Titration of Basal and Prandial Insulin Doses With the Initiation of Glucagon-Like Peptide-1 Receptor Agonist Therapy.

Objective Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant efficacy in improving glycemic control in type 2 diabetes mellitus, which often results in decreased insulin dose requirements. The purpose of this study was to examine the changes in basal and prandial insulin dose requirements from baseline to three months following initiation of a GLP-1 RA. Methodology A retrospective chart review was conducted of adult insulin-treated patients at the Chertow Diabetes Center, Huntington, WV, who were started on GLP-1 RAs for 24 months. Results Mean daily basal insulin doses decreased by 8.7 units (P = 0.29; mean 8.3% change) and mean daily prandial insulin doses decreased by 9.4 units (P = 0.10; mean 18.4% change) from baseline to three months after starting a GLP-1 RA. Average hemoglobin A1c significantly decreased from 8.8% (73 mmol/mol) at baseline to 8.0% (64 mmol/mol) at three months (P < 0.001). Significant decreases from baseline to three months were also observed in mean body weight, mean low-density lipoprotein (LDL) cholesterol, and mean total cholesterol. Conclusions GLP-1 RA therapy was associated with a significant decrease in hemoglobin A1c, body weight, and LDL-cholesterol from baseline to three months after initiation. Therapy with GLP-1 RAs was also associated with an overall decrease in daily basal and prandial insulin dose requirements, although this finding did not reach statistical significance.

Exposure to Operative Anesthesia in Childhood and Subsequent Neurobehavioral Diagnoses: A Natural Experiment using Appendectomy.

BACKGROUND: Observational studies of anesthetic neurotoxicity may be biased because children requiring anesthesia commonly have medical conditions associated with neurobehavioral problems. This study takes advantage of a natural experiment associated with appendicitis, in order to determine if anesthesia and surgery in childhood were specifically associated with subsequent neurobehavioral outcomes. METHODS: We identified 134,388 healthy children with appendectomy and examined the incidence of subsequent externalizing or behavioral disorders (conduct, impulse control, oppositional defiant, or attention-deficit/hyperactivity disorder); or internalizing or mood/anxiety disorders (depression, anxiety, or bipolar disorder) when compared to 671,940 matched healthy controls as identified in Medicaid data between 2001-2018. For comparison, we also examined 154,887 otherwise healthy children admitted to the hospital for pneumonia, cellulitis, and gastroenteritis, of which only 8% received anesthesia, and compared them to 774,435 matched healthy controls. We also examined the difference-in-differences between matched appendectomy patients and their controls and matched medical admission patients and their controls. RESULTS: Compared to controls, children with appendectomy were more likely to have subsequent behavioral disorders (the hazard ratio (HR) was 1.04 (95% CI 1.01, 1.06), P = 0.0010), and mood/anxiety disorders (HR: 1.15 (95% CI 1.13, 1.17), P < 0.0001). Relative to controls, children with medical admissions were also more likely to have subsequent behavioral (HR: 1.20 (95% CI 1.18, 1.22), P < 0.0001), and mood/anxiety (HR: 1.25 (95% CI 1.23, 1.27), P < 0.0001) disorders. Comparing the difference between matched appendectomy patients and their matched controls to the difference between matched medical patients and their matched controls, medical patients had more subsequent neurobehavioral problems than appendectomy patients. CONCLUSIONS: Although there is an association between neurobehavioral diagnoses and appendectomy, this association is not specific to anesthesia exposure, and is stronger in medical admissions. Medical admissions, generally without anesthesia exposure, displayed significantly higher rates of these disorders than appendectomy-exposed patients.

Impact of Hospital Affiliation With a Flagship Hospital System on Surgical Outcomes.

