Critical appraisal and assessment of bias among studies evaluating risk prediction models for in-hospital and 30-day mortality after percutaneous coronary intervention: a systematic review.

OBJECTIVE: We systematically assessed prediction models for the risk of in-hospital and 30-day mortality in post-percutaneous coronary intervention (PCI) patients. DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Searched PubMed, Web of Science, Embase, Cochrane Library, CINAHL, CNKI, Wanfang Database, VIP Database and SinoMed for literature up to 31 August 2023. ELIGIBILITY CRITERIA: The included literature consists of studies in Chinese or English involving PCI patients aged ≥18 years. These studies aim to develop risk prediction models and include designs such as cohort studies, case-control studies, cross-sectional studies or randomised controlled trials. Each prediction model must contain at least two predictors. Exclusion criteria encompass models that include outcomes other than death post-PCI, literature lacking essential details on study design, model construction and statistical analysis, models based on virtual datasets, and publications such as conference abstracts, grey literature, informal publications, duplicate publications, dissertations, reviews or case reports. We also exclude studies focusing on the localisation applicability of the model or comparative effectiveness. DATA EXTRACTION AND SYNTHESIS: Two independent teams of researchers developed standardised data extraction forms based on CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies to extract and cross-verify data. They used Prediction model Risk Of Bias Assessment Tool (PROBAST) to assess the risk of bias and applicability of the model development or validation studies included in this review. RESULTS: This review included 28 studies with 38 prediction models, showing area under the curve values ranging from 0.81 to 0.987. One study had an unclear risk of bias, while 27 studies had a high risk of bias, primarily in the area of statistical analysis. The models constructed in 25 studies lacked clinical applicability, with 21 of these studies including intraoperative or postoperative predictors. CONCLUSION: The development of in-hospital and 30-day mortality prediction models for post-PCI patients is in its early stages. Emphasising clinical applicability and predictive stability is vital. Future research should follow PROBAST's low risk-of-bias guidelines, prioritising external validation for existing models to ensure reliable and widely applicable clinical predictions. PROSPERO REGISTRATION NUMBER: CRD42023477272.

Evaluation and Assessment of the ABATE Framework to Enhance Implicit Bias Training for Virtual Interviews in Medical Schools.

Introduction: The influence of implicit biases in virtual interviews must be addressed to ensure equity within the admissions process. ABATE is a mnemonic framework of five specific categories of implicit bias (affinity-based, backdrop-based, appearance-based, technology and media-based, and enunciation-based biases) that should be anticipated and mitigated for faculty, staff, health professionals, and medical students who conduct virtual interviews at medical schools. Methods: A 60-minute workshop was developed to educate medical school admissions interviewers about the ABATE model and strategies to mitigate implicit bias during virtual interviews. Four workshops were held over 1 year totaling 217 individual attendees. The workshops were evaluated using a single-group, pre-post questionnaire designed with the Kirkpatrick evaluation model. Results: Attendees reported that they found the ABATE workshop useful and relevant to improving their ability to minimize implicit bias during virtual interviews. Significant improvements were found in attendee reactions to the utility of implicit bias training (M pre = 2.6, M post = 3.1, p = .002). Significant changes were also reported in attendees' attitudes about interviewing confidence (M pre = 3.0, M post = 3.2, p = .04), bias awareness (M pre = 3.0, M post = 3.4, p = .002), and identifying and applying bias mitigation solutions (M pre = 2.5, M post = 3.0, p = .003). Knowledge specific to backdrop-based biases also significantly increased (M pre = 3.2, M post = 3.4, p = .04). Discussion: The ABATE workshop demonstrates promise in mitigating implicit bias in virtual medical school interviews.

[Epidemiological signatures and surveillance bias in cancer]. / Signatures épidémiologiques et biais de surveillance du cancer.

Surveillance bias occurs when variations in cancer incidence are the result of changes in screening or diagnostic practices rather than increases in the true occurrence of cancer. This bias is linked to the issue of overdiagnosis and can be apprehended by looking at epidemiological signatures of cancer. We explain the concept of epidemiological signatures using the examples of melanoma and of lung and prostate cancer. Accounting for surveillance bias is particularly important for assessing the true burden of cancer and for accurately communicating cancer information to the population and decision-makers.

Le biais de surveillance se produit lorsque les variations d'incidence d'un cancer sont le résultat d'un changement dans les pratiques de dépistage ou de diagnostic plutôt que d'une augmentation de la fréquence réelle de ce cancer. Ce biais est lié au concept du surdiagnostic et peut être appréhendé en examinant les signatures épidémiologiques des cancers. Nous expliquons le concept de signature épidémiologique à l'aide des exemples du mélanome et des cancers du poumon et de la prostate. La prise en compte des biais de surveillance est particulièrement importante pour évaluer le fardeau réel du cancer et communiquer avec précision l'information sur le cancer à la population et aux décideurs.

Does chubby can get lower grades than skinny Sophie? Using an intersectional approach to uncover grading bias in German secondary schools.

