ACR Appropriateness Criteria® Dizziness and Ataxia: 2023 Update.

Diagnostic evaluation of a patient with dizziness or vertigo is complicated by a lack of standardized nomenclature, significant overlap in symptom descriptions, and the subjective nature of the patient's symptoms. Although dizziness is an imprecise term often used by patients to describe a feeling of being off-balance, in many cases dizziness can be subcategorized based on symptomatology as vertigo (false sense of motion or spinning), disequilibrium (imbalance with gait instability), presyncope (nearly fainting or blacking out), or lightheadedness (nonspecific). As such, current diagnostic paradigms focus on timing, triggers, and associated symptoms rather than subjective descriptions of dizziness type. Regardless, these factors complicate the selection of appropriate diagnostic imaging in patients presenting with dizziness or vertigo. This document serves to aid providers in this selection by using a framework of definable clinical variants. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Response trajectory to left dorsolateral prefrontal rTMS in major depressive disorder: A systematic review and meta-analysis: Trajectory of rTMS.

The depression response trajectory after a course of repetitive transcranial magnetic stimulation(rTMS) remains understudied. We searched for blinded randomized controlled trials(RCTs) that examined conventional rTMS over left dorsolateral prefrontal cortex(DLPFC) for major depressive episodes(MDE). The effect size was calculated as the difference in depression improvement, between active and sham rTMS. We conducted a random-effects dose-response meta-analysis to model the response trajectory from the beginning of rTMS to the post-treatment follow-up phase. The area under curve (AUC) of the first 8-week response trajectory was calculated to compare antidepressant efficacy between different rTMS protocols. We included 40 RCTs(n = 2012). The best-fitting trajectory model exhibited a logarithmic curve(X2=17.7, P < 0.001), showing a gradual ascent with tapering off around the 3-4th week mark and maintaining until week 16. The maximum effect size was 6.1(95 %CI: 1.25-10.96) at week 16. The subgroup analyses showed distinct trajectories across different rTMS protocols. Besides, the comparisons of AUC showed that conventional rTMS protocols with more pulse/session group or more total pulses were associated with greater efficacy than those with fewer pulse/session or fewer total pulses, respectively. A course of conventional left DLPFC rTMS could lead to both acute antidepressant effects and sustained after-effects, which were modeled by different rTMS protocols in MDE.

The Potential Role of Angiotensin-Converting Enzyme Inhibitors and Beta-Blockers in Reducing Pneumonia Severity in Older Adults.

Background Understanding the impact of pharmacological therapy on pneumonia severity is crucial for effective clinical management. The impact of angiotensin-converting enzyme inhibitors (ACEis) and beta-blockers (BBs) on pneumonia severity remains unknown, warranting further investigation. Methodology This retrospective study examined the hospital records of inpatients (≥75 years) admitted with community-acquired pneumonia in 2021. Pneumonia severity associated with the use of pre-established ACEi and BB therapy was documented using CURB-65 (confusion, uraemia, respiratory rate, blood pressure, age ≥65 years) and pneumonia severity index (PSI) scores. Descriptive statistics and multivariable linear regression were used to analyse differences across BB therapy, ACEi therapy, their combination, or neither (control group). Results A total of 803 patient records were examined, of whom 382 (47.6%) were male and 421 (52.4%) were female. Sample sizes for each group were as follows: control (n = 492), BB only (n = 185), ACEi only (n = 68), and BB + ACEi (n = 58). Distribution of aspiration pneumonia (AP) versus non-AP for each group, respectively, was control (21.1% vs. 78.9%), BB only (9.7% vs. 90.3%), ACEi only (7.3% vs. 92.7%), and ACEi + BB (12.1% vs. 87.9%). No significant differences in PSI and CURB-65 scores were found between intervention groups even after controlling for patient characteristics and irrespective of AP or non-AP aetiology. Patients with AP had significantly higher CURB-65 (p = 0.026) and PSI scores (p = 0.044) compared to those with non-AP. Conclusions Pre-prescribed ACEi or BB therapy did not appear to be associated with differences in pneumonia severity. There were no differences in pneumonia severity scores with ACEi and BB monotherapy or combined ACEi and BB therapy.

The dose-effect relationship of six stimulation parameters with rTMS over left DLPFC on treatment-resistant depression: A systematic review and meta-analysis.