OBJECTIVE: To compare general surgery outcomes at flagship systems, flagship hospitals, and flagship hospital affiliates versus matched controls. SUMMARY BACKGROUND DATA: It is unknown whether flagship hospitals perform better than flagship hospital affiliates for surgical patients. METHODS: Using Medicare claims for 2018 to 2019, we matched patients undergoing inpatient general surgery in flagship system hospitals to controls who underwent the same procedure at hospitals outside the system but within the same region. We defined a "flagship hospital" within each region as the major teaching hospital with the highest patient volume that is also part of a hospital system; its system was labeled a "flagship system." We performed 4 main comparisons: patients treated at any flagship system hospital versus hospitals outside the flagship system; flagship hospitals versus hospitals outside the flagship system; flagship hospital affiliates versus hospitals outside the flagship system; and flagship hospitals versus affiliate hospitals. Our primary outcome was 30-day mortality. RESULTS: We formed 32,228 closely matched pairs across 35 regions. Patients at flagship system hospitals (32,228 pairs) had lower 30-day mortality than matched control patients [3.79% vs. 4.36%, difference=-0.57% (-0.86%, -0.28%), P<0.001]. Similarly, patients at flagship hospitals (15,571/32,228 pairs) had lower mortality than control patients. However, patients at flagship hospital affiliates (16,657/32,228 pairs) had similar mortality to matched controls. Flagship hospitals had lower mortality than affiliate hospitals [difference-in-differences=-1.05% (-1.62%, -0.47%), P<0.001]. CONCLUSIONS: Patients treated at flagship hospitals had significantly lower mortality rates than those treated at flagship hospital affiliates. Hence, flagship system affiliation does not alone imply better surgical outcomes.

Assessing the Ambulatory Surgery Center Volume-Outcome Association.

Importance: In surgical patients, it is well known that higher hospital procedure volume is associated with better outcomes. To our knowledge, this volume-outcome association has not been studied in ambulatory surgery centers (ASCs) in the US. Objective: To determine if low-volume ASCs have a higher rate of revisits after surgery, particularly among patients with multimorbidity. Design, Setting, and Participants: This matched case-control study used Medicare claims data and analyzed surgeries performed during 2018 and 2019 at ASCs. The study examined 2328 ASCs performing common ambulatory procedures and analyzed 4751 patients with a revisit within 7 days of surgery (defined to be either 1 of 4735 revisits or 1 of 16 deaths without a revisit). These cases were each closely matched to 5 control patients without revisits (23 755 controls). Data were analyzed from January 1, 2018, through December 31, 2019. Main Outcomes and Measures: Seven-day revisit in patients (cases) compared with the matched patients without the outcome (controls) in ASCs with low volume (less than 50 procedures over 2 years) vs higher volume (50 or more procedures). Results: Patients at a low-volume ASC had a higher odds of a 7-day revisit vs patients who had their surgery at a higher-volume ASC (odds ratio [OR], 1.21; 95% CI, 1.09-1.36; P = .001). The odds of revisit for patients with multimorbidity were higher at low-volume ASCs when compared with higher-volume ASCs (OR, 1.57; 95% CI, 1.27-1.94; P < .001). Among patients with multimorbidity in low-volume ASCs, for those who underwent orthopedic procedures, the odds of revisit were 84% higher (OR, 1.84; 95% CI, 1.36-2.50; P < .001) vs higher-volume centers, and for those who underwent general surgery or other procedures, the odds of revisit were 36% higher (OR, 1.36; 95% CI, 1.01-1.83; P = .05) vs a higher-volume center. The findings were not statistically significant for patients without multimorbidity. Conclusions and Relevance: In this observational study, the surgical volume of an ASC was an important indicator of patient outcomes. Older patients with multimorbidity should discuss with their surgeon the optimal location of their care.

Effects of Voice Pitch on Social Perceptions Vary With Relational Mobility and Homicide Rate.

Fundamental frequency ( fo) is the most perceptually salient vocal acoustic parameter, yet little is known about how its perceptual influence varies across societies. We examined how fo affects key social perceptions and how socioecological variables modulate these effects in 2,647 adult listeners sampled from 44 locations across 22 nations. Low male fo increased men's perceptions of formidability and prestige, especially in societies with higher homicide rates and greater relational mobility in which male intrasexual competition may be more intense and rapid identification of high-status competitors may be exigent. High female fo increased women's perceptions of flirtatiousness where relational mobility was lower and threats to mating relationships may be greater. These results indicate that the influence of fo on social perceptions depends on socioecological variables, including those related to competition for status and mates.

