Nested case–control study - Wikipedia

 

nested case study

Printer-friendly version. A case-cohort study is similar to a nested case-control study in that the cases and non-cases are within a parent cohort; cases and non-cases are identified at time t 1, after niudgets.gq a case-cohort study, the cohort members were assessed for risk factros at any time prior to t niudgets.gq-cases are randomly selected from the parent cohort, forming a subcohort. the nested case-control design requires the selection of a new set of controls for each distinct disease outcome. Case-cohort study designs were proposed as an alternative to the nested case-control study design. Case-cohort study requires only the selection of a . Feb 14,  · a) The nested case-control study is a retrospective design. b) The study design minimised selection bias compared with a case-control study. c) Recall bias was minimised compared with a case-control study. d) Causality could be inferred from the association between prescription of antipsychotic drugs and venous thromboembolismCited by:


A Nested Case-Control Study


Selection of cases and controls for the analysis based on exposures in the 1 to 11 years before index date, nested case study. Proportions of cases and controls prescribed different types nested case study anticholinergic drug in the 1 to 11 years before diagnosis. Recording of dementia type and recorded source of diagnosis in cases. Numbers of cases and controls prescribed individual anticholinergic drugs in the 1 to 11 years before the index date.

Numbers of cases and controls prescribed different types of anticholinergic drugs in the 3 to 13 years before the index date. Numbers of cases and controls prescribed different types of anticholinergic drugs in the 5 to 20 years before the index date.

Adjusted odds ratios for cumulative use of anticholinergic drug types in the 1 to 11, 3 to 13 and 5 to 20 years before the index date. Numbers of cases and controls prescribed anticholinergic drug types in the 1 to 11, 3 to 13 and 5 to 20 years before the index date.

Adjusted odds ratios for cumulative use of anticholinergic drugs in the 1 to 11 years before index date: separate analyses in cases aged less than 80 at diagnosis of dementia and cases aged 80 and over at diagnosis, with their respective matched controls, nested case study.

Adjusted odds ratios for cumulative use of anticholinergic drugs in the 1 to 11 years before the index date: separate analyses in men and women, with their respective matched controls. Adjusted odds ratios for total cumulative nested case study in DDDs of anticholinergic drugs in 1 to 11, 3 to 13 and 5 to 20 years before the index date. Adjusted odds ratios for cumulative use of anticholinergic drugs in 1 to11 years before index date: multiple imputation results.

Adjusted odds ratios for nested case study use of anticholinergic drugs in the 1 to 11 years before index date: restricted to the anticholinergic drugs included in Gray study. Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, nested case study, consultancies, honoraria or payment, nested case study, speaker's bureaus, stock ownership or options, expert testimony, royalties, nested case study, donation of medical equipment, or patents planned, pending, or issued.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response, nested case study. Not all submitted comments are published. Please see our commenting policy for details, nested case study. Published online June 24, 8 — Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure.

Data were analyzed from May to June The adjusted OR for dementia increased from 1. There were significant increases in dementia risk for the anticholinergic antidepressants adjusted OR [AOR], 1. Results were similar when exposures were restricted to exposure windows of 3 to 13 years AOR, 1. Associations were stronger in cases diagnosed before the age of 80 years.

The population-attributable fraction associated with total anticholinergic drug exposure during the 1 to 11 years before diagnosis was These findings nested case study the importance of reducing exposure to anticholinergic drugs in middle-aged and older people. An estimated 47 million people worldwide were living with dementia in1 while in the United States around 5.

This broad group of drugs acts by blocking the neurotransmitter acetylcholine in the central and peripheral nervous system and includes some nested case study, antidepressants, and medications for gastrointestinal and bladder disorders. These medicines can have short-term adverse effects, including confusion and memory loss in older people, 3 - 6 but it is less certain whether long-term use increases the risk of dementia.

Observational studies of anticholinergic drugs and dementia risk 7 - 10 have generally been relatively small, only assessed short-term exposure, or were subject to recall bias.

These studies were also susceptible to protopathic bias because they did not account for anticholinergic drugs being prescribed to treat early symptoms of dementia before diagnosis, nested case study.

A cohort study 11 that reduced protopathic bias by excluding prescriptions in the final year of follow-up found that higher cumulative anticholinergic drug use was associated with a significantly increased risk of dementia but had limited power for analysis of separate types of anticholinergic drug. A recent larger study 12 found varying risks associated with different types of anticholinergic drugs and concluded that further research should examine individual anticholinergic drug classes.