We aim to uncover grading bias by gender, socio-economic status, ethnic/migration background as well as body weight in the German secondary school system. Following an intersectional approach, we test whether-controlling for ability-students receive different grades depending on (the specific combination of) ascriptive characteristics. Using data from the fourth starting cohort (SC4, 13.0.0, first survey in year 9 in 2010) of the National Educational Panel Study (NEPS) consisting of more than 14,000 ninth graders, we compute the predicted differences in grades for the different groups of students depending on whether they are a boy or a girl, whether they are obese/overweight or not, their socio-economic status (SES) and ethnic background. We rely on a grade equation approach, assuming that discrepancies between observed grades and achievement as measured in standardised tests are evidence of biased grading. We control for two different competence tests-the Domain General Cognitive Functions (DGCF) and a standardised domain-specific competence test-as objective measures of ability as well as secondary school track. Even after controlling for different personality and behavioural traits-the "big five", the Strengths and Difficulties Questionnaire (SDQ), the Sick, Control, One, Fat and Food (SCOFF), health satisfaction and class retention-substantial differentials in grading across almost all factors and subjects remain. To account for the fact that many students may face bias on multiple grounds, we then compare the differences in predicted grades for groups with overlapping (dis)advantaging characteristics (e.g. low SES overweight Turkish boy vs a high SES non-overweight majority girl), while controlling for the objective ability measures. Significant differentials in grades are found in almost all cases, with the largest effect sizes for the subject German. We also compute models including all 2-way or 4-way interactions between the four axes of inequality and find the main effects largely unchanged. On the whole our findings are indicative of widespread additive intersectional effects of gender, social and ethnic origin as well as body weight on grading bias.

Preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery.

BACKGROUND: Postoperative myocardial infarction (POMI) is associated with major surgeries and remains the leading cause of mortality and morbidity in people undergoing vascular surgery, with an incidence rate ranging from 5% to 20%. Preoperative coronary interventions, such as coronary artery bypass grafting (CABG) or percutaneous coronary interventions (PCI), may help prevent acute myocardial infarction in the perioperative period of major vascular surgery when used in addition to routine perioperative drugs (e.g. statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents), CABG by creating new blood circulation routes that bypass the blockages in the coronary vessels, and PCI by opening up blocked blood vessels. There is currently uncertainty around the benefits and harms of preoperative coronary interventions. OBJECTIVES: To assess the effects of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery. SEARCH METHODS: We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, and CINAHL EBSCO on 13 March 2023. We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs that compared the use of preoperative coronary interventions plus usual care versus usual care for preventing acute myocardial infarction during major open vascular or endovascular surgery. We included participants of any sex or any age undergoing major open vascular surgery, major endovascular surgery, or hybrid vascular surgery. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes of interest were acute myocardial infarction, all-cause mortality, and adverse events resulting from preoperative coronary interventions. Our secondary outcomes were cardiovascular mortality, quality of life, vessel or graft secondary patency, and length of hospital stay. We reported perioperative and long-term outcomes (more than 30 days after intervention). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included three RCTs (1144 participants). Participants were randomised to receive either preoperative coronary revascularisation with PCI or CABG plus usual care or only usual care before major vascular surgery. One trial enrolled participants if they had no apparent evidence of coronary artery disease. Another trial selected participants classified as high risk for coronary disease through preoperative clinical and laboratorial testing. We excluded one trial from the meta-analysis because participants from both the control and the intervention groups were eligible to undergo preoperative coronary revascularisation. We identified a high risk of performance bias in all included trials, with one trial displaying a high risk of other bias. However, the risk of bias was either low or unclear in other domains. We observed no difference between groups for perioperative acute myocardial infarction, but the evidence is very uncertain (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.02 to 4.57; 2 trials, 888 participants; very low-certainty evidence). One trial showed a reduction in incidence of long-term (> 30 days) acute myocardial infarction in participants allocated to the preoperative coronary interventions plus usual care group, but the evidence was very uncertain (RR 0.09, 95% CI 0.03 to 0.28; 1 trial, 426 participants; very low-certainty evidence). There was little to no effect on all-cause mortality in the perioperative period when comparing the preoperative coronary intervention plus usual care group to usual care alone, but the evidence is very uncertain (RR 0.79, 95% CI 0.31 to 2.04; 2 trials, 888 participants; very low-certainty evidence). The evidence is very uncertain about the effect of preoperative coronary interventions on long-term (follow up: 2.7 to 6.2 years) all-cause mortality (RR 0.74, 95% CI 0.30 to 1.80; 2 trials, 888 participants; very low-certainty evidence). One study reported no adverse effects related to coronary angiography, whereas the other two studies reported five deaths due to revascularisations. There may be no effect on cardiovascular mortality when comparing preoperative coronary revascularisation plus usual care to usual care in the short term (RR 0.07, 95% CI 0.00 to 1.32; 1 trial, 426 participants; low-certainty evidence). Preoperative coronary interventions plus usual care in the short term may reduce length of hospital stay slightly when compared to usual care alone (mean difference -1.17 days, 95% CI -2.05 to -0.28; 1 trial, 462 participants; low-certainty evidence). We downgraded the certainty of the evidence due to concerns about risk of bias, imprecision, and inconsistency. None of the included trials reported on quality of life or vessel graft patency at either time point, and no study reported on adverse effects, cardiovascular mortality, or length of hospital stay at long-term follow-up. AUTHORS' CONCLUSIONS: Preoperative coronary interventions plus usual care may have little or no effect on preventing perioperative acute myocardial infarction and reducing perioperative all-cause mortality compared to usual care, but the evidence is very uncertain. Similarly, limited, very low-certainty evidence shows that preoperative coronary interventions may have little or no effect on reducing long-term all-cause mortality. There is very low-certainty evidence that preoperative coronary interventions plus usual care may prevent long-term myocardial infarction, and low-certainty evidence that they may reduce length of hospital stay slightly, but not cardiovascular mortality in the short term, when compared to usual care alone. Adverse effects of preoperative coronary interventions were poorly reported in trials. Quality of life and vessel or graft patency were not reported. We downgraded the certainty of the evidence most frequently for high risk of bias, inconsistency, or imprecision. None of the analysed trials provided significant data on subgroups of patients who could potentially experience more substantial benefits from preoperative coronary intervention (e.g. altered ventricular ejection fraction). There is a need for evidence from larger and homogeneous RCTs to provide adequate statistical power to assess the role of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery.