Nonverbal displays of dominance and prestige: Evidence for cross-cultural and early-emerging recognition.

Two universal strategies for attaining influence-dominance, or the use of intimidation and force to obtain power, and prestige, or garnering respect by demonstrating knowledge and expertise-are communicated through distinct nonverbal displays in North America. Given evidence for the emergence and effectiveness of these strategies across cultures, including non-Western, Educated, Industrialized, Rich, and Democratic small-scale, traditional societies in Africa, Asia, and South America, the nonverbal displays that are used to reliably communicate these strategies also might be universal. Here, we demonstrate that the dominance display is recognized by the Mayangna, a small-scale society in rural Nicaragua, and by Canadian children as young as 2 and 3 years old. We also find that the prestige display is reliably differentiated from dominance by both groups, and judged as a high-rank signal by the Mayangna. However, members of the Mayangna confused the prestige display with happiness, and children confused the prestige display with a neutral expression. Overall, findings are consistent with a ubiquitous and early-emerging ability to recognize dominance, and with the suggestion that the prestige display is more culturally variable and ontogenetically slower to emerge. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Mortality Among Older Medical Patients at Flagship Hospitals and Their Affiliates.

BACKGROUND: We define a "flagship hospital" as the largest academic hospital within a hospital referral region and a "flagship system" as a system that contains a flagship hospital and its affiliates. It is not known if patients admitted to an affiliate hospital, and not to its main flagship hospital, have better outcomes than those admitted to a hospital outside the flagship system but within the same hospital referral region. OBJECTIVE: To compare mortality at flagship hospitals and their affiliates to matched control patients not in the flagship system but within the same hospital referral region. DESIGN: A matched cohort study PARTICIPANTS: The study used hospitalizations for common medical conditions between 2018-2019 among older patients age ≥ 66 years. We analyzed 118,321 matched pairs of Medicare patients admitted with pneumonia (N=57,775), heart failure (N=42,531), or acute myocardial infarction (N=18,015) in 35 flagship hospitals, 124 affiliates, and 793 control hospitals. MAIN MEASURES: 30-day (primary) and 90-day (secondary) all-cause mortality. KEY RESULTS: 30-day mortality was lower among patients in flagship systems versus control hospitals that are not part of the flagship system but within the same hospital referral region (difference= -0.62%, 95% CI [-0.88%, -0.37%], P<0.001). This difference was smaller in affiliates versus controls (-0.43%, [-0.75%, -0.11%], P=0.008) than in flagship hospitals versus controls (-1.02%, [-1.46%, -0.58%], P<0.001; difference-in-difference -0.59%, [-1.13%, -0.05%], P=0.033). Similar results were found for 90-day mortality. LIMITATIONS: The study used claims-based data. CONCLUSIONS: In aggregate, within a hospital referral region, patients treated at the flagship hospital, at affiliates of the flagship hospital, and in the flagship system as a whole, all had lower mortality rates than matched controls outside the flagship system. However, the mortality advantage was larger for flagship hospitals than for their affiliates.

Profiling of repetitive RNA sequences in the blood plasma of patients with cancer.

Liquid biopsies provide a means for the profiling of cell-free RNAs secreted by cells throughout the body. Although well-annotated coding and non-coding transcripts in blood are readily detectable and can serve as biomarkers of disease, the overall diagnostic utility of the cell-free transcriptome remains unclear. Here we show that RNAs derived from transposable elements and other repeat elements are enriched in the cell-free transcriptome of patients with cancer, and that they serve as signatures for the accurate classification of the disease. We used repeat-element-aware liquid-biopsy technology and single-molecule nanopore sequencing to profile the cell-free transcriptome in plasma from patients with cancer and to examine millions of genomic features comprising all annotated genes and repeat elements throughout the genome. By aggregating individual repeat elements to the subfamily level, we found that samples with pancreatic cancer are enriched with specific Alu subfamilies, whereas other cancers have their own characteristic cell-free RNA profile. Our findings show that repetitive RNA sequences are abundant in blood and can be used as disease-specific diagnostic biomarkers.