This study aimed to evaluate the association of the six parameters, namely stimulation intensity, stimulation frequency, pulses per session, treatment duration, number of sessions, and total number of pulses with the efficacy of conventional transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex for patients with treatment-resistant depression (TRD). A random-effects dose-response meta-analysis of blinded randomized controlled trials (RCTs) involving 2391 participants were conducted to examine the dose-effect relationship of six stimulation parameters. Any of the six parameters significantly individually predicted proportion of variance in efficacy: pulses per session (R²=52.7%), treatment duration (R²=51.2%), total sessions (R²=50.9%), frequency (R²=49.6%), total pulses (R²=49.5%), and intensity (R²= 40.4%). Besides, we identified frequency as a potential parameter interacting with the other five parameters, resulting in a significant increase in variance(ΔR2) ranging from 5.0% to 16.7%. Finally, we found that RCTs using frequency > 10 Hz compared to those of 10 Hz showed better dose-effect relationships. We conclude that the six stimulation parameters significantly predict the dose-effect relationship of conventional rTMS on TRD. Besides, higher stimulation frequency, higher stimulation intensity, and adequate number of pulses were associated with treatment efficacy.

Incidence and survival of pediatric and adult hepatocellular carcinoma, United States, 2001-2020.

Importance: Hepatocellular carcinoma accounts for approximately 80% of liver neoplasms. Globally, hepatocellular carcinoma ranks as the third most lethal cancer, with the number of deaths expected to further increase by 2040. In adults, disparities in incidence and survival are well described while pediatric epidemiology is not well characterized. Objective: To describe incidence and survival for pediatric (ages 0-19 years) hepatocellular carcinoma cases and compare these measures to adults (ages ≥20 years) diagnosed with hepatocellular carcinoma. We evaluated demographic factors and clinical characteristics that influence incidence and outcomes. Design: Population-based cohort study. Setting: Incidence data from the US Cancer Statistics database from 2003 to 2020 and 5-year relative survival from the National Program of Cancer Registries from 2001 to 2019, covering 97% and 83% of the US population, respectively. Participants: 355,349 US Cancer Statistics and 257,406 the National Program of Cancer Registries patients were identified using ICD-O-3 C22.0 and 8170-5 codes. Main Outcomes and Measures: Incidence annual percent change (APC) and average APC (AAPC) using joinpoint regression. Five-year relative survival. All-cause survival estimated using multivariate Cox modeling. Corresponding 95% confidence intervals (CI) were calculated. Results: Incidence rate per 100,000 persons was 0.056 (95%CI:0.052-0.060) for pediatric cases and 7.793 (7.767-7.819) for adults. Incidence was stable in the pediatric population (0.3 AAPC, -1.1-1.7). In contrast, after periods of increase, incidence declined in adults after 2015 (-1.5 APC). Relative survival increased over time for both pediatric and adult ages and was higher for children and adolescents (46.4%, 95%CI:42.4-50.3) than adults (20.7%, 95%CI:20.5-20.9) overall and when stratified by stage. Regression modeling showed that non-Hispanic Black race and ethnicity was associated with higher risk of death in children and adolescents (1.48, 95%CI:1.07-2.05) and adults (1.11, 95%CI:1.09-1.12) compared to non-Hispanic white race and ethnicity. Conclusions and Relevance: Between 2003 and 2020 in the United States, pediatric incidence was stable while incidence in adults began to decline after 2015. Survival was higher across all stages for children and adolescents compared to adults. Non-Hispanic Black race and ethnicity showed a higher risk of death for both age groups. Further studies could explore the factors that influence these outcome disparities.

The Impact of Adjusting for Hysterectomy Prevalence on Cervical Cancer Incidence Rates and Trends Among Women Aged 30 Years and Older - United States, 2001-2019.

