Is primary care ready for a potential new public health emergency in the wake of the COVID-19 pandemic, now subsided?

INTRODUCTION: The lingering burden of the COVID-19 pandemic on primary care clinicians and practices poses a public health emergency for the United States. This study uses clinician-reported data to examine changes in primary care demand and capacity. METHODS: From March 2020 to March 2022, 36 electronic surveys were fielded among primary care clinicians responding to survey invitations as posted on listservs and identified through social media and crowd sourcing. Quantitative and qualitative analyses were performed on both closed- and open-ended survey questions. RESULTS: An average of 937 respondents per survey represented family medicine, pediatrics, internal medicine, geriatrics, and other specialties. Responses reported increases in patient health burden, including worsening chronic care management and increasing volume and complexity. A higher frequency of dental- and eyesight-related issues was noted by respondents, as was a substantial increase in mental or emotional health needs. Respondents also noted increased demand, "record high" wait times, and struggles to keep up with patient needs and the higher volume of patient questions. Frequent qualitative statements highlighted the mismatch of patient needs with practice capacity. Staffing shortages and the inability to fill open clinical positions impaired clinicians' ability to meet patient needs and a substantial proportion of respondents indicated an intention to leave the profession or knew someone who had. CONCLUSION: These data signal an urgent need to take action to support the ability of primary care to meet ongoing patient and population health care needs.

Synergic association of the consortium Arthrospira maxima with the microalga growth-promoting bacterium Azospirillum cultured under the stressful biogas composition.

The present study evaluates the association of the blue-green microalga Arthrospira maxima (Spirulina), which is known for its CO2 fixation, biomass, and high-value metabolite production, with the microalga growth-promoting bacterium Azospirillum brasilense under the stressful composition of biogas. The results demonstrated that A. maxima co-cultured with A. brasilense under the high CO2 (25%) and methane (CH4; 75%) concentrations of biogas recorded a CO2 fixation rate of 0.24 ± 0.03 g L-1 days-1, thereby attaining a biomass production of 1.8 ± 0.03 g L-1. Similarly, the biochemical composition quality of this microalga enhanced the attainment of higher contents of carbohydrates, proteins, and phycocyanin than cultured alone. However, metabolites other than tryptophan (Trp) and indole-3-acetic acid could have supported this beneficial interaction. Overall, the results demonstrate that this prokaryotic consortium of A. maxima-A. brasilense established a synergic association under biogas, which represents a sustainable strategy to improve the bio-refinery capacity of this microalga and increase the usefulness of A. brasilense in multiple economic sectors.

Maintaining the Region of the Americas free of polio: best practices for incident management support teams.

The Pan American Health Organization (PAHO) and its Member States have been leading the efforts to eradicate wild poliovirus in the Region of Americas since smallpox's successful elimination in 1971. The region became the first to be certified free of wild poliovirus in 1994. However, in July 2022, an unvaccinated patient with no recent travel history was diagnosed with poliomyelitis in the United States of America. In response to the emergence of a circulating vaccine-derived poliovirus in the United States, PAHO established the Polio Incident Management Support Team. This team has been coordinating response efforts, focusing on: coordination, planning, and monitoring; risk communication and community engagement; surveillance and case investigation; vaccination; and rapid response. In this paper, we identified and documented best practices observed following establishment of the Incident Management Support Team (September 2022-2023) through a comprehensive review and analysis of various data sources and country-specific data from the polio surveillance dashboard. The aim was to share these best practices, highlighting technical support and implementation of polio measures by Member States. Despite several challenges, the Americas region remains polio-free. Polio risk is declining, with a July 2023 assessment showing fewer countries at medium, high, and very high risk. This progress reflects improved immunization coverage, surveillance, containment, health determinants, and outbreak preparedness and response. The PAHO Polio Incident Management Support Team has played a key role in supporting these efforts.

