Commutability is where the measurement response for a reference material (RM) is the same as for an individual patient sample with the same concentration of analyte measured using two or more measurement systems. Assessment of commutability is essential when the RM is used in a calibration hierarchy or to ensure that clinical measurements are comparable across different measurement procedures and at different times. The commutability of three new Standard Reference Materials(®) (SRMs) for determining serum total 25-hydroxyvitamin D [25(OH)D], defined as the sum of 25-hydroxyvitamin D(2) [25(OH)D(2)] and 25-hydroxyvitamin D(3) [25(OH)D(3)], was assessed through an interlaboratory study. The following SRMs were assessed: (1) SRM 2969 Vitamin D Metabolites in Frozen Human Serum (Total 25-Hydroxyvitamin D Low Level), (2) SRM 2970 Vitamin D Metabolites in Frozen Human Serum (25-Hydroxyvitamin D(2) High Level), and (3) SRM 1949 Frozen Human Prenatal Serum. These SRMs represent three clinically relevant situations including (1) low levels of total 25(OH)D, (2) high level of 25(OH)D(2), and (3) 25(OH)D levels in nonpregnant women and women during each of the three trimesters of pregnancy with changing concentrations of vitamin D-binding protein (VDBP). Twelve laboratories using 17 different ligand binding assays and eight laboratories using nine commercial and custom liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays provided results in this study. Commutability of the SRMs with patient samples was assessed using the Clinical and Laboratory Standards Institute (CLSI) approach based on 95% prediction intervals or a pre-set commutability criterion and the recently introduced International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) approach based on differences in bias for the clinical and reference material samples using a commutability criterion of 8.8%. All three SRMs were deemed as commutable with all LC-MS/MS assays using both CLSI and IFCC approaches. SRM 2969 and SRM 2970 were deemed noncommutable for three and seven different ligand binding assays, respectively, when using the IFCC approach. Except for two assays, one or more of the three pregnancy levels of SRM 1949 were deemed noncommutable or inconclusive using different ligand binding assays and the commutability criterion of 8.8%. Overall, a noncommutable assessment for ligand binding assays is determined for these SRMs primarily due to a lack of assay selectivity related to 25(OH)D(2) or an increasing VDBP in pregnancy trimester materials rather than the quality of the SRMs. With results from 17 different ligand binding and nine LC-MS/MS assays, this study provides valuable knowledge for clinical laboratories to inform SRM selection when assessing 25(OH)D status in patient populations, particularly in subpopulations with low levels of 25(OH)D, high levels of 25(OH)D(2), women only, or women who are pregnant.

The HIV integrase inhibitor, dolutegravir (DTG), in the absence of eliciting integrase (int) resistance, has been reported to select mutations in the virus 3'-polypurine tract (3'-PPT) adjacent to the 3'-LTR U3. An analog of DTG, cabotegravir (CAB), has a high genetic barrier to drug resistance and is used in formulations for treatment and long-acting pre-exposure prophylaxis. We examined whether mutations observed for DTG would emerge in vitro with CAB. HIV-1IIIB was cultured in paired experiments of continuous high (300 nM) CAB initiated 2 h or 24 h after infection. After eight months of CAB treatment, no int resistance was detected. Conversely, HIV RNA 3'-PPT mutants were detected within one month and were the majority virus by day 98. The appearance of 3'-PPT variants coincided with a rapid accumulation of HIV 1-LTR and 2-LTR circles. RNA amplification from the 3'-LTR TAR identified transcripts crossing 2-LTR circle junctions, which incorporated the adjacent U5 sequence identical to the 3'-PPT mutants. 3'-PPT variants were only identified in LTR circles and transcripts. Additionally, we found evidence of linear HIV and LTR circle recombination with human DNA at motifs homologous to 3'-PPT sequences. HIV persistence under CAB was associated with transcription and recombination of LTR circle sequences.

OBJECTIVES: It is important to monitor national HIV preexposure prophylaxis (PrEP) use in the United States. However, PrEP use data in the Veterans Health Administration (VHA) system are not included in the current monitoring surveillance. To address this gap, we examined the trends in PrEP use among U.S. Veterans receiving health services in the VHA system. METHODS: We analyzed 2014-2022 VHA data to identify the annual number and prevalence of persons aged ≥18 years prescribed PrEP, stratified by sex, age, race/ethnicity, and region. We also assessed trends by calculating the estimated annual percent change and 95% confidence intervals using Poisson models. RESULTS: The number of Veterans prescribed PrEP increased from 361 in 2014 to 6050 in 2022 with an estimated annual percent change of 29.6% (95% CI: 22.6 to 37.1). Of 6050 Veterans with PrEP prescriptions in 2022, 95.2% were men, 4.8% were women, 50.4% were White, 24.5% Black or African American (Black), and 14.0% Hispanic or Latino. The prevalence of Black and Hispanic or Latino individuals prescribed PrEP increased significantly from 2014 to 2022. CONCLUSIONS: VHA data fill a gap in monitoring PrEP use in the United States. We observed an increasing trend in the number of Veterans prescribed PrEP similar to trends among persons with commercial or public health insurance.