Hysterectomy protects against cervical cancer when the cervix is removed. However, measures of cervical cancer incidence often fail to exclude women with a hysterectomy from the population at risk denominator, underestimating and distorting disease burden. In this study, we estimated hysterectomy prevalence from the Behavioral Risk Factor Surveillance System surveys to remove the women who were not at risk of cervical cancer from the denominator and combined these estimates with the United States Cancer Statistics data. From these data, we calculated age-specific and age-standardized incidence rates for women aged >30 years from 2001-2019, adjusted for hysterectomy prevalence. We calculated the difference between unadjusted and adjusted incidence rates and examined trends by histology, age, race and ethnicity, and geographic region using Joinpoint regression. The hysterectomy-adjusted cervical cancer incidence rate from 2001-2019 was 16.7 per 100,000 women-34.6% higher than the unadjusted rate. After adjustment, incidence rates were higher by approximately 55% among Black women, 56% among those living in the East South Central division, and 90% among women aged 70-79 and >80 years. These findings underscore the importance of adjusting for hysterectomy prevalence to avoid underestimating cervical cancer incidence rates and masking disparities by age, race, and geographic region.

Characteristics and outcomes of a hospitalized cohort with reduced mortality from COVID-19, White Mountain apache tribal lands, April 1 - July 31, 2020.

BACKGROUND: Widespread transmission of COVID-19 continues to threaten public health, particularly of rural, American Indian communities. Although COVID-19 risk factors for severe disease and clinical characteristics are well described in the general population, there has been little shared on hospitalized American Indian populations. METHODS: In this observational study, we performed chart extractions on all persons hospitalized with COVID-19 from April 1 through July 31, 2020 among an exclusively American Indian population living on or near Tribal lands in eastern Arizona. We provide descriptive statistics for the cohort stratified by presentation, comparing those who self-presented or were referred by an outreach program. Exploratory analyses were performed to identify risk factors for morbidity and mortality. RESULTS: During the observation period, 2262 persons were diagnosed with COVID-19 and 490 (22%) were hospitalized. Hospitalized persons had a median age of 54 years; 92% had at least one comorbidity, 72% had greater than one comorbidity, and 60% had a BMI of > 30. Most persons required supplemental oxygen (83%), but the majority (62%) only required nasal cannula and only 11% were intubated. The case fatality rates were 1.7% for the population, 7.1% among hospitalizations, and 9.3% among hospitalized patients 50 years and older. All rates that are significantly lower than those reported nationally during the same period. CONCLUSIONS: We observed a cohort of American Indian patients hospitalized secondary to COVID-19 with greater number of comorbidities compared to the general population but with lower mortality rates. We posit that the primary driver of mortality reduction for this population and the hospitalized cohort was a community-based referral program that led to disproportionately lower fatality rates among the oldest persons.

Residual effects of medications for sleep disorders on driving performance: A systematic review and network meta-analysis of randomized controlled trials: NMA driving and hypnotics.

Sleep medications often carry residual effects potentially affecting driving safety, warranting network meta-analysis (NMA). PubMed/EMBASE/TRID/Clinicaltrials.gov/WHO-ICTRP/WebOfScience were inquired for randomized controlled trials of hypnotic driving studies in persons with insomnia and healthy subjects up to 05/28/2023, considering the vehicle's standard deviation of lateral position - SDLP (Standardized Mean Difference/SMD) and driving impairment rates on the first morning (co-primary outcomes) and endpoint. Risk-of-bias, global/local inconsistencies were measured, and CINeMA was used to assess the confidence in the evidence. Of 4,805 identified records, 26 cross-over RCTs were included in the systematic review, of which 22 entered the NMA, focusing on healthy subjects only. After a single administration, most molecules paralleled the placebo, outperforming zopiclone regarding SDLP. In contrast, ramelteon 8 mg, daridorexant 100 mg, zolpidem 10 mg bedtime, zolpidem middle-of-the-night 10 mg and 20 mg, mirtazapine 15-30 mg, and triazolam 0.5 mg performed significantly worse than placebo. Lemborexant 2.5-5 mg, suvorexant 15-20 mg, and zolpidem 3.5 mg middle-of-the-night associated with lower impairment than zopiclone. Repeated administration (maximum follow-up time of ten days) caused fewer residual effects than acute ones, except for flurazepam. Heterogeneity and inconsistency were negligible. Confidence in the evidence was low/very low. Sensitivity analyses confirmed the main analyses. Most FDA-approved hypnotics overlapped placebo at in-label doses, outperforming zopiclone. Repeated administration for 15 days or less reduced residual effects, warranting further research on the matter.

Prognostic factors of poor outcomes in pneumonia in older adults: aspiration or frailty?

