Prevalence of SARS-CoV-2 Infection among Children and Adults in 15 US Communities, 2021

During January-August 2021, the Community Prevalence of SARS-CoV-2 Study used time/location sampling to recruit a cross-sectional, population-based cohort to estimate SARS-CoV-2 seroprevalence and nasal swab sample PCR positivity across 15 US communities. Survey-weighted estimates of SARS-CoV-2 infection and vaccine willingness among participants at each site were compared within demographic groups by using linear regression models with inverse variance weighting. Among 22,284 persons >2 months of age and older, median prevalence of infection (prior, active, or both) was 12.9% across sites and similar across age groups. Within each site, average prevalence of infection was 3 percentage points higher for Black than White persons and average vaccine willingness was 10 percentage points lower for Black than White persons and 7 percentage points lower for Black persons than for persons in other racial groups. The higher prevalence of SARS-CoV-2 infection among groups with lower vaccine willingness highlights the disparate effect of COVID-19 and its complications.

Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women.

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).

The National Association of Medical Examiners Position Paper on the Investigation and Certification of Pediatric Deaths From Environmental Neglect.

ABSTRACT: Pediatric deaths that occur because of environmental neglect often involve 4 common scenarios: (1) hyperthermia due to environmental exposure, (2) ingestion of an accessible drug or poison, (3) unwitnessed/unsupervised drownings, and (4) unsafe sleep practices. Given the same fact pattern, the manner of death will vary from accident to homicide to undetermined based on local custom and/or the certifier's training and experience. Medical examiner/coroner death certifications are administrative public health determinations made for vital statistical purposes. Because the manner of death is an opinion, it is understandable that manner determinations may vary among practitioners. No prosecutor, judge, or jury is bound by the opinions expressed on the death certificate. This position paper does not dictate how these deaths should be certified. Rather, it describes the challenges of the investigations and manner determinations in these deaths. It provides specific criteria that may improve consistency of certification. Because pediatric deaths often are of public interest, this paper provides the medical examiner/coroner with a professional overview of such manner determination issues to assist various stakeholders in understanding these challenges and variations.

Recommendations for neuroradiological examinations in children living with achondroplasia: a European Society of Pediatric Radiology and European Society of Neuroradiology opinion paper.

Children living with achondroplasia are at an increased risk of developing neurological complications, which may be associated with acute and life-altering events. To remediate this risk, the timely acquisition of effective neuroimaging that can help to guide clinical management is essential. We propose imaging protocols and follow-up strategies for evaluating the neuroanatomy of these children and to effectively identify potential neurological complications, including compression at the cervicomedullary junction secondary to foramen magnum stenosis, spinal deformity and spinal canal stenosis. When compiling these recommendations, emphasis has been placed on reducing scan times and avoiding unnecessary radiation exposure. Standardized imaging protocols are important to ensure that clinically useful neuroimaging is performed in children living with achondroplasia and to ensure reproducibility in future clinical trials. The members of the European Society of Pediatric Radiology (ESPR) Neuroradiology Taskforce and European Society of Neuroradiology pediatric subcommittee, together with clinicians and surgeons with specific expertise in achondroplasia, wrote this opinion paper. The research committee of the ESPR also endorsed the final draft. The rationale for these recommendations is based on currently available literature, supplemented by best practice opinion from radiologists and clinicians with subject-specific expertise.

Acceptability of a Dapivirine/Placebo Gel Administered Rectally to HIV-1 Seronegative Adults (MTN-026).

This study describes the acceptability of a rectal microbicide gel formulation using dapivirine (DPV) among men and women from two countries (United States and Thailand) participating in the Microbicide Trials Network-026 trial. We evaluated participants' acceptability of a rectal DPV/placebo gel as part of a Phase I trial (N = 26; 18 male, 8 female). Participants reported favorable acceptability of the study gel, with most participants reporting that they liked the gel the same (n = 14; 53.8%) or more (n = 11; 42.4%) than when they started the trial. Over half of participants noted that they would prefer the gel over condoms (n = 13; 50%) or that they liked condoms and the gel equally (n = 8; 30.8%). Side effects across products included leakage (n = 8; 30.8%), diarrhea (n = 4; 15.4%), or soiling (n = 1; 3.8%). The high acceptability of a rectal gel underscores its promise as a short-acting biomedical prevention, warranting future research for HIV prevention.Trial Registration: NCT03239483.

