HIV-1 remission and possible cure in a woman after haplo-cord blood transplant.

Previously, two men were cured of HIV-1 through CCR5Δ32 homozygous (CCR5Δ32/Δ32) allogeneic adult stem cell transplant. We report the first remission and possible HIV-1 cure in a mixed-race woman who received a CCR5Δ32/Δ32 haplo-cord transplant (cord blood cells combined with haploidentical stem cells from an adult) to treat acute myeloid leukemia (AML). Peripheral blood chimerism was 100% CCR5Δ32/Δ32 cord blood by week 14 post-transplant and persisted through 4.8 years of follow-up. Immune reconstitution was associated with (1) loss of detectable replication-competent HIV-1 reservoirs, (2) loss of HIV-1-specific immune responses, (3) in vitro resistance to X4 and R5 laboratory variants, including pre-transplant autologous latent reservoir isolates, and (4) 18 months of HIV-1 control with aviremia, off antiretroviral therapy, starting at 37 months post-transplant. CCR5Δ32/Δ32 haplo-cord transplant achieved remission and a possible HIV-1 cure for a person of diverse ancestry, living with HIV-1, who required a stem cell transplant for acute leukemia.

NUDC is critical for rod photoreceptor function, maintenance, and survival.

NUDC (nuclear distribution protein C) is a mitotic protein involved in nuclear migration and cytokinesis across species. Considered a cytoplasmic dynein (henceforth dynein) cofactor, NUDC was shown to associate with the dynein motor complex during neuronal migration. NUDC is also expressed in postmitotic vertebrate rod photoreceptors where its function is unknown. Here, we examined the role of NUDC in postmitotic rod photoreceptors by studying the consequences of a conditional NUDC knockout in mouse rods (rNudC-/- ). Loss of NUDC in rods led to complete photoreceptor cell death at 6 weeks of age. By 3 weeks of age, rNudC-/- function was diminished, and rhodopsin and mitochondria were mislocalized, consistent with dynein inhibition. Levels of outer segment proteins were reduced, but LIS1 (lissencephaly protein 1), a well-characterized dynein cofactor, was unaffected. Transmission electron microscopy revealed ultrastructural defects within the rods of rNudC-/- by 3 weeks of age. We investigated whether NUDC interacts with the actin modulator cofilin 1 (CFL1) and found that in rods, CFL1 is localized in close proximity to NUDC. In addition to its potential role in dynein trafficking within rods, loss of NUDC also resulted in increased levels of phosphorylated CFL1 (pCFL1), which would purportedly prevent depolymerization of actin. The absence of NUDC also induced an inflammatory response in Müller glia and microglia across the neural retina by 3 weeks of age. Taken together, our data illustrate the critical role of NUDC in actin cytoskeletal maintenance and dynein-mediated protein trafficking in a postmitotic rod photoreceptor.

Cerebrospinal Fluid Protein Markers Indicate Neuro-Damage in SARS-CoV-2-Infected Nonhuman Primates.

Neurologic manifestations are among the most frequently reported complications of COVID-19. However, given the paucity of tissue samples and the highly infectious nature of the etiologic agent of COVID-19, we have limited information to understand the neuropathogenesis of COVID-19. Therefore, to better understand the impact of COVID-19 on the brain, we used mass-spectrometry-based proteomics with a data-independent acquisition mode to investigate cerebrospinal fluid (CSF) proteins collected from two different nonhuman primates, Rhesus Macaque and African Green Monkeys, for the neurologic effects of the infection. These monkeys exhibited minimal to mild pulmonary pathology but moderate to severe central nervous system (CNS) pathology. Our results indicated that CSF proteome changes after infection resolution corresponded with bronchial virus abundance during early infection and revealed substantial differences between the infected nonhuman primates and their age-matched uninfected controls, suggesting these differences could reflect altered secretion of CNS factors in response to SARS-CoV-2-induced neuropathology. We also observed the infected animals exhibited highly scattered data distributions compared to their corresponding controls indicating the heterogeneity of the CSF proteome change and the host response to the viral infection. Dysregulated CSF proteins were preferentially enriched in functional pathways associated with progressive neurodegenerative disorders, hemostasis, and innate immune responses that could influence neuroinflammatory responses following COVID-19. Mapping these dysregulated proteins to the Human Brain Protein Atlas found that they tended to be enriched in brain regions that exhibit more frequent injury following COVID-19. It, therefore, appears reasonable to speculate that such CSF protein changes could serve as signatures for neurologic injury, identify important regulatory pathways in this process, and potentially reveal therapeutic targets to prevent or attenuate the development of neurologic injuries following COVID-19.

Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines.

BACKGROUND: Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in attenuating coronavirus disease 2019 (Covid-19) when administered in real-world conditions. METHODS: We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. From December 14, 2020, to April 10, 2021, the participants completed weekly SARS-CoV-2 testing by providing mid-turbinate nasal swabs for qualitative and quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis. The formula for calculating vaccine effectiveness was 100% × (1 - hazard ratio for SARS-CoV-2 infection in vaccinated vs. unvaccinated participants), with adjustments for the propensity to be vaccinated, study site, occupation, and local viral circulation. RESULTS: SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (≥14 days after dose 2), 11 partially vaccinated (≥14 days after dose 1 and <14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (<14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7). CONCLUSIONS: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination. (Funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention.).

Patterns, predictors, and patient-reported reasons for antidepressant discontinuation in the WHO World Mental Health Surveys.

BACKGROUND: Despite their documented efficacy, substantial proportions of patients discontinue antidepressant medication (ADM) without a doctor's recommendation. The current report integrates data on patient-reported reasons into an investigation of patterns and predictors of ADM discontinuation. METHODS: Face-to-face interviews with community samples from 13 countries (n = 30 697) in the World Mental Health (WMH) Surveys included n = 1890 respondents who used ADMs within the past 12 months. RESULTS: 10.9% of 12-month ADM users reported discontinuation-based on recommendation of the prescriber while 15.7% discontinued in the absence of prescriber recommendation. The main patient-reported reason for discontinuation was feeling better (46.6%), which was reported by a higher proportion of patients who discontinued within the first 2 weeks of treatment than later. Perceived ineffectiveness (18.5%), predisposing factors (e.g. fear of dependence) (20.0%), and enabling factors (e.g. inability to afford treatment cost) (5.0%) were much less commonly reported reasons. Discontinuation in the absence of prescriber recommendation was associated with low country income level, being employed, and having above average personal income. Age, prior history of psychotropic medication use, and being prescribed treatment from a psychiatrist rather than from a general medical practitioner, in comparison, were associated with a lower probability of this type of discontinuation. However, these predictors varied substantially depending on patient-reported reasons for discontinuation. CONCLUSION: Dropping out early is not necessarily negative with almost half of individuals noting they felt better. The study underscores the diverse reasons given for dropping out and the need to evaluate how and whether dropping out influences short- or long-term functioning.

Post hospital admission blood lactate measurements are associated with mortality but not neurologic morbidity in children with cerebral malaria.