PURPOSE: Little is known about the long-term and functional prognoses of older adults with pneumonia, which complicates their management. There is a common belief that aspiration is a poor prognostic factor; however, the diagnosis of aspiration pneumonia (AP) lacks consensus criteria and is mainly based on clinical characteristics typical of the frailty syndrome. Therefore, the poor prognosis of AP may also be a result of frailty rather than aspiration. This study investigated the impact of AP and other prognostic factors in older patients with pneumonia. METHODS: We performed a retrospective cohort study of patients aged 75 years and older, admitted with pneumonia in 2021. We divided patients according to their initial diagnosis (AP or non-AP), compared outcomes using Kaplan-Meier curves, and used logistic regression to identify independent prognostic factors. RESULTS: 803 patients were included, with a median age of 84 years and 52.7% were male. 17.3% were initially diagnosed with AP. Mortality was significantly higher in those diagnosed with AP than non-AP during admission (27.6% vs 19.0%, p = 0.024) and at 1 year (64.2% vs 53.1%, p = 0.018), with survival analysis showing a median survival time of 62 days and 274 days in AP and non-AP, respectively (χ2 = 9.2, p = 0.002). However, the initial diagnosis of AP was not an independent risk factor for poor prognosis in multivariable analysis. Old age, frailty and cardio-respiratory comorbidities were the main factors associated with death. CONCLUSION: The greater mortality in AP may be a result of increased frailty rather than the diagnosis of aspiration itself. This supports our proposal for a paradigm shift from making predictions based on the potentially futile labelling of AP or non-AP, to considering frailty and overall condition of the patient.

Predictors of increased affective symptoms and suicidal ideation during the COVID-19 pandemic: results from a large-scale study of 14 271 Thai adults.

BACKGROUND: Increasing data suggest emergent affective symptoms during the COVID-19 pandemic. OBJECTIVES: To study the impact of the COVID-19 pandemic on affective symptoms and suicidal ideation in Thai adults. METHODS: The Collaborative Outcomes Study on Health and Functioning during Infection Times uses non-probability sampling (chain referring and voluntary response sampling) and stratified probability sampling to identify risk factors of mental health problems and potential treatment targets to improve mental health outcomes during pandemics. FINDINGS: Analysing 14 271 adult survey participants across all four waves of the COVID-19 pandemic in Thailand, covering all 77 provinces from 1 June 2020 to 30 April 2022, affective symptoms and suicidality increased during COVID-19 pandemic. Affective symptoms were strongly predicted by pandemic (feelings of isolation, fear of COVID-19, loss of social support, financial loss, lack of protective devices) and non-pandemic (female sex, non-binary individuals, adverse childhood experiences (ACEs), negative life events, student status, multiple mental health and medical conditions, physical pain) risk factors. ACEs, prior mental health conditions and physical pain were the top three risk factors associated with both increased affective symptoms and suicidal ideation during the COVID-19 pandemic. Partial least squares analysis showed that ACEs were the most important risk factor as they impacted most pandemic and non-pandemic risk factors. CLINICAL IMPLICATIONS: Rational policymaking during a pandemic should aim to identify the groups at highest risk (those with ACEs, psychiatric and medical disease, women, non-binary individuals) and implement both immediate and long-term strategies to mitigate the impact of ACEs, while effectively addressing associated psychiatric and medical conditions.

Glymphatic fluid transport is suppressed by the aquaporin-4 inhibitor AER-271.

The glymphatic system transports cerebrospinal fluid (CSF) into the brain via arterial perivascular spaces and removes interstitial fluid from the brain along perivenous spaces and white matter tracts. This directional fluid flow supports the clearance of metabolic wastes produced by the brain. Glymphatic fluid transport is facilitated by aquaporin-4 (AQP4) water channels, which are enriched in the astrocytic vascular endfeet comprising the outer boundary of the perivascular space. Yet, prior studies of AQP4 function have relied on genetic models, or correlated altered AQP4 expression with glymphatic flow in disease states. Herein, we sought to pharmacologically manipulate AQP4 function with the inhibitor AER-271 to assess the contribution of AQP4 to glymphatic fluid transport in mouse brain. Administration of AER-271 inhibited glymphatic influx as measured by CSF tracer infused into the cisterna magna and inhibited increases in the interstitial fluid volume as measured by diffusion-weighted MRI. Furthermore, AER-271 inhibited glymphatic efflux as assessed by an in vivo clearance assay. Importantly, AER-271 did not affect AQP4 localization to the astrocytic endfeet, nor have any effect in AQP4 deficient mice. Since acute pharmacological inhibition of AQP4 directly decreased glymphatic flow in wild-type but not in AQP4 deficient mice, we foresee AER-271 as a new tool for manipulation of the glymphatic system in rodent brain.