Group size and mating system predict sex differences in vocal fundamental frequency in anthropoid primates.

Vocalizations differ substantially between the sexes in many primates, and low-frequency male vocalizations may be favored by sexual selection because they intimidate rivals and/or attract mates. Sexual dimorphism in fundamental frequency may be more pronounced in species with more intense male mating competition and in those with large group size, where social knowledge is limited and efficient judgment of potential mates and competitors is crucial. These non-mutually exclusive explanations have not been tested simultaneously across primate species. In a sample of vocalizations (n = 1914 recordings) across 37 anthropoid species, we investigated whether fundamental frequency dimorphism evolved in association with increased intensity of mating competition (H1), large group size (H2), multilevel social organization (H3), a trade-off against the intensity of sperm competition (H4), and/or poor acoustic habitats (H5), controlling for phylogeny and body size dimorphism. We show that fundamental frequency dimorphism increased in evolutionary transitions towards larger group size and polygyny. Findings suggest that low-frequency male vocalizations in primates may have been driven by selection to win mating opportunities by avoiding costly fights and may be more important in larger groups, where limited social knowledge affords advantages to rapid assessment of status and threat potential via conspicuous secondary sexual characteristics.

Impact of Magnetic Resonance Imaging Targeting on Pathologic Upgrading and Downgrading at Prostatectomy: A Systematic Review and Meta-analysis.

CONTEXT: The evidence supporting multiparametric magnetic resonance imaging (MRI) targeting for biopsy is nearly exclusively based on biopsy pathologic outcomes. This is problematic, as targeting likely allows preferential identification of small high-grade areas of questionable oncologic significance, raising the likelihood of overdiagnosis and overtreatment. OBJECTIVE: To estimate the impact of MRI-targeted, systematic, and combined biopsies on radical prostatectomy (RP) grade group concordance. EVIDENCE ACQUISITION: PubMed MEDLINE and Cochrane Library were searched from July 2018 to January 2022. Studies that conducted systematic and MRI-targeted prostate biopsies and compared biopsy results with pathology after RP were included. We performed a meta-analysis to assess whether pathologic upgrading and downgrading were influenced by biopsy type and a net-benefit analysis using pooled risk difference estimates. EVIDENCE SYNTHESIS: Both targeted only and combined biopsies were less likely to result in upgrading (odds ratio [OR] vs systematic of 0.70, 95% confidence interval [CI] 0.63-0.77, p < 0.001, and 0.50, 95% CI 0.45-0.55, p < 0.001), respectively). Targeted only and combined biopsies increased the odds of downgrading (1.24 (95% CI 1.05-1.46), p = 0.012, and 1.96 (95% CI 1.68-2.27, p < 0.001) compared with systematic biopsies, respectively. The net benefit of targeted and combined biopsies is 8 and 7 per 100 if harms of up- and downgrading are considered equal, but 7 and -1 per 100 if the harm of downgrading is considered twice that of upgrading. CONCLUSIONS: The addition of MRI-targeting results in lower rates of upgrading as compared to systematic biopsy at RP (27% vs 42%). However, combined MRI-targeted and systematic biopsies are associated with more downgrading at RP (19% v 11% for combined vs systematic). Strong heterogeneity suggests further research into factors that influence the rates of up- and downgrading and that distinguishes clinically relevant from irrelevant grade changes is needed. Until then, the benefits and harms of combined MRI-targeted and systematic biopsies cannot be fully assessed. PATIENT SUMMARY: We reviewed the ability of magnetic resonance imaging (MRI)-targeted biopsies to predict cancer grade at prostatectomy. We found that combined MRI-targeted and systematic biopsies result in more cancers being downgraded than systematic biopsies.

