Colorectal cancer (CRC) incidence and mortality of China account for nearly 30% of the global attributable fraction. We aimed to estimate the yield and effectiveness of a 2-sample fecal immunochemical test (FIT)-based screening program in China.

Eligible individuals were invited for 2-sample FIT between 2007 and 2021, with positive ones (cutoff 40 μg/g before 2013 and 20 μg/g thereafter) referred for colonoscopy. Participation rates, detection rates, and positive predictive values were calculated. Participants were classified into: FIT+/colonoscopy compliers, FIT+/colonoscopy noncompliers, and FIT- as control subjects. We compared CRC incidence and mortality and calculated the age reaching comparable risk.

Among 246,349 invitees, 150,524 (61.10%) participated in 2-sample FIT, with 16,994 (11.29%) identified as FIT+; 12,816 (75.41%) underwent colonoscopy, yielding a detection rate and positive predictive value of 0.57% and 6.70% for advanced neoplasia, respectively. Median follow-up was 10.58 years. Compared with FIT- participants, CRC incidence and mortality were relatively similar among FIT+/colonoscopy compliers with hazard ratios of 0.94 (95% confidence interval [CI], 0.75-1.19) and 1.62 (95% CI, 1.09 to 2.41) but higher among noncompliers, with hazard ratios of 3.52 (95% CI, 2.85-4.34) and 4.41 (95% CI, 2.96-6.55). Taking CRC incidence and mortality risk of FIT- participants at 50.0 years of age as the benchmark, FIT+/colonoscopy compliers reached same risk at 50.6 and 46.1 years of age, while noncompliers reached the same risk at 38.0 and 37.9 years of age, respectively.

Two-sample FIT could effectively identify high-risk populations, and colonoscopy compliance is associated with a lower risk of CRC incidence and mortality. This strategy might facilitate CRC screening practice in countries with large populations.

Guidelines recommend individualized decision making for screening colonoscopy for colorectal cancer (CRC) in patients after the age of 75 years due to low additional benefits. That should be taken with a grain of salt, as these recommendations are based on expert opinion and simulation models which do not consider (1) the differences in pathogenesis and cancer biology of CRC in elderly; (2) the risks of colonoscopy in this patient population; (3) and the impact of new surgical and nonsurgical therapies for CRC. In this review, our goal is to bring a surgeon's perspective to understand the role of screening colonoscopy in patients older than 75 years.

Background and ObjectivesHearing aids may reduce the risk of dementia among individuals with hearing loss. However, no evidence is available from randomized controlled trials (RCTs) on the effectiveness of hearing aids use in reducing incident dementia. Using target trial emulation, we leveraged an existing longitudinal cohort study to estimate the association between hearing aids initiation and risk of dementia.Research Design and MethodsThe Health and Retirement Study was used to emulate target trials among non-institutionalized participants aged ≥50 years with self-reported hearing loss, without dementia at baseline, and without use of hearing aids in the previous 2 years. Intention-to-treat analysis was conducted to estimate the risk of dementia associated with hearing aids initiation vs controls who did not initiate hearing aids. Pooled logistic regression models with inverse-probability of treatment and censoring weights were applied to estimate risk ratios, and 95% confidence intervals were calculated using 1000 sets of bootstrapping.ResultsAmong 2314 participants (328 in the intervention group and 1986 in the control group; average age: 72.3 ± 9.7 years, 49% women, and 81% White), after 8 years of follow-up, risk of dementia was significantly lower among individuals who initiated hearing aids (risk difference (RD): -0.05, 95% confidence interval (CI): -0.08, -0.01). A lower risk was observed particularly among adults aged 50-74 years, men, and individuals with cardiovascular disease.Discussion and ImplicationsHearing aids use was associated with a significant reduction of incident dementia. Future interventional studies are needed to further assess the effectiveness of hearing aids in preventing dementia.

We aimed to evaluate the association between colonoscopy and colorectal cancer (CRC) occurrence and related mortality in an older population.This retrospective, nationwide, population-based cohort study used data of adults aged ≥40 years from the Health Insurance Review and Assessment Service database. After excluding colonoscopy within 6 months of CRC diagnosis during enrollment, CRC occurrence and related mortality were compared between colonoscopy and non-colonoscopy groups using a time-dependent Cox proportional hazard model. Subgroup analysis was conducted among four age groups: young, middle-aged, old, and very old.Among 748986 individuals followed for 9.64 (SD 0.99) years, the colonoscopy group had a 65% lower CRC occurrence (adjusted hazard ratio [HRa] 0.35, 95%CI 0.32-0.38) and 76% lower CRC-related mortality (HRa 0.24, 95%CI 0.18-0.31) after 5 years compared with the non-colonoscopy group. Colonoscopy was associated with the most significant reduction in CRC occurrence in the middle-aged group (HRa 0.32, 95%CI 0.29-0.35) and in CRC-related mortality in the young group (HRa 0.04, 95%CI 0.01-0.33); the very old group had the least reduction in both CRC occurrence and CRC-related mortality (HRa 0.44, 95%CI 0.33-0.59 and HRa 0.28, 95%CI 0.15-0.53, respectively).We found a significant association between colonoscopy and reduction in CRC occurrence and CRC-related mortality in adults aged ≥40 years after 5 years of follow-up; however, these associations were weaker in the very old group. More research is needed on the association between colonoscopy and older age.

Determining optimal management of colorectal polyps in patients with limited life expectancy of under 10 years can be difficult, due to challenges balancing an uncertain natural history of polyp progression to symptomatic malignancy versus the increased risk and consequences of polypectomy complications.

This British Society of Gastroenterology and Association of Coloproctologists of Great Britain and Ireland guidance aims to help clinicians and patients consider these risks to aid decision-making for polypectomy versus a conservative approach.

A guidance development group comprising 28 members was established, including gastroenterologists, colorectal surgeons, elderly care physicians, anaesthetists, epidemiologists, nurse endoscopists, a general practitioner and patient representatives. Estimates on life expectancy stratified by age and comorbidity, polyp dwell time for differing polyp sizes, cancer sojourn time and polypectomy complication rates for comorbid/elderly patients both on and off antithrombotic medication were collated from various literature searches. A model was created to compare the risk of symptomatic malignancy in a patient's lifetime against the risk of significant complications.