La Organización Panamericana de la Salud (OPS) y sus Estados Miembros han liderado los esfuerzos para erradicar el poliovirus salvaje en la Región de las Américas desde la eliminación exitosa de la viruela en 1971. En 1994, la Región fue la primera en obtener la certificación de libre del poliovirus salvaje. Sin embargo, en julio del 2022, se diagnosticó poliomielitis a un paciente de Estados Unidos de América no vacunado y sin antecedentes de viajes recientes. Para responder a la aparición de un poliovirus circulante derivado de la vacuna en ese país, la OPS creó el equipo de apoyo a la gestión de incidentes de poliomielitis. Este equipo ha asumido la coordinación de los esfuerzos de respuesta y se ha centrado en la coordinación, la planificación y seguimiento; la comunicación de riesgos y la participación de la comunidad; la vigilancia e investigación de casos; la vacunación; y la respuesta rápida. En este artículo, se determinan y documentan las mejores prácticas observadas después de la creación del equipo de apoyo a la gestión de incidentes (septiembre del 2022-2023) mediante una revisión y un análisis pormenorizados de datos procedentes de diversas fuentes y de datos específicos de los países del panel de vigilancia de la poliomielitis. El objetivo fue poner en común estas mejores prácticas y resaltar el apoyo técnico y la aplicación de medidas contra la poliomielitis por parte de los Estados Miembros. A pesar de los diversos desafíos, la Región de las Américas se mantiene libre de poliomielitis. El riesgo de esta enfermedad es cada vez menor, y la evaluación de julio del 2023 muestra una disminución del número de países con un riesgo medio, alto o muy alto. Este progreso refleja la mejora de la cobertura de inmunización, la vigilancia, la contención, los determinantes de la salud y la preparación y respuesta ante brotes. El equipo de apoyo a la gestión de incidentes relacionados con la poliomielitis de la OPS ha desempeñado un papel fundamental para brindar apoyo a estas iniciativas.

Desde a eliminação bem-sucedida da varíola em 1971, a Organização Pan-Americana da Saúde (OPAS) e seus Estados Membros têm estado à frente de iniciativas para erradicar o poliovírus selvagem na Região das Américas. Em 1994, a região foi a primeira do mundo a ser certificada como livre do poliovírus selvagem. Entretanto, em julho de 2022, um paciente não vacinado e sem histórico de viagens recentes foi diagnosticado com poliomielite nos Estados Unidos da América. Em resposta ao surgimento de um poliovírus derivado de vacina circulante nos Estados Unidos, a OPAS criou a Equipe de Apoio à Gestão de Incidentes de Poliomielite. A equipe vem administrando os esforços de resposta, concentrando-se em: coordenação, planejamento e monitoramento; comunicação de risco e envolvimento da comunidade; vigilância e investigação de casos; vacinação; e resposta rápida. Neste documento, identificamos e documentamos as melhores práticas observadas após a criação da Equipe de Apoio à Gestão de Incidentes (setembro de 2022 a 2023) por meio de uma revisão e análise abrangentes de diversas fontes de dados e dados específicos de cada país fornecidos por meio do painel de vigilância da poliomielite. O objetivo foi compartilhar essas melhores práticas, destacando o apoio técnico e a implementação de medidas contra a poliomielite pelos Estados Membros. Apesar de vários desafios, a Região das Américas continua livre da poliomielite. Um levantamento de julho de 2023 demonstrou que o risco da poliomielite vem diminuindo, com menos países com risco médio, alto ou muito alto. Essa evolução é resultado de melhoras na cobertura vacinal, vigilância, contenção, preparação, determinantes de saúde e resposta a surtos. A Equipe de Apoio à Gestão de Incidentes de Poliomielite da OPAS foi fundamental para apoiar esses esforços.

You Cannot Function in "Overwhelm": Helping Primary Care Navigate the Slow End of the Pandemic.