Racial and Ethnic Disparities in the Prescribing of Pain Medication in US Primary Care Settings, 1999-2019: Where Are We Now?

BACKGROUND: Policy initiatives have attempted to reduce healthcare inequalities in the USA, but evidence on whether these initiatives have reduced racial and ethnic disparities in pain treatment in primary care is lacking. OBJECTIVE: To determine whether racial and ethnic disparities in medication prescribed for pain in primary care settings have diminished over a 21-year period from 1999 to 2019. DESIGN: An annual, representative cross-sectional probability sample of visits to US primary care physicians, taken from the National Ambulatory Medical Care Survey. PATIENTS: Pain-related visits to primary care physicians. MAIN MEASURES: Prescriptions for opioid and non-opioid analgesics. KEY RESULTS: Of 599,293 (16%) sampled visits, 94,422 were pain-related, representing a population-weighted estimate of 143 million visits made annually to primary care physicians for pain. Relative risk analysis controlling for insurance, pain type, and other potential confounds showed no difference in pain medication prescribed between Black and White patients (p = .121). However, White patients were 1.61 (95% CI 1.32-1.97) and Black patients 1.57 (95% CI 1.26-1.95) times more likely to be prescribed opioids than a more underrepresented group consisting of Asian, Native-Hawaiian/Pacific-Islander, and American-Indian/Alaska-Natives (ps < .001). Non-Hispanic/Latino patients were 1.32 (95% CI 1.18-1.45) times more likely to receive opioids for pain than Hispanic/Latino patients (p < .001). Penalized cubic spline regression found no substantive narrowing of disparities over time. CONCLUSIONS: These findings suggest that additional intervention strategies, or better implementation of existing strategies, are needed to eliminate ethnic and racial disparities in pain treatment towards the goal of equitable healthcare.

The association of total pulses with the efficacy of repetitive transcranial magnetic stimulation for treatment-resistant major depression: A dose-response meta-analysis.

AIM: This study aimed to examine dose-effects of total pulses on improvement of depressive symptoms in patients with treatment-resistant depression (TRD) receiving repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (DLPFC). MATERIALS AND METHODS: The MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, PsycINFO, and ClinicalTrial.gov databases were systematically searched. We included randomized, double-blind, placebo-controlled trials (RCT) that used rTMS over left DLPFC in patients with TRD. Excluded studies were non-TRD, non-RCTs, or combined other brain stimulation interventions. The outcome of interest was the difference between rTMS arms and sham controls in improvement of depressive symptoms in a dose-response manner. A random-effects meta-analysis and dose-response meta-analysis(DRMA) was used to examine antidepressant efficacy of rTMS and association with total pulses. RESULTS: We found that rTMS over left DLPFC is superior to sham controls (reported as standardized mean difference[SMD] with 95% confidence interval: 0.77; 0.56-0.98). The best-fitting model of DRMA was bell-shaped (estimated using restricted cubic spline model; R2 =0.42), indicating that higher doses (>26,660 total pulses) were not associated with increased improvement of depressive symptoms. Stimulation frequency(R2 =0.53) and age(R2 =0.51) were significant moderators for the dose-response curve. Furthermore, 15-20 Hz rTMS was superior to 10 Hz rTMS (0.61, 0.15-1.10) when combining all doses. CONCLUSIONS: Our findings suggest higher doses(total pulses) of rTMS were not always associated with increased improvement of depressive symptoms in patients with TRD, and that the dose-response relationship was moderated by stimulation frequency and age. These associations emphasize the importance of determining dosing parameters to achieve maximum efficacy.

Trends in Racial Inequalities in the Administration of Opioid and Non-opioid Pain Medication in US Emergency Departments Across 1999-2020.

