No evidence for magnetic field effects on the behaviour of Drosophila.

Migratory songbirds have the remarkable ability to extract directional information from the Earth's magnetic field1,2. The exact mechanism of this light-dependent magnetic compass sense, however, is not fully understood. The most promising hypothesis focuses on the quantum spin dynamics of transient radical pairs formed in cryptochrome proteins in the retina3-5. Frustratingly, much of the supporting evidence for this theory is circumstantial, largely because of the extreme challenges posed by genetic modification of wild birds. Drosophila has therefore been recruited as a model organism, and several influential reports of cryptochrome-mediated magnetic field effects on fly behaviour have been widely interpreted as support for a radical pair-based mechanism in birds6-23. Here we report the results of an extensive study testing magnetic field effects on 97,658 flies moving in a two-arm maze and on 10,960 flies performing the spontaneous escape behaviour known as negative geotaxis. Under meticulously controlled conditions and with vast sample sizes, we have been unable to find evidence for magnetically sensitive behaviour in Drosophila. Moreover, after reassessment of the statistical approaches and sample sizes used in the studies that we tried to replicate, we suggest that many-if not all-of the original results were false positives. Our findings therefore cast considerable doubt on the existence of magnetic sensing in Drosophila and thus strongly suggest that night-migratory songbirds remain the organism of choice for elucidating the mechanism of light-dependent magnetoreception.

Double-Negative Results Matter: A Reevaluation of Sensitivities for Detecting SARS-CoV-2 Infection Using Saliva Versus Nasopharyngeal Swabs.

In a recent systematic review, Bastos et al. (Ann Intern Med. 2021;174(4):501-510) compared the sensitivities of saliva sampling and nasopharyngeal swabs in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by assuming a composite reference standard defined as positive if either test is positive and negative if both tests are negative (double negative). Even under a perfect specificity assumption, this approach ignores the double-negative results and risks overestimating the sensitivities due to residual misclassification. In this article, we first illustrate the impact of double-negative results in the estimation of the sensitivities in a single study, and then propose a 2-step latent class meta-analysis method for reevaluating both sensitivities using the same published data set as that used in Bastos et al. by properly including the observed double-negative results. We also conduct extensive simulation studies to compare the performance of the proposed method with Bastos et al.'s method for varied levels of prevalence and between-study heterogeneity. The results demonstrate that the sensitivities are overestimated noticeably using Bastos et al.'s method, and the proposed method provides a more accurate evaluation with nearly no bias and close-to-nominal coverage probability. In conclusion, double-negative results can significantly impact the estimated sensitivities when a gold standard is absent, and thus they should be properly incorporated.

Null results of oxytocin and vasopressin administration on mentalizing in a large fMRI sample: evidence from a randomized controlled trial.

BACKGROUND: Although potential links between oxytocin (OT), vasopressin (AVP), and social cognition are well-grounded theoretically, most studies have included all male samples, and few have demonstrated consistent effects of either neuropeptide on mentalizing (i.e. understanding the mental states of others). To understand the potential of either neuropeptide as a pharmacological treatment for individuals with impairments in social cognition, it is important to demonstrate the beneficial effects of OT and AVP on mentalizing in healthy individuals. METHODS: In the present randomized, double-blind, placebo-controlled study (n = 186) of healthy individuals, we examined the effects of OT and AVP administration on behavioral responses and neural activity in response to a mentalizing task. RESULTS: Relative to placebo, neither drug showed an effect on task reaction time or accuracy, nor on whole-brain neural activation or functional connectivity observed within brain networks associated with mentalizing. Exploratory analyses included several variables previously shown to moderate OT's effects on social processes (e.g., self-reported empathy, alexithymia) but resulted in no significant interaction effects. CONCLUSIONS: Results add to a growing literature demonstrating that intranasal administration of OT and AVP may have a more limited effect on social cognition, at both the behavioral and neural level, than initially assumed. Randomized controlled trial registrations: ClinicalTrials.gov; NCT02393443; NCT02393456; NCT02394054.

Effects of Proton Pump Inhibitors on the Small Bowel and Stool Microbiomes.