GOAL: This study was developed to explicate underlying organizational factors contributing to the deterioration of primary care clinicians' mental health during the COVID-19 pandemic. METHODS: Using data from the Larry A. Green Center for the Advancement of Primary Health Care for the Public Good's national survey of primary care clinicians from March 2020 to March 2022, a multidisciplinary team analyzed more than 11,150 open-ended comments. Phase 1 of the analysis happened in real-time as surveys were returned, using deductive and inductive coding. Phase 2 used grounded theory to identify emergent themes. Qualitative findings were triangulated with the survey's quantitative data. PRINCIPAL FINDINGS: The clinicians shifted from feelings of anxiety and uncertainty at the start of the pandemic to isolation, lack of fulfillment, moral injury, and plans to leave the profession. The frequency with which they spoke of depression, burnout, and moral injury was striking. The contributors to this distress included crushing workloads, worsening staff shortages, and insufficient reimbursement. Consequences, both felt and anticipated, included fatigue and demoralization from the inability to manage escalating workloads. Survey findings identified responses that could alleviate the mental health crisis, namely: (1) measuring and customizing workloads based on work capacity; (2) quantifying resources needed to return to sufficient staffing levels; (3) promoting state and federal support for sustainable practice infrastructures with less administrative burden; and (4) creating patient visits of different lengths to rebuild relationships and trust and facilitate more accurate diagnoses. PRACTICAL APPLICATIONS: Attention to clinicians' mental health should be rapidly directed to on-demand, confidential mental health support so they can receive the care they need and not worry about any stigma or loss of license for accepting that help. Interventions that address work-life balance, workload, and resources can improve care, support retention of the critically important primary care workforce, and attract more trainees to primary care careers.

Hypoxia and HIFs in Ewing sarcoma: new perspectives on a multi-facetted relationship.

Hypoxia develops during the growth of solid tumors and influences tumoral activity in multiple ways. Low oxygen tension is also present in the bone microenvironment where Ewing sarcoma (EwS) - a highly aggressive pediatric cancer - mainly arises. Hypoxia inducible factor 1 subunit alpha (HIF-1-a) is the principal molecular mediator of the hypoxic response in cancer whereas EWSR1::FLI1 constitutes the oncogenic driver of EwS. Interaction of the two proteins has been shown in EwS. Although a growing body of studies investigated hypoxia and HIFs in EwS, their precise role for EwS pathophysiology is not clarified to date. This review summarizes and structures recent findings demonstrating that hypoxia and HIFs play a role in EwS at multiple levels. We propose to view hypoxia and HIFs as independent protagonists in the story of EwS and give a perspective on their potential clinical relevance as prognostic markers and therapeutic targets in EwS treatment.

Phase 1/1b open-label, dose-escalation study of fruquintinib in patients with advanced solid tumors in the United States.

This open-label, phase 1/1b study was conducted to evaluate the safety, tolerability, and pharmacokinetics (PK) of fruquintinib in United States (U.S.) patients to confirm the recommended phase 2 dose (RP2D) established in China. Patients with advanced solid tumors who had progressed on approved systemic therapy, were enrolled into 2 successive dose escalation cohorts, fruquintinib 3 mg (n = 7) or 5 mg (n = 7), orally, once daily (QD), 3 weeks on and 1 week off (3/1) with a 3 + 3 design followed by a dose expansion cohort at the RP2D 5 mg dose (n = 6). PK samples were collected on Days 1, 14, and 21 (Cycle 1). One of 6 dose-limiting toxicity (DLT)-evaluable patients in the 3 mg cohort had a DLT of grade 4 hypertension; there were no DLTs in the 5 mg cohort. The RP2D was confirmed to be 5 mg QD 3/1. All 20 patients experienced a treatment-emergent adverse event; grade ≥ 3 in 5 (71.4%; 3 mg dose) and 12 (92.3%; 5 mg dose) patients. Two patients had a confirmed partial response. After single and multiple doses, median peak plasma concentrations occurred at 2 h post-dose. Steady-state was achieved after 14 days of QD dosing with systemic exposure four-fold higher than that after a single dose. Fruquintinib was well tolerated, and the safety and PK profile at the 5 mg RP2D in U.S. patients with advanced solid tumors was consistent with dose-finding studies in China. Preliminary anticancer activity was observed. This study is registered at Clinicaltrials.gov NCT03251378.

Telemedicine in Primary Care: Lessons Learned About Implementing Health Care Innovations During the COVID-19 Pandemic.