Following a modified Delphi consensus process and after three rounds of voting, 33 recommendations were made within 10 domains (principles, diagnostic investigation, life expectancy, polyp and cancer natural history, polypectomy risks, management recommendations, follow-up, decision-making practicalities, training and education, future research). A table was created, summarising whether polypectomy or conservative management might be the favoured option for 40 clinical scenarios of patients with differing life expectancy, polyp sizes and use of antithrombotic medication.

This guidance provides a framework to facilitate more objective and informed decision-making, from which an individualised plan can be developed between the patient and their clinician.

We conducted a retrospective observational study to examine whether anti-inflammatory medications prescribed peri-operatively of resective brain surgery can reduce long-term seizure recurrence for individuals with drug-resistant focal epilepsy. We used insurance-claims data from across the United States to screen medications prescribed to 1,993 individuals undergoing epilepsy. We then validated the results in a well-characterized cohort of 671 epilepsy patients from a major surgical center. Twelve medications met the screening criteria and were evaluated, identifying dexamethasone and zonisamide as potentially beneficial. Dexamethasone reduced seizure recurrence by 42% over 9 years of follow-up (hazard-ratio = 0.742; 95% CI = 0.662, 0.831), and zonisamide reduced recurrence by 33% (HR = 0.782; 95% CI = 0.667, 0.917). While dexamethasone could not be validated, analysis of zonisamide in the clinical cohort corroborated the beneficial effect (HR = 0.828; 95% CI = 0.706, 0.971). If prospectively validated, this study suggests surgeons could improve long-term outcomes of epilepsy surgery by medically reducing neuro-inflammation in the surgical bed.

Estimating effects of interventions is a central task in perioperative and critical care outcomes research. While randomized trials remain the accepted standard for causal inference, trial data are not always available to inform clinical decisions, and some questions cannot be answered feasibly or efficiently with trials. In these settings, studies using observational healthcare data may be used to inform practice. Causal inference from observational data has been reconsidered in recent years, challenging the prevailing notion among clinical researchers that causal conclusions cannot be drawn from observational studies. The "target trial framework" is one contribution within a growing methodologic field that helps investigators avoid common pitfalls in observational study design and analysis. Importantly, researchers must understand which biases this framework can-and cannot-help avoid. The authors present an overview of target trial emulation and describe the promise and limitations of this framework for improving observational perioperative and critical care outcomes research.

To investigate the incidence and risk factors of cardiovascular disease (CVD) in adolescent and young adult survivors of cervical cancer.

This retrospective cohort study used data from the Korean National Health Insurance Service. Adolescent and young adult (AYA) cervical cancer survivors (n=7,803) were matched with non-cancer controls (n=23,327) using 1:3 propensity score matching, and hazard ratios (HRs) for CVD were determined using Cox regression models. Multivariable Cox regressions were used to assess CVD incidence according to cancer treatment and identify risk factors.

A total of 7,803 AYA survivors with cervical cancer were analyzed in this study during a median 8.9 years of follow-up. They developed any CVD with an adjusted HR of 1.47 (95% confidence interval [CI]=1.33-1.62) compared with the non-cancer controls. Those who underwent concurrent chemoradiotherapy had markedly elevated risks of heart failure (subHR=2.66; 95% CI=1.24-5.72), ischemic heart disease (subHR=1.78, 95% CI=1.11-2.86), deep vein thrombosis (subHR=15.32; 95% CI=9.16-25.63), and pulmonary embolism (subHR=14.99; 95% CI=6.31-35.62). Diabetes, hypertension and chemoradiation therapy were identified as potential risk factors that increase the risk of CVD by 1.55-fold, 1.62-fold and 2.64-fold, respectively.

These findings indicate a need to pay increased attention to cardiovascular health management in adolescent and young adult cervical cancer survivors, particularly those treated with chemoradiotherapy.

Although adolescent and young adult (AYA) cancer survivors have an increased risk of psychiatric disorders, limited evidence has been suggested. We aimed to determine the risk of psychiatric disorders among AYA cancer survivors.

A retrospective population-based cohort study based on the Korea National Health Insurance Service database was carried out. All men and women aged 15-39 years diagnosed with cancer between 2006 and 2019 (N = 88 965) were included and matched with controls (1 : 4). The prevalence ratios (PRs) of psychiatric disorders were calculated in cancer patients and compared with those in the control group every 6 months before and after cancer diagnosis.

The mean age of the participants was 32.2 years and the majority were 30-39 years of age (72.9%). There was no difference in the PRs of psychiatric disorders between AYA cancer patients and the control group before cancer diagnosis, but it increased sharply after cancer diagnosis [PR 2.50, 95% confidence interval (CI) 2.42-2.58 in the first 6 months]. During a median follow-up of 6.5 years, 54 733 participants developed psychiatric disorders. The overall risk of psychiatric disorders among AYA cancer survivors compared with the control group had a sub-distribution hazard ratio of 1.42 (95% CI 1.39-1.45) after considering competing risks.

Our study confirmed a 42% increased risk of psychiatric disorders among AYA cancer survivors compared with controls across various cancer types. Our findings suggest that AYA cancer survivors require long-term psychological support following their cancer diagnosis.