BACKGROUND: Despite initiatives to eradicate racial inequalities in pain treatment, there is no clear picture on whether this has translated to changes in clinical practice. OBJECTIVE: To determine whether racial disparities in the receipt of pain medication in the emergency department have diminished over a 22-year period from 1999 to 2020. DESIGN: We used data from the National Hospital Ambulatory Medical Care Survey, an annual, cross-sectional probability sample of visits to emergency departments of non-federal general and short-stay hospitals in the USA. PATIENTS: Pain-related visits to the ED by Black or White patients. MAIN MEASURES: Prescriptions for opioid and non-opioid analgesics. KEY RESULTS: A total of 203,854 of all sampled 625,433 ED visits (35%) by Black or White patients were pain-related, translating to a population-weighted estimate of over 42 million actual visits to US emergency departments for pain annually across 1999-2020. Relative risk regression found visits by White patients were 1.26 (95% CI, 1.22-1.30; p<0.001) times more likely to result in an opioid prescription for pain compared to Black patients (40% vs. 32%). Visits by Black patients were also 1.25 (95% CI, 1.21-1.30; p<0.001) times more likely to result in non-opioid analgesics only being prescribed. Results were not substantively altered after adjusting for insurance status, type and severity of pain, geographical region, and other potential confounders. Spline regression found no evidence of meaningful change in the magnitude of racial disparities in prescribed pain medication over 22 years. CONCLUSIONS: Initiatives to create equitable healthcare do not appear to have resulted in meaningful alleviation of racial disparities in pain treatment in the emergency department.

The difference in all-cause mortality between COVID-19 patients treated with standard of care plus placebo and those treated with standard of care alone: a network meta-analysis of randomised controlled trials of immunomodulatory kinase inhibitors.

OBJECTIVES: The aim of this network meta-analysis (NMA) was to assess whether participants assigned to a placebo and standard of care (SoC) group had different major coronavirus disease 2019 (COVID-19)-related outcomes than those assigned to SoC alone. DESIGN: Frequentist model-based NMA. SETTING: We searched for randomised controlled trials (RCTs) of Janus kinase/Bruton tyrosine kinase inhibitors for the management of COVID-19. PARTICIPANTS: Patients with COVID-19 infection. MAIN OUTCOME MEASURES: The primary outcome was the 28-day all-cause mortality, and secondary outcomes were: (1) use of mechanical ventilation; (2) secondary bacterial infection; (3) acceptability (i.e. drop-out rate); and (4) safety (i.e. serious adverse events). We conducted an NMA using the frequentist model. Effect sizes were estimated using odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: We identified 14 eligible RCTs enrolling a total of 13,568 participants with COVID-19. Participants assigned to placebo plus SoC had a significantly higher risk of 28-day all-cause mortality than those receiving SoC alone (OR = 1.39, 95% CI = 1.07-1.79). This finding did not change substantially by subgroup analysis stratified by epidemiology factor, pandemic history progression and statistical methodologic consideration. In addition, none of the treatments investigated were associated with a significantly different risk of secondary bacterial infection, acceptability or safety compared with the SoC group. CONCLUSIONS: This NMA suggested a higher all-cause mortality in patients treated with placebo plus SoC compared with those treated with SoC alone. However, caution is advised in interpreting these results due to the absence of a direct head-to-head comparison. Future research should critically evaluate the necessity of placebo administration in COVID-19 RCTs and consider alternative study designs to minimise potential biases.Trial registration: The current study was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (TSGHIRB No. B-109-29) and registered in PROSPERO (CRD42022376217).

Integrated Response to Address a Resurgent Syphilis Epidemic in a Rural American Indian Community, Whiteriver, Arizona, January 2022 to June 2023.

BACKGROUND: The United States has seen a significant rise in syphilis over the past 20 years with a disparate impact on American Indian communities. We conducted a thorough review of the local epidemiology that guided an innovative response to curb the epidemic. METHODS: We analyzed syphilis data from a hospital in rural Arizona that serves an American Indian population of more than 18,000. Testing data were extracted from 2017 to 2023 with detailed chart reviews of all reactive results since January 2022. Descriptive and comparative statistics were computed using parametric and nonparametric methods where appropriate. RESULTS: Among 5888 tested persons, 555 (9.4%) had reactive results and 277 (4.7%) represented new infections. Among new cases, 151 (54.5%) were female and 55 (19.9%) were reinfections. The annualized incidence rate was 10.0 cases per 1000 persons with peak annualized incidence among women aged 30 to 34 years of 22.6 infections per 1000 persons. During the observation period and after the implementation of programmatic changes in June 2022, there were statistically significant reductions in median time to treatment (-80%), test positivity (-70%), infections (-60%), and no congenital syphilis cases during the observation period. CONCLUSIONS: We observed significantly elevated syphilis rates in American Indian/Alaska Native persons compared with the general population. Strategic implementation of new policies and practices led to a measurable and meaningful improvement in several epidemic variables, and our experience may serve as a model to other communities.

