, and outcomes, such as disease states or complications. Recognizing that well-designed observational studies can provide valid results is important among the plastic surgery community, so that investigators can both critically appraise and appropriately design observational studies to address important clinical research questions. The investigator planning an observational study can certainly use the STROBE statement as a tool to outline key features of a study as well as coming back to it again at the end to enhance transparency in methodology reporting.
Supported in part by a Midcareer Investigator Award in Patient-Oriented Research (K24 AR053120) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (to Dr. Kevin C. Chung).
None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Case-Control Studies
The des case-control study.
E pi_Tools.XLSX
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Given the greater efficiency of case-control studies, they are particularly advantageous in the following situations:
Another advantage of their greater efficiency, of course, is that they are less time-consuming and much less costly than prospective cohort studies.
A classic example of the efficiency of the case-control approach is the study (Herbst et al.: N. Engl. J. Med. Herbst et al. (1971;284:878-81) that linked in-utero exposure to diethylstilbesterol (DES) with subsequent development of vaginal cancer 15-22 years later. In the late 1960s, physicians at MGH identified a very unusual cancer cluster. Eight young woman between the ages of 15-22 were found to have cancer of the vagina, an uncommon cancer even in elderly women. The cluster of cases in young women was initially reported as a case series, but there were no strong hypotheses about the cause.
In retrospect, the cause was in-utero exposure to DES. After World War II, DES started being prescribed for women who were having troubles with a pregnancy -- if there were signs suggesting the possibility of a miscarriage, DES was frequently prescribed. It has been estimated that between 1945-1950 DES was prescribed for about 20% of all pregnancies in the Boston area. Thus, the unborn fetus was exposed to DES in utero, and in a very small percentage of cases this resulted in development of vaginal cancer when the child was 15-22 years old (a very long latent period). There were several reasons why a case-control study was the only feasible way to identify this association: the disease was extremely rare (even in subjects who had been exposed to DES), there was a very long latent period between exposure and development of disease, and initially they had no idea what was responsible, so there were many possible exposures to consider.
In this situation, a case-control study was the only reasonable approach to identify the causative agent. Given how uncommon the outcome was, even a large prospective study would have been unlikely to have more than one or two cases, even after 15-20 years of follow-up. Similarly, a retrospective cohort study might have been successful in enrolling a large number of subjects, but the outcome of interest was so uncommon that few, if any, subjects would have had it. In contrast, a case-control study was conducted in which eight known cases and 32 age-matched controls provided information on many potential exposures. This strategy ultimately allowed the investigators to identify a highly significant association between the mother's treatment with DES during pregnancy and the eventual development of adenocarcinoma of the vagina in their daughters (in-utero at the time of exposure) 15 to 22 years later.
For more information see the DES Fact Sheet from the National Cancer Institute .
An excellent summary of this landmark study and the long-range effects of DES can be found in a Perspective article in the New England Journal of Medicine. A cohort of both mothers who took DES and their children (daughters and sons) was later formed to look for more common outcomes. Members of the faculty at BUSPH are on the team of investigators that follow this cohort for a variety of outcomes, particularly reproductive consequences and other cancers.
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Some people who have been infected with the virus that causes COVID-19 can experience long-term effects from their infection, known as Long COVID or Post-COVID Conditions (PCC). Long COVID is broadly defined as signs, symptoms, and conditions that continue or develop after acute COVID-19 infection. This definition of Long COVID was developed by the Department of Health and Human Services (HHS) in collaboration with CDC and other partners.
People call Long COVID by many names, including Post-COVID Conditions, long-haul COVID, post-acute COVID-19, long-term effects of COVID, and chronic COVID. The term post-acute sequelae of SARS CoV-2 infection (PASC) is also used to refer to a subset of Long COVID.
In July 2021, Long COVID was added as a recognized condition that could result in a disability under the Americans with Disabilities Act (ADA). Learn more: Guidance on “Long COVID” as a Disability Under the ADA .