BACKGROUND: Proton pump inhibitor (PPI) use is extremely common. PPIs have been suggested to affect the gut microbiome, and increase risks of Clostridium difficile infection and small intestinal bacterial overgrowth (SIBO). However, existing data are based on stool analyses and PPIs act on the foregut. AIMS: To compare the duodenal and stool microbiomes in PPI and non-PPI users. METHODS: Consecutive subjects presenting for upper endoscopy without colonoscopy were recruited. Current antibiotic users were excluded. Subjects taking PPI were age- and gender-matched 1:2 to non-PPI controls. Subjects completed medical history questionnaires, and duodenal aspirates were collected using a validated protected catheter. A subset also provided stool samples. Duodenal and stool microbiomes were analyzed by 16S rRNA sequencing. RESULTS: The duodenal microbiome exhibited no phylum-level differences between PPI (N = 59) and non-PPI subjects (N = 118), but demonstrated significantly higher relative abundances of families Campylobacteraceae (3.13-fold, FDR P value < 0.01) and Bifidobacteriaceae (2.9-fold, FDR P value < 0.01), and lower relative abundance of Clostridiaceae (88.24-fold, FDR P value < 0.0001), in PPI subjects. SIBO rates were not significantly different between groups, whether defined by culture (> 103 CFU/ml) or 16S sequencing, nor between subjects taking different PPIs. The stool microbiome exhibited significantly higher abundance of family Streptococcaceae (2.14-fold, P = 0.003), and lower Clostridiaceae (2.60-fold, FDR P value = 8.61E-13), in PPI (N = 22) versus non-PPI (N = 47) subjects. CONCLUSIONS: These findings suggest that PPI use is not associated with higher rates of SIBO. Relative abundance of Clostridiaceae was reduced in both the duodenal and stool microbiomes, and Streptococcaceae was increased in stool. The clinical implications of these findings are unknown.

Metabolic syndrome is not associated to an increased risk of low bone mineral density in men at risk for osteoporosis.

PURPOSE: We have recently demonstrated a significant association between osteoporosis (Op) and metabolic syndrome (MetS) in Caucasian women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. This cross-sectional study was performed to evaluate the association between MetS and Op in Caucasian men enrolled in the same geographical area, with identical criteria and in the same time range. METHODS: Among subjects enrolled in the SIMON study, we selected the medical records of all free-living men who performed a contextual evaluation of both bone mineral density (BMD) by DXA and MetS constitutive elements (arterial blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose). All enrolled subjects refer to "COMEGEN" general practitioners' cooperative operating in Naples, Southern Italy. RESULTS: Overall, the medical records of 880 men were examined. No significant association between MetS and Op was observed. Among MetS constitutive elements, waist circumference was inversely related to Op risk. CONCLUSION: In Caucasian men examined by DXA for suspected Op, no significant association was observed between Op and MetS. The study results contrast to those observed in women enrolled in the same geographical area, with identical criteria and in the same time range and may be related to sexual dimorphism occurring in clinical expressiveness of both MetS and Op.

Promoting Learning from Null or Negative Results in Prevention Science Trials.

There can be a tendency for investigators to disregard or explain away null or negative results in prevention science trials. Examples include not publicizing findings, conducting spurious subgroup analyses, or attributing the outcome post hoc to real or perceived weaknesses in trial design or intervention implementation. This is unhelpful for several reasons, not least that it skews the evidence base, contributes to research "waste", undermines respect for science, and stifles creativity in intervention development. In this paper, we identify possible policy and practice responses when interventions have null (ineffective) or negative (harmful) results, and argue that these are influenced by: the intervention itself (e.g., stage of gestation, perceived importance); trial design, conduct, and results (e.g., pattern of null/negative effects, internal and external validity); context (e.g., wider evidence base, state of policy); and individual perspectives and interests (e.g., stake in the intervention). We advance several strategies to promote more informative null or negative effect trials and enable learning from such results, focusing on changes to culture, process, intervention design, trial design, and environment.

Non-Malaria Causes of Fever among under-5 Children with Negative Results for Malaria Rapid Diagnostic Test in South-Western Nigeria.