BACKGROUND: In children with cerebral malaria (CM) admission blood lactate has previously guided intravenous fluid therapy and been validated as a prognostic biomarker associated with death. The usefulness of post-admission measurements of blood lactate in children with CM is less clear. The strength of association between blood lactate and neurological sequelae in CM survivors, as well as the optimal duration of post-admission measurements of blood lactate to identify children at higher risk of adverse outcomes is unknown. METHODS: A retrospective cohort study of 1674 Malawian children with CM hospitalized from 2000 to 2018 who had blood lactate measurements every 6 h for the first 24 h after admission was performed. The strength of association between admission lactate or values measured at any time point in the first 24 h post-admission and outcomes (mortality and neurological morbidity in survivors) was estimated. The duration of time after admission that lactate remained a valid prognostic biomarker was assessed. RESULTS: When lactate is analysed as a continuous variable, children with CM who have higher values at admission have a 1.05-fold higher odds (95% CI 0.99-1.11) of death compared to those with lower lactate values. Children with higher blood lactate at 6 h have 1.16-fold higher odds (95% CI 1.09-1.23) of death, compared to those with lower values. If lactate levels are dichotomized into hyperlactataemic (lactate > 5.0 mmol/L) or not, the strength of association between admission lactate and mortality increases (OR = 2.49, 95% CI 1.47-4.22). Blood lactate levels obtained after 18 h post-admission are not associated with outcomes. Similarly, the change in lactate concentrations through time during the first 24 h of hospital admission is not associated with outcomes. Blood lactate during hospitalization is not associated with adverse neurologic outcomes in CM survivors. CONCLUSIONS: In children with CM, blood lactate is associated with death but not neurologic morbidity in survivors. To comprehensively estimate prognosis, blood lactate in children with CM should be assessed at admission and for 18 h afterwards.

Development and characterization of a portable electrochemical aptasensor for IsdA protein and Staphylococcus aureus detection.

Staphylococcus aureus (S. aureus) is recognized as one of the most common causes of gastroenteritis worldwide. This pathogen is a major foodborne pathogen that can cause many different types of various infections, from minor skin infections to lethal blood infectious diseases. Iron-regulated surface determinant protein A (IsdA) is an important protein on the S. aureus surface. It is responsible for iron scavenging via interaction with hemoglobin, haptoglobin, and hemoglobin-haptoglobin complexes. This study develops a portable aptasensor for IsdA and S. aureus detection using aptamer-modified gold nanoparticles (AuNPs) integrated into screen-printed carbon electrodes (SPCEs). The electrode system was made of three parts, including a carbon counter electrode, an AuNPs/carbon working electrode, and a silver reference electrode. The aptamer by Au-S bonding was conjugated on the electrode surface to create the aptasensor platform. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were utilized to investigate the binding interactions between the aptasensor and the IsdA protein. CV studies showed a linear correlation between varying S. aureus concentrations within the range of 101 to 106 CFU/mL, resulting in a limit of detection (LOD) of 0.2 CFU/mL. The results demonstrated strong reproducibility, selectivity, and sensitivity of the aptasensor for enhanced detection of IsdA, along with about 93% performance stability after 30 days. The capability of the aptasensor to directly detect S. aureus via the IsdA surface protein binding was further investigated in a food matrix. Overall, the aptasensor device showed the potential for rapid detection of S. aureus, serving as a robust approach to developing real-time aptasensors to identify an extensive range of targets of foodborne pathogens and beyond.

Suicidal ideation, suicide plans and suicide attempts among Australian adults: Findings from the 2020-2022 National Study of Mental Health and Wellbeing.

OBJECTIVE: This study aimed to describe the epidemiology of suicidal ideation, suicide plans and suicide attempts, examine services received for suicide attempts, and explore the relationship between suicide attempts and self-harm without suicidal intent. METHODS: We used survey data from the 2020-2022 National Study of Mental Health and Wellbeing, which involved a nationally representative sample of Australian adults aged 16-85 (n = 15,893). Comparisons were made with the 2007 National Study of Mental Health and Wellbeing (n = 8841). RESULTS: In 2020-2022, the proportions of adults who had experienced suicidal ideation, suicide plans and suicide attempts during their lifetime were 16.6%, 7.5% and 4.9%, respectively. The proportions who had experienced these in the past 12 months were 3.3%, 1.1% and 0.3%. The odds of experiencing suicidal ideation and making a suicide plan were significantly higher in 2020-2022 than in 2007. Groups at heightened risk of suicidal ideation, suicide plans and/or suicide attempts in the previous 12 months were males, young people, people who were gay, lesbian, or bisexual or used some other term to describe their sexual identity, people outside the labour force, people from disadvantaged areas and people with mental disorders. Two-fifths of those who attempted suicide during the previous 12 months did not use health services following their attempt, and two-thirds also self-harmed without suicidal intent. CONCLUSION: The implications of these findings for the forthcoming National Suicide Prevention Strategy are discussed. Suicidal thoughts and behaviours confer risk for suicide and are significant problems in their own right. Their prevention requires a strong whole-of-government response.