Long COVID is a wide range of new, returning, or ongoing health problems that people experience after being infected with the virus that causes COVID-19. Most people with COVID-19 get better within a few days to a few weeks after infection, so at least 4 weeks after infection is the start of when Long COVID could first be identified. Anyone who was infected can experience Long COVID. Most people with Long COVID experienced symptoms days after first learning they had COVID-19, but some people who later experienced Long COVID did not know when they got infected.
There is no test that determines if your symptoms or condition is due to COVID-19. Long COVID is not one illness. Your healthcare provider considers a diagnosis of Long COVID based on your health history, including if you had a diagnosis of COVID-19 either by a positive test or by symptoms or exposure, as well as based on a health examination.
Science behind Long COVID
RECOVER: Researching COVID to Enhance Recovery
People with Long COVID may experience many symptoms.
People with Long COVID can have a wide range of symptoms that can last weeks, months, or even years after infection. Sometimes the symptoms can even go away and come back again. For some people, Long COVID can last weeks, months, or years after COVID-19 illness and can sometimes result in disability.
Long COVID may not affect everyone the same way. People with Long COVID may experience health problems from different types and combinations of symptoms that may emerge, persist, resolve, and reemerge over different lengths of time. Though most patients’ symptoms slowly improve with time, speaking with your healthcare provider about the symptoms you are experiencing after having COVID-19 could help determine if you might have Long COVID.
People who experience Long COVID most commonly report:
General symptoms ( Not a Comprehensive List)
Respiratory and heart symptoms
Neurological symptoms
Digestive symptoms
Other symptoms
Some people with Long COVID have symptoms that are not explained by tests or easy to manage.
People with Long COVID may develop or continue to have symptoms that are hard to explain and manage. Clinical evaluations and results of routine blood tests, chest X-rays, and electrocardiograms may be normal. The symptoms are similar to those reported by people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other poorly understood chronic illnesses that may occur after other infections. People with these unexplained symptoms may be misunderstood by their healthcare providers, which can result in a delay in diagnosis and receiving the appropriate care or treatment.
Review these tips to help prepare for a healthcare provider appointment for Long COVID.
Some people experience new health conditions after COVID-19 illness.
Some people, especially those who had severe COVID-19, experience multiorgan effects or autoimmune conditions with symptoms lasting weeks, months, or even years after COVID-19 illness. Multi-organ effects can involve many body systems, including the heart, lung, kidney, skin, and brain. As a result of these effects, people who have had COVID-19 may be more likely to develop new health conditions such as diabetes, heart conditions, blood clots, or neurological conditions compared with people who have not had COVID-19.
People experiencing any severe illness, hospitalization, or treatment may develop problems such as post-intensive care syndrome (PICS).
PICS refers to the health effects that may begin when a person is in an intensive care unit (ICU), and which may persist after a person returns home. These effects can include muscle weakness, problems with thinking and judgment, and symptoms of post-traumatic stress disorder (PTSD), a long-term reaction to a very stressful event. While PICS is not specific to infection with SARS-CoV-2, it may occur and contribute to the person’s experience of Long COVID. For people who experience PICS following a COVID-19 diagnosis, it is difficult to determine whether these health problems are caused by a severe illness, the virus itself, or a combination of both.
Some people may be more at risk for developing Long COVID.
Researchers are working to understand which people or groups of people are more likely to have Long COVID, and why. Studies have shown that some groups of people may be affected more by Long COVID. These are examples and not a comprehensive list of people or groups who might be more at risk than other groups for developing Long COVID:
Some people are at increased risk of getting sick from COVID-19 because of where they live or work, or because they can’t get health care. Health inequities may put some people from racial or ethnic minority groups and some people with disabilities at greater risk for developing Long COVID. Scientists are researching some of those factors that may place these communities at higher risk of getting infected or developing Long COVID.