This study was designed to assess the association between cumulative anticholinergic drug use and risk of dementia in a large, representative British population. The study objectives were to estimate dementia risks associated with different types of nested case study medication including analyses of prescriptions up to 20 years before diagnosis.

Quiz Ref ID This was a nested case-control study within a cohort of patients registered with practices in England contributing to the QResearch database version QResearch is an anonymized research database of more than 30 million individuals in over general practices that includes data recorded prospectively from routine health care.

The data include demographic information, medical diagnoses, prescriptions, referrals, laboratory results, and clinical values. The study was approved in accordance with the agreed procedure with the East Midlands Derby Research Ethics Committee, waiving written informed consent for deidentified patient data. The cohort were followed up until the earliest date of death, transfer to another practice, or the study end date January 31, Case patients were those diagnosed with dementia during follow-up, nested case study, identified using clinical codes recorded in the practice records or linked Office of National Statistics death records.

Patients with prescriptions for acetylcholinesterase-inhibiting drugs donepezil, galantamine, memantine, and rivastigmine but without a recorded diagnosis of dementia were also included because these drugs are licensed only for patients with dementia.

Case patients with diagnostic codes for specific subtypes of dementia associated with Huntington disease, Parkinson disease, Creutzfeldt-Jakob disease, or human immunodeficiency virus HIV were excluded, as were patients diagnosed with Parkinson disease, Huntington disease, or multiple sclerosis to reduce indication bias. Each case patient was matched to 5 controls by age within 1 yearsex, nested case study, general practice, and calendar time using incidence density sampling, nested case study.

Controls were excluded if they had a diagnosis of Nested case study disease, Huntington disease, or multiple nested case study. For the primary analyses, case patients and controls were only included if they had at least 11 years of recorded data prior to the index date, so that anticholinergic drug exposure could be assessed nested case study a complete period of 10 years excluding the 1-year period prior to the index date.

There is incomplete consensus on which drugs are considered as having anticholinergic properties. We used the approach of Gray et al, 11 which included drugs identified as having strong anticholinergic properties by the American Geriatrics Society Beers Criteria Update Expert Panel. We extracted details of prescriptions for the included anticholinergic drugs.

To reduce protopathic biases, we did not include prescriptions issued in the year before the index date. In 2 additional analyses, we only included prescriptions issued up to 3 and up to 5 years before diagnosis. The primary exposure variable was total cumulative anticholinergic drug exposure, which combined the different types of anticholinergic medications based on the method used by Gray et al.

These values were then divided by minimum effective daily dose values recommended for use in older adults to give a number of standardized daily doses for each prescription.

We used minimum effective dose values from the Geriatric Dosage Handbook 18 where available, and for the nested case study drugs we used the lowest recommended dose values in older people if stated in the British National Formulary see eTable 1 in the Supplement. We summed these standardized values over all anticholinergic prescriptions in the exposure time windows of interest to obtain total standardized daily doses TSDDs nested case study each patient.

These variables were evaluated at the start of the exposure window for the primary analysis. We used conditional logistic regression to estimate odds ratios ORs adjusted for the confounding variables, nested case study. The exposure window in the main analyses comprised the 1 to 11 nested case study before the index date.

We carried out subgroup analyses and interaction tests by age at index date younger than 80 years and 80 years and olderby sex, and separately in nested case study patients diagnosed with Alzheimer disease including mixedvascular dementia, nested case study, and other or unspecified types of dementia with their respective matched controls. We created 10 multiply imputed data sets and combined results using Rubin rules 29 ; and. We calculated population-attributable fractions by combining adjusted odds ratios AORs with the proportions of cases in the different categories of anticholinergic drug exposure.

We used Stata version Case patients had a mean SD age of Table 2 presents information on comorbidities and prescribed medications. Prevalence values were slightly higher in case patients than in controls for all the comorbidities and prescribed medications.

Quiz Ref ID In the 1 to 11 years before the index date, nested case study, The most frequently prescribed types of anticholinergic drugs were antidepressants The AOR associated with total cumulative anticholinergic exposure in the 1 to 11 years before the index date increased from 1.

Results were similar but with slightly lower ORs when restricted to the 3 to 13 and 5 to 20 years before the index date; for example, for the 5 to 20 years before the index date the AOR was 1, nested case study.

Quiz Ref ID Among specific types of anticholinergic drugs there were significant increases in risk associated with use of antidepressants, antiparkinson drugs, antipsychotics, bladder antimuscarinics, and antiepileptic drugs Table 5.

There were no significant increases in risk associated with antihistamines, skeletal muscle relaxants, gastrointestinal antispasmodics, antiarrhythmics, or antimuscarinic bronchodilators, although the numbers of patients exposed were small for skeletal muscle relaxants and antiarrhythmics.