Cognitive behavioural therapy and third-wave approaches for anxiety and related disorders in older people.

BACKGROUND: Cognitive behavioural therapy (CBT) is the most researched psychological therapy for anxiety disorders in adults, and known to be effective in this population. However, it remains unclear whether these results apply to older adults, as most studies include participants between 18 and 55 years of age. This systematic review aims to provide a comprehensive and up-to-date synthesis of the available evidence on CBT and third wave approaches for older adults with anxiety and related disorders. OBJECTIVES: To assess the effects of Cognitive Behavioural Therapy (CT, BT, CBT and third-wave CBT interventions) on severity of anxiety symptoms compared with minimal management (not providing therapy) for anxiety and related disorders in older adults, aged 55 years or over. To assess the effects of CBT and related therapies on severity of anxiety symptoms compared with other psychological therapies for anxiety and related disorders in older adults, aged 55 years or over. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled studies Register (CCMDCTR), CENTRAL, Ovid MEDLINE, Ovid Embase and Ovid PsycINFO to 21 July 2022. These searches were updated on 2 February 2024. We also searched the international studies registries, including Clinicalstudies.gov and the WHO International Clinical Trials Registry Platform (ICTRP), to identify additional ongoing and unpublished studies. These sources were manually searched for studies up to 12 February 2024. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in older adults (≥ 55 years) with an anxiety disorder, or a related disorder, including obsessive compulsive disorder (OCD), acute stress disorder and post-traumatic stress disorder (PTSD), that compared CBT to either minimal management or an active (non-CBT) psychological therapy. Eligible studies had to have an anxiety-related outcome. DATA COLLECTION AND ANALYSIS: Several authors independently screened all titles identified by the searches. All full texts were screened for eligibility according to our prespecified selection criteria. Data were extracted and the risk of bias was assessed using the Cochrane tool for RCTs. The certainty of evidence was evaluated using GRADE. Meta-analyses were performed for outcomes with quantitative data from more than one study. MAIN RESULTS: We included 21 RCTs on 1234 older people allocated to either CBT or control conditions. Ten studies focused on generalised anxiety disorder; others mostly included a mix of clinical diagnoses. Nineteen studies focused on the comparison between CBT and minimal management. Key issues relating to risk of bias were lack of blinding of participants and personnel, and participants dropping out of studies, potentially due to treatment preference and allocation. CBT may result in a small-to-moderate reduction of anxiety post-treatment (SMD -0.51, 95% CI -0.66 to -0.36, low-certainty evidence). However, compared to this benefit with CBT immediately after treatment, at three to six months post-treatment, there was little to no difference between CBT and minimal management (SMD -0.29, 95% CI -0.59 to 0.01, low-certainty evidence). CBT may have little or no effect on clinical recovery/ improvement post-treatment compared to minimal management, but the evidence is very uncertain (RR 1.56, 95% CI 1.20 to 2.03, very low-certainty evidence). Results indicate that five people would need to receive treatment for one additional person to benefit (NNTB = 5). Compared to minimal management, CBT may result in a reduction of comorbid depression symptoms post-treatment (SMD -0.57, 95% CI -0.74 to -0.40, low-certainty evidence). There was no difference in dropout rates post-treatment, although the certainty of the evidence was low (RR 1.19, 95% CI 0.80 to 1.78). Two studies reported adverse events, both of which related to medication in the control groups (very low-certainty evidence, no quantitative estimate). Only two studies compared CBT to other psychological therapies, both of which only included participants with post-traumatic stress disorder. Low-certainty evidence showed no difference in anxiety severity post-treatment and at four to six months post-treatment, symptoms of depression post-treatment, and dropout rates post-treatment. Other outcomes and time points are reported in the results section of the manuscript. AUTHORS' CONCLUSIONS: CBT may be more effective than minimal management in reducing anxiety and symptoms of worry and depression post-treatment in older adults with anxiety disorders. The evidence is less certain longer-term and for other outcomes including clinical recovery/improvement. There is not enough evidence to determine whether CBT is more effective than alternative psychological therapies for anxiety in older adults.

Reverse causation bias: A simulation study comparing first- and second-line treatments with an overlap of symptoms between treatment indication and studied outcome.