Colorectal cancer (CRC) ranks third in terms of global cancer prevalence and is the second most common cause of cancer-related mortality. Although CRC rates are decreasing in the United States, inequalities still exist despite the effectiveness of invasive screening methods, such as colonoscopy, flexible sigmoidoscopy, and computed tomography (CT) colonography in detecting colorectal cancer. Many current interventions promoting CRC screening do not utilize a modern theory-based approach, which has led to the low utilization of these screening methods. This cross-sectional study aims to address the lack of theory-based treatments for promoting visual CRC screening examinations by applying the multi-theory model (MTM) of health behavior change to explicate the health-related factors for individuals to seek visual colorectal cancer screening examinations for CRC screening. A 57-item validated questionnaire assessing MTM constructs and CRC screening was administered online. The survey questionnaire was administered to a sample of 640 adults from the United States. The participants were between the ages of 45 and 75 years. Hierarchical multiple regression was used to assess the relationship between MTM constructs with the initiation and sustenance of CRC screening behaviors. Out of the total participants in this nationwide sample, 71.4% (n = 457) reported that they had undergone a visual CRC screening examination. MTM subscales, specifically participatory dialogue, changes in the physical environment along with age, recommendation for CRC screening from a healthcare provider, and previous experience with colonoscopy, were found to be significant factors in predicting the initiation of visual CRC screening behavior. These factors accounted for 22% of the variation in initiation among this group (R2 = 0.222, F = 3.521, p < 0.001). The MTM can be a valuable framework for designing educational media, information media, social media platforms, and clinical interventions to promote visual colorectal cancer screening examinations.

Comparisons between randomized trial analyses and observational analyses that attempt to address similar research questions have generated many controversies in epidemiology and the social sciences. There has been little consensus on when such comparisons are reasonable, what their implications are for the validity of observational analyses, or whether trial and observational analyses can be integrated to address effectiveness questions. Here, we consider methods for using observational analyses to complement trial analyses when assessing treatment effectiveness. First, we review the framework for designing observational analyses that emulate target trials and present an evidence map of its recent applications. We then review approaches for estimating the average treatment effect in the target population underlying the emulation, using observational analyses of the emulation data alone and using transportability analyses to extend inferences from a trial to the target population. We explain how comparing treatment effect estimates from the emulation against those from the trial can provide evidence on whether observational analyses can be trusted to deliver valid estimates of effectiveness-a process we refer to as benchmarking-and, in some cases, allow the joint analysis of the trial and observational data. We illustrate different approaches using a simplified example of a pragmatic trial and its emulation in registry data. We conclude that synthesizing trial and observational data-in transportability, benchmarking, or joint analyses-can leverage their complementary strengths to enhance learning about comparative effectiveness, through a process combining quantitative methods and epidemiologic judgments.

Colorectal cancer (CRC) has the third highest incidence in the Philippines. Currently, there is a paucity in literature that is focused on the knowledge, attitudes, and perceptions of Filipinos regarding CRC screening. This is the first study in the Philippines that describes this.

This is a cross-sectional study that validated a 52-item Filipino questionnaire on the knowledge on colorectal cancer, willingness to undergo CRC screening, and perceived benefits and barriers to fecal occult blood test (FOBT) and colonoscopy. The study enrolled household heads more than 20 years of age residing in both urban and rural communities in the Philippines.

The UP-PGH CRC KAP (University of the Philippines - Philippine General Hospital Colorectal Cancer Knowledge, Attitudes, and Practices) and Rawl Questionnaire's validity and internal consistency were established in a pilot study of 30 respondents. A total of 288 respondents were then enrolled to the main study group with a median age of 54.0. Knowledge scores for prognosis and utility of CRC screening were modest (6.3/12 and 8.4/20, respectively). Perceived benefit scores to FOBT and colonoscopy were high (9.9/12 and 13.9/16, respectively). Median scores to barriers to FOBT and colonoscopy were intermediate (22.5/36 and 35.8/60, respectively). Notably, a vast majority (86.1%) were willing to participate in CRC screening programs initiated by the government, and 46.9% agreed to undergo screening tests even as out-of-pocket expense.

The UP-PGH CRC KAP Questionnaire as well as the Filipino translation of the Rawl Questionnaire are reliable and valid tools in extensively assessing the knowledge of Filipinos on CRC and willingness to undergo screening, as well as the benefits of and barriers to FOBT and colonoscopy. Knowledge scores were modest suggesting that directed educational campaigns and awareness programs can aid in increasing awareness about CRC and its screening. Household income and highest educational attainment were significantly positively correlated with knowledge scores, and perceived benefits of and barriers to CRC screening. Scores were generally comparable between urban and rural communities.

Physical activity is associated with lower risk of dementia and cognitive impairment, but existing randomized controlled trials have shown conflicting results. As cognitive decline occurs decades before the onset of dementia, physical activity interventions initiated in late life may have missed the potential window for prevention. An ideal trial of physical activity initiated from midlife and lasts till incident dementia and cognitive impairment in late life is not feasible. We aimed to estimate the effectiveness of a hypothetical physical activity intervention initiated from midlife on reducing dementia and cognitive impairment by emulating target trials using observational data.

The Health and Retirement Study was used to emulate target trials among noninstitutionalized participants aged 45 to 65 years with normal cognition who were physically inactive in the previous 2 years. Cognitive status was determined based on Langa-Weir classification of cognitive function (including immediate and delayed word recall tests, serial sevens subtraction, counting backward). Individuals were categorized as initiating physical activity or not, based on the self-reported physical activity. Intention-to-treat and per-protocol analysis were conducted with pooled logistic regression models with inverse-probability of treatment and censoring weights to estimate risk ratios (RRs), and 95% confidence intervals (95% CIs) were calculated with 200 sets of bootstrapping.

Among 1505 participants (average age 57.6 ± 4.8 years, 67% women, 76.5% White), 72 cases of dementia and 409 cases of cognitive impairment occurred. After 12 years of follow-up, physical activity reduced dementia (RR = 0.70, 95% CI: 0.43, 0.99) for intention-to-treat analysis, and reduced dementia (RR = 0.51, 95% CI: 0.19, 0.99) and cognitive impairment (RR = 0.77, 95% CI: 0.61, 0.92) for per-protocol analysis. No significant reduction was found among older adults.

Physical activity initiated during midlife may reduce dementia and cognitive impairment in late life, which highlights the importance of preventing cognitive outcomes at an earlier stage of life.

Multilevel barriers to colonoscopy after a positive fecal blood test for colorectal cancer (CRC) are well-documented. A less-explored barrier to appropriate follow-up is repeat fecal testing after a positive test. We investigated this phenomenon using mixed methods.

This sequential mixed methods study included quantitative data from a large cohort of patients 50-89 years from four healthcare systems with a positive fecal test 2010-2018 and qualitative data from interviews with physicians and patients.