Intramolecular O···H Hydrogen Bonding of Salicylic Acid: Further Insights from O 1s XPS and 1H NMR Spectra Using DFT Calculations.

Intramolecular hydrogen bonding (HB) is a complex phenomenon that extends beyond a simple valence event, affecting the core electrons of a molecule. Salicylic acid (SA) and its conformers provide an excellent model compound for studying intramolecular HB as the proton donor (H) and acceptor (O) can be toggled by rotating the C-O and C-C bonds to form up to seven potential conformers through various HB. In this study, we computationally investigated intramolecular interactions in SA conformers with and without such HB, by examining their calculated O 1s core electron-binding energy (CEBE) and 1H NMR chemical shifts validated using recent measurements. The quantum mechanically stable SA conformers are fully defined by three rotatable bonds in the compound, which are abstracted as SA(η1η2η3) digital structures, where ηi = 0 if the ηi angles match the most stable SA conformer (000) and ηi = 1 otherwise. Our findings suggest that the stability is dominated by the appearance of the intergroup intramolecular HB of Hp···O (where O is in the carboxylic acid functional group and Hp is the phenolic proton in -OHp), and η3 serves as a switch of such HB. As a result, the (η1η20) SA conformers containing such Hp···O HB are more stable than other SA conformers (η1η21) without such the Hp···O HB. The present density functional theory calculations reveal that this Hp···O HB results in splitting of the O 1s CEBEs of two hydroxyl groups (-OH) by up to 1 eV and deshielding the Hp proton 1H NMR (δHp) up to 11.68 ppm for the (η1η20) conformers. Without such Hp···O HB, the O 1s XPS binding energies of two -OH groups will be closely located in the same band, and the 1H NMR chemical shift of the Hp atom will be as small as an 4.09 ppm SA conformer [SA-G(101)]. The present study indicates that the O 1s CEBE splitting between two -OH groups serves as an indicator of the presence of the Hp···O HB in SA conformers, which is also supported by the 1H NMR results.

Redefining Multimorbidity in Older Surgical Patients.

BACKGROUND: Multimorbidity in surgery is common and associated with worse postoperative outcomes. However, conventional multimorbidity definitions (≥2 comorbidities) label the vast majority of older patients as multimorbid, limiting clinical usefulness. We sought to develop and validate better surgical specialty-specific multimorbidity definitions based on distinct comorbidity combinations. STUDY DESIGN: We used Medicare claims for patients aged 66 to 90 years undergoing inpatient general, orthopaedic, or vascular surgery. Using 2016 to 2017 data, we identified all comorbidity combinations associated with at least 2-fold (general/orthopaedic) or 1.5-fold (vascular) greater risk of 30-day mortality compared with the overall population undergoing the same procedure; we called these combinations qualifying comorbidity sets. We applied them to 2018 to 2019 data (general = 230,410 patients, orthopaedic = 778,131 patients, vascular = 146,570 patients) to obtain 30-day mortality estimates. For further validation, we tested whether multimorbidity status was associated with differential outcomes for patients at better-resourced (based on nursing skill-mix, surgical volume, teaching status) hospitals vs all other hospitals using multivariate matching. RESULTS: Compared with conventional multimorbidity definitions, the new definitions labeled far fewer patients as multimorbid: general = 85.0% (conventional) vs 55.9% (new) (p < 0.0001); orthopaedic = 66.6% vs 40.2% (p < 0.0001); and vascular = 96.2% vs 52.7% (p < 0.0001). Thirty-day mortality was higher by the new definitions: general = 3.96% (conventional) vs 5.64% (new) (p < 0.0001); orthopaedic = 0.13% vs 1.68% (p < 0.0001); and vascular = 4.43% vs 7.00% (p < 0.0001). Better-resourced hospitals offered significantly larger mortality benefits than all other hospitals for multimorbid vs nonmultimorbid general and orthopaedic, but not vascular, patients (general surgery difference-in-difference = -0.94% [-1.36%, -0.52%], p < 0.0001; orthopaedic = -0.20% [-0.34%, -0.05%], p = 0.0087; and vascular = -0.12% [-0.69%, 0.45%], p = 0.6795). CONCLUSIONS: Our new multimorbidity definitions identified far more specific, higher-risk pools of patients than conventional definitions, potentially aiding clinical decision-making.