BACKGROUND: Reverse causation is a challenge in many drug-cancer associations, where the cancer symptoms are potentially mistaken for drug indication symptoms. However, tools to assess the magnitude of this type of bias are currently lacking. We used a simulation-based approach to investigate the impact of reverse causation on the association between the use of topical tacrolimus and cutaneous T-cell lymphoma (CTCL) in a multinational, population-based study using topical corticosteroids (TCS) as comparator. METHODS: We used a multistate model to simulate patients' use over time of a first- (TCS) and second-line treatment (topical tacrolimus), onset of atopic dermatitis (indication for drugs) and CTCL (the studied outcome). We simulated different scenarios to mimic real-life use of the two treatments. In all scenarios, it was assumed that there was no causal effect of the first- or second-line treatment on the occurrence of CTCL. Simulated data were analysed using Cox proportional hazards models. RESULTS: The simulated hazard ratios (HRs) of CTCL for patients treated with tacrolimus vs. TCS were consistently above 1 in all 9 settings in the main scenario. In our main analysis, we observed a median HR of 3.09 with 95% of the observed values between 2.11 and 4.69. CONCLUSIONS: We found substantial reverse causation bias in the simulated CTCL risk estimates for patients treated with tacrolimus vs. TCS. Reverse causation bias may result in a false positive association between the second-line treatment and the studied outcome, and this simulation-based framework can be adapted to quantify the potential reverse causation bias.

A global survey of the attitudes and perspectives of cognitive bias in forensic anthropology.

It is now well established that decision making can be susceptible to cognitive bias in a broad range of fields, with forensic science being no exception. Previously published research has revealed a bias blind spot in forensic science where examiners do not recognise bias within their own domain. A survey of 101 forensic anthropology practitioners (n = 52) and students (n = 38) was undertaken to assess their level of awareness of cognitive bias and investigate their attitudes towards cognitive bias within forensic anthropology. The results revealed that the forensic anthropology community (∼90%) had a high level of awareness of cognitive bias. Overall ∼89% expressed concerns about cognitive bias in the broad discipline of forensic science, their own domain of forensic anthropology, and in the evaluative judgments they made in reconstruction activities, identifying a significant reduction in the bias blind spot. However, more than half of the participants believed that bias can be reduced by sheer force of will, and there was a lack of consensus about implementing blinding procedures or context management. These findings highlight the need to investigate empirically the feasibility of proposed mitigating strategies within the workflow of forensic anthropologists and their capabilities for increasing the transparency in decision making.

Contextual bias by Forensic Document Examination trainees: An empirical study from China.

The impact of contextual bias has been repeatedly demonstrated across forensic domains; however, research on this topic in China is scarce. To examine the prevalence of contextual bias in pattern feature-comparison disciplines, we conducted an experiment involving 24 forensic document examination students. The aim was to determine whether knowledge of different contextual information influenced their forensic decision-making. Participants were divided into different context groups and tasked with examining whether questioned signatures with ambiguous features matched reference signatures. The results of independent-samples t-tests for their decision score data in the two context groups exhibited a statistically significant difference (p < 0.05, Cohen's d > 0.8). Moreover, the submitted forensic reports by participants disclosed a biased evaluation of handwriting features. These findings show how contextual information can bias forensic decision-making in handwriting examination. Context management with complementary strategies such as case triage, cognitive training and decision-making transparency must be implemented to minimize bias in handwriting examination.

Strategies for cessation of caffeine administration in preterm infants.