Logistic regression was used to evaluate whether repeat testing was associated with failure to complete subsequent colonoscopy and to identify factors associated with repeat testing. Interviews were coded and analyzed to explore reasons for repeat testing.

A total of 316,443 patients had a positive fecal test. Within 1 year, 76.3% received a colonoscopy without repeat fecal testing, 3% repeated testing and then received a colonoscopy, 4.4% repeated testing without colonoscopy, and 16.3% did nothing. Among repeat testers (7.4% of total cohort, N = 23,312), 59% did not receive a colonoscopy within 1 year. In adjusted models, those with an initial positive test followed by a negative second test were significantly less likely to receive colonoscopy than those with two successive positive tests (OR 0.37, 95% CI 0.35-0.40). Older age (65-75 vs. 50-64 years: OR 1.37, 95% CI 1.33-1.41) and higher comorbidity score (≥ 4 vs. 0: OR 1.75, 95% CI 1.67-1.83) were significantly associated with repeat testing compared to those who received colonoscopy without repeat tests. Qualitative interview data revealed reasons underlying repeat testing, including colonoscopy avoidance, bargaining, and disbelief of positive results.

Among patients in this cohort, 7.4% repeated fecal testing after an initial positive test. Of those, over half did not go on to receive a colonoscopy within 1 year. Efforts to improve CRC screening must address repeat fecal testing after a positive test as a barrier to completing colonoscopy.

To assess the effect of contemporary menopausal hormone therapy on the risk of cardiovascular disease according to the route of administration and combination of hormones.

Nationwide register based emulated target trial.

Swedish national registries.

919 614 women aged 50-58 between 2007 and 2020 without hormone therapy use in the previous two years, identified from the Swedish population.

138 nested trials were designed, starting each month from July 2007 until December 2018. Using the prescription registry data for that specific month, women who had not used hormone therapy in the previous two years were assigned to one of eight treatment groups: oral combined continuous, oral combined sequential, oral unopposed oestrogen, oral oestrogen with local progestin, tibolone, transdermal combined, transdermal unopposed oestrogen, or non-initiators of menopausal hormone therapy.

Hazard ratios with 95% confidence intervals were estimated for venous thromboembolism, as well as for ischaemic heart disease, cerebral infarction, and myocardial infarction separately and as a composite cardiovascular disease outcome. Treatment effects were estimated by contrasting initiators and non-initiators in observational analogues to "intention-to-treat" analyses and continuous users versus never users in "per protocol" analyses.

A total of 77 512 women were initiators of any menopausal hormone therapy and 842 102 women were non-initiators. 24 089 women had an event recorded during the follow-up: 10 360 (43.0%) had an ischaemic heart disease event, 4098 (17.0%) had a cerebral infarction event, 4312 (17.9%) had a myocardial infarction event, and 9196 (38.2%) had a venous thromboembolic event. In intention-to-treat analyses, tibolone was associated with an increased risk of cardiovascular disease (hazard ratio 1.52, 95% confidence interval 1.11 to 2.08) compared with non-initiators. Initiators of tibolone or oral oestrogen-progestin therapy had a higher risk of ischaemic heart disease (1.46 (1.00 to 2.14) and 1.21 (1.00 to 1.46), respectively). A higher risk of venous thromboembolism was observed for oral continuous oestrogen-progestin therapy (1.61, 1.35 to 1.92), sequential therapy (2.00, 1.61 to 2.49), and oestrogen-only therapy (1.57, 1.02 to 2.44). Additional results in per protocol analyses showed that use of tibolone was associated with a higher risk of cerebral infarction (1.97, 1.02 to 3.78) and myocardial infarction (1.94, 1.01 to 3.73).

Use of oral oestrogen-progestin therapy was associated with an increased risk of heart disease and venous thromboembolism, whereas the use of tibolone was associated with an increased risk of ischaemic heart disease, cerebral infarction, and myocardial infarction but not venous thromboembolism. These findings highlight the diverse effects of different hormone combinations and administration methods on the risk of cardiovascular disease.

Previous studies have investigated cardiovascular disease (CVD) risks in cancer patients, but there is limited knowledge concerning the CVD risk in adult and young adolescent (AYA) survivors of gastric cancer.

This study aims to investigate the incidence of CVD in AYA gastric cancer survivors, analyzing it by treatment type and identifying associated risk factors.

We conducted a retrospective cohort study using Korean National Health Insurance Service data collected from 2006 to 2019. Propensity score matching (1:3, caliper < 0.1) was performed using the variables age, sex, income, residential area, and presence of comorbidities, and we classified participants into gastric cancer (n = 6562) and non-cancer control (n = 19,678) groups. Cox regression models were used to calculate hazard ratios (HRs) for CVD incidence. The study assessed CVD incidence by cancer treatment and identified risk factors through multivariable Cox regression.

During a median 6.5-year follow-up, AYA gastric cancer survivors consistently exhibited greater CVD incidence. Their risk of CVD was significantly elevated compared to that of controls (HR, 1.18; 95% confidence interval [CI] 1.05-1.33). In particular, deep vein thrombosis (HR, 3.93; 95% CI 3.06-14.67) and pulmonary embolism (HR, 6.58; 95% CI 3.06-14.67) risks were notably increased. Chemotherapy was associated with an increased risk of stroke, heart failure, atrial fibrillation, deep vein thrombosis, and pulmonary embolism. Hypertension (HR, 1.58; 95% CI 1.10-2.26) and dyslipidemia (HR, 1.46; 95% CI 1.06-2.20) emerged as risk factors for CVD development.

This study reports elevated risks of CVD in AYA gastric cancer survivors and emphasizes the need for vigilant monitoring of CVD in this population.