RESUMEN: Este estudio describe la aceptabilidad de un microbicida rectal (RM) con dapivirina (DPV) formulado como un gel por hombres y mujeres de dos países (Estados Unidos y Tailandia) que participaron como parte del Microbicide Trials Network (MTN)-026. Evaluamos la aceptabilidad de un gel rectal de DPV y un placebo como parte de un estudio de Fase I (N = 26; 18 hombres, 8 mujeres). Los participants informaron una aceptabilidad favorable sobre el gel del estudio; la mayoría de los participantes informaron que les gustó el gel igual (n = 14; 53.8%) o más (n = 11; 42.4%) que cuando comenzaron el estudio. Más de la mitad de los participantes señalaron que preferirían el gel sobre los condones (n = 13; 50%) o que les gustaban los condones y el gel por igual (n = 8; 30,8%). Los efectos de los productos incluyeron fugas (n = 8; 30,8%), diarrea (n = 4; 15,4%) o ensuciamiento (n = 1; 3,8%). La alta aceptabilidad de un gel rectal enfatiza su promesa para la prevención biomédica de acción corta y justifica futuras investigaciones para la prevención del VIH.

Hangings: Lessons Learned from the Coroner's Office.

BACKGROUND: Hangings are an infrequent wounding mechanism among patients arriving alive to hospital but are frequently encountered by the Coroner's Office. It is unclear if classically described hanging injuries, such as the Hangman's fracture, are common among contemporary hangings patients who typically do not suspend from height. This study was undertaken to define patient and injury characteristics after hangings causing death. METHODS: All patients presenting to the Los Angeles County Medical Examiner/Coroner's Office (January 2016 - May 2020) who died by hanging were included. Demographics, psychiatric history, hanging details, autopsy type, and sustained injuries were collected. Data variables were summarized with descriptive statistics and the diagnostic yield of a ligature mark in the diagnosis/exclusion of cervical injuries was calculated. RESULTS: Over the study, 1,401 patients died by hanging. Patients underwent external exam alone (n = 1,282, 92%), traditional neck autopsy (n = 114, 8%), or traditional neck autopsy plus postmortem computed tomography scan (n = 5, <1%). Home was the most frequent hanging setting (n = 1,028, 73%) followed by public spaces (n = 80, 6%) and jail (n = 28, 2%). The manner of death was almost exclusively suicide (n = 1,395, >99%) and psychiatric disease was common (n = 968, 69%). Of the patients undergoing traditional autopsy, most had a ligature mark (n = 109, 92%) and only 9 (8%) had a cervical injury (hyoid fractures, n = 6, 5%; thyroid cartilage fractures, n = 4, 3%). None had a vertebral fracture/dislocation. Sensitivity, specificity, positive predictive value, and negative predictive value of a ligature mark were 100%, 5%, 8%, and 100%. CONCLUSIONS: Hangings are a frequent cause of death in Los Angeles County. Patients typically have a psychiatric history and die almost exclusively from suicide. Hangings commonly occur at home, in public places, and in jail. Injuries were exceedingly rare and no patient sustained a Hangman's fracture, which may be related to the lack of significant suspension with modern hangings.

SCN1A variants associated with sudden infant death syndrome.

We identified SCN1A variants in 2 infants who died of sudden infant death syndrome (SIDS) with hippocampal abnormalities from an exome sequencing study of 10 cases of SIDS but no history of seizures. One harbored SCN1A G682V, and the other had 2 SCN1A variants in cis: L1296M and E1308D, a variant previously associated with epilepsy. Functional evaluation in a heterologous expression system demonstrated partial loss of function for both G682V and the compound variant L1296M/E1308D. Our cases represent a novel association between SCN1A and SIDS, extending the SCN1A spectrum from epilepsy to SIDS. Our findings provide insights into SIDS and support genetic evaluation focused on epilepsy genes in SIDS.

Long-Term Improvements in Chronic Axial Low Back Pain Patients Without Previous Spinal Surgery: A Cohort Analysis of 10-kHz High-Frequency Spinal Cord Stimulation over 36 Months.