BACKGROUND: Apnea and intermittent hypoxemia (IH) are common developmental disorders in infants born earlier than 37 weeks' gestation. Caffeine administration has been shown to lower the incidence of these disorders in preterm infants. Cessation of caffeine treatment is based on different post-menstrual ages (PMA) and resolution of symptoms. There is uncertainty about the best timing for caffeine discontinuation. OBJECTIVES: To evaluate the effects of early versus late discontinuation of caffeine administration in preterm infants. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, and three trial registries in August 2023; we applied no date limits. We checked the references of included studies and related systematic reviews. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in preterm infants born earlier than 37 weeks' gestation, up to a PMA of 44 weeks and 0 days, who received caffeine for any indication for at least seven days. We compared three different strategies for caffeine cessation: 1. at different PMAs, 2. before or after five days without symptoms, and 3. at a predetermined PMA versus at the resolution of symptoms. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Primary outcomes were: restarting caffeine therapy, intubation within one week of treatment discontinuation, and the need for non-invasive respiratory support within one week of treatment discontinuation. Secondary outcomes were: number of episodes of apnea in the seven days after treatment discontinuation, number of infants with at least one episode of apnea in the seven days after treatment discontinuation, number of episodes of intermittent hypoxemia (IH) within seven days of treatment discontinuation, number of infants with at least one episode of IH in the seven days after of treatment discontinuation, all-cause mortality prior to hospital discharge, major neurodevelopmental disability, number of days of respiratory support after treatment discontinuation, duration of hospital stay, and cost of neonatal care. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included three RCTs (392 preterm infants). Discontinuation of caffeine at PMA less than 35 weeks' gestation versus PMA equal to or longer than 35 weeks' gestation This comparison included one single completed RCT with 98 premature infants with a gestational age between 25 + 0 and 32 + 0 weeks at birth. All infants had discontinued caffeine treatment for five days at randomization. The infants received either an oral loading dose of caffeine citrate (20 mg/kg) at randomization followed by oral maintenance dosage (6 mg/kg/day) until 40 weeks PMA, or usual care (controls), during which caffeine was stopped before 37 weeks PMA. Early cessation of caffeine administration in preterm infants at PMA less than 35 weeks' gestation may result in an increase in the number of IH episodes in the seven days after discontinuation of treatment, compared to prolonged caffeine treatment beyond 35 weeks' gestation (mean difference [MD] 4.80, 95% confidence interval [CI] 2.21 to 7.39; 1 RCT, 98 infants; low-certainty evidence). Early cessation may result in little to no difference in all-cause mortality prior to hospital discharge compared to late discontinuation after 35 weeks PMA (risk ratio [RR] not estimable; 98 infants; low-certainty evidence). No data were available for the following outcomes: restarting caffeine therapy, intubation within one week of treatment discontinuation, need for non-invasive respiratory support within one week of treatment discontinuation, number of episodes of apnea, number of infants with at least one episode of apnea in the seven days after discontinuation of treatment, or number of infants with at least one episode of IH in the seven days after discontinuation of treatment. Discontinuation based on PMA versus resolution of symptoms This comparison included two RCTs with a total of 294 preterm infants. Discontinuing caffeine at the resolution of symptoms compared to discontinuing treatment at a predetermined PMA may result in little to no difference in all-cause mortality prior to hospital discharge (RR 1.00, 95% CI 0.14 to 7.03; 2 studies, 294 participants; low-certainty evidence), or in the number of infants with at least one episode of apnea within the seven days after discontinuing treatment (RR 0.60, 95% CI 0.31 to 1.18; 2 studies; 294 infants; low-certainty evidence). Discontinuing caffeine based on the resolution of symptoms probably results in more infants with IH in the seven days after discontinuation of treatment (RR 0.38, 95% CI 0.20 to 0.75; 1 study; 174 participants; moderate-certainty evidence). No data were available for the following outcomes: restarting caffeine therapy, intubation within one week of treatment discontinuation, need for non-invasive respiratory support within one week of treatment discontinuation, or number of episodes of IH in the seven days after treatment discontinuation. Adverse effects In the Rhein 2014 study, five of the infants randomized to caffeine had the caffeine treatment discontinued at the discretion of the clinical team, because of tachycardia. The Pradhap 2023 study reported adverse events, including recurrence of apnea of prematurity (15% in the short and 13% in the regular course caffeine therapy group), varying severities of bronchopulmonary dysplasia, hyperglycemia, extrauterine growth restriction, retinopathy of prematurity requiring laser treatment, feeding intolerance, osteopenia, and tachycardia, with no significant differences between the groups. The Prakash 2021 study reported that adverse effects of caffeine therapy for apnea of prematurity included tachycardia, feeding intolerance, and potential neurodevelopmental impacts, though most were mild and transient. We identified three ongoing studies. AUTHORS' CONCLUSIONS: There may be little or no difference in the incidence of all-cause mortality and apnea in infants who were randomized to later discontinuation of caffeine treatment. However, the number of infants with at least one episode of IH was probably reduced with later cessation. No data were found to evaluate the benefits and harms of later caffeine discontinuation for: restarting caffeine therapy, intubation within one week of treatment discontinuation, or need for non-invasive respiratory support within one week of treatment discontinuation. Further studies are needed to evaluate the short-term and long-term effects of different caffeine cessation strategies in premature infants.

A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data.

BACKGROUND: CRISPR-Cas9 dropout screens are formidable tools for investigating biology with unprecedented precision and scale. However, biases in data lead to potential confounding effects on interpretation and compromise overall quality. The activity of Cas9 is influenced by structural features of the target site, including copy number amplifications (CN bias). More worryingly, proximal targeted loci tend to generate similar gene-independent responses to CRISPR-Cas9 targeting (proximity bias), possibly due to Cas9-induced whole chromosome-arm truncations or other genomic structural features and different chromatin accessibility levels. RESULTS: We benchmarked eight computational methods, rigorously evaluating their ability to reduce both CN and proximity bias in the two largest publicly available cell-line-based CRISPR-Cas9 screens to date. We also evaluated the capability of each method to preserve data quality and heterogeneity by assessing the extent to which the processed data allows accurate detection of true positive essential genes, established oncogenetic addictions, and known/novel biomarkers of cancer dependency. Our analysis sheds light on the ability of each method to correct biases under different scenarios. AC-Chronos outperforms other methods in correcting both CN and proximity biases when jointly processing multiple screens of models with available CN information, whereas CRISPRcleanR is the top performing method for individual screens or when CN information is not available. In addition, Chronos and AC-Chronos yield a final dataset better able to recapitulate known sets of essential and non-essential genes. CONCLUSIONS: Overall, our investigation provides guidance for the selection of the most appropriate bias-correction method, based on its strengths, weaknesses and experimental settings.

Haloperidol (oral) versus olanzapine (oral) for people with schizophrenia and schizophrenia-spectrum disorders.