Colorectal cancer (CRC) ranks as the 3rd most common cancer globally and is the 2nd leading cause of cancer-related death. Owing to the lack of specific early symptoms and the limitations of existing early diagnostic methods, most patients with CRC are diagnosed at advanced stages. To overcome these challenges, researchers have increasingly focused on molecular biomarkers, with particular interest in long non-coding RNAs (lncRNAs). These non-protein-coding RNAs, which exceed 200 nucleotides in length, play critical roles in the development and progression of CRC. The stability and detectability of lncRNAs in the circulatory system make them promising candidate biomarkers. The analysis of circulating lncRNAs in peripheral blood represents a potential option for minimally invasive diagnostic tests based on liquid biopsy samples. The present review aimed to evaluate the efficacy of lncRNAs with altered expression levels in peripheral blood as diagnostic markers for CRC. Additionally, the clinical significance of lncRNAs as prognostic markers for this disease were summarized.

CRC poses a significant challenge in the global health domain, with a high number of deaths attributed to this disease annually. If CRC is detected only in its advanced stages, the difficulty of treatment increases significantly. Therefore, biomarkers for the early detection of CRC play a crucial role in improving patient outcomes and increasing survival rates. The development of a reliable biomarker for early detection of CRC is particularly important for timely diagnosis and treatment. However, current methods for CRC detection, such as endoscopic examination, blood, and stool tests, have certain limitations and often only detect cases in the late stages. To overcome these constraints, researchers have turned their attention to molecular biomarkers, which are considered a promising approach to improving CRC detection. Non-invasive methods using biomarkers such as mRNA, circulating cell-free DNA, microRNA, LncRNA, and proteins can provide more reliable diagnostic information. These biomarkers can be found in blood, tissue, stool, and volatile organic compounds. Identifying molecular biomarkers with high sensitivity and specificity for the early and safe, economic, and easily measurable detection of CRC remains a significant challenge for researchers.

Colorectal cancer guidelines recommend screening colonoscopy every 10 years after a negative procedure. If risk reduction extends past 10 years, the recommended interval could be extended, reducing the burden on the individual and health-care system. We aimed to estimate the duration that patients remain at reduced risk of colorectal cancer incidence and mortality after a complete colonoscopy.

We did a population-based cohort study of individuals aged 50-65 years between Jan 1, 1994, to Dec 31, 2017. We excluded individuals with previous exposure to colonoscopy or colorectal surgery, those previously diagnosed with colorectal cancer, or a history of hereditary or other bowel disorders. We followed up participants until Dec 31, 2018, and identified all colonoscopies performed in this time period. We used a 9-level time-varying measure of exposure, capturing time since last complete colonoscopy (no complete colonoscopy, ≤5 years, >5-10 years, >10-15 years, and >15 years) and whether an intervention was performed (biopsy or polypectomy). A Cox proportional hazards regression model adjusting for age, sex, comorbidity, residential income quintile, and immigration status was used to estimate the association between exposure to a complete colonoscopy and colorectal cancer incidence and mortality.

5 298 033 individuals (2 609 060 [49·2%] female and 2 688 973 [50·8%] male; no data on ethnicity were available) were included in the cohort, with a median follow-up of 12·56 years (IQR 6·26-20·13). 90 532 (1·7%) individuals were diagnosed with colorectal cancer and 44 088 (0·8%) died from colorectal cancer. Compared with those who did not have a colonoscopy, the risk of colorectal cancer in those who had a complete negative colonoscopy was reduced at all timepoints, including when the procedure occurred more than 15 years earlier (hazard ratio [HR] 0·62 [95% CI 0·51-0·77] for female individuals and 0·57 [0·46-0·70] for male individuals. A similar finding was observed for colorectal cancer mortality, with lower risk at all timepoints, including when the procedure occurred more than 15 years earlier (HR 0·64 [95% CI 0·49-0·83] for female participants and 0·65 [0·50-0·83] for male participants). Those who had a colonoscopy with intervention had a significantly lower colorectal cancer incidence than those who did not undergo colonoscopy if the procedure occurred within 10 years for females (HR 0·70 [95% CI 0·63-0·77]) and up to 15 years for males (0·62 [(0·53-0·72]).

Compared with those who do not receive colonoscopy, individuals who have a negative colonoscopy result remain at lower risk for colorectal cancer incidence and mortality more than 15 years after the procedure. The current recommendation of repeat screening at 10 years in these individuals should be reassessed.

Canadian Institutes of Health Research.

Currently, non-vitamin K-antagonist oral anticoagulant (NOAC) monotherapy has been suggested as the optimal antithrombotic therapy for atrial fibrillation (AF) beyond one year after coronary revascularization. The aim of this study was to compare the outcomes between NOAC monotherapy and NOAC plus antiplatelet combination therapy using real-world data.

Between 2015 and 2020, patients with AF who had received NOACs beyond one year after coronary revascularization were enrolled from Korean national insurance data. We emulated a pragmatic sequence of trials between the NOAC monotherapy and the antiplatelet combination therapy followed by propensity score matching. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke.

Among 206,407 person-trials from 4,465 individuals, we compared 3,275 pairs of the monotherapy and the matched combination therapy. During a median follow-up of 1.24 years, the incidence rate of MACCE was 19.4% and 20.0% per patient-year in the monotherapy group and the antiplatelet combination group, respectively (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88-1.05; P = 0.422). Compared with the antiplatelet combination group, the monotherapy group had a significantly lower incidence rate of major bleeding, defined as intracranial bleeding or gastrointestinal bleeding requiring hospitalization (2.8% vs. 3.6% per patient-year; HR, 0.78; 95% CI, 0.62-0.97; P = 0.024).

As an antithrombotic therapy for AF beyond one year after coronary revascularization, NOAC monotherapy was associated with a similar risk of MACCE and a lower risk of major bleeding compared to NOAC plus antiplatelet combination therapy.

Observational studies are frequently used to estimate the comparative effectiveness of different colorectal cancer (CRC) screening methods due to the practical limitations and time needed to conduct large clinical trials. However, time-varying confounders, e.g. polyp detection in the last screening, can bias statistical results. Recently, generalized methods, or G-methods, have been used for the analysis of observational studies of CRC screening, given their ability to account for such time-varying confounders. Discretization, or the process of converting continuous functions into discrete counterparts, is required for G-methods when the treatment and outcomes are assessed at a continuous scale.

This paper evaluates the interplay between time-varying confounding and discretization, which can induce bias in assessing screening effectiveness. We investigate this bias in evaluating the effect of different CRC screening methods that differ from each other in typical screening frequency.