Cardiovascular disease (CVD) is the leading cause of illness and death in the US and is substantially affected by social determinants of health, such as social, economic, and environmental factors. CVD disproportionately affects groups that have been economically and socially marginalized, yet health care and public health professionals often lack tools for collecting and using data to understand and address CVD inequities among their populations of focus. The Health Equity Indicators for Cardiovascular Disease Toolkit (HEI for CVD Toolkit) seeks to address this gap by providing metrics, measurement guidance, and resources to support users collecting, measuring, and analyzing data relevant to their CVD work. The toolkit includes a conceptual framework (a visual model for understanding health inequities in CVD); a comprehensive list of health equity indicators (metrics of inequities that influence CVD prevention, care, and management); guidance in definitions, measures, and data sources; lessons learned and examples of HEI implementation; and other resources to support health equity measurement. To develop this toolkit, we performed literature scans to identify primary topics and themes relevant to addressing inequities in CVD, engaged with subject matter experts in health equity and CVD, and conducted pilot studies to understand the feasibility of gathering and analyzing data on the social determinants of health in various settings. This comprehensive development process resulted in a toolkit that can help users understand the drivers of inequities in their communities or patient populations, assess progress, evaluate intervention outcomes, and guide actions to address CVD disparities.

Interest in utilizing exoskeletons to mitigate the risks of musculoskeletal disorders (MSDs) among construction workers is growing, spurred by encouraging results in other industries. However, it is crucial to carefully examine their impact on workers' stability and balance before implementation. In this study, seven male participants lifted a 35-lb cinder block from a production table to a simulated wall at two heights—elbow and shoulder levels—using three different exoskeleton models on an unstable platform, where their balance and shoulder muscle activity were assessed. Balance-related parameters, included mean distance (MDIST), total excursion (EXCUR), and mean velocity (VEL) of the center of pressure, were derived from force plate data. Muscle activity in six shoulder and upper arm muscles was estimated using electromyography (EMG) data. The results indicated that wearing two of the exoskeletons significantly increased both total and medio-lateral (ML) MDIST compared to not wearing an exoskeleton. Wearing one of the exoskeletons significantly increased total and ML VEL and ML EXCUR. Although lifting level did not have a significant impact on the balance parameters, it did affect the muscle activity in most of the measured muscles. Moreover, only one exoskeleton significantly reduced the activity in a particular shoulder muscle compared to no exoskeleton use. In conclusion, the evaluated shoulder-assist exoskeletons showed limited benefits for preventing upper extremity MSDs and may negatively affect whole-body balance during a block-laying task on an unstable platform. These findings underscore the importance of comprehensive evaluations of balance and effectiveness prior to adopting exoskeletons in construction. © 2024

In Mozambique, targeted provider-initiated HIV testing and counselling (PITC) is recommended where universal PITC is not feasible, but its effectiveness depends on healthcare providers' training. This study aimed to evaluate the effect of a Ministry of Health training module in targeted PITC on the HIV positivity yield, and identify factors associated with a positive HIV test. We conducted a single-group pre-post study between November 2018 and November 2019 in the triage and emergency departments of four healthcare facilities in Manhiça District, a resource-constrained semi-rural area. It consisted of two two-month phases split by a one-week targeted PITC training module ("observation phases"). The HIV positivity yield of targeted PITC was estimated as the proportion of HIV-positive individuals among those recommended for HIV testing by the provider. Additionally, we extracted aggregated health information system data over the four months preceding and following the observation phases to compare yield in real-world conditions ("routine phases"). Logistic regression analysis from observation phase data was conducted to identify factors associated with a positive HIV test. Among the 7,102 participants in the pre- and post-training observation phases (58.5% and 41.5% respectively), 68% were women, and 96% were recruited at triage. In the routine phases with 33,261 individuals (45.8% pre, 54.2% post), 64% were women, and 84% were seen at triage. While HIV positivity yield between pre- and post-training observation phases was similar (10.9% (269/2470) and 11.1% (207/1865), respectively), we observed an increase in yield in the post-training routine phase for women in triage, rising from 4.8% (74/1553) to 7.3% (61/831) (Yield ratio = 1.54; 95%CI: 1.11-2.14). Age (25-49 years) (OR = 2.43; 95%CI: 1.37-4.33), working in industry/mining (OR = 4.94; 95%CI: 2.17-11.23), unawareness of partner's HIV status (OR = 2.50; 95%CI: 1.91-3.27), and visiting a healer (OR = 1.74; 95%CI: 1.03-2.93) were factors associated with a positive HIV test. Including these factors in the targeted PITC algorithm could have increased new HIV diagnoses by 2.6%. In conclusion, providing refresher training and adapting the current targeted PITC algorithm through further research can help reach undiagnosed PLHIV, treat all, and ultimately eliminate HIV, especially in resource-limited rural areas.