BACKGROUND: Schizophrenia is often a severe and disabling psychiatric disorder. Antipsychotics remain the mainstay of psychotropic treatment for people with psychosis. In limited resource and humanitarian contexts, it is key to have several options for beneficial, low-cost antipsychotics, which require minimal monitoring. We wanted to compare oral haloperidol, as one of the most available antipsychotics in these settings, with a second-generation antipsychotic, olanzapine. OBJECTIVES: To assess the clinical benefits and harms of haloperidol compared to olanzapine for people with schizophrenia and schizophrenia-spectrum disorders. SEARCH METHODS: We searched the Cochrane Schizophrenia study-based register of trials, which is based on monthly searches of CENTRAL, CINAHL, ClinicalTrials.gov, Embase, ISRCTN, MEDLINE, PsycINFO, PubMed and WHO ICTRP. We screened the references of all included studies. We contacted relevant authors of trials for additional information where clarification was required or where data were incomplete. The register was last searched on 14 January 2023. SELECTION CRITERIA: Randomised clinical trials comparing haloperidol with olanzapine for people with schizophrenia and schizophrenia-spectrum disorders. Our main outcomes of interest were clinically important change in global state, relapse, clinically important change in mental state, extrapyramidal side effects, weight increase, clinically important change in quality of life and leaving the study early due to adverse effects. DATA COLLECTION AND ANALYSIS: We independently evaluated and extracted data. For dichotomous outcomes, we calculated risk ratios (RR) and their 95% confidence intervals (CI) and the number needed to treat for an additional beneficial or harmful outcome (NNTB or NNTH) with 95% CI. For continuous data, we estimated mean differences (MD) or standardised mean differences (SMD) with 95% CIs. For all included studies, we assessed risk of bias (RoB 1) and we used the GRADE approach to create a summary of findings table. MAIN RESULTS: We included 68 studies randomising 9132 participants. We are very uncertain whether there is a difference between haloperidol and olanzapine in clinically important change in global state (RR 0.84, 95% CI 0.69 to 1.02; 6 studies, 3078 participants; very low-certainty evidence). We are very uncertain whether there is a difference between haloperidol and olanzapine in relapse (RR 1.42, 95% CI 1.00 to 2.02; 7 studies, 1499 participants; very low-certainty evidence). Haloperidol may reduce the incidence of clinically important change in overall mental state compared to olanzapine (RR 0.70, 95% CI 0.60 to 0.81; 13 studies, 1210 participants; low-certainty evidence). For every eight people treated with haloperidol instead of olanzapine, one fewer person would experience this improvement. The evidence suggests that haloperidol may result in a large increase in extrapyramidal side effects compared to olanzapine (RR 3.38, 95% CI 2.28 to 5.02; 14 studies, 3290 participants; low-certainty evidence). For every three people treated with haloperidol instead of olanzapine, one additional person would experience extrapyramidal side effects. For weight gain, the evidence suggests that there may be a large reduction in the risk with haloperidol compared to olanzapine (RR 0.47, 95% CI 0.35 to 0.61; 18 studies, 4302 participants; low-certainty evidence). For every 10 people treated with haloperidol instead of olanzapine, one fewer person would experience weight increase. A single study suggests that haloperidol may reduce the incidence of clinically important change in quality of life compared to olanzapine (RR 0.72, 95% CI 0.57 to 0.91; 828 participants; low-certainty evidence). For every nine people treated with haloperidol instead of olanzapine, one fewer person would experience clinically important improvement in quality of life. Haloperidol may result in an increase in the incidence of leaving the study early due to adverse effects compared to olanzapine (RR 1.99, 95% CI 1.60 to 2.47; 21 studies, 5047 participants; low-certainty evidence). For every 22 people treated with haloperidol instead of olanzapine, one fewer person would experience this outcome. Thirty otherwise relevant studies and several endpoints from 14 included studies could not be evaluated due to inconsistencies and poor transparency of several parameters. Furthermore, even within studies that were included, it was often not possible to use data for the same reasons. Risk of bias differed substantially for different outcomes and the certainty of the evidence ranged from very low to low. The most common risks of bias leading to downgrading of the evidence were blinding (performance bias) and selective reporting (reporting bias). AUTHORS' CONCLUSIONS: Overall, the certainty of the evidence was low to very low for the main outcomes in this review, making it difficult to draw reliable conclusions. We are very uncertain whether there is a difference between haloperidol and olanzapine in terms of clinically important global state and relapse. Olanzapine may result in a slightly greater overall clinically important change in mental state and in a clinically important change in quality of life. Different side effect profiles were noted: haloperidol may result in a large increase in extrapyramidal side effects and olanzapine in a large increase in weight gain. The drug of choice needs to take into account side effect profiles and the preferences of the individual. These findings and the recent inclusion of olanzapine alongside haloperidol in the WHO Model List of Essential Medicines should increase the likelihood of it becoming more easily available in low- and middle- income countries, thereby improving choice and providing a greater ability to respond to side effects for people with lived experience of schizophrenia. There is a need for additional research using appropriate and equivalent dosages of these drugs. Some of this research needs to be done in low- and middle-income settings and should actively seek to account for factors relevant to these. Research on antipsychotics needs to be person-centred and prioritise factors that are of interest to people with lived experience of schizophrenia.

Bias due to coarsening of time intervals in the inference for the effectiveness of colorectal cancer screening.

BACKGROUND: 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. DEVELOPMENT: 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. APPLICATION: 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. CONCLUSIONS: 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.