The Safety of Performing Surgery at Ambulatory Surgery Centers Versus Hospital Outpatient Departments in Older Patients With or Without Multimorbidity.

BACKGROUND: Surgery for older Americans is increasingly being performed at ambulatory surgery centers (ASCs) rather than hospital outpatient departments (HOPDs), while rates of multimorbidity have increased. OBJECTIVE: To determine whether there are differential outcomes in older patients undergoing surgical procedures at ASCs versus HOPDs. RESEARCH DESIGN: Matched cohort study. SUBJECTS: Of Medicare patients, 30,958 were treated in 2018 and 2019 at an ASC undergoing herniorrhaphy, cholecystectomy, or open breast procedures, matched to similar HOPD patients, and another 32,702 matched pairs undergoing higher-risk procedures. MEASURES: Seven and 30-day revisit and complication rates. RESULTS: For the same procedures, HOPD patients displayed a higher baseline predicted risk of 30-day revisits than ASC patients (13.09% vs 8.47%, P < 0.0001), suggesting the presence of considerable selection on the part of surgeons. In matched Medicare patients with or without multimorbidity, we observed worse outcomes in HOPD patients: 30-day revisit rates were 8.1% in HOPD patients versus 6.2% in ASC patients ( P < 0.0001), and complication rates were 41.3% versus 28.8%, P < 0.0001. Similar patterns were also found for 7-day outcomes and in higher-risk procedures examined in a secondary analysis. Similar patterns were also observed when analyzing patients with and without multimorbidity separately. CONCLUSIONS: The rates of revisits and complications for ASC patients were far lower than for closely matched HOPD patients. The observed initial baseline risk in HOPD patients was much higher than the baseline risk for the same procedures performed at the ASC, suggesting that surgeons are appropriately selecting their riskier patients to be treated at the HOPD rather than the ASC.

Defining Multimorbidity in Older Patients Hospitalized with Medical Conditions.

BACKGROUND: The term "multimorbidity" identifies high-risk, complex patients and is conventionally defined as ≥2 comorbidities. However, this labels almost all older patients as multimorbid, making this definition less useful for physicians, hospitals, and policymakers. OBJECTIVE: Develop new medical condition-specific multimorbidity definitions for patients admitted with acute myocardial infarction (AMI), heart failure (HF), and pneumonia patients. We developed three medical condition-specific multimorbidity definitions as the presence of single, double, or triple combinations of comorbidities - called Qualifying Comorbidity Sets (QCSs) - associated with at least doubling the risk of 30-day mortality for AMI and pneumonia, or one-and-a-half times for HF patients, compared to typical patients with these conditions. DESIGN: Cohort-based matching study PARTICIPANTS: One hundred percent Medicare Fee-for-Service beneficiaries with inpatient admissions between 2016 and 2019 for AMI, HF, and pneumonia. MAIN MEASURES: Thirty-day all-location mortality KEY RESULTS: We defined multimorbidity as the presence of ≥1 QCS. The new definitions labeled fewer patients as multimorbid with a much higher risk of death compared to the conventional definition (≥2 comorbidities). The proportions of patients labeled as multimorbid using the new definition versus the conventional definition were: for AMI 47% versus 87% (p value<0.0001), HF 53% versus 98% (p value<0.0001), and pneumonia 57% versus 91% (p value<0.0001). Thirty-day mortality was higher among patients with ≥1 QCS compared to ≥2 comorbidities: for AMI 15.0% versus 9.5% (p<0.0001), HF 9.9% versus 7.0% (p <0.0001), and pneumonia 18.4% versus 13.2% (p <0.0001). CONCLUSION: The presence of ≥2 comorbidities identified almost all patients as multimorbid. In contrast, our new QCS-based definitions selected more specific combinations of comorbidities associated with substantial excess risk in older patients admitted for AMI, HF, and pneumonia. Thus, our new definitions offer a better approach to identifying multimorbid patients, allowing physicians, hospitals, and policymakers to more effectively use such information to consider focused interventions for these vulnerable patients.