Objective: This prospective, open-label study was designed to evaluate the long-term effectiveness of 10-kHz high-frequency spinal cord stimulation (SCS) in the treatment of chronic axial low back pain with no history of spinal surgery. Methods: Patients with chronic low back pain without previous spinal surgery underwent assessment by a multidisciplinary pain and surgical team to confirm eligibility. After a successful temporary trial of 10-kHz HF-SCS therapy, defined by ≥50% back pain reduction, enrolled subjects underwent permanent system implantation and were followed up for 36 months. Outcome measures consisted of a 100-mm visual analog scale (VAS) for pain intensity, the Oswestry Disability Index (ODI), and a standard measure of health-related quality of life. Results: Twenty-one patients satisfied the inclusion/exclusion criteria. Following a temporary trial, 20 of 21 (95%) subjects were implanted with a pulse generator, and 17 of 20 reached the 36-month time point. From baseline to 36 months, the average VAS pain intensity decreased from 79 ± 12 mm to 10 ± 12 mm, the average ODI score decreased from 53 ± 13 to 19.8 ± 13, and use of opioids decreased from 18 subjects to two subjects. One subject was deceased, unrelated to the study, one subject was explanted due to loss of effectiveness, and one subject was lost to follow-up. Conclusions: These results suggest that 10-kHz high-frequency SCS may provide significant, long-term back pain relief, improvement in disability and quality of life, and reduction in opioids for nonsurgical refractory back pain.

MTN-017: A Rectal Phase 2 Extended Safety and Acceptability Study of Tenofovir Reduced-Glycerin 1% Gel.

Background: Human immunodeficiency virus (HIV) disproportionately affects men who have sex with men (MSM) and transgender women (TGW). Safe and acceptable topical HIV prevention methods that target the rectum are needed. Methods: MTN-017 was a phase 2, 3-period, randomized sequence, open-label, expanded safety and acceptability crossover study comparing rectally applied reduced-glycerin (RG) 1% tenofovir (TFV) and oral emtricitabine/TFV disoproxil fumarate (FTC/TDF). In each 8-week study period participants were randomized to RG-TFV rectal gel daily, or RG-TFV rectal gel before and after receptive anal intercourse (RAI; or at least twice weekly in the event of no RAI), or daily oral FTC/TDF. Results: MSM and TGW (n = 195) were enrolled from 8 sites in the United States, Thailand, Peru, and South Africa with mean age of 31.1 years (range 18-64). There were no differences in ≥grade 2 adverse event rates between daily gel (incidence rate ratio [IRR], 1.09; P = .59) or RAI gel (IRR, 0.90; P = .51) compared to FTC/TDF. High adherence (≥80% of prescribed doses assessed by unused product return and Short Message System reports) was less likely in the daily gel regimen (odds ratio [OR], 0.35; P < .001), and participants reported less likelihood of future daily gel use for HIV protection compared to FTC/TDF (OR, 0.38; P < .001). Conclusions: Rectal application of RG TFV gel was safe in MSM and TGW. Adherence and product use likelihood were similar for the intermittent gel and daily oral FTC/TDF regimens, but lower for the daily gel regimen. Clinical Trials Registration: NCT01687218.

Health Care Usage and Suicide Risk Screening within 1 Year of Suicide Death.

BACKGROUND: Research indicates patients often seek medical care within 1 year of suicide. Health care encounters are a crucial opportunity for health professionals to identify patients at highest risk and provide preventative services. OBJECTIVE: Study aims were to determine the characteristics of persons seeking health care within 12 months of suicide death and evaluate suicide risk screening (SRS) frequency in the emergency department (ED) vs. clinic settings. METHODS: Medical examiner and hospital data of patients who died by suicide from 2007 to 2013 were evaluated. Descriptive analyses included demographics and frequency of ED vs. clinic visits. We also compared SRS before and after implementation of The Joint Commission's recommendation to assess suicide risk. RESULTS: The 224 deceased patients were primarily single white males (mean age 67 years). Mental health issues, substance abuse, and prior suicide attempts were present alone or in combination in 74%. Visits were primarily behavioral health or substance abuse problems in the ED, and medical issues in the clinic. After implementation of universal SRS in the ED, screening increased from 39% to 92%. Among patients screened in the ED, 73% (37 of 51) screened negative for suicide risk. CONCLUSIONS: Universal SRS increased the number of people screened in the ED. However, negative SRS may not equate to reduced risk for future suicide within 1 year. Future studies might investigate targeted screening of individuals with known suicide risk factors, as well as alternatives to patient self-report of intent to self-harm for patients with mental health or substance abuse problems.

10 kHz High-Frequency Spinal Cord Stimulation for Chronic Axial Low Back Pain in Patients With No History of Spinal Surgery: A Preliminary, Prospective, Open Label and Proof-of-Concept Study.