The epidemiology of mental and substance use disorders in Australia 2020-22: Prevalence, socio-demographic correlates, severity, impairment and changes over time.

OBJECTIVE: Mental and substance use disorders are the leading causes of disability worldwide. Contemporary estimates of prevalence, severity and impairment are essential for service planning. This study provides estimates of prevalence, severity, impairment and demographic correlates of mental and substance use disorders in 2020-22 and changes in prevalence since 2007. METHODS: Data were from the two Australian National Surveys of Mental Health and Wellbeing conducted in 2020-22 (N = 15,893) and 2007 (N = 8841). Descriptive statistics report prevalence of lifetime and 12-month mental and substance use disorder by sex and age, proportion of people with each mental disorder by levels of severity (mild, moderate and severe) and mean days out of role by mental disorder class (mood, anxiety, substance use). Logistic regression analyses examined demographic correlates of mental disorder class and assessed changes over time. RESULTS: The lifetime prevalence of any mental or substance use disorder in 2020-22 was 40.2%. The 12-month prevalence was 20.2% (mood disorder - 7.4%, anxiety disorder - 15.7% and substance use disorder - 3.1%). Mood disorders were associated with significant impairment. The prevalence of mental disorders has changed over time, with mood and anxiety disorders increasing and substance use disorders decreasing. These changes were most evident among young adults. CONCLUSION: Mental disorders are common in Australia. Impairment associated with mental disorders remains significant. Particular focus should be paid to young adults aged 16-24 years who have shown the largest increases in anxiety and mood disorder prevalence over the past 13 years.

Preoperative Symptoms of Depression are Associated With Worse Capability 6-weeks and 6-months After Total Hip Arthroplasty for Osteoarthritis.

BACKGROUND: Symptoms of depression have been associated with greater incapability following total hip arthroplasty (THA). A brief, 2-question, measure of symptoms of depression - the Patient Health Questionnaire-2 (PHQ-2) - may be sufficient to measure associations with the magnitude of incapability during recovery from THA. This study investigated whether preoperative symptoms of depression (measured with the PHQ-2) correlated with levels of incapability 6 weeks and 6 months after THA, accounting for demographic and clinical factors. METHODS: We performed a prospective cohort study across 5 centers and recruited 101 patients undergoing THA, of whom 90 (89%) completed follow-up. Patients completed demographics, a preoperative 2-item (PHQ-2) measure of symptoms of depression, and the Hip Dysfunction and Osteoarthritis Outcome Score for Joint Replacement (HOOS JR) at 6-weeks and 6-months postoperatively. Negative binomial regression models determined factors associated with HOOS JR at 6 weeks and 6 months, accounting for potential confounders. RESULTS: Accounting for potential confounding factors, we found that higher preoperative PHQ-2 scores (reflecting greater symptoms of depression) were associated with lower HOOS JR scores (reflecting a greater level of hip disability) at both 6 weeks (regression coefficient = -0.67, P < .001) and 6 months (regression coefficient = -1.9, P < .001) after THA. CONCLUSIONS: Symptoms of depression on a 2-question preoperative questionnaire are common, and greater symptoms of depression are associated with reduced capability within the first year following THA. These findings support the prioritization of routine mental health assessments before THA. Measuring mindset using relatively brief instruments will be important considering the current shift toward implementing self-reported measures of health status in clinical practice and incorporating them within alternative payment models.