BACKGROUND: Although the global malaria burden is decreasing, there are still concerns about overdiagnosis of malaria and the danger of misdiagnosis of non-malaria causes of fever. Clinicians continue to face the challenge of differentiating between these causes despite the introduction of malaria rapid diagnostic tests (mRDTs). AIM: To determine the prevalence and causes of non-malaria-caused fever in children in South-Western Nigeria. METHODS: Secondary analysis of data obtained to evaluate the effect of restricting antimalarial treatment to positive mRDT children in rural and urban areas of southwest Nigeria. Clinical examinations, laboratory tests for malaria parasites (including thick blood film and mRDT) and bacterial identification were performed on children aged 3-59 months (n = 511). The non-malaria group comprised febrile children who had both negative mRDT and microscopy results, while the malaria group included those who were positive for either mRDT or microscopy. We compared the causes of fever among children with non-malaria fever and those with malaria. RESULTS: The prevalence of non-malaria fever and bacteria-malaria co-infection was 37.2% and 2.0%, respectively. Non-malarial pathogens identified were viral (54.7%) and bacterial (32.1%) infections. The bacterial infections included bacteriaemia (2.7%), urinary tract infections (21.6%), skin infections (11.6%) and otitis media (2.6%). The leading bacterial isolates were Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae. CONCLUSION: The high prevalence and wide range of non-malarial infections reinforces the need for point-of-care tests to identify bacterial and viral infections to optimize the treatment of febrile illnesses in malaria-endemic areas.

Publish without bias or perish without replications.

There is mounting evidence that a large portion of experimental results cannot be replicated, leading many to believe that science is now in the throes of a replicability crisis. In response, there have been calls to reduce publication bias against negative results because of the effect that publication bias has on the publication record. Others, however, argue that publication bias need not be detrimental to scientific progress. Here, we propose a novel mechanism by dint of which reducing publication bias can benefit science regardless of the effect that publication bias has on the publication record. To do so, we introduce a series of increasingly complex mathematical models. Our models represent a scientific community consisting of discovery researchers who test novel hypotheses, and confirmation researchers who test known hypotheses. Results show that reducing publication bias can have the surprising consequence of increasing the share of confirmation researchers who conduct replications. When a large share of scientists conduct confirmation research, scientists have an incentive to conduct high-quality research as others are likely to check their findings. Our models therefore suggest an underappreciated reasons why reducing publication bias might benefit science.

Steady-State Visually Evoked Potentials and Feature-based Attention: Preregistered Null Results and a Focused Review of Methodological Considerations.

Feature-based attention is the ability to selectively attend to a particular feature (e.g., attend to red but not green items while looking for the ketchup bottle in your refrigerator), and steady-state visually evoked potentials (SSVEPs) measured from the human EEG signal have been used to track the neural deployment of feature-based attention. Although many published studies suggest that we can use trial-by-trial cues to enhance relevant feature information (i.e., greater SSVEP response to the cued color), there is ongoing debate about whether participants may likewise use trial-by-trial cues to voluntarily ignore a particular feature. Here, we report the results of a preregistered study in which participants either were cued to attend or to ignore a color. Counter to prior work, we found no attention-related modulation of the SSVEP response in either cue condition. However, positive control analyses revealed that participants paid some degree of attention to the cued color (i.e., we observed a greater P300 component to targets in the attended vs. the unattended color). In light of these unexpected null results, we conducted a focused review of methodological considerations for studies of feature-based attention using SSVEPs. In the review, we quantify potentially important stimulus parameters that have been used in the past (e.g., stimulation frequency, trial counts) and we discuss the potential importance of these and other task factors (e.g., feature-based priming) for SSVEP studies.

Null effects of levodopa on reward- and error-based motor adaptation, savings, and anterograde interference.