OBJECTIVE: To explore the effectiveness of 10 kHz high frequency spinal cord stimulation (HF10 therapy) treatment of chronic low back pain in patients who have not had spinal surgery. METHODS: Patients with chronic low back pain without prior spinal surgery were evaluated by a team of spine surgeons to rule out any spinal pathology amenable to surgical interventions and by a multidisciplinary pain team to confirm eligibility for the study. After a successful (>50% back pain reduction) trial of HF10 therapy, enrolled subjects underwent permanent system implantation and were followed-up one year post-implant. RESULTS: About 95% of the enrolled subjects (20/21) received the permanent system. At 12 months post-implant, both back pain VAS score and ODI were significantly reduced compared with baseline values (by 73% and 48%, respectively); an estimated quality-adjusted life year gain of 0.47 and a reduction in opioid use by 64% was observed. Four more patients among those unable to work at baseline due to back pain were employed at 12 months post-implant. There were no serious adverse events. CONCLUSION: HF10 therapy may provide significant back pain relief, reduction in disability, improvement quality of life, and reduction in opioid use in chronic low back pain not resulting from spinal surgery.

Who is prescribing controlled medications to patients who die of prescription drug abuse?

BACKGROUND: Prescription drug-related fatalities remain a significant issue in the United States, yet there is a relative lack of knowledge on the specialty-specific prescription patterns for drug-related deaths. METHODS: We designed a study that investigated medical examiner reports of prescription drug-related deaths that occurred in San Diego County during 2013. A Prescription Drug Monitoring Program search was performed on each of these cases to ascertain which physician specialties had prescribed controlled substances to these patients. The data were analyzed for each specialty, including pills per prescription, type of prescription, doctor shoppers (4 physicians + 4 pharmacies over 1 year), and chronic users (≥3 consecutive months of medications). MAIN FINDINGS: In 2013, 4.5% of all providers in San Diego County wrote a prescription for a patient who died a prescription-related death. There were a total of 713 providers who prescribed 4366 medications totaling 328928 pills. Overall, emergency physicians gave the lowest number of prescriptions per provider (1.6), whereas pain management provided the highest amount per provider (12.9). Most prescriptions went to doctor shoppers (>50%) and chronic users (95.8%). Hydrocodone was the most frequently prescribed medication to those patients whose deaths were related to prescription drugs. CONCLUSIONS: Emergency physicians appear to provide fewer prescriptions to those patients who die due to prescription drugs. Emergency physicians do, however, account for a significant proportion of total providers in this study. These results highlight the need to use Prescription Drug Monitoring Program data to closely monitor prescription patterns and to intervene when necessary.

A description of Medical Examiner prescription-related deaths and prescription drug monitoring program data.

BACKGROUND: The Centers of Disease Control and Prevention have declared prescription drug abuse an epidemic in the United States. However, demographic data correlating prescription-related deaths with actual prescriptions written is not well described. The purpose of this study is to compare toxicology reports on autopsy for prescription-related deaths with Prescription Drug Monitor Program (PDMP) data. METHODS: This is a retrospective analysis comparing 2013 San Diego Medical Examiner data on 254 unintentional prescription-related deaths obtained for 12 months before death with data from the California PDMP. Data were analyzed on age, sex, whether there was information on the PDMP, types and quantities of prescribed medications, number of pharmacies and providers involved, and whether there was a match between the Medical Examiner toxicology report and data from the PDMP. RESULTS: In 2013, there were 254 unintentional prescription-related deaths; 186 patients (73%) had PDMP data 12 months before death. Ingesting prescription medications with illicit drugs, alcohol, and/or over-the-counter medications accounted for 40% of the unintentional deaths. Opioids were responsible for the majority of single medication deaths (36; 70.6%). The average number of prescriptions was 23.5 per patient, and the average patient used 3 pharmacies and had 4.5 providers. Chronic prescription use was found in 68.8% of patients with PDMP data. CONCLUSIONS: The PDMP data highlight important patterns that can provide valuable insight to clinicians making decisions regarding types and amounts of medications they prescribe. Although there is no guaranteed solution to prevent prescription-related deaths, PDMP data can be useful to prevent coprescribing and medication interaction and by following best clinical practices.

Fifteen-minute consultation: neuromuscular spinal deformity in disabled children.

Spinal deformity is common and occasionally inevitable in children with disabilities. This article concentrates on non-ambulant children with a spinal deformity, and aims to help the paediatrician understand the challenges families and spinal surgeons face.

Characterisation of the novel HLA-DRB4*01:01:12 allele by sequencing-based typing.