Effect of Repeat Vaccination on Immunogenicity of Quadrivalent Cell-Culture and Recombinant Influenza Vaccines Among Healthcare Personnel Aged 18-64 Years: A Randomized, Open-Label Trial.

BACKGROUND: Antibody responses to non-egg-based standard-dose cell-culture influenza vaccine (containing 15 µg hemagglutinin [HA]/component) and recombinant vaccine (containing 45 µg HA/component) during consecutive seasons have not been studied in the United States. METHODS: In a randomized trial of immunogenicity of quadrivalent influenza vaccines among healthcare personnel (HCP) aged 18-64 years over 2 consecutive seasons, HCP who received recombinant-HA influenza vaccine (RIV) or cell culture-based inactivated influenza vaccine (ccIIV) during the first season (year 1) were re-randomized the second season of 2019-2020 (year 2 [Y2]) to receive ccIIV or RIV, resulting in 4 ccIIV/RIV combinations. In Y2, hemagglutination inhibition antibody titers against reference cell-grown vaccine viruses were compared in each ccIIV/RIV group with titers among HCP randomized both seasons to receive egg-based, standard-dose inactivated influenza vaccine (IIV) using geometric mean titer (GMT) ratios of Y2 post-vaccination titers. RESULTS: Y2 data from 414 HCP were analyzed per protocol. Compared with 60 IIV/IIV recipients, 74 RIV/RIV and 106 ccIIV/RIV recipients showed significantly elevated GMT ratios (Bonferroni corrected P < .007) against all components except A(H3N2). Post-vaccination GMT ratios for ccIIV/ccIIV and RIV/ccIIV were not significantly elevated compared with IIV/IIV except for RIV/ccIIV against A(H1N1)pdm09. CONCLUSIONS: In adult HCP, receipt of RIV in 2 consecutive seasons or the second season was more immunogenic than consecutive egg-based IIV for 3 of the 4 components of quadrivalent vaccine. Immunogenicity of ccIIV/ccIIV was similar to that of IIV/IIV. Differences in HA antigen content may play a role in immunogenicity of influenza vaccination in consecutive seasons. CLINICAL TRIALS REGISTRATION: NCT03722589.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection History and Antibody Response to 3 Coronavirus Disease 2019 Messenger RNA Vaccine Doses.

BACKGROUND: Data on antibody kinetics are limited among individuals previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From a cohort of healthcare personnel and other frontline workers in 6 US states, we assessed antibody waning after messenger RNA (mRNA) dose 2 and response to dose 3 according to SARS-CoV-2 infection history. METHODS: Participants submitted sera every 3 months, after SARS-CoV-2 infection, and after each mRNA vaccine dose. Sera were tested for antibodies and reported as area under the serial dilution curve (AUC). Changes in AUC values over time were compared using a linear mixed model. RESULTS: Analysis included 388 participants who received dose 3 by November 2021. There were 3 comparison groups: vaccine only with no known prior SARS-CoV-2 infection (n = 224); infection prior to dose 1 (n = 123); and infection after dose 2 and before dose 3 (n = 41). The interval from dose 2 and dose 3 was approximately 8 months. After dose 3, antibody levels rose 2.5-fold (95% confidence interval [CI] = 2.2-3.0) in group 2 and 2.9-fold (95% CI = 2.6-3.3) in group 1. Those infected within 90 days before dose 3 (and median 233 days [interquartile range, 213-246] after dose 2) did not increase significantly after dose 3. CONCLUSIONS: A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection <3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster.

Risk Factors for Reinfection with SARS-CoV-2 Omicron Variant among Previously Infected Frontline Workers.

In a cohort of essential workers in the United States previously infected with SARS-CoV-2, risk factors for reinfection included being unvaccinated, infrequent mask use, time since first infection, and being non-Hispanic Black. Protecting workers from reinfection requires a multipronged approach including up-to-date vaccination, mask use as recommended, and reduction in underlying health disparities.