Dopamine signaling is thought to mediate reward-based learning. We tested for a role of dopamine in motor adaptation by administering the dopamine precursor levodopa to healthy participants in two experiments involving reaching movements. Levodopa has been shown to impair reward-based learning in cognitive tasks. Thus, we hypothesized that levodopa would selectively impair aspects of motor adaptation that depend on the reinforcement of rewarding actions. In the first experiment, participants performed two separate tasks in which adaptation was driven either by visual error-based feedback of the hand position or binary reward feedback. We used EEG to measure event-related potentials evoked by task feedback. We hypothesized that levodopa would specifically diminish adaptation and the neural responses to feedback in the reward learning task. However, levodopa did not affect motor adaptation in either task nor did it diminish event-related potentials elicited by reward outcomes. In the second experiment, participants learned to compensate for mechanical force field perturbations applied to the hand during reaching. Previous exposure to a particular force field can result in savings during subsequent adaptation to the same force field or interference during adaptation to an opposite force field. We hypothesized that levodopa would diminish savings and anterograde interference, as previous work suggests that these phenomena result from a reinforcement learning process. However, we found no reliable effects of levodopa. These results suggest that reward-based motor adaptation, savings, and interference may not depend on the same dopaminergic mechanisms that have been shown to be disrupted by levodopa during various cognitive tasks.NEW & NOTEWORTHY Motor adaptation relies on multiple processes including reinforcement of successful actions. Cognitive reinforcement learning is impaired by levodopa-induced disruption of dopamine function. We administered levodopa to healthy adults who participated in multiple motor adaptation tasks. We found no effects of levodopa on any component of motor adaptation. This suggests that motor adaptation may not depend on the same dopaminergic mechanisms as cognitive forms or reinforcement learning that have been shown to be impaired by levodopa.

Absence of classical and atypical (H- and L-) BSE infectivity in the blood of bovines in the clinical end stage of disease as confirmed by intraspecies blood transfusion.

While the presence of bovine spongiform encephalopathy (BSE) infectivity in the blood of clinically affected sheep has been proven by intraspecies blood-transfusion experiments, this question has remained open in the case of BSE-affected cattle. Although the absence of infectivity can be anticipated from the restriction of the agent to neuronal tissues in this species, evidence for this was still lacking. This particularly concerns the production and use of medicinal products and other applications containing bovine blood or preparations thereof. We therefore performed a blood-transfusion experiment from cattle in the clinical end stage of disease after experimental challenge with either classical (C-BSE) or atypical (H- and l-) BSE into calves at 4-6 months of age. The animals were kept in a free-ranging group for 10 years. Starting from 24 months post-transfusion, a thorough clinical examination was performed every 6 weeks in order to detect early symptoms of a BSE infection. Throughout the experiment, the clinical picture of all animals gave no indication of a BSE infection. Upon necropsy, the brainstem samples were analysed by BSE rapid test as well as by the highly sensitive Protein Misfolding Cyclic Amplification (PMCA), all with negative results. These results add resilient data to confirm the absence of BSE infectivity in the donor blood collected from C-, H- and l-BSE-affected cattle even in the final clinical phase of the disease. This finding has important implications for the risk assessment of bovine blood and blood products in the production of medicinal products and other preparations.

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. FINDINGS: Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. INTERPRETATION: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. FUNDING: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.

Association of kidney function and atrial fibrillation progression to clinical outcomes in patients with cardiac implantable electronic devices.

BACKGROUND: Kidney function may promote progression of AF. OBJECTIVE: We evaluated the association of kidney function to AF progression and resultant clinical outcomes in patients with cardiac implantable electronic devices (CIED). METHODS: We performed a retrospective cohort study using national clinical data from the Veterans Health Administration linked to CIED data from the Carelink® remote monitoring data warehouse (Medtronic Inc, Mounds View, MN). All devices had atrial leads and at least 75% of remote monitoring transmission coverage. Patients were included at the date of the first AF episode lasting ≥6 minutes, and followed until the occurrence of persistent AF in the first year, defined as ≥7 consecutive days with continuous AF. We used Cox regression analyses with persistent AF as a time-varying covariate to examine the association to stroke, myocardial infarction, heart failure and death. RESULTS: Of, 10,323 eligible patients, 1,771 had a first CIED-detected AF (mean age 69 ± 10 years, 1.2% female). In the first year 355 (20%) developed persistent AF. Kidney function was not associated with persistent AF after multivariable adjustment including CHA2DS2-VASc variables and prior medications. Only higher age increased the risk (HR: 1.37 per 10 years; 95% CI:1.22-1.54). Persistent AF was associated to higher risk of heart failure (HR: 2.27; 95% CI: 1.88-2.74) and death (HR: 1.60; 95% CI: 1.30-1.96), but not stroke (HR: 1.28; 95% CI: 0.62-2.62) or myocardial infarction (HR: 1.43; 95% CI: 0.91-2.25). CONCLUSION: Kidney function was not associated to AF progression, whereas higher age was. Preventing AF progression could reduce the risk of heart failure and death.