PURPOSE: During the COVID-19 pandemic, telemedicine emerged as an important tool in primary care. Technology and policy-related challenges, however, revealed barriers to adoption and implementation. This report describes the findings from weekly and monthly surveys of primary care clinicians regarding telemedicine during the first 2 years of the pandemic. METHODS: From March 2020 to March 2022, we conducted electronic surveys using convenience samples obtained through social networking and crowdsourcing. Unique tokens were used to confidentially track respondents over time. A multidisciplinary team conducted quantitative and qualitative analyses to identify key concepts and trends. RESULTS: A total of 36 surveys resulted in an average of 937 respondents per survey, representing clinicians from all 50 states and multiple specialties. Initial responses indicated general difficulties in implementing telemedicine due to poor infrastructure and reimbursement mechanisms. Over time, attitudes toward telemedicine improved and respondents considered video and telephone-based care important tools for their practice, though not a replacement for in-person care. CONCLUSIONS: The implementation of telemedicine during COVID-19 identified barriers and opportunities for technology adoption and highlighted steps that could support primary care clinics' ability to learn, adapt, and implement technology.

Equity throughout the life course and the evolving role of the Pan American Health Organization.

The objective of this article is to summarize the evolution of the regional commitments of the Pan American Health Organization (PAHO) on health promotion and strategies to improve the health and well-being of women, children, adolescents, and older persons. PAHO regional strategies approved by Member States in the last 20 years are used as the main source of information. The article presents the challenges of making health promotion a public health strategy widely applied in the Region of the Americas and the efforts to renew Member States' collective actions. The article also describes current PAHO efforts to include the positive aspects of health (i.e., well-being, optimal development, and functional ability) and the life course approach as opportunities to advance equity. The article reflects on immunization as a public good and the urgency to address the current challenges as a core element of the regional efforts to transform health systems after more than two years of the COVID-19 pandemic.

El objetivo de este artículo es resumir la evolución de los compromisos regionales de la Organización Panamericana de la Salud (OPS) en materia de promoción de la salud y estrategias para mejorar la salud y el bienestar de mujeres, niños y niñas, adolescentes y personas mayores. Se han empleado como principal fuente de información las estrategias regionales de la OPS aprobadas por los Estados Miembros en los últimos 20 años. En el artículo se presentan los desafíos de convertir la promoción de la salud en una estrategia de salud pública de amplia ejecución en la Región de las Américas y los esfuerzos para renovar las medidas colectivas de los Estados Miembros. Asimismo, se describe la labor actual de la OPS para incluir los aspectos positivos de la salud (como el bienestar, el desarrollo óptimo y la capacidad funcional) y el enfoque del curso de vida como oportunidades para fomentar la equidad. Finalmente, se reflexiona sobre la inmunización como bien público y la urgencia de abordar los desafíos actuales como elemento central de los esfuerzos regionales para transformar los sistemas de salud tras más de dos años de pandemia de COVID-19.

O objetivo deste artigo é resumir a evolução dos compromissos regionais da Organização Pan-Americana da Saúde (OPAS) relativos à promoção da saúde e estratégias para melhorar a saúde e o bem-estar de mulheres, crianças, adolescentes e pessoas idosas. As estratégias regionais da OPAS aprovadas pelos Estados Membros nos últimos 20 anos são a principal fonte de informação. O artigo apresenta os desafios enfrentados para fazer da promoção da saúde uma estratégia de saúde pública amplamente aplicada na Região das Américas e os esforços para renovar as ações coletivas dos Estados Membros. O artigo também descreve os atuais esforços da OPAS para incluir os aspectos positivos da saúde (isto é, bem-estar, desenvolvimento ideal e habilidade funcional) e a abordagem de curso da vida como oportunidades para promover a equidade. O artigo faz reflexões sobre a imunização como um bem público e a urgência de abordar os desafios atuais como um elemento central dos esforços regionais para transformar os sistemas de saúde após mais de dois anos da pandemia de COVID-19.

Significant heterogeneity in the diagnosis and long-term management of Wilson disease: Results from a large multicenter Spanish study.

There is uncertainty regarding Wilson's disease (WD) management. OBJECTIVES: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers. METHODS: Data on WD patients followed at 32 Spanish hospitals were collected. RESULTS: 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response. CONCLUSIONS: Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored.

Estimating global and regional disruptions to routine childhood vaccine coverage during the COVID-19 pandemic in 2020: a modelling study.