The best way to prevent Long COVID is to protect yourself and others from becoming infected. For people who are eligible, CDC recommends staying up to date on COVID-19 vaccination , along with improving ventilation, getting tested for COVID-19 if needed, and seeking treatment for COVID-19 if eligible. Additional preventative measures include avoiding close contact with people who have a confirmed or suspected COVID-19 illness and washing hands or using alcohol-based hand sanitizer.
Research suggests that people who get a COVID-19 infection after vaccination are less likely to report Long COVID, compared to people who are unvaccinated.
CDC, other federal agencies, and non-federal partners are working to identify further measures to lessen a person’s risk of developing Long COVID. Learn more about protecting yourself and others from COVID-19 .
Living with Long COVID can be hard, especially when there are no immediate answers or solutions.
People experiencing Long COVID can seek care from a healthcare provider to come up with a personal medical management plan that can help improve their symptoms and quality of life. Review these tips to help prepare for a healthcare provider appointment for Long COVID. In addition, there are many support groups being organized that can help patients and their caregivers.
Although Long COVID appears to be less common in children and adolescents than in adults, long-term effects after COVID-19 do occur in children and adolescents .
Talk to your doctor if you think you or your child has Long COVID. Learn more: Tips for Talking to Your Healthcare Provider about Post-COVID Conditions
Studies are in progress to better understand Long COVID and how many people experience them.
CDC is using multiple approaches to estimate how many people experience Long COVID. Each approach can provide a piece of the puzzle to give us a better picture of who is experiencing Long COVID. For example, some studies look for the presence of Long COVID based on self-reported symptoms, while others collect symptoms and conditions recorded in medical records. Some studies focus only on people who have been hospitalized, while others include people who were not hospitalized. The estimates for how many people experience Long COVID can be quite different depending on who was included in the study, as well as how and when the study collected information. Estimates of the proportion of people who had COVID-19 that go on to experience Long COVID can vary.
CDC posts data on Long COVID and provides analyses, the most recent of which can be found on the U.S. Census Bureau’s Household Pulse Survey .
CDC and other federal agencies, as well as academic institutions and research organizations, are working to learn more about the short- and long-term health effects associated with COVID-19 , who gets them and why.
Scientists are also learning more about how new variants could potentially affect Long COVID. We are still learning to what extent certain groups are at higher risk, and if different groups of people tend to experience different types of Long COVID. CDC has several studies that will help us better understand Long COVID and how healthcare providers can treat or support patients with these long-term effects. CDC will continue to share information with healthcare providers to help them evaluate and manage these conditions.
CDC is working to:
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How to circumvent and beat the ransomware in android operating system—a case study of locker.cbtr.
2.1. methods for detecting ransomware, 2.2. methods for preventing ransomware, 2.3. methods for mitigating ransomware, 3. a method to mitigate the ransomware—the case study of locker.cbtr, 3.1. overview of locker.cbtr, 3.2. methodology and materials.
3.4. details of defeating locker.cbtr ransomware.
4.1. validation tests, 4.2. effectiveness of the proposed solution.
Author contributions, data availability statement, conflicts of interest.