Polymorphisms of ACE (I/D) and ACE2 receptor gene (Rs2106809, Rs2285666) are not related to the clinical course of COVID-19: A case study.

Coronavirus disease 2019 (COVID-19) is an infectious disease, and the reason behind the currently ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme (ACE2) has been recognized as the specific receptor of the SARS-CoV-2 virus. Although the possible effect of ACE2 gene polymorphism remains unknown, human ACE2 receptor expression influences SARS-CoV-2 susceptibility and COVID-19 disease outcome. In this study, we aimed to investigate the relationship between ACE gene I/D polymorphism, ACE2 receptor gene polymorphism, and COVID-19 severity. ACE gene insertion/deletion (I/D) polymorphism and ACE2 receptor gene rs2106809 and rs2285666 polymorphisms were determined using polymerase chain reaction (PCR) and PCR-based restriction fragment length polymorphism methods, respectively, in 155 COVID-19 patients who were divided into three groups (mild, moderate, and severe) according to clinical symptoms. However, the distribution of genotype and allele frequencies of ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not statistically significant in all groups. In conclusion, in the study population, ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not associated with the severity of COVID-19 infection. Although ACE2 receptor gene expression may affect the susceptibility to COVID-19, there is no existing evidence that the ACE or ACE2 gene polymorphisms are directly associated with COVID-19 severity. Interindividual differences in COVID-19 severity might be related to epigenetic mechanisms of ACE2 receptor gene expression or variations in other genes suggested to play a critical role in COVID-19 pathogenesis such as pro-inflammatory cytokines and coagulation indicators.

Effects of prebiotics on postprandial GLP-1, GLP-2 and glucose regulation in patients with type 2 diabetes: A randomised, double-blind, placebo-controlled crossover trial.

AIMS: We aimed to investigate the effect of prebiotic inulin-type fructans (ITF) versus a control supplement on postprandial levels of glucagon-like peptide-1 and -2 (GLP-1 and -2), glucose and insulin in people with type 2 diabetes. METHODS: Adult men and women with type 2 diabetes were randomised in a double-blind, placebo-controlled crossover study. The study participants received 16 g/d ITF and 16 g/d control supplement (maltodextrin) for 6 weeks each in two phases separated by a 4-week washout. A standardised mixed-meal test was performed before and after each intake period. The primary end point was changes in the GLP-1 response, and secondary end points were GLP-2, glucose and insulin responses. Data were analysed using mixed-model analysis. RESULTS: A total of 29 participants were included in the study. Differences between and within the two treatments in estimated area under the curves were not significant. Yet, the predicted means for meal-induced GLP-1 response in plasma showed a 4.8% decline after the prebiotic treatment and an 8.6% increase after the control treatment (difference in changes between the treatments, p < 0.001). Fasting or postprandial glucose, insulin or GLP-2 levels were not changed. CONCLUSIONS: Our findings do not support that ITF improve incretin responses or glucose regulations in this population. Clinicaltrials.gov (NCT02569684).

Safe egg yolk consumption after a negative result for low-dose egg oral food challenge.