Harm-to-Benefit of Three Decades of Prostate Cancer Screening in Black Men.

BACKGROUND: Prostate-specific antigen screening has profoundly affected the epidemiology of prostate cancer in the United States. Persistent racial disparities in outcomes for Black men warrant re-examination of the harms of screening relative to its cancer-specific mortality benefits in this population. METHODS: We estimated overdiagnoses and overtreatment of prostate cancer for men of all races and for Black men 50 to 84 years of age until 2016, the most recent year with treatment data available, using excess incidence relative to 1986 based on the Surveillance, Epidemiology, and End Results registry and U.S. Census data as well as an established microsimulation model of prostate cancer natural history. Combining estimates with plausible mortality benefit, we calculated numbers needed to diagnose (NND) and treat (NNT) to prevent one prostate cancer death. RESULTS: For men of all races, we estimated 1.5 to 1.9 million (range between estimation approaches) overdiagnosed and 0.9 to 1.5 million overtreated prostate cancers by 2016. Assuming that half of the 270,000 prostate cancer deaths avoided by 2016 were attributable to screening, the NND and the NNT would be 11 to 14 and 7 to 11 for men of all races and 8 to 12 and 5 to 9 for Black men, respectively. Alternative estimates incorporating a lag between incidence and mortality resulted in a NND and a NNT for Black men that reached well into the low single digits. CONCLUSIONS: Complementary approaches to quantifying overdiagnosis indicate a harm-benefit tradeoff of prostate-specific antigen screening that is more favorable for Black men than for men of all races considered together. Our findings highlight the need to account for the increased value of screening in Black men in clinical guidelines. (Funded by the Patient-Centered Outcomes Research Institute, the National Cancer Institute, the Bristol Myers Squibb Foundation, and the Damon Runyon Cancer Research Foundation.).

Optimising the deployment of vector control tools against malaria: a data-informed modelling study.

BACKGROUND: Concern that insecticide resistant mosquitoes are threatening malaria control has driven the development of new types of insecticide treated nets (ITNs) and indoor residual spraying (IRS) of insecticide. Malaria control programmes have a choice of vector control interventions although it is unclear which controls should be used to combat the disease. The study aimed at producing a framework to easily compare the public health impact and cost-effectiveness of different malaria prevention measures currently in widespread use. METHODS: We used published data from experimental hut trials conducted across Africa to characterise the entomological effect of pyrethroid-only ITNs versus ITNs combining a pyrethroid insecticide with the synergist piperonyl butoxide (PBO). We use these estimates to parameterise a dynamic mathematical model of Plasmodium falciparum malaria which is validated for two sites by comparing simulated results to empirical data from randomised control trials (RCTs) in Tanzania and Uganda. We extrapolated model simulations for a series of potential scenarios likely across the sub-Saharan African region and include results in an online tool (Malaria INtervention Tool [MINT]) that aims to identify optimum vector control intervention packages for scenarios with varying budget, price, entomological and epidemiological factors. FINDINGS: Our model indicates that switching from pyrethroid-only to pyrethroid-PBO ITNs could averted up to twice as many cases, although the additional benefit is highly variable and depends on the setting conditions. We project that annual delivery of long-lasting, non-pyrethroid IRS would prevent substantially more cases over 3-years, while pyrethroid-PBO ITNs tend to be the most cost-effective intervention per case averted. The model was able to predict prevalence and efficacy against prevalence in both RCTs for the intervention types tested. MINT is applicable to regions of sub-Saharan Africa with endemic malaria and provides users with a method of designing intervention packages given their setting and budget. INTERPRETATION: The most cost-effective vector control package will vary locally. Models able to recreate results of RCTs can be used to extrapolate outcomes elsewhere to support evidence-based decision making for investment in vector control. FUNDING: Medical Research Council, IVCC, Wellcome Trust. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Is a downwards head tilt a cross-cultural signal of dominance? Evidence for a universal visual illusion.