First, using theory, we establish the direction of the bias. Then, we use simulations of hypothetical settings to study the bias magnitude for varying levels of discretization, frequency of screening and length of the study period. We develop a method to assess possible bias due to coarsening in simulated situations.

The proposed method can inform future studies of screening effectiveness, especially for CRC, by determining the choice of interval lengths where data are discretized to minimize bias due to coarsening while balancing computational costs.

No studies have reported the long-term outcomes of initiating sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with estimated glomerular filtration rates less than 20 mL/min/1.73 m2 to predialysis.

To compare the risk for dialysis, cardiovascular events, and death between SGLT2i users and nonusers in patients with type 2 diabetes (T2D) and stage 5 chronic kidney disease (CKD).

Target trial emulation study.

Taiwan's National Health Insurance Research Database (NHIRD).

By applying sequential target trial emulation principle, 23 854 SGLT2i users and 23 892 SGLT2i nonusers were selected from the NHIRD for patients with T2D and stage 5 CKD from 1 May 2016 to 31 October 2021.

Conditional Cox proportional hazards models were used to compare the risks for dialysis, hospitalization for heart failure, acute myocardial infarction (AMI), diabetic ketoacidosis (DKA), acute kidney injury (AKI), and all-cause mortality between SGLT2i users and nonusers.

In the intention-to-treat model, compared with no SGLT2i use, SGLT2i use was associated with lower risks for dialysis (hazard ratio [HR], 0.34 [95% CI, 0.27 to 0.43]), hospitalization for heart failure (HR, 0.80 [CI, 0.73 to 0.86]), AMI (HR, 0.61 [CI, 0.52 to 0.73]), DKA (HR, 0.78 [CI, 0.71 to 0.85]), and AKI (HR, 0.80 [CI, 0.70 to 0.90]), but there was no difference in the risk for all-cause mortality (HR, 1.11 [CI, 0.99 to 1.24]). The Kaplan-Meier curves and subgroup analyses also showed that initiation of an SGLT2i in stage 5 CKD was associated with a lower risk for long-term dialysis than no SGLT2i use.

This result may not apply to patients without T2D.

This emulated target trial showed that SGLT2i use was associated with a lower risk for dialysis, cardiovascular events, DKA, and AKI than no SGLT2i use in patients with T2D and stage 5 CKD.

National Health Research Institutes, Taiwan.

Few studies have evaluated the effectiveness of interventions for distress during cancer diagnosis on clinical outcomes in a real-world setting. We aimed to evaluate whether routine information and psychosocial support to patients experiencing distress at the time of diagnosis could decrease the risk of mortality within 1 and 3 years after diagnosis.

We conducted a retrospective cohort study of 4880 newly diagnosed cancer patients who reported distress scores of ≥4 using the tablet or kiosk-based screening between July 2014 and December 2017 at a university-affiliated cancer center in Seoul, South Korea. We performed an emulated target trial with two groups: those that received information and psychosocial support and those that did not. Cox proportional hazards models were used to identify the associations between information and psychosocial support and all-cause mortality.

Of all the patients, 16.6 % had routine information and psychosocial support. The hazard ratio (HR) for one-year mortality comparing participants with information and psychosocial support to those without it were 0.73 (95 % confidence interval (CI) = 0.54, 0.99). Age < 50 and 50 - <60 group had a stronger effect of information and psychosocial support on reducing mortality within one-year than these in age ≥ 60 (p for interaction = 0.03). In terms of three-year mortality, the HR comparing participants with information and psychosocial support to those without it was 0.93 (95 % CI = 0.76, 1.14).

This large-scale real-world study suggests that timely psychosocial care benefits newly diagnosed cancer patients who had distress during pre-treatment period.

Prospective benchmarking of an observational analysis against a randomized trial increases confidence in the benchmarking process as it relies exclusively on aligning the protocol of the trial and the observational analysis, while the trials findings are unavailable. The Randomized Evaluation of Decreased Usage of Betablockers After Myocardial Infarction (REDUCE-AMI, ClinicalTrials.gov ID: NCT03278509) trial started recruitment in September 2017 and results are expected in 2024. REDUCE-AMI aimed to estimate the effect of long-term use of beta blockers on the risk of death and myocardial following a myocardial infarction with preserved left ventricular systolic ejection fraction. We specified the protocol of a target trial as similar as possible to that of REDUCE-AMI, then emulated the target trial using observational data from Swedish healthcare registries. Had everyone followed the treatment strategy as specified in the target trial protocol, the observational analysis estimated a reduction in the 5-year risk of death or myocardial infarction of 0.8 percentage points for beta blockers compared with no beta blockers; effects ranging from an absolute reduction of 4.5 percentage points to an increase of 2.8 percentage points in the risk of death or myocardial infarction were compatible with our data under conventional statistical criteria. Once results of REDUCE-AMI are published, we will compare the results of our observational analysis against those from the trial. If this prospective benchmarking is successful, it supports the credibility of additional analyses using these observational data, which can rapidly deliver answers to questions that could not be answered by the initial trial. If benchmarking proves unsuccessful, we will conduct a "postmortem" analysis to identify the reasons for the discrepancy. Prospective benchmarking shifts the investigator focus away from an endeavour to use observational data to obtain similar results as a completed randomized trial, to a systematic attempt to align the design and analysis of the trial and the observational analysis.

The incidence of colorectal cancer (CRC) and preinvasive CRC (e.g., early colon cancer and advanced adenoma) is gradually increasing in several countries.

To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in Korea.

This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC, and assess the numbers of diagnostic colonoscopies and colonoscopic polypectomies. Colonoscopy-related complications by age group were also determined.

The incidence of CRC showed a rapid increase, then decreased after 2012 in the 50-75 year-age group. During the study period, the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of age. Since 2009, the increase has been rapid, showing a pattern similar to the increase in colonoscopies. The rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after 2007. The rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of age.

The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies performed. As the risk of colonoscopy-related hospitalization and death is high in the elderly, if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75, colonoscopy-related complications can be reduced for those aged 76 years or over.