Treatment of uncomplicated hepatic cystic echinococcosis (hydatid disease).

BACKGROUND: Cystic echinococcosis is a parasitic infection mainly impacting people living in low- and middle-income countries. Infection may lead to cyst development within organs, pain, non-specific symptoms or complications including abscesses and cyst rupture. Treatment can be difficult and varies by country. Treatments include oral medication, percutaneous techniques and surgery. One Cochrane review previously assessed the benefits and harms of percutaneous treatment compared with other treatments. However, evidence for oral medication, percutaneous techniques and surgery in specific cyst stages has not been systematically investigated and the optimal choice remains uncertain. OBJECTIVES: To assess the benefits and harms of medication, percutaneous and surgical interventions for treating uncomplicated hepatic cystic echinococcosis. SEARCH METHODS: We searched CENTRAL, MEDLINE, two other databases and two trial registries to 4 May 2023. We searched the reference lists of included studies, and contacted experts and researchers in the field for relevant studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in people with a diagnosis of uncomplicated hepatic cystic echinococcosis of World Health Organization (WHO) cyst stage CE1, CE2, CE3a or CE3b comparing either oral medication (albendazole) to albendazole plus percutaneous interventions, or to surgery plus albendazole. Studies comparing praziquantel plus albendazole to albendazole alone prior to or following an invasive intervention (surgery or percutaneous treatment) were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were symptom improvement, recurrence, inactive cyst at 12 months and all-cause mortality at 30 days. Our secondary outcomes were development of secondary echinococcosis, complications of treatment and duration of hospital stay. We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included three RCTs with 180 adults and children with hepatic cystic echinococcosis. Two studies enrolled people aged 5 to 72 years, and one study enrolled children aged 6 to 14 years. One study compared standard catheterization plus albendazole with puncture, aspiration, injection and re-aspiration (PAIR) plus albendazole, and two studies compared laparoscopic surgery plus albendazole with open surgery plus albendazole. The three RCTs were published between 2020 and 2022 and conducted in India, Pakistan and Turkey. There were no other comparisons. Standard catheterization plus albendazole versus PAIR plus albendazole The cyst stages were CE1 and CE3a. The evidence is very uncertain about the effect of standard catheterization plus albendazole compared with PAIR plus albendazole on cyst recurrence (risk ratio (RR) 3.67, 95% confidence interval (CI) 0.16 to 84.66; 1 study, 38 participants; very low-certainty evidence). The evidence is very uncertain about the effects of standard catheterization plus albendazole on 30-day all-cause mortality and development of secondary echinococcosis compared to open surgery plus albendazole. There were no cases of mortality at 30 days or secondary echinococcosis (1 study, 38 participants; very low-certainty evidence). Major complications were reported by cyst and not by participant. Standard catheterization plus albendazole may increase major cyst complications compared with PAIR plus albendazole, but the evidence is very uncertain (RR 10.74, 95% CI 1.39 to 82.67; 1 study, 53 cysts; very low-certainty evidence). Standard catheterization plus albendazole may make little to no difference on minor complications compared with PAIR plus albendazole, but the evidence is very uncertain (RR 1.03, 95% CI 0.60 to 1.77; 1 study, 38 participants; very low-certainty evidence). Standard catheterization plus albendazole may increase the median duration of hospital stay compared with PAIR plus albendazole, but the evidence is very uncertain (4 (range 1 to 52) days versus 1 (range 1 to 15) days; 1 study, 38 participants; very low-certainty evidence). Symptom improvement and inactive cysts at 12 months were not reported. Laparoscopic surgery plus albendazole versus open surgery plus albendazole The cyst stages were CE1, CE2, CE3a and CE3b. The evidence is very uncertain about the effect of laparoscopic surgery plus albendazole on cyst recurrence in participants with CE2 and CE3b cysts compared to open surgery plus albendazole (RR 3.00, 95% CI 0.13 to 71.56; 1 study, 82 participants; very low-certainty evidence). The second study involving 60 participants with CE1, CE2 or CE3a cysts reported no recurrence in either group. The evidence is very uncertain about the effect of laparoscopic surgery plus albendazole on 30-day all-cause mortality in participants with CE1, CE2, CE3a or CE3b cysts compared to open surgery plus albendazole. There was no mortality in either group (2 studies, 142 participants; very low-certainty evidence). The evidence is very uncertain about the effect of laparoscopic surgery plus albendazole on major complications in participants with CE1, CE2, CE3a or CE3b cysts compared to open surgery plus albendazole (RR 0.50, 95% CI 0.13 to 1.92; 2 studies, 142 participants; very low-certainty evidence). Laparoscopic surgery plus albendazole may lead to slightly fewer minor complications in participants with CE1, CE2, CE3a or CE3b cysts compared to open surgery plus albendazole (RR 0.13, 95% CI 0.02 to 0.98; 2 studies, 142 participants; low-certainty evidence). Laparoscopic surgery plus albendazole may reduce the duration of hospital stay compared with open surgery plus albendazole (mean difference (MD) -1.90 days, 95% CI -2.99 to -0.82; 2 studies, 142 participants; low-certainty evidence). Symptom improvement, inactive cyst at 12 months and development of secondary echinococcosis were not reported. AUTHORS' CONCLUSIONS: Percutaneous and surgical interventions combined with albendazole can be used to treat uncomplicated hepatic cystic echinococcosis; however, there is a scarcity of randomised evidence directly comparing these interventions. There is very low-certainty evidence to indicate that standard catheterization plus albendazole may lead to fewer cases of recurrence, more major complications and similar complication rates compared to PAIR plus albendazole in adults and children with CE1 and CE3a cysts. There is very low-certainty evidence to indicate that laparoscopic surgery plus albendazole may result in fewer cases of recurrence or fewer major complications compared to open surgery plus albendazole in adults and children with CE1, CE2, CE3a and CE3b cysts. Laparoscopic surgery plus albendazole may lead to slightly fewer minor complications. Firm conclusions cannot be drawn due to the limited number of studies, small sample size and lack of events for some outcomes.