BACKGROUND: The COVID-19 pandemic and efforts to reduce SARS-CoV-2 transmission substantially affected health services worldwide. To better understand the impact of the pandemic on childhood routine immunisation, we estimated disruptions in vaccine coverage associated with the pandemic in 2020, globally and by Global Burden of Disease (GBD) super-region. METHODS: For this analysis we used a two-step hierarchical random spline modelling approach to estimate global and regional disruptions to routine immunisation using administrative data and reports from electronic immunisation systems, with mobility data as a model input. Paired with estimates of vaccine coverage expected in the absence of COVID-19, which were derived from vaccine coverage models from GBD 2020, Release 1 (GBD 2020 R1), we estimated the number of children who missed routinely delivered doses of the third-dose diphtheria-tetanus-pertussis (DTP3) vaccine and first-dose measles-containing vaccine (MCV1) in 2020. FINDINGS: Globally, in 2020, estimated vaccine coverage was 76·7% (95% uncertainty interval 74·3-78·6) for DTP3 and 78·9% (74·8-81·9) for MCV1, representing relative reductions of 7·7% (6·0-10·1) for DTP3 and 7·9% (5·2-11·7) for MCV1, compared to expected doses delivered in the absence of the COVID-19 pandemic. From January to December, 2020, we estimated that 30·0 million (27·6-33·1) children missed doses of DTP3 and 27·2 million (23·4-32·5) children missed MCV1 doses. Compared to expected gaps in coverage for eligible children in 2020, these estimates represented an additional 8·5 million (6·5-11·6) children not routinely vaccinated with DTP3 and an additional 8·9 million (5·7-13·7) children not routinely vaccinated with MCV1 attributable to the COVID-19 pandemic. Globally, monthly disruptions were highest in April, 2020, across all GBD super-regions, with 4·6 million (4·0-5·4) children missing doses of DTP3 and 4·4 million (3·7-5·2) children missing doses of MCV1. Every GBD super-region saw reductions in vaccine coverage in March and April, with the most severe annual impacts in north Africa and the Middle East, south Asia, and Latin America and the Caribbean. We estimated the lowest annual reductions in vaccine delivery in sub-Saharan Africa, where disruptions remained minimal throughout the year. For some super-regions, including southeast Asia, east Asia, and Oceania for both DTP3 and MCV1, the high-income super-region for DTP3, and south Asia for MCV1, estimates suggest that monthly doses were delivered at or above expected levels during the second half of 2020. INTERPRETATION: Routine immunisation services faced stark challenges in 2020, with the COVID-19 pandemic causing the most widespread and largest global disruption in recent history. Although the latest coverage trajectories point towards recovery in some regions, a combination of lagging catch-up immunisation services, continued SARS-CoV-2 transmission, and persistent gaps in vaccine coverage before the pandemic still left millions of children under-vaccinated or unvaccinated against preventable diseases at the end of 2020, and these gaps are likely to extend throughout 2021. Strengthening routine immunisation data systems and efforts to target resources and outreach will be essential to minimise the risk of vaccine-preventable disease outbreaks, reach children who missed routine vaccine doses during the pandemic, and accelerate progress towards higher and more equitable vaccination coverage over the next decade. FUNDING: Bill & Melinda Gates Foundation.

Apixaban vs Enoxaparin for Post-Surgical Extended-Duration Venous Thromboembolic Event Prophylaxis: A Prospective Quality Improvement Study.

PURPOSE: Venous thromboembolic events (VTEs) are a major cause of morbidity following abdominopelvic oncologic surgery. Enoxaparin, a subcutaneous injectable low molecular weight heparin, is commonly used for extended-duration VTE prophylaxis (EP), but has been associated with noncompliance. Newer direct oral anticoagulants have not been prospectively studied in the urologic oncology post-discharge setting. We aimed to improve compliance with EP following abdominopelvic oncologic surgery and secondarily test the hypothesis that apixaban is noninferior to enoxaparin for EP. MATERIALS AND METHODS: A single-center prospective quality improvement study measuring patient compliance and safety with EP was conducted between August 10, 2020 and September 21, 2021. Baseline data were continuously collected for 6 months, followed by a uniform departmental change from enoxaparin to apixaban. The duration of data collection was determined a priori using a noninferiority sample size estimation (145 per group). The primary outcome was compliance events (real or potential barriers to EP use). The secondary outcome was 30-day post-discharge safety events (symptomatic VTE or major bleed). RESULTS: A total of 161 patients were discharged with enoxaparin (baseline period) and 154 with apixaban (intervention period). Safety events occurred in 3.1% vs 0% of patients receiving enoxaparin and apixaban, respectively. The absolute risk difference of 3.1% (95% CI: 0.043%-5.8%) met the prespecified noninferiority threshold (p=0.028 for apixaban superiority). Compliance events occurred in 33.5% of enoxaparin patients and 14.3% of apixaban patients (p=0.0001). CONCLUSIONS: There were fewer compliance events using apixaban for EP than enoxaparin after urologic oncology surgery. Regarding safety, apixaban is noninferior to enoxaparin and may in fact have fewer associated major complications.