Moderate to vigorous physical activity (MVPA) in patients with COPD affects their overall health outcomes, including symptom relief and improved quality of life. However, the magnitude of the effect of MVPA initiation on real-world clinical outcomes has not been well investigated.

How does MVPA initiation affect mortality and severe exacerbation in patients who have not engaged in MVPA prior to COPD diagnosis?

This study included patients with COPD aged ≥ 40 years who were not performing MVPA prior to COPD diagnosis and who had at least one health screening visit prior to and following their COPD diagnosis between January 1, 2010, and December 31, 2018. The main exposure was MVPA, defined as vigorous aerobic exercise > 20 min per day on ≥ 3 days per week or moderate aerobic exercise > 30 min per day on ≥ 5 days per week. The primary end point was all-cause mortality, and the secondary end point was initial severe exacerbation as the time to event following COPD diagnosis.

In total, 110,097 person-trials were included (27,564 MVPA increases and 82,533 control groups). No differences were observed between the covariates following matching. The adjusted hazards ratio of all-cause mortality for the MVPA group compared with the control group was 0.84 (95% CI, 0.79-0.89). In the subgroup analysis, patients aged > 65 years, female patients, those who had never smoked, and patients with a higher Charlson Comorbidity Index score displayed a stronger effect of MVPA on reducing mortality than younger male patients, those who had ever smoked, and patients with a lower Charlson Comorbidity Index score (Pinteraction < .05). The fully adjusted hazards ratio for the risk of severe exacerbation (MVPA group vs control) was 0.90 (95% CI, 0.87-0.94).

Initiation of MVPA can potentially reduce mortality and severe exacerbations in patients with COPD, although personalized interventions and further clinical trials are necessary.

Studies suggest a lower colorectal cancer (CRC) risk and lower or similar CRC screening among people with HIV (PWH) compared with the general population. We evaluated the incidence of lower endoscopy and average-onset (diagnosed at ≥50) and early-onset (diagnosed at <50) colon cancer by HIV status among Medicaid beneficiares with comparable sociodemographic factors and access to care.

We obtained Medicaid Analytic eXtract (MAX) data from 2001 to 2015 for 14 states. We included 41 727 243 and 42 062 552 unique individuals with at least 7 months of continuous eligibility for the endoscopy and colon cancer analysis, respectively. HIV and colon cancer diagnoses and endoscopy procedures were identified from inpatient and other nondrug claims. We used Cox proportional hazards regression models to assess endoscopy and colon cancer incidence, controlling for age, sex, race/ethnicity, calendar year and state of enrollment, and comorbidities conditions.

Endoscopy and colon cancer incidence increased with age in both groups. Compared with beneficiaries without HIV, PWH had an increased hazard of endoscopy; this association was strongest among those 18-39 years [hazard ratio: 1.85, 95% confidence interval (95% CI) 1.77-1.92] and attenuated with age. PWH 18-39 years also had increased hazard of early-onset colon cancer (hazard ratio: 1.66, 95% CI:1.05-2.62); this association was attenuated after comorbidity adjustment. Hazard ratios were null among all beneficiaries less than 50 years of age. PWH had a lower hazard of average-onset colon cancer compared with those without HIV (hazard ratio: 0.79, 95% CI: 0.66-0.94).

PWH had a higher hazard of endoscopy, particularly at younger ages. PWH had a lower hazard of average-onset colon cancer. Early-onset colon cancer was higher among the youngest PWH but not associated with HIV overall.

CRC is a major global health concern and is responsible for a significant number of cancer-related deaths each year. The successful treatment of CRC becomes more difficult when it goes undetected until it has advanced to a later stage. Diagnostic biomarkers can play a critical role in the early detection of CRC, which leads to improved patient outcomes and increased survival rates. It is important to develop reliable biomarkers for the early detection of CRC to enable timely diagnosis and treatment. To date, CRC detection methods such as endoscopy, blood, and stool tests are imperfect and often only identify cases in the later stages of the disease. To overcome these limitations, researchers are turning to molecular biomarkers as a promising avenue for improving CRC detection. Diagnostic information can be provided more reliably through a noninvasive approach using biomarkers such as mRNA, circulating cell-free DNA, micro-RNA, long non-coding RNA, and proteins. These biomarkers can be found in blood, tissue, feces, and volatile organic compounds. The identification of molecular biomarkers with high sensitivity and specificity for early detection of CRC that are safe, cost-effective, and easily measurable remains a significant challenge for researchers. In this article, we will explore the latest advancements in blood-based diagnostic biomarkers for CRC and their potential impact on improving patient survival rates.

Since the early 2000s, there has been a rapid decline in colorectal cancer (CRC) mortality, due in large part to screening and removal of precancerous polyps. Despite these improvements, CRC remains the second leading cause of cancer deaths in the United States, with approximately 53,000 deaths projected in 2023. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to describe how individuals should be risk-stratified for CRC screening and post-polypectomy surveillance and to highlight opportunities for future research to fill gaps in the existing literature.

This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: All individuals with a first-degree relative (defined as a parent, sibling, or child) who was diagnosed with CRC, particularly before the age of 50 years, should be considered at increased risk for CRC. BEST PRACTICE ADVICE 2: All individuals without a personal history of CRC, inflammatory bowel disease, hereditary CRC syndromes, other CRC predisposing conditions, or a family history of CRC should be considered at average risk for CRC. BEST PRACTICE ADVICE 3: Individuals at average risk for CRC should initiate screening at age 45 years and individuals at increased risk for CRC due to having a first-degree relative with CRC should initiate screening 10 years before the age at diagnosis of the youngest affected relative or age 40 years, whichever is earlier. BEST PRACTICE ADVICE 4: Risk stratification for initiation of CRC screening should be based on an individual's age, a known or suspected predisposing hereditary CRC syndrome, and/or a family history of CRC. BEST PRACTICE ADVICE 5: The decision to continue CRC screening in individuals older than 75 years should be individualized, based on an assessment of risks, benefits, screening history, and comorbidities. BEST PRACTICE ADVICE 6: Screening options for individuals at average risk for CRC should include colonoscopy, fecal immunochemical test, flexible sigmoidoscopy plus fecal immunochemical test, multitarget stool DNA fecal immunochemical test, and computed tomography colonography, based on availability and individual preference. BEST PRACTICE ADVICE 7: Colonoscopy should be the screening strategy used for individuals at increased CRC risk. BEST PRACTICE ADVICE 8: The decision to continue post-polypectomy surveillance for individuals older than 75 years should be individualized, based on an assessment of risks, benefits, and comorbidities. BEST PRACTICE ADVICE 9: Risk-stratification tools for CRC screening and post-polypectomy surveillance that emerge from research should be examined for real-world effectiveness and cost-effectiveness in diverse populations (eg, by race, ethnicity, sex, and other sociodemographic factors associated with disparities in CRC outcomes) before widespread implementation.