Application of information from external data to correct for collider bias in a Covid-19 hospitalised cohort.

BACKGROUND: Throughout the Covid-19 pandemic, researchers have made use of electronic health records to research this disease in a rapidly evolving environment of questions and discoveries. These studies are prone to collider bias as they restrict the population of Covid-19 patients to only those with severe disease. Inverse probability weighting is typically used to correct for this bias but requires information from the unrestricted population. Using electronic health records from a South London NHS trust, this work demonstrates a method to correct for collider bias using externally sourced data while examining the relationship between minority ethnicities and poor Covid-19 outcomes. METHODS: The probability of inclusion within the observed hospitalised cohort was modelled based on estimates from published national data. The model described the relationship between patient ethnicity, hospitalisation, and death due to Covid-19 - a relationship suggested to be susceptible to collider bias. The obtained probabilities (as applied to the observed patient cohort) were used as inverse probability weights in survival analysis examining ethnicity (and covariates) as a risk factor for death due to Covid-19. RESULTS: Within the observed cohort, unweighted analysis of survival suggested a reduced risk of death in those of Black ethnicity - differing from the published literature. Applying inverse probability weights to this analysis amended this aberrant result to one more compatible with the literature. This effect was consistent when the analysis was applied to patients within only the first wave of Covid-19 and across two waves of Covid-19 and was robust against adjustments to the modelled relationship between hospitalisation, patient ethnicity, and death due to Covid-19 made as part of a sensitivity analysis. CONCLUSIONS: In conclusion, this analysis demonstrates the feasibility of using external publications to correct for collider bias (or other forms of selection bias) induced by the restriction of a population to a hospitalised cohort using an example from the recent Covid-19 pandemic.

How debunking biases in research and development decisions could lead to more equitable healthcare?

Decades of research have demonstrated that a variety of cognitive biases can affect our judgment and ability to make rational decisions in personal and professional environments. The lengthy, risky, and costly nature of pharmaceutical research and development (R&D) makes it vulnerable to biased decision-making. Moreover, cognitive biases can play a role in regulatory and clinical decision-making, the latter impacting diagnostic and treatment decisions in the therapeutic use of medicines. These inherent and/or institutionalized biases (e.g., in assumptions, data, or decision-making practices) could conceivably contribute to health inequities. In this mini-review, we provide a broad perspective on how cognitive biases can affect pharmaceutical R&D, regulatory evaluation, and therapeutic decision-making. Example approaches to mitigate the effect of common biases in the development, approval, and use of new therapeutics, such as quantitative decision criteria, multidisciplinary reviews, regulatory and treatment guidelines, and evidence-based clinical decision support systems are illustrated. Mitigating the impact of cognitive biases could increase pharma R&D efficiency, change the perspective and prioritization of unmet medical needs, increase representativeness and quality of evidence generated through clinical trials and real-world research, leading to higher quality insights and more effective medication use, and as such could eventually contribute to more equitable healthcare.

Revealing biases in insect observations: A comparative analysis between academic and citizen science data.

Citizen Science is a powerful tool for biodiversity research, as it facilitates data recording at large scales that would otherwise be impossible to cover by standard academic research. Despite its benefits, the accuracy of citizen science data remains a subject of concern among scientists, with varying results reported so far. Neither citizen science data nor academic records are immune to biases, which can significantly impact the quality and reliability of observations. Here, using insects in the Iberian Peninsula as a case study, we compare data collected by participatory platforms to those obtained through academic research projects, and assess their taxonomic, spatial, temporal, and environmental biases. Results show a prominent taxonomic bias in both academic and citizen science data, with certain insect orders receiving more attention than others. These taxonomic biases are conserved between different participatory platforms, as well as between groups of users with different levels of contribution performance. The biases captured by leading contributors in participatory platforms mirrored those of sporadic users and academic data. Citizen science data had higher spatial coverage and less spatial clustering than academic data, showing also clearer trends in temporal seasonality. Environmental coverage over time was more stable in citizen science than in academic records. User behaviour, preference, taxonomical expertise, data collection methodologies and external factors may contribute to these biases. This study shows the multifaceted nature of biases present in academic records and citizen science platforms. The insights gained from this analysis emphasize the need for careful consideration of these biases when making use of biodiversity data from different sources. Combining academic and citizen science data enhances our understanding of biodiversity, as their integration offers a more comprehensive perspective than relying solely on either dataset alone, especially since biases in these two types of data are not always the same.