BACKGROUND: Because COVID-19 case data do not capture most SARS-CoV-2 infections, the actual risk of severe disease and death per infection is unknown. Integrating sociodemographic data into analysis can show consequential health disparities. METHODS: Data were merged from September 2020 to November 2021 from 6 national surveillance systems in matched geographic areas and analyzed to estimate numbers of COVID-19-associated cases, emergency department visits, and deaths per 100 000 infections. Relative risks of outcomes per infection were compared by sociodemographic factors in a data set including 1490 counties from 50 states and the District of Columbia, covering 71% of the US population. RESULTS: Per infection with SARS-CoV-2, COVID-19-related morbidity and mortality were higher among non-Hispanic American Indian and Alaska Native persons, non-Hispanic Black persons, and Hispanic or Latino persons vs non-Hispanic White persons; males vs females; older people vs younger; residents in more socially vulnerable counties vs less; those in large central metro areas vs rural; and people in the South vs the Northeast. DISCUSSION: Meaningful disparities in COVID-19 morbidity and mortality per infection were associated with sociodemography and geography. Addressing these disparities could have helped prevent the loss of tens of thousands of lives.

Substantive and significant advances have been made in the last two decades in the characterization of human immunodeficiency virus (HIV) infections using molecular techniques. These advances include the use of real-time measurements, isothermal amplification, the inclusion of internal quality assurance protocols, device miniaturization and the automation of specimen processing. The result has been a significant increase in the availability of results to a high level of accuracy and quality. Molecular assays are currently widely used for diagnostics, antiretroviral monitoring and drug resistance characterization in developed countries. Simple and cost-effective point-of-care versions are also being vigorously developed with the eventual goal of providing timely healthcare services to patients residing in remote areas and those in resource-constrained countries. In this review, we discuss the evolution of these molecular technologies, not only in the context of the virus, but also in the context of tests focused on human genomics and transcriptomics.

BACKGROUND: Amalgam has been used for more than 150 years as a safe and reliable restorative material. The authors described the occurrence of amalgam and nonamalgam restorations in the United States in primary and permanent teeth across age groups and according to sociodemographic characteristics. METHODS: The authors used clinical examination data from the National Health and Nutrition Examination Survey 2015-2018 for participants 2 years and older (n = 17,040). The authors estimated the prevalence and mean number of amalgam and nonamalgam restorations in primary and permanent teeth according to age groups (2-5 years, 6-11 years, 12-15 years, 16-19 years, 20-39 years, 40-59 years, 60-79 years, and ≥ 80 years), race and ethnicity, federal poverty guideline, education, and pregnancy status. RESULTS: The prevalence of amalgam restorations ranged from 4% through 69%. Overall, amalgam restorations were more prevalent in children and adolescents from racial and ethnic minority groups and families at lower poverty levels and with lower education. The mean number of teeth with nonamalgam restorations was higher than those with amalgam restorations in primary teeth of children aged 6 through 11 years, permanent teeth of those 12 through 15 years and 20 through 39 years, and women aged 20 through 49 years, regardless of pregnancy status. The mean number of amalgam restorations was higher than that for nonamalgam restorations in older age groups. CONCLUSIONS: Nonamalgam restorations were the most common in the primary teeth of children older than 5 years and in the permanent teeth of adults younger than 40 years. Amalgam restorations were more common in older adults. Amalgam and nonamalgam restorations were equally common in children younger than 5 years. PRACTICAL IMPLICATIONS: The study findings suggest a shift from amalgam to alternative restorative materials in the United States.

Since its beginning more than 75 years ago [1], epigenetics has been an evolving field with growing applications to the study of cancer, aging, and gene expression in response to environmental exposures. The emergence of high-throughput technology for measuring epigenetic markers has enabled population-based studies [2]. The relatively new field of epigenetic epidemiology investigates epigenetic associations from a population perspective for insights into disease risk, prevention, and progression. Unlike genetic variants, epigenetic markers are dynamic, offering epidemiologists a new approach to linking early life and environmental exposures with disease risk [3]. | | Scientific publications on epigenetic epidemiology have been rapidly increasing in number and variety over the past 20 years. The literature now includes studies of epigenetic markers beyond DNA methylation (DNAm), such as histone modification and non-coding RNA, and consists of a variety of study designs including epigenome-wide association studies (EWAS), candidate gene studies, and clinical trials. Epigenetic markers are investigated as risk factors, such as DNAm in association with type 2 diabetes incidence [4], or outcomes, such as DNAm changes in response to air pollution [5]. The objective of the Epigenetic Epidemiology Publications Database (EEPD) is to offer a user-friendly website to explore the expanding literature in epigenetics, epidemiology, and public health.