Despite recommendations for universal screening, adherence to colorectal cancer screening in the US is approximately 60%. Liquid biopsy tests are in development for cancer early detection, but it is unclear whether they are cost-effective for colorectal cancer screening.

To estimate the cost-effectiveness of liquid biopsy for colorectal cancer screening in the US.

In this economic evaluation, a Markov model was developed to compare no screening and 5 colorectal cancer screening strategies: colonoscopy, liquid biopsy, liquid biopsy following nonadherence to colonoscopy, stool DNA, and fecal immunochemical test. Adherence to first-line screening with colonoscopy, stool DNA, or fecal immunochemical test was assumed to be 60.6%, and adherence for liquid biopsy was assumed to be 100%. For colonoscopy, stool DNA, and fecal immunochemical test, patients who did not adhere to testing were not offered other screening. In colonoscopy-liquid biopsy hybrid, liquid biopsy was second-line screening for those who deferred colonoscopy. Scenario analyses were performed to include the possibility of polyp detection for liquid biopsy.

No screening, colonoscopy, fecal immunochemical test, stool DNA, liquid biopsy, and colonoscopy-liquid biopsy hybrid screening.

Model outcomes included life expectancy, total cost, and incremental cost-effectiveness ratios. A strategy was considered cost-effective if it had an incremental cost-effectiveness ratio less than the US willingness-to-pay threshold of $100 000 per life-year gained.

This study used a simulated cohort of patients aged 45 years with average risk of colorectal cancer. In the base case, colonoscopy was the preferred, or cost-effective, strategy with an incremental cost-effectiveness ratio of $28 071 per life-year gained. Colonoscopy-liquid biopsy hybrid had the greatest gain in life-years gained but had an incremental cost-effectiveness ratio of $377 538. Colonoscopy-liquid biopsy hybrid had a greater gain in life-years if liquid biopsy could detect polyps but remained too costly.

In this economic evaluation of liquid biopsy for colorectal cancer screening, colonoscopy was a cost-effective strategy for colorectal cancer screening in the general population, and the inclusion of liquid biopsy as a first- or second-line screening strategy was not cost-effective at its current cost and screening performance. Liquid biopsy tests for colorectal cancer screening may become cost-effective if their cost is substantially lowered.

No randomized controlled trials have been completed to see whether statin can decrease hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. We used large-scale, population-based, observational data to emulate a target trial with two groups, statin user and statin non-user.

Among 1,379,708 nonunique individuals from the Korean National Health Insurance Service data, 2,915 CHB patients with serum cholesterol level of 200 mg/dL or higher who started statin therapy and 8,525 propensity-score matched CHB patients with serum cholesterol level of 200 mg/dL or higher who did not start statin therapy were analyzed for the development of HCC. In addition, liver cancer or liver-related mortality and all-cause mortality were assessed.

During follow-up, 207 participants developed HCC. Incidence rate of HCC was 0.2 per 1,000 person-years in the statin user group and 0.3 per 1,000 person-years in the statin non-user group. Fully adjusted hazard ratio (HR) for incident HCC comparing statin user group to statin nonuser group was 0.56 (95% confidence interval [CI]: 0.39 to 0.80). The association between statin use and decreased HCC risk was consistent in all subgroups analyzed. Fully adjusted HR comparing statin user to statin nonuser was 0.59 (95% CI: 0.35 to 0.99) for liver cancer or liver-related mortality and 0.93 (95% CI: 0.78 to 1.11) for all-cause mortality.

Statin might have a benefit for preventing HCC in CHB patients with elevated cholesterol levels. Statin should be actively considered for CHB patients with dyslipidemia.

Colonoscopy is the cornerstone examination for colorectal cancer (CRC) screening and it is recommended as the first examination in the context of individuals with high risk of CRC development. Thereby, this examination is of choice in the setting of patients with hereditary CRC syndromes or in patients with long-standing inflammatory bowel disease with colon involvement. However, its role is less clear in the average risk-risk population and in patients with family history of CRC not linked to hereditary CRC syndromes. Despite this, current guidelines, include colonoscopy as alternative for CRC screening either in average risk population with the same evidence level that other screening strategies or in the familial risk population. The present manuscript reviews the clinical evidence on the role of colonoscopy in preventing CRC in different screening settings.

We aim to investigate the implementation of Target Trial Emulation (TTE) for causal inference, involving research topics, frequently used strategies, and issues indicating the need for future improvements.

We performed a scoping review by following the Joanna Briggs Institute (JBI) guidance and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. A health research-focused librarian searched multiple medical databases, and two independent reviewers completed screening and extraction within covidence review management software.

Our search resulted in 1,240 papers, of which 96 papers were eligible for data extraction. Results show a significant increase in the use of TTE in 2018 and 2021. The study topics varied and focused primarily on cancer, cardiovascular and cerebrovascular diseases, and infectious diseases. However, not all papers specified well all three critical components for generating robust causal evidence: time-zero, random assignment simulation, and comparison strategy. Some common issues were observed from retrieved papers, and key limitations include residual confounding, limited generalizability, and a lack of reporting guidance that need to be improved.

Uneven adherence to the TTE framework exists, and future improvements are needed to progress applications using causal inference with observational data.

Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.

The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.

Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.

Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.

To assess the reporting of observational studies that explicitly aimed to emulate a target trial.

We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation.

A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation.

In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.