HLA-DRB4*01:01:12 differs from HLA-DRB4*01:01:01:01 by one nucleotide substitution in codon 175 in exon 3.

The novel HLA-F*01:16 and HLA-F*01:17 alleles identified in hematopoietic cell donors.

Two novel non-classical HLA class I alleles have been characterized, HLA-F*01:16 and -F*01:17.

Can postoperative Cobb and pelvic obliquity corrections be predicted using supine traction X-rays in non-ambulatory patients with cerebral palsy fused to L5? A case series study.

PURPOSE: This study aimed to determine whether Cobb and pelvic obliquity corrections can be predicted using supine traction radiographs in patients with cerebral palsy (CP) who underwent posterior spinal fusion (PSF) from T2/3 to L5. METHODS: From January 2010 to January 2020, 167 non-ambulatory patients with CP scoliosis underwent PSF using pedicle screws in two quaternary centers with a minimum of 2 years follow-up (FU). Radiological measurements and chart reviews were performed. RESULTS: A total of 106 patients aged 15.6 ± 0.4 years were included. All patients had significant correction of the Cobb angle (MC), pelvic obliquity (PO), thoracic kyphosis (TK), and lumbar lordosis (LL) without loss of correction at the last FU (LFU). Curve flexibility was significantly correlated with Cobb correction (δMC) immediately postoperatively (p < 0.0001, r = 0.8950), followed by the amount of correction in pelvic obliquity under traction (δPOT) (p = 0.0252, r = 0.2174). For correction in PO (δPO), the most significant variable was δPOT (p < 0.0001, r = 0.7553), followed by curve flexibility (p = 0.0059, r = 0.26) and the amount of correction in Cobb under traction (p = 0.0252, r = 0.2174). CONCLUSIONS: Cobb and PO corrections can be predicted using supine traction films for non-ambulatory CP patients treated with PSF from T2/3 to L5. The variables evaluated were interconnected, reinforcing preoperative planning for these patients. Comparative large-scale studies on patient-related clinical outcomes are required to determine whether this predicted correction is associated with improved surgical outcomes and reduced complication rates. LEVEL OF EVIDENCE: IV.

A randomized trial looking at planning prompts to reduce opioid prescribing.

Prior work has demonstrated that personalized letters are effective at reducing opioid and benzodiazepine prescribing, but it is unclear whether If/when-then planning prompts would enhance this effect. We conducted a decedent-clustered trial which randomized 541 clinicians in Los Angeles County to receive a standard (n = 284), or comparator (n = 257) version of a letter with If/when-then prompts. We found a significant 12.85% (6.83%, 18.49%) and 8.32% (2.34%, 13.93%) decrease in the primary outcomes morphine (MME) and diazepam milligram equivalents (DME), respectively. This study confirms the benefit of planning prompts, and repeat letter exposure among clinicians with poor patient outcomes. Limitations include lack of generalizability and small sample size. Clinicaltrials.gov registration: NCT03856593.

Improved Selectivity and Stability in Methane Dry Reforming by Atomic Layer Deposition on Ni-CeO2-ZrO2/Al2O3 Catalysts.

Ni can be used as a catalyst for dry reforming of methane (DRM), replacing more expensive and less abundant noble metal catalysts (Pt, Pd, and Rh) with little sacrifice in activity. Ni catalysts deactivate quickly under realistic DRM conditions. Rare earth oxides such as CeO2, or as CeO2-ZrO2-Al2O3 (CZA), are supports that improve both the activity and stability of Ni DRM systems due to their redox activity. However, redox-active supports can also enhance the undesired reverse water gas shift (RWGS) reaction, reducing the hydrogen selectivity. In this work, Ni on CZA was coated with an ultrathin Al2O3 overlayer using atomic layer deposition (ALD) to study the effects of the overlayer on catalyst activity, stability, and H2/CO ratio. A low-conversion screening method revealed improved DRM activity and lower coking rate upon the addition of the Al2O3 ALD overcoat, and improvements were subsequently confirmed in a high-conversion reactor at long times onstream. The overcoated samples gave an H2/CO ratio of ∼1 at high conversion, much greater than uncoated catalysts, and no evidence of deactivation. Characterization of used (but still active) catalysts using several techniques suggests that active Ni is in formal oxidation state >0, Ni-Ce-Al is most likely present as a mixed oxide at the surface, and a nominal thickness of 0.5 nm for the Al2O3 overcoat is optimal.