BACKGROUND AND OBJECTIVES: HIV preexposure prophylaxis (PrEP) is safe, effective, and was approved for adolescents in 2018. Adolescents and young adults make up 20% of HIV diagnoses in the United States. Our objective was to describe trends in adolescents prescribed PrEP during 2018 through 2021 and characteristics of these adolescents and their PrEP providers. METHODS: We identified adolescents aged 13 to 19 years with oral PrEP prescriptions during 2018 through 2021 in a national pharmacy database using a validated algorithm. We assessed trends by calculating the overall percentage change and estimated annual percentage change with 95% confidence intervals. We described characteristics of adolescents and their PrEP providers in 2021. We performed χ2 analyses to assess differences by sex and age group. RESULTS: The number of adolescents prescribed PrEP increased 76.2% from 2018 to 2021 (estimated annual percentage change: 18.0% [95% confidence interval: 16.6-19.5]), despite decreases in 2020. We observed increases among all sex and age groups, with larger increases among older adolescents aged 18 to 19 years. The majority of the 6444 adolescents prescribed PrEP in 2021 were male (82.6%) and aged 18 to 19 years (87.8%). Among 2455 physician PrEP providers, 29.6% were pediatricians, with varying specialty distributions by adolescent age group (P < .001). Among the 217 pediatricians who prescribed PrEP to adolescents aged 13 to 17 years, 67.7% were general pediatricians. CONCLUSIONS: PrEP provision for adolescents has increased, largely among older and male adolescents. The availability of PrEP provides an important opportunity for pediatric providers to take an active role in HIV prevention.

BACKGROUND: To inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine (mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV). METHODS: We conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6-10-14 weeks/fIPV at 6 weeks (A); mOPV1 at 6-10-14 weeks/fIPV at 10 weeks (B); mOPV1 at 6-10-14 weeks (C); and bOPV at 6-10-14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004). FINDINGS: During 18 December 2018 - 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% [95% CI: 91-97%]) versus two mOPV1 doses with fIPV at 6 weeks (96% [93-98%]) or 10 weeks (96% [93-98%]). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines. INTERPRETATION: Given with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV. FUNDING: U.S. Centers for Disease Control and Prevention.

BACKGROUND: Non-disclosure of known HIV status by people living with HIV but undergoing HIV testing leads to waste of HIV testing resources and distortion of estimates of HIV indicators. In Mozambique, an estimated one-third of persons who tested positive already knew their HIV-positive status. To our knowledge, this study is the first to assess the factors that prevent people living with HIV (PLHIV) from disclosing their HIV-positive status to healthcare providers during a provider-initiated counseling and testing (PICT) campaign. METHODS: This analysis was nested in a larger PICT cross-sectional study performed in the Manhiça District, Southern Mozambique from January to July 2019, in which healthcare providers actively asked patients about their HIV-status. Patients who tested positive for HIV were crosschecked with the hospital database to identify those who had previously tested positive and were currently or previously enrolled in care. PLHIV who did not disclose their HIV-positive status were invited to participate and provide consent, and were interviewed using a questionnaire designed to explore barriers, patterns of community/family disclosure, and stigma and discrimination. RESULTS: We found that 16.1% of participants who tested positive during a PICT session already knew their HIV-positive status but did not disclose it to the healthcare provider. All the participants reported previous mistreatment by general healthcare providers as a reason for nondisclosure during PICT. Other reasons included the desire to know if they were cured (33.3%) or to re-engage in care (23.5%). Among respondents, 83.9% reported having disclosed their HIV-status within their close community, 48.1% reported being victims of verbal or physical discrimination following their HIV diagnosis, and 46.7% reported that their HIV status affected their daily activities. CONCLUSION: Previous mistreatment by healthcare workers was the main barrier to disclosing HIV-positive status. The high proportion of those disclosing their HIV status to their community but not to healthcare providers suggests that challenges with patient-provider relationships affect this care behavior rather than social stigma and discrimination. Improving patient-provider relationships could increase trust in healthcare providers, reduce non-disclosures, and help optimize resources and provide accurate estimates of the UNAIDS first 95 goal.

Background: The origin of divergent SARS-CoV-2 spike sequences found in wastewater, but not in clinical surveillance, remains unclear. These "cryptic" wastewater sequences have harbored many of the same mutations that later emerged in Omicron lineages. We first detected a cryptic lineage in municipal wastewater in Wisconsin in January 2022. Named the "Wisconsin Lineage", we sought to determine this virus's geographic origin and characterize its persistence and evolution over time. Method(s): We systematically sampled maintenance holes to trace the Wisconsin Lineage's origin. We sequenced spike RBD domains, and where possible, whole viral genomes, to characterize the evolution of this lineage over the 13 consecutive months that it was detectable. Finding(s): The persistence of the Wisconsin Lineage signal allowed us to trace it from a central wastewater plant to a single facility, with a high concentration of viral RNA. The viral sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in Wisconsin at low levels from October 2020 to February 2021, while mutations in the spike gene resembled those subsequently found in Omicron variants. Interpretation(s): We propose that prolonged detection of the Wisconsin Lineage in wastewater represents persistent shedding of SARS-CoV-2 from an infected individual, with ongoing within-host viral evolution leading to an ancestral B.1.234 virus accumulating "Omicron-like" mutations. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.