Collection of Nitrogen Dioxide for Nitrogen and Oxygen Isotope Determination─Laboratory and Environmental Chamber Evaluation.

The family of atmospheric oxides of nitrogen, NOy (e.g., nitrogen oxides (NOx) + nitric acid (HNO3) + nitrous acid (HONO) + peroxyacetyl nitrate (PAN) + particulate nitrate (pNO3-) + other), have an influential role in atmospheric chemistry, climate, and the environment. The nitrogen (δ15N) and oxygen (δ18O and Δ17O) stable isotopes of NOy are novel tools for potentially tracking emission sources and quantifying oxidation chemistry. However, there is a lack of well-established methods, particularly for speciated gas-phase components of NOy, to accurately quantify δ15N, δ18O, and Δ17O. This work presents controlled laboratory experiments and complex chamber α-pinene/NOx oxidation experiments of a sampling apparatus constructed for the simultaneous capture of multiple NOy species for isotope analysis using a series of coated denuders, with a focus on nitrogen dioxide (NO2•). The laboratory tests indicate complete NO2• capture for the targeted concentration of 15 ppbv for at least 24 h collections at 10 liters per minute, with δ15N and δ18O precisions of ±1.3‰ and 1.0‰, respectively, and minimal (2.2% ± 0.1%) NO2• collection on upstream denuders utilized for the capture of HNO3 and other acidic gases. The multispecies NOy collection system showed excellent concentration correlations with online instrumentation for both HNO3 and NO2• and isotope reproducibility of ±1.7‰, ±1.8‰, and ±0.7‰ for δ15N, δ18O, and Δ17O, respectively, for replicate experiments and highly time-resolved collections. This work demonstrates a new method that can enable the simultaneous collection of HNO3 and NO2• for accurate quantification of concentration and isotopic composition.

What Is New in Fungal Infections?

Invasive fungal infections are an increasingly important cause of morbidity and mortality. We provide a summary of important changes in the epidemiology of invasive fungal infections, citing examples of new emerging pathogens, expanding populations who are at-risk, and increasing antifungal resistance. We review how human activity and climate change may play a role in some of these changes. Finally, we discuss how these changes create the need for advances in fungal diagnostics. The limitations of existing fungal diagnostic testing emphasize the critically important role of histopathology in the early recognition of fungal disease.

Retinal electrophysiologic response to IOP elevation in living human eyes.

PURPOSE: The relationships between intraocular pressure (IOP), ocular perfusion pressure (OPP), retinal perfusion, and retinal electrophysiologic responses have been explored experimentally across several animal models. These studies have demonstrated that elevated IOP reduces OPP, and when this reduction in OPP exceeds the autoregulatory capacity of the retina vasculature, retinal perfusion and electrophysiologic responses are reduced. This study aimed to evaluate these interactions for the first time in the living human eye. METHODS: Five eyes from three research-consented brain-dead organ donors underwent optical coherence tomography with angiographic (OCT/A; Spectralis, Heidelberg Engineering) and electroretinographic (ERG, Diagnosys LLC) measurements while IOP was manometrically-elevated stepwise to pressures of 10, 30 and 50 mmHg. Systemic blood pressure (BP) was monitored continuously during testing. Correlation analysis was applied to assess association between ERG and OPP changes. In a single eye, prolonged IOP elevation was induced with viscoelastic injection and serial ERG measurements were obtained. RESULTS: Reductions in inner retinal function defined by photopic ERG were observed with elevation in IOP and concomitant reduction in OPP. Reductions, especially in b-wave, and photopic negative response (PhNR) amplitudes and implicit times were significantly correlated with elevation in IOP and reduction in OPP. There were more appreciable changes in perfusion and functional responses in eyes tested while systemic blood pressure was lower. With prolonged IOP elevation, selective loss of the PhNR response was observed. CONCLUSIONS: In the living human eye, retinal perfusion and inner retinal function are acutely impacted by elevation of IOP, and this impact is related to systemic BP and OPP. This novel approach provides a viable model to study the autoregulatory responses to IOP elevation in the living human eye.