A comprehensive analysis of neuroblastoma incidence, survival, and racial and ethnic disparities from 2001 to 2019.

BACKGROUND: We characterize the incidence and 5-year survival of children and adolescents with neuroblastoma stratified by demographic and clinical factors based on the comprehensive data from United States Cancer Statistics (USCS) and the National Program of Cancer Registries (NPCR). METHODS: We analyzed the incidence of neuroblastoma from USCS (2003-2019) and survival data from NPCR (2001-2018) for patients less than 20 years old. Incidence trends were calculated by average annual percent change (AAPC) using joinpoint regression. Differences in relative survival were estimated comparing non-overlapping confidence intervals (CI). RESULTS: We identified 11,543 primary neuroblastoma cases in USCS. Age-adjusted incidence was 8.3 per million persons [95% CI: 8.2, 8.5], with an AAPC of 0.4% [95% CI: -0.1, 0.9]. Five-year relative survival from the NPCR dataset (n = 10,676) was 79.7% [95% CI: 78.9, 80.5]. Patients aged less than 1 year had the highest 5-year relative survival (92.5%). Five-year relative survival was higher for non-Hispanic White patients (80.7%) or Hispanic patients (80.8%) compared to non-Hispanic Black patients (72.6%). CONCLUSION: Neuroblastoma incidence was stable during 2003-2019. Differences in relative survival exist by sex, age, race/ethnicity, and stage; patients who were male, older, non-Hispanic Black, or with distant disease had worse survival. Future studies could seek to assess the upstream factors driving disparities in survival, and evaluate interventions to address inequities and improve survival across all groups.

Up-to-Date Breast, Cervical, and Colorectal Cancer Screening Test Use in the United States, 2021.

INTRODUCTION: We examined national estimates of breast, cervical, and colorectal cancer (CRC) screening test use and compared them with Healthy People 2030 national targets. Test use in 2021 was compared with prepandemic estimates. METHODS: In 2022, we used 2021 National Health Interview Survey (NHIS) data to estimate proportions of adults up to date with US Preventive Services Task Force recommendations for breast (women aged 50-74 y), cervical (women aged 21-65 y), and CRC screening (adults aged 50-75 y) across sociodemographic and health care access variables. We compared age-standardized estimates from the 2021 and 2019 NHIS. RESULTS: Percentages of adults up to date in 2021 were 75.7% (95% CI, 74.4%-76.9%), 75.2% (95% CI, 73.9%-76.4%), and 72.2% (95% CI, 71.2%-73.2%) for breast, cervical, and CRC screening, respectively. Estimates were below 50% among those without a wellness check in 3 years (all screening types), among those without a usual source of care or insurance (aged <65 y) (breast and CRC screening), and among those residing in the US for less than 10 years (CRC screening). Percentages of adults who were up to date with breast and cervical cancer screening and colonoscopy were similar in 2019 and 2021. Fecal occult blood/fecal immunochemical test (FOBT/FIT) use was modestly higher in 2021 (P < .001). CONCLUSIONS: In 2021, approximately 1 in 4 adults of screening age were not up to date with breast, cervical, and CRC screening recommendations, and Healthy People 2030 national targets were not met. Disparities existed across several characteristics, particularly those related to health care access. Breast, cervical, and colonoscopy test use within recommended screening intervals approximated prepandemic levels. FOBT/FIT estimates were modestly higher in 2021.

Genetic Inhibition of APOL1 Pore-Forming Function Prevents APOL1-Mediated Kidney Disease.