BACKGROUND: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. METHODS: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. RESULTS: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. CONCLUSIONS: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. FUNDING: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

BACKGROUND: National data indicate that working-aged adults (20-64 years) are more likely to report financial barriers to receiving needed oral health care relative to other age groups. The aim of this study was to examine the burden of untreated caries (UC) and its association with reporting an unmet oral health care need among working-aged adults. METHODS: The authors used National Health and Nutrition Examination Survey data from 2011 through 2016 for 10,286 dentate adults to examine the prevalence of mild to moderate (1-3 affected teeth) and severe (≥ 4 affected teeth) UC. The authors used multivariable logistic regression to identify factors that were associated with reporting an unmet oral health care need. RESULTS: Low-income adults had mild to moderate UC (26.2%) 2 times more frequently and severe UC (13.2%) 3 times more frequently than higher-income adults. After controlling for covariates, the variables most strongly associated with reporting an unmet oral health care need were UC, low income, fair or poor general health, smoking, and no private health insurance. The model-adjusted prevalence of reporting an unmet oral health care need among low-income adults with mild to moderate and severe UC were 35.7% and 45.1%, respectively. CONCLUSIONS: The burden of UC among low-income adults is high; prevalence was approximately 40% with approximately 3 affected teeth per person on average. Reporting an unmet oral health care need appears to be capturing primarily differences in UC, health, and financial access to oral health care. PRACTICAL IMPLICATIONS: Data on self-reported unmet oral health care need can have utility as a surveillance tool for monitoring UC and targeting resources to decrease UC among low-income adults.

BACKGROUND: Untreated caries (UC), although highly prevalent, is largely preventable. Information on the contribution of different teeth to UC prevalence and severity could be helpful in evaluating UC surveillance protocols and the relative benefits of caries prevention interventions. METHODS: The authors combined data from 3 cycles (2011-2016) of the National Health and Nutrition Examination Survey for participants aged 6 through 11 years, 12 through 19 years, 20 through 34 years, 35 through 49 years, 50 through 64 years, 65 through 74 years, and 75 years and older. For each age group the authors calculated the contribution of successive permanent tooth types (for example, first molars and second molars) to UC prevalence and severity. RESULTS: UC prevalence and the percentage of prevalence detected by means of screening molars were, respectively, 5% and 95% among participants aged 6 through 11 years; 16% and 92% among participants aged 12 through 19 years; 29% and 86% among participants aged 20 through 34 years; 26% and 70% among participants aged 35 through 49 years; 21% and 48% among participants aged 50 through 64 years; 16% and 36% among participants aged 65 through 74 years; and 17% and 25% among participants 75 years and older. Among adults aged 50 years and older, no teeth appeared to capture a disproportionate share of UC prevalence. Molars accounted for 87%, 79%, and 56% of severity among participants aged 6 through 11 years, 12 through 19 years, and 20 through 34 years, respectively. After age 34 years, molars accounted for less than 50% of severity. CONCLUSIONS: Molars are the tooth type most susceptible to UC well into adulthood. PRACTICAL IMPLICATIONS: Molars could be used as sentinel teeth for surveillance of UC and adults could benefit from caries prevention that targets molars.

This commentary describes the creation of the Zika Virus Individual Participant Data Consortium, a global collaboration to address outstanding questions in Zika virus (ZIKV) epidemiology through conducting an individual participant data meta-analysis (IPD-MA). The aims of the IPD-MA are to (1) estimate the absolute and relative risks of miscarriage, fetal loss, and short- and long-term sequelae of fetal exposure; (2) identify and quantify the relative importance of different sources of heterogeneity (e.g., immune profiles, concurrent flavivirus infection) for the risk of adverse fetal, infant, and child outcomes among infants exposed to ZIKV in utero; and (3) develop and validate a prognostic model for the early identification of high-risk pregnancies and inform communication between health care providers and their patients and public health interventions (e.g., vector control strategies, antenatal care, and family planning programs). By leveraging data from a diversity of populations across the world, the IPD-MA will provide a more precise estimate of the risk of adverse ZIKV-related outcomes within clinically relevant subgroups and a quantitative assessment of the generalizability of these estimates across populations and settings. The ZIKV IPD Consortium effort is indicative of the growing recognition that data sharing is a central component of global health security and outbreak response.

BACKGROUND: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. METHODS: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1-59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. FINDINGS: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6-97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3-65·6) of causes, whereas bacteria accounted for 27·3% (23·3-31·6) and Mycobacterium tuberculosis for 5·9% (3·9-8·3). Viruses were less common (54·5%, 95% CrI 47·4-61·5 vs 68·0%, 62·7-72·7) and bacteria more common (33·7%, 27·2-40·8 vs 22·8%, 18·3-27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4-34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus-enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. INTERPRETATION: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. FUNDING: Bill & Melinda Gates Foundation.

Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.

We conducted environmental surveillance to detect avian influenza viruses circulating at live poultry markets (LPMs) and poultry farms in Guangxi Autonomous Region, China, where near the China-Vietnam border. From November through April 20172018 and 20182019, we collected environmental samples from 14 LPMs, 4 poultry farm, and 5 households with backyard poultry in two counties of Guangxi and tested for avian influenza A, H5, H7, and H9 by real-time reverse transcription-polymerase chain reaction (rRT-PCR). In addition, we conducted four cross-sectional questionnaire surveys among stall owners on biosecurity practices in LPMs of two study sites. Among 16,713 environmental specimens collected and tested, the median weekly positive rate for avian influenza A was 53.6% (range = 33.5% 66.0%), including 25.2% for H9, 4.9% for H5, and 21.2% for other avian influenza viruses A subtypes, whereas a total of two H7 positive samples were detected. Among the 189 LPM stalls investigated, most stall owners (73.0%) sold chickens and ducks. Therefore, continued surveillance of the avian influenza virus is necessary for detecting and responding to emerging trends in avian influenza virus epidemiology. 2023

We conducted environmental surveillance to detect avian influenza viruses circulating at live poultry markets (LPMs) and poultry farms in Guangxi Autonomous Region, China, where near the China-Vietnam border. From November through April 2017–2018 and 2018–2019, we collected environmental samples from 14 LPMs, 4 poultry farm, and 5 households with backyard poultry in two counties of Guangxi and tested for avian influenza A, H5, H7, and H9 by real-time reverse transcription-polymerase chain reaction (rRT-PCR). In addition, we conducted four cross-sectional questionnaire surveys among stall owners on biosecurity practices in LPMs of two study sites. Among 16,713 environmental specimens collected and tested, the median weekly positive rate for avian influenza A was 53.6% (range = 33.5% − 66.0%), including 25.2% for H9, 4.9% for H5, and 21.2% for other avian influenza viruses A subtypes, whereas a total of two H7 positive samples were detected. Among the 189 LPM stalls investigated, most stall owners (73.0%) sold chickens and ducks. Therefore, continued surveillance of the avian influenza virus is necessary for detecting and responding to emerging trends in avian influenza virus epidemiology. © 2023

BACKGROUND: . The Vaccine Adverse Event Reporting System (VAERS) is the United States national passive vaccine safety surveillance system. We updated the data on the safety of single-antigen varicella vaccine (VAR) and assessed the safety of combination measles, mumps, rubella, and varicella vaccine (MMRV) licensed in the United States using VAERS data. METHODS: US VAERS reports received after administration of VAR and MMRV during 2006-2020 were identified. Reports were analyzed by vaccine type, age, seriousness, most common adverse events (AEs), and concomitant vaccines. We reviewed medical records of selected reports of AEs of special interest and conducted empirical Bayesian data mining to identify disproportionally reported AEs. RESULTS: During 2006-2020, approximately 132.8 million VAR doses were distributed; 40 684 reports were received in VAERS (30.6/100 000 doses distributed), with 4.1% classified as serious (1.3/100 000 doses distributed). Approximately 35.5 million MMRV doses were distributed; 13 325 reports were received (37.6/100 000 doses distributed) with 3.3% classified as serious (1.3/100 000 doses distributed). The most common adverse health events after both VAR and MMRV were injection site reactions (31% and 27%), rash (28% and 20%), and fever (12% and 14%), respectively. Vaccination errors accounted for 23% of reports after VAR administration and 41% after MMRV administration, but ≥95% of them did not describe an adverse health event. AEs associated with evidence of vaccine strain varicella-zoster virus (vVZV) infection included meningitis, encephalitis, herpes zoster, and 6 deaths (all in immunocompromised persons with contraindications for vaccination). No new or unexpected AE was disproportionally reported. CONCLUSIONS: No new or unexpected safety findings were detected for VAR and MMRV given as recommended, reinforcing the favorable safety profiles of these vaccines. Providers should obtain specimens for viral testing and strain-typing for serious AEs if they consider vVZV as the possible causative agent.