BACKGROUND: Hen's egg is one of the most common allergens causing infantile food allergy. Consuming heated egg yolk slightly contaminated with egg white (EY with scEW) improves diet quality. Most children with egg allergies can safely consume 1/25 of a heated whole egg (low-dose egg). Although low-dose egg has similar antigenicity to EY with scEW, clinical reproducibility is unknown. We aimed to examine the safety of EY with scEW consumption after a negative result of low-dose egg oral food challenge (OFC). METHODS: In this prospective study, children aged <18 years with a history of immediate reaction to eggs were enrolled. We advised children and guardians to consume EY with scEW after a negative result of low-dose egg OFC and to record symptoms, if any. RESULTS: We evaluated 276 children with negative results for low-dose egg OFC who had previously shown reactivity to eggs. Their median age was 1.2 years. Boys accounted for 188 (68%) of the children. The median egg white-specific immunoglobulin E level was 11.7 kUA /L. At home, six children experienced mild symptoms. Skin symptoms were the most common. Among the six children, five were confirmed to continue the consumption of EY with scEW and one developed mild respiratory symptoms and continued to avoid eating eggs. CONCLUSION: Although a few children with egg allergies experience mild symptoms, most of them can ultimately consume EY with scEW. Consumption of EY with scEW after low-dose egg OFC seems safe and may improve their quality of life by making egg yolk products available.

Modeling the mean time to interval cancer after negative results of periodic cancer screening.

Interval cancers are cancers detected symptomatically between screens or after the last screen. A mathematical model for the development of interval cancers can provide useful information for evaluating cancer screening. In this regard a useful quantity is MIC, the mean duration in years of progressive preclinical cancer (PPC) that leads to interval cancers. Estimation of MIC involved extending a previous model to include three negative screens, invoking the multinomial-Poisson transformation to avoid estimating background cancer trends, and varying screening test sensitivity. Simulations show that when the true MIC is 0.5, the method yields a reasonably narrow range of estimated MICs over the range of screening test sensitivities from 0.5 to 1.0. If the lower bound on the screening test sensitivity is 0.7, the method performs considerably better even for larger MICs. The application of the method involved annual lung cancer screening in the Prostate, Lung, Colorectal, and Ovarian trial. Assuming a normal distribution for PPC duration, the estimated MIC (95% confidence interval) ranged from 0.00 (0.00 to 0.34) at a screening test sensitivity of 1.0 to 0.54 (0.03, 1.00) at a screening test sensitivity of 0.5 Assuming an exponential distribution for PPC duration, which did not fit as well, the estimated MIC ranged from 0.27 (0.08, 0.49) at a screening test sensitivity of 0.5 to 0.73 (0.32, 1.26) at a screen test sensitivity of 1.0 Based on these results, investigators may wish to investigate more frequent lung cancer screening.

Modest alcohol intake not associated with significant hepatic steatosis or more severe liver disease among patients with diabetes mellitus.

BACKGROUND: The effect of modest alcohol intake on prevalence of significant hepatic steatosis and severity of liver disease in patients with type 2 diabetes mellitus (T2DM) is unclear. METHODS: This is a cross-sectional study on T2DM patients. Modest alcohol intake was defined as alcohol intake ≤ 21 units/week in men and ≤ 14 units/week in women. Significant hepatic steatosis was diagnosed on the basis of controlled attenuation parameter > 263 dB/m, while advanced fibrosis was diagnosed on the basis of liver stiffness measurement ≥ 9.6 kPa using M probe or ≥ 9.3 kPa using XL probe. Patients with liver stiffness measurement ≥ 8.0 kPa were offered liver biopsy. RESULTS: Five hundred fifty-seven patients underwent transient elastography, and 71 patients underwent liver biopsy. The prevalence of modest drinking was 16.5%. Modest drinking was equally prevalent among ethnic Indians and Chinese at 22.9% and 23.3%, respectively, but uncommon among ethnic Malays at 1.7%. Modest drinkers were more likely to be male, smoked, and had significantly lower glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, and platelet count. There was no significant difference in the prevalence of significant hepatic steatosis or advanced fibrosis based on transient elastography and steatohepatitis or advanced fibrosis between modest drinkers and nondrinkers. The prevalence of significant hepatic steatosis was higher among ethnic Malays and Indians compared with ethnic Chinese, but the Chinese did not have a lower prevalence of more severe liver disease. CONCLUSION: Modest alcohol intake is not associated with higher prevalence of significant hepatic steatosis or more severe liver disease among patients with T2DM.