ADB | Android Debug Bridge |
AES | Advanced Encryption Standard |
API | Application Programming Interface |
APK | Android Package Kit |
AVD | Android Virtual Device |
C&C | Command and Control |
DGAs | Domain Generation Algorithms |
DEX | Dalvik Executable |
FSM | Finite State Machine |
HTTP | HyperText Transfer Protocol |
IDE | Integrated Development Environment |
JAR | Java ARchive |
JSON | JavaScript Object Notation |
MFA | Multi-Factor Authentication |
MIMEs | Multipurpose Internet Mail Extensions |
ML | Machine Learning |
OS | Operating System |
SBOM | Software Bill of Materials |
SD card | Secure Digital card |
SMS | Short Message Service |
TCP | Transmission Control Protocol |
URL | Uniform Resource Locator |
XML | Extended Markup Language |
Specific URL Element | Name of Implementing Class | Meaning |
---|---|---|
/eaction/ | CommandConfirmRequest | Confirmation of the previous command completion |
/gac/ | CommandRequest | Request for the next command |
/sc/ | ContactsRequest | List of contacts read from the infected terminal |
/pha/ | DeviceDataRequest | Information about the infected terminal |
/cpm/ | PaymentRequest | Information about the payment (ransom) |
/scs/ | ReceivedSmsRequest | Information about the SMS captured at the infected terminal (content and delivery information) |
/ssms/ | SmsRequest | List of SMSes read from the infected terminal |
/gfsf/ | SmsToSendRequest | Request for data to send an SMS from the infected terminal (SMS destination address and content) |
/gt | UserAddressRequest | Request for information about the country, city, and IP address of the infected terminal |
/logsms/ | SuccessCountRequest | Information about the number of SMSes successfully sent from the infected terminal |
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Drabent, K.; Janowski, R.; Mongay Batalla, J. How to Circumvent and Beat the Ransomware in Android Operating System—A Case Study of Locker.CB!tr. Electronics 2024 , 13 , 2212. https://doi.org/10.3390/electronics13112212
Drabent K, Janowski R, Mongay Batalla J. How to Circumvent and Beat the Ransomware in Android Operating System—A Case Study of Locker.CB!tr. Electronics . 2024; 13(11):2212. https://doi.org/10.3390/electronics13112212
Drabent, Kornel, Robert Janowski, and Jordi Mongay Batalla. 2024. "How to Circumvent and Beat the Ransomware in Android Operating System—A Case Study of Locker.CB!tr" Electronics 13, no. 11: 2212. https://doi.org/10.3390/electronics13112212
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A case-control study (also known as case-referent study) is a type of observational study in which two existing groups differing in outcome are identified and compared on the basis of some supposed causal attribute. Case-control studies are often used to identify factors that may contribute to a medical condition by comparing subjects who have the condition with patients who do not have ...
Revised on June 22, 2023. A case-control study is an experimental design that compares a group of participants possessing a condition of interest to a very similar group lacking that condition. Here, the participants possessing the attribute of study, such as a disease, are called the "case," and those without it are the "control.".
A case-control study is a type of observational study commonly used to look at factors associated with diseases or outcomes.[1] The case-control study starts with a group of cases, which are the individuals who have the outcome of interest. The researcher then tries to construct a second group of individuals called the controls, who are similar to the case individuals but do not have the ...
Examples. A case-control study is an observational study where researchers analyzed two groups of people (cases and controls) to look at factors associated with particular diseases or outcomes. Below are some examples of case-control studies: Investigating the impact of exposure to daylight on the health of office workers (Boubekri et al., 2014).
A case control study is a retrospective, observational study that compares two existing groups. Researchers form these groups based on the existence of a condition in the case group and the lack of that condition in the control group. They evaluate the differences in the histories between these two groups looking for factors that might cause a ...
Introduction. A case-control study is designed to help determine if an exposure is associated with an outcome (i.e., disease or condition of interest). In theory, the case-control study can be described simply. First, identify the cases (a group known to have the outcome) and the controls (a group known to be free of the outcome).
General Overview of Case-Control Studies. In observational studies, also called epidemiologic studies, the primary objective is to discover and quantify an association between exposures and the outcome of interest, in hopes of drawing causal inference. Observational studies can have a retrospective study design, a prospective design, a cross ...
Compared with prospective cohort studies, which involve observing a cohort of subjects with variable levels of the exposure of interest over time to relate the occurrence of the outcome of interest to the exposure, case-control studies start with case subjects and control subjects (ie, the outcome of interest is known) and look back retrospectively at the subjects' exposures to find an ...