OBJECTIVE: Despite the high HIV associated burden, Mozambique lacks data on HIV counselling and testing (HCT) costs. To help guide national HIV/AIDS programs, we estimated the cost per test for voluntary counselling and testing (VCT) from the patient's perspective and the costs per person tested and per HIV-positive individual linked to care to the healthcare provider for VCT, provider-initiated counselling and testing (PICT) and home-based testing (HBT). We also assessed the cost-effectiveness of these strategies for linking patients to care. METHODS: Data from a cohort study conducted in the Manhia District were used to derive costs and linkage-to-care outcomes of the three HCT strategies. A decision tree was used to model HCT costs according to the likelihood of HCT linking individuals to care and to obtain the incremental cost-effectiveness ratios (ICERs) of PICT and HBT with VCT as the comparator. Sensitivity analyses were performed to assess robustness of base-case findings. FINDINGS: Based on costs and valuations in 2015, average and median VCT costs to the patient per individual tested were US$1.34 and US$1.08, respectively. Costs per individual tested were greatest for HBT (US$11.07), followed by VCT (US$7.79), and PICT (US$7.14). The costs per HIV-positive individual linked to care followed a similar trend. PICT was not cost-effective in comparison with VCT at a willingness-to-accept threshold of US$4.53, but only marginally given a corresponding base-case ICER of US$4.15, while HBT was dominated, with higher costs and lower impact than VCT. Base-case results for the comparison between PICT and VCT presented great uncertainty, whereas findings for HBT were robust. CONCLUSION: PICT and VCT are likely equally cost-effective in Manhia. We recommend that VCT be offered as the predominant HCT strategy in Mozambique, but expansion of PICT could be considered in limited-resource areas. HBT without facilitated linkage or reduced costs is unlikely to be cost-effective.

OBJECTIVE: To determine viral load (VL) nonsuppression (VLN) rates, HIV drug resistance (HIVDR) prevalence, and associated factors among female sex workers (FSWs) in Ethiopia. METHODS: A cross-sectional biobehavioral survey was conducted among FSWs in 11 cities in Ethiopia in 2014. Whole blood was collected, and HIVDR genotyping was performed. Logistic regression analysis was performed to identify factors associated with VLN and HIVDR. RESULTS: Among 4900 participants, 1172 (23.9%) were HIV-positive and 1154 (98.5%) had a VL result. Participants were categorized into antiretroviral therapy (ART) (n = 239) and ART-naive (n = 915) groups based on self-report. From the 521 specimens (ART, 59; ART-naive, 462) with VL ≥1000 copies/mL, genotyping was successful for 420 (80.6%) and 92 (21.9%) had drug resistance mutations (DRMs). Pretreatment drug resistance (PDR) was detected in 16.5% (63/381) of the ART-naive participants. Nucleoside reverse transcriptase inhibitor (NRTI), non-NRTIs (NNRTIs), and dual-class DRMs were detected in 40 (10.5%), 55 (14.4%), and 35 (9.2%) of the participants, respectively. Among 239 participants on ART, 59 (24.7%) had VLN. Genotyping was successfully performed for 39 (66.1%). DRMs were detected in 29 (74.4%). All 29 had NNRTI, 23 (79.3%) had NRTI or dual-class DRMs. VLN was associated with age 35 years or older, CD4+ T-cell count <350 cells/mm3, and being forced into selling sex. PDR and acquired drug resistance were associated with CD4+ T-cell count <350 cells/mm3 (P < 0.001). CONCLUSIONS: The high VLN and HIVDR rates among FSWs underscore the need for targeted interventions to improve ART access and virologic monitoring to maximize the benefit of ART and limit the spread of HIV and HIVDR.

Introduction HIV self-testing (HIVST) is a WHO recommended strategy to increase testing, especially among key populations, men, and young adults. Between May - December 2019, a pilot was implemented in Zambézia province, Mozambique, allowing clients to purchase HIV self-tests in 14 public/private pharmacies. The study assessed the strategy's acceptability and uptake. Methods Pharmacy-based exit-surveys were conducted in a random sample of clients, during the first three months of the pilot, independent of HIVST purchase. Another random sample of clients who bought an HIVST completed a survey 1-12 weeks after purchase. Chi-square and Mann-Whitney tests were used for the analysis, comparing clients who purchased an HIVST versus not. Results 1139 adults purchased 1344 tests. Buyers were predominantly male (70%) and younger (52% between 15-34 years of age). Surveys were completed by 280 exiting pharmacy clients and 82 clients who purchased an HIVST. Main advantages were confidentiality and lack of need of a health provider visit, with main disadvantages being absence of nearby counseling and fear of results. No differences between buyers and non-buyers were seen for these factors. Among all undergoing HIVST, the 71 (92%) perceived the instructions to be clear, however, 29 (38%) stated they would have benefitted from additional pre-test information or counseling. Ten (13%) reported following up at a nearby health facility to confirm results and/or receive care. Conclusions Offering HIVST at public/private pharmacies was acceptable among people who traditionally tend to have a lower HIV testing coverage, such as males and young adults. However, additional resources and/or enhanced educational materials to address the lack of counseling, and linkage-to-care systems need to be put into place before scaling up this strategy.