The present pre-registered research provides the first evidence that a downwards head tilt is sufficient to communicate dominance from a neutral facial expression among the Mayangna, members of an unindustrialized, small-scale traditional society in Nicaragua who have had minimal exposure to North American culture. Consistent with the Action Unit imposter effect observed in North American populations (Witkower and Tracy in Psychol Sci 30:893-906, 2019), changes to the appearance of the upper face caused by a downwards head tilt were sufficient to elicit perceptions of dominance among this population. Given that the Mayangna are unlikely to associate a downwards head tilt or related apparent facial changes with dominance as a result of cross-cultural learning, the present results suggest that perceptions of dominance formed from a downwards head tilt, and the visual illusion shaping these perceptions, are a widely generalizable, and possibly universal, feature of human psychology.

Incidence of Kidney Stones in the United States: The Continuous National Health and Nutrition Examination Survey.

PURPOSE: The incidence of kidney stones in the United States is currently unknown. Here, we assessed the incidence of kidney stones using recent, nationally representative data. MATERIALS AND METHODS: We used the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2018. During this time participants were asked, "Have you ever had a kidney stone?" and "In the past 12 months, have you passed a kidney stone?" Demographics analyzed include age, race, gender, body mass index, history of smoking, diabetes, hypertension, hypercholesterolemia and gout. Multivariable models were used to assess the independent impact of subject characteristics on kidney stone prevalence and incidence. RESULTS: Data were available on 10,521 participants older than age 20. The prevalence of kidney stones was 11.0% (95% CI 10.1-12.0). The 12-month incidence of kidney stones was 2.1% (95% CI 1.5-2.7), or 2,054 stones per 100,000 adults. We identified significant relationships between stone incidence and subject age, body mass index, race and history of hypertension. CONCLUSIONS: Here we find a substantially higher 12-month incidence of kidney stones than previous reports. We also validate known risk factors for stone prevalence as associated with incidence. The remarkable incidence and prevalence of stones is concerning and has implications for disease prevention and allocation of medical resources.

Alzheimer's Dementia After Exposure to Anesthesia and Surgery in the Elderly: A Matched Natural Experiment Using Appendicitis.

OBJECTIVE: The aim of this study was to determine whether surgery and anesthesia in the elderly may promote Alzheimer disease and related dementias (ADRD). BACKGROUND: There is a substantial conflicting literature concerning the hypothesis that surgery and anesthesia promotes ADRD. Much of the literature is confounded by indications for surgery or has small sample size. This study examines elderly patients with appendicitis, a common condition that strikes mostly at random after controlling for some known associations. METHODS: A matched natural experiment of patients undergoing appendectomy for appendicitis versus control patients without appendicitis using Medicare data from 2002 to 2017, examining 54,996 patients without previous diagnoses of ADRD, cognitive impairment, or neurological degeneration, who developed appendicitis between ages 68 through 77 years and underwent an appendectomy (the ''Appendectomy'' treated group), matching them 5:1 to 274,980 controls, examining the subsequent hazard for developing ADRD. RESULTS: The hazard ratio (HR) for developing ADRD or death was lower in the Appendectomy group than controls: HR = 0.96 [95% confidence interval (CI) 0.94-0.98], P < 0.0001, (28.2% in Appendectomy vs 29.1% in controls, at 7.5 years). The HR for death was 0.97 (95% CI 0.95-0.99), P = 0.002, (22.7% vs 23.1% at 7.5 years). The HR for developing ADRD alone was 0.89 (95% CI 0.86-0.92), P < 0.0001, (7.6% in Appendectomy vs 8.6% in controls, at 7.5 years). No subgroup analyses found significantly elevated rates of ADRD in the Appendectomy group. CONCLUSION: In this natural experiment involving 329,976 elderly patients, exposure to appendectomy surgery and anesthesia did not increase the subsequent rate of ADRD.