Abstract. Case-control studies are observational studies in which cases are subjects who have a characteristic of interest, such as a clinical diagnosis, and controls are (usually) matched subjects who do not have that characteristic. After cases and controls are identified, researchers "look back" to determine what past events (exposures ...
case-control study, in epidemiology, observational (nonexperimental) study design used to ascertain information on differences in suspected exposures and outcomes between individuals with a disease of interest (cases) and comparable individuals who do not have the disease (controls). Analysis yields an odds ratio (OR) that reflects the relative probabilities of exposure in the two populations.
Case control studies are also known as "retrospective studies" and "case-referent studies." Advantages. Good for studying rare conditions or diseases; ... A case-control study was conducted to investigate if exposure to zinc oxide is a more effective skin cancer prevention measure. The study involved comparing a group of former lifeguards that ...
A case-control study is a type of observational study commonly used to look at factors associated with diseases or outcomes. The case-control study starts with a group of cases, which are the individuals who have the outcome of interest. The researcher then tries to construct a second group of individuals called the controls, who are similar to ...
Case-control studies. Case-control studies are retrospective. They clearly define two groups at the start: one with the outcome/disease and one without the outcome/disease. They look back to assess whether there is a statistically significant difference in the rates of exposure to a defined risk factor between the groups.
A case-control study (also known as a case-referent study) is a type of observational study in which two existing groups differing in outcome are identified and compared on the basis of some supposed causal attribute. It is designed to help determine if an exposure is associated with an outcome (i.e., disease or condition of interest).
Case-Control Study. In a case-control study (also known as a case-referent study), two groups of individuals are selected for study, of which one has the disease whose causation is to be studied (the cases) and the other does not (the controls). In the context of the chemical industry, the aim of a case-control study is to evaluate the ...
However, a special type of case-control study, known as nested case-control study (discussed later in this chapter), is a hybrid design (partly prospective and partly retrospective). In traditional case-control study, cases and controls are selected at the starting point of the study - cases having the disease of interest, and control ...
"Case-control studies are best understood by considering as the starting point a source population, which represents a hypothetical study population in which a cohort study might have been conducted.The source population is the population that gives rise to the cases included in the study. If a cohort study were undertaken, we would define the exposed and unexposed cohorts (or several cohorts ...
Case Control. In a Case-Control study there are two groups of people: one has a health issue (Case group), and this group is "matched" to a Control group without the health issue based on characteristics like age, gender, occupation. ... There is a known link between Omgea-3 depletion and depression;
Cohort studies and case-control studies are two primary types of observational studies that aid in evaluating associations between diseases and exposures. In this review article, we describe these study designs, methodological issues, and provide examples from the plastic surgery literature. Keywords: observational studies, case-control study ...
Case-control studies are particularly useful for studying the cause of an outcome that is rare and for studying the effects of prolonged exposure. For example, a case-control study could be used ...
In a case-crossover study, each case serves as its own control because at the beginning of the study and prior to the onset of the acute event the individual belongs to the control group. For each person, there is a period during which the person was a case, called a "case window," and a period associated with not being a case, known as the ...
When the study population is dynamic. When little is known about the risk factors for the disease, case-control studies provide a way of testing associations with multiple potential risk factors. (This isn't really a unique advantage to case-control studies, however, since cohort studies can also assess multiple exposures.)
Case control studies are also known as "retrospective studies" and "case-referent studies." Advantages Good for studying rare conditions or diseases ... A case-control study was conducted to investigate if exposure to zinc oxide is a more effective skin cancer prevention measure. The study involved comparing a group of former lifeguards that ...
Some people who have been infected with the virus that causes COVID-19 can experience long-term effects from their infection, known as Long COVID or Post-COVID Conditions (PCC). Long COVID is broadly defined as signs, symptoms, and conditions that continue or develop after acute COVID-19 infection. This definition of Long COVID was developed by ...
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Ransomware is one of the most extended cyberattacks. It consists of encrypting a user's files or locking the smartphone in order to blackmail a victim. The attacking software is ordered on the infected device from the attacker's remote server, known as command and control. In this work, we propose a method to recover from a Locker.CB!tr ransomware attack after it has infected and hit a ...