AIMS: We examined changes in the prevalence of elevated depressive symptoms among US adults with diabetes, prediabetes, and normal glycemic status during 2005-2016. METHODS: We analyzed data from 32,676 adults in the 2005-2016 National Health and Nutrition Examination Surveys. We defined diabetes as self-reporting a physician diagnosis of diabetes or A1C ≥ 6.5% [48 mmol/mol], and prediabetes as A1C 5.7-6.4% [39-46 mmol/mol]. We used the 9-item Patient Health Questionnaire (PHQ-9) score ≥ 10 or antidepressant use to define 'clinically significant depressive symptoms' (CSDS) and PHQ-9 score ≥ 12 as 'Major Depressive Disorder' (MDD). We calculated prevalence age-standardized to the 2000 US census and used logistic-regression to compute adjusted odds of CSDS and MDD for 2005-2008, 2009-2012, and 2015-2016. We analyzed the prevalence of A1C ≥ 9.0% [75 mmol/mol], systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, non-HDL cholesterol ≥ 130 mg/dL, and current smoking among adults with diagnosed diabetes by depressive status. RESULTS: The prevalence of CSDS increased among individuals with normal glycemic status from 15.0% (13.5-16.2) to 17.3% (16.0-18.7) (p = 0.03) over 2005-2016. The prevalence of CSDS and MDD remained stable among adults with prediabetes (~ 16% and 1%, respectively) and diabetes (~ 26% and ~3%). After controlling for glycemic, sociodemographic, economic, and self-rated health variables, we found 2-fold greater odds of CSDS among unemployed individuals and 3-fold greater odds among those with fair/poor self-rated health across all survey periods. Cardiometabolic care targets for adults with diagnosed diabetes were stable from 2005 to 2016 and similar across depressive status. CONCLUSIONS: One-fourth of adults with diabetes have comorbid CSDS; this prevalence remained stable over 2005-2016 with no change in diabetes care. At the population level, depression does not appear to impact diabetes care, but further research could explore subgroups that may be more vulnerable and could benefit from integrated care that addresses both conditions.

Limited data are available for how biomarkers of tobacco exposure (BOE) change when cigarette smokers transition to using electronic nicotine delivery systems (ENDS). Using biomarker data from Waves 1 (20132014) and 2 (20142015) of the PATH Study, we examined how mean BOE concentrations, including metabolites of nicotine, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOCM) and metals, changed when 2475 adult smokers transitioned to using ENDS or quit tobacco products. Exclusive smokers who transitioned to dual use had a significant decrease in NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), but not nicotine metabolites, most PAHs, metals, or VOCMs. Exclusive smokers who became dual users had significant reductions in total nicotine equivalents, NNAL, and 2CyEMA (acrylonitrile metabolite), but only in those who reduced cigarettes per day (CPD) by >=50%. Smokers who transitioned to exclusive ENDS use had significant reductions in most TSNAs, PAHs, and VOCMs; however, nicotine metabolites did not decrease in dual users who became exclusive ENDS users. Smokers who quit tobacco use had significant decreases in nicotine metabolites, all TSNAs, most PAHs, and most VOCMs. Cigarette smokers who became dual users did not experience significant reductions in most BOEs. Reductions were impacted by changes in CPD. However, transitioning from smoking to no tobacco or exclusive ENDS use was associated with reduced exposure to most BOEs measured. Future analyses could incorporate additional waves of PATH data and examine changes in biomarker exposure by ENDS device type and CPD. 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, with low-income settings characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. Funding: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

A method for aerosol chemical analysis using handheld Raman spectrometer has been developed and its application to measurement of crystalline silica concentration in workplace atmosphere is described. The approach involves collecting aerosol as a spot sample using a wearable optical aerosol monitor, followed by direct-on-filter quantitative analysis of the spot sample for crystalline silica using handheld Raman spectrometer. The filter cassette of a commercially available optical aerosol monitor (designed to collect aerosol for post-shift analysis) was modified to collect 1.5-mm-diameter spot sample, which provided adequate detection limits for short-term measurements over a few tens of minutes or hours. The method was calibrated using aerosolized α-quartz standard reference material in the laboratory. Two Raman spectrometers were evaluated, one a handheld unit (weighing less than 410 g) and the other a larger probe-based field-portable unit (weighing about 5 kg). The lowest limit of quantification for α-quartz of 16.6 μg m-3 was obtained using the handheld Raman unit at a sample collection time of 1 h at 0.4 l min-1. Short-term measurement capability and sensitivity of the Raman method were demonstrated using a transient simulated workplace aerosol. Workplace air and personal breathing zone concentrations of crystalline silica of workers at a hydraulic fracturing worksite were measured using the Raman method. The measurements showed good agreement with the co-located samples analyzed using the standard X-ray powder diffraction (XRD) method, agreeing within 0.15-23.2% of each other. This magnitude of difference was comparable to the inter- and intra-laboratory analytical precision of established XRD and infrared methods. The pilot study shows that for silica-containing materials studied in this work it is possible to obtain quantitative measurements with good analytical figures of merit using handheld or portable Raman spectrometers. Further studies will be needed to assess matrix interferences and measurement uncertainty for several other types of particle matrices to assess the broader applicability of the method.