Patterns of risk were similar in the 3- to and 5- to year exposure windows eTable 6 in the Supplementexcept for antipsychotic drug exposure in the 5- to year window, where there were no statistically significant increases in risk; the AOR for more than TSDDs was 1. For some drug types, numbers were too small to allow analysis for the 5 to 20 years before the index date eTable 7 in the Supplement. For the 3 to 13 years before diagnosis, it was 9.

There were stronger associations in case patients diagnosed before age 80 years than at 80 years or older, both for total drug exposure and for antidepressants, antipsychotics, and bladder antimuscarinics eTable 8 in the Supplement. Associations were similar in men and women eTable 9 in the Supplement. Adjusted odds ratios were generally higher for vascular dementia than Alzheimer disease eTable 10 nested case study the Supplement ; for example, in the 1- to year exposure window, the AOR nested case study more than TSDDs was 1.

Results were similar when DDD values were used to calculate cumulative exposure eTable 12 in the Supplement. Sensitivity analyses using multiply imputed data eTable 13 in the Supplement or restricted to anticholinergic drugs included nested case study the study by Gray et al 11 eTable 14 in the Supplement did not change study findings, nested case study.

This large, nested case-control study found an increased risk of dementia associated with anticholinergic medication use. Associations were strongest for the anticholinergic antidepressants, bladder antimuscarinics, antipsychotics, and antiepileptic drugs. Quiz Ref ID Associations were also stronger in cases diagnosed before the age of 80 years and in cases diagnosed with vascular dementia rather than with Alzheimer disease.

There were no significantly increased risks for antihistamines, gastrointestinal antispasmodics, antimuscarinic bronchodilators, antiarrhythmics, or skeletal muscle relaxants, although the numbers of patients prescribed skeletal muscle relaxants and antiarrhythmic drugs were small, giving imprecise estimates.

This observational study has shown associations, but is not able to evaluate causality. The finding of more pronounced associations for vascular dementia than for other types is novel.

It raises questions about the mechanisms by which anticholinergic drugs may increase the risk of subsequent dementia, nested case study. These may include vascular and inflammatory changes, 3334 as well as the more obvious mechanism of chronic cholinergic depletion.

Perhaps the mechanism underlying the potential effects of anticholinergic drugs is not solely through blocking acetylcholine and causing an excess of Alzheimer disease, so future research should give consideration to possible mechanisms. We included a large representative sample of people diagnosed with dementia and matched controls, nested case study. All eligible case patients and controls were included, so there nested case study no selection bias due to nonresponse, nested case study data were recorded prospectively, so results are not susceptible to recall bias.

Comprehensive data on prescriptions meant that we could derive a nested case study of total anticholinergic drug exposure, which accounted for the quantity and dose prescribed. Our findings are consistent with other studies, including a US cohort study nested case study participants, 11 which nested case study a hazard ratio of 1.

With our larger sample size we could also examine specific types of anticholinergic drugs and account nested case study a broader range of confounders. A study by Richardson et al, 12 using another United Kingdom primary care database CPRDreported findings similar to ours, despite some differences in the drugs included, exposure measures used, exposure windows, nested case study, and the confounding variables accounted for.

For example, we included drugs based on those identified as having strong anticholinergic properties by the American Geriatrics Society Beers Criteria Update Expert Panel, 14 whereas Richardson et al 12 used drugs included in the update of the Anticholinergic Cognitive Burden scale.

The coherence of findings in these 3 studies provides strong evidence for reliability and robustness of the associations across different study designs, countries, and settings. Nevertheless, the possibility of residual confounding remains, and it is impossible to entirely exclude protopathic effects arising from treatment for very early preclinical effects of dementia. A limitation is that some patients may not have taken their prescribed medication nested case study not taken the dose prescribed, leading to exposure misclassification.

 

Are nested case-control studies biased?

 

nested case study

 

Nested Case-Control Study: This is a case-control study within a cohort study. At the beginning of the cohort study (t 0), members of the cohort are assessed for risk factors. Cases and controls are identified subsequently at time t 1. A nested case-control study is a type of case-control study in which cases and controls are drawn from the population in a fully enumerated cohort. A set of controls is selected from subjects (i.e. Printer-friendly version. A case-cohort study is similar to a nested case-control study in that the cases and non-cases are within a parent cohort; cases and non-cases are identified at time t 1, after niudgets.gq a case-cohort study, the cohort members were assessed for risk factros at any time prior to t niudgets.gq-cases are randomly selected from the parent cohort, forming a subcohort.