SIGNIFICANCE STATEMENT: African Americans are at increased risk of CKD in part due to high-risk (HR) variants in the apolipoprotein L1 ( APOL1 ) gene, termed G1/G2. A different APOL1 variant, p.N264K , reduced the risk of CKD and ESKD among carriers of APOL1 HR variants to levels comparable with individuals with APOL1 low-risk variants in an analysis of 121,492 participants of African ancestry from the Million Veteran Program (MVP). Functional genetic studies in cell models showed that APOL1 p.N264K blocked APOL1 pore-forming function and ion channel conduction and reduced toxicity of APOL1 HR mutations. Pharmacologic inhibitors that mimic this mutation blocking APOL1 -mediated pore formation may be able to prevent and/or treat APOL1 -associated kidney disease. BACKGROUND: African Americans are at increased risk for nondiabetic CKD in part due to HR variants in the APOL1 gene. METHODS: We tested whether a different APOL1 variant, p.N264K , modified the association between APOL1 HR genotypes (two copies of G1/G2) and CKD in a cross-sectional analysis of 121,492 participants of African ancestry from the MVP. We replicated our findings in the Vanderbilt University Biobank ( n =14,386) and National Institutes of Health All of Us ( n =14,704). Primary outcome was CKD and secondary outcome was ESKD among nondiabetic patients. Primary analysis compared APOL1 HR genotypes with and without p.N264K . Secondary analyses included APOL1 low-risk genotypes and tested for interaction. In MVP, we performed sequential logistic regression models adjusting for demographics, comorbidities, medications, and ten principal components of ancestry. Functional genomic studies expressed APOL1 HR variants with and without APOL1 p.N264K in cell models. RESULTS: In the MVP cohort, 15,604 (12.8%) had two APOL1 HR variants, of which 582 (0.5%) also had APOL1 p.N264K . In MVP, 18,831 (15%) had CKD, 4177 (3%) had ESKD, and 34% had diabetes. MVP APOL1 HR, without p.N264K , was associated with increased odds of CKD (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.60 to 1.85) and ESKD (OR, 3.94; 95% CI, 3.52 to 4.41). In MVP, APOL1 p.N264K mitigated the renal risk of APOL1 HR, in CKD (OR, 0.43; 95% CI, 0.28 to 0.65) and ESKD (OR, 0.19; CI 0.07 to 0.51). In the replication cohorts meta-analysis, APOL1 p.N264K mitigated the renal risk of APOL1 HR in CKD (OR, 0.40; 95% CI, 0.18 to 0.92) and ESKD (OR, 0.19; 95% CI, 0.05 to 0.79). In the mechanistic studies, APOL1 p.N264K blocked APOL1 pore-forming function and ion channel conduction and reduced toxicity of APOL1 HR variants. CONCLUSIONS: APOL1 p.N264K is associated with reduced risk of CKD and ESKD among carriers of APOL1 HR to levels comparable with individuals with APOL1 low-risk genotypes.

Placebo effects on all-cause mortality of patients with COVID-19 in randomized controlled trials of interleukin 6 antagonists: A systematic review and network meta-analysis.

AIM: Many randomized controlled trials (RCTs) have investigated the use of interleukin 6 antagonists for the treatment of coronavirus disease 2019 (COVID-19), yielding inconsistent results. This network meta-analysis (NMA) aimed to identify the source of these inconsistent results by reassessing whether participants treated with standard of care (SoC) plus placebo have different all-cause mortality from those treated with SoC alone and to reevaluate the efficacy of interleukin 6 antagonists in the treatment of COVID-19. METHODS: We conducted a systematic search for relevant RCTs from the inception of electronic databases through 1 September 2022. The primary outcome was all-cause mortality. The secondary outcomes were the incidences of major medical events, secondary infections, all-cause discontinuation, and serious adverse events. RESULTS: The results of NMA of 33 RCTs showed that patients with COVID-19 treated with SoC plus placebo had lower odds of all-cause mortality than those who received SoC alone (OR, 0.75 [95% confidence interval, 0.58-0.97]). This finding remained consistent after excluding studies with no incident deaths. In addition, when we consider the impact of the widely promoted COVID-19 vaccination and newly developed antiviral treatment strategy, the results from the analysis of the RCT published in 2021 and 2022 remained similar. CONCLUSION: These findings suggest the potential influence of placebo effects on the treatment outcomes of COVID-19 in RCTs. When evaluating the efficacy of treatment strategies for COVID-19, it is crucial to consider the use of placebo in the design of clinical trials.