Antidepressant use in low- middle- and high-income countries: a World Mental Health Surveys report.

BACKGROUND: The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries. METHODS: Face-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents. RESULTS: 3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2-4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness. CONCLUSION: ADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.

Recommendations for Use of Video Directly Observed Therapy During Tuberculosis Treatment - United States, 2023.

U.S. clinical practice guidelines recommend directly observed therapy (DOT) as the standard of care for tuberculosis (TB) treatment (1). DOT, during which a health care worker observes a patient ingesting the TB medications, has typically been conducted in person. Video DOT (vDOT) uses video-enabled devices to facilitate remote interactions between patients and health care workers to promote medication adherence and clinical monitoring. Published systematic reviews, a published meta-analysis, and a literature search through 2022 demonstrate that vDOT is associated with a higher proportion of medication doses being observed and similar proportions of cases with treatment completion and microbiologic resolution when compared with in-person DOT (2-5). Based on this evidence, CDC has updated the recommendation for DOT during TB treatment to include vDOT as an equivalent alternative to in-person DOT. vDOT can assist health department TB programs meet the U.S. standard of care for patients undergoing TB treatment, while using resources efficiently.

Effects of Air Pollutants from Wildfires on Downwind Ecosystems: Observations, Knowledge Gaps, and Questions for Assessing Risk.

Wildfires have increased in frequency and area burned, trends expected to continue with climate change. Among other effects, fires release pollutants into the atmosphere, representing a risk to human health and downwind terrestrial and aquatic ecosystems. While human health risks are well studied, the ecological impacts to downwind ecosystems are not, and this gap may present a constraint on developing an adequate assessment of the ecological risks associated with downwind wildfire exposure. Here, we first screened the scientific literature to assess general knowledge about pathways and end points of a conceptual model linking wildfire generated pollutants and other materials to downwind ecosystems. We found a substantial body of literature on the composition of wildfire derived pollution and materials in the atmosphere and subsequent transport, yet little observational or experimental work on their effects on downwind ecological end points. This dearth of information raises many questions related to adequately assessing the ecological risk of downwind exposure, especially given increasing wildfire trends. To guide future research, we pose eight questions within the well-established US EPA ecological risk assessment paradigm that if answered would greatly improve ecological risk assessment and, ultimately, management strategies needed to reduce potential wildfire impacts.

Chronic pain interference assessment tools for children and adults who are unable to self-report: A systematic review of psychometric properties.

AIM: To identify and evaluate psychometric properties of assessment tools for assessing pain interference in children, adolescents, and adults with chronic pain and the inability to self-report. METHOD: The protocol was registered with PROSPERO (CRD42022310102). A search was run in MEDLINE, Embase, and PsycInfo (29th March 2022) to identify articles reporting psychometric properties of pain interference assessment tools for children, adolescents, and adults with chronic pain and the inability to objectively self-report pain. Retrieved studies were reviewed by two authors (MGS, LCF) and study quality was assessed using COSMIN. RESULTS: Psychometric properties of 10 pain interference tools were assessed from 33 studies. The Paediatric Pain Profile (PPP) had low-quality evidence for content validity and internal consistency with children and adolescents who are unable to self-report. No tools for adults had evidence for content validity and internal consistency. No tool had evidence for all nine psychometric properties. INTERPRETATION: The PPP is recommended for pain interference assessment in children and adolescents with chronic pain and the inability to self-report. Few tools are available for adults. Three tools for children (Patient-Reported Outcome Measurement Information System Pediatric Proxy Pain Interference Scale; Bath Adolescent Pain Questionnaire for Parents; modified Brief Pain Inventory-Proxy [mBPI]) and three tools for adults (Doloplus-2; Patient-Reported Outcome Measurement Information System Pain Interference Scale-proxy; Brief Pain Inventory-proxy) are promising but require further investigation.