Systematic review on reducing missed opportunities for vaccinations in Latin America.

Objectives: To estimate the prevalence of missed opportunities for vaccination (MOV) in Latin America and the effect of interventions targeting health systems, health workers, patients, and communities on MOV. Methods: Searches were conducted in MEDLINE, EMBASE, CINAHL, and LILACS electronic databases and relevant organizations were contacted, including the Pan American Health Organization (PAHO), to identify studies meeting eligibility criteria. A pair of reviewers identified 27 randomized and non-randomized studies quantifying the effectiveness of any intervention for reducing MOV and 5 studies assessing the rate of MOV in Latin America. Results are reported narratively when criteria to pool results were not met, and the certainty of this evidence was assessed using the GRADE approach. Results: Evidence suggests the rate of MOV in Latin America ranged from 5% to 37% with a pooled estimate of 17% (95% CI [9, 32]) (low certainty) and that monetary incentives to healthcare teams, training for healthcare teams on how to communicate with patients, and educational interventions for caregivers probably reduce MOV (moderate to very low certainty). Conclusions: There is insufficient evidence supporting the implementation of any intervention as policy based only on the potential reduction of MOV without considering several factors, including costs, feasibility, acceptability, and equity.

Self-Assembled Monolayer of Monomercaptoundecahydro-closo-dodecaborate on a Polycrystalline Gold Surface.

In this work, we present an electrochemical study of the boron cage monomercaptoundecahydro-closo-dodecaborate [B12H11SH]2- in solution and in a self-assembled monolayer over a polycrystalline gold electrode. Cyclic voltammetry of the anion [B12H11SH]2- in solution showed a shift in the peak potentials related to the redox processes of gold hydroxides, which evidences the interaction between the boron cage and the gold surface. For an Au electrode modified with the anion [B12H11SH]2-, cyclic voltammetry response of the probe Fe(CN)63-/Fe(CN)64- showed a ΔEp value typical for a surface modification. Electrochemical impedance spectroscopy presented Rtc and Cdl values related to the formation of a self-assembled monolayer (SAM). A comparison of electrochemical responses of a modified electrode with thioglycolic acid (TGA) reveals that the boron cage [B12H11SH]2- diminishes the actives sites over the Au surface due to the steric effects. Differential capacitance measurements for bare gold electrode and those modified with [B12H11SH]2- and (TGA), indicate that bulky thiols enhance charge accumulation at the electrode-solution interface. In addition to electrochemical experiments, DFT calculations and surface plasmon resonance measurements (SPR) were carried out to obtain quantum chemical descriptors and to evaluate the molecular length and the dielectric constant of the Boron cage. From SPR experiments, the adsorption kinetics of [B12H11SH]2- were studied. The data fit for a Langmuir kinetic equation, typical for the formation of a monolayer.

HPV vaccination introduction worldwide and WHO and UNICEF estimates of national HPV immunization coverage 2010-2019.

WHO/UNICEF estimates for HPV vaccination coverage from 2010 to 2019 are analyzed against the backdrop of the 90% coverage target for HPV vaccination by 2030 set in the recently approved global strategy for cervical cancer elimination as a public health problem. As of June 2020, 107 (55%) of the 194 WHO Member States have introduced HPV vaccination. The Americas and Europe are by far the WHO regions with the most introductions, 85% and 77% of their countries having already introduced respectively. A record number of introductions was observed in 2019, most of which in low- and middle- income countries (LMIC) where access has been limited. Programs had an average performance coverage of around 67% for the first dose and 53% for the final dose of HPV. LMICs performed on average better than high- income countries for the first dose, but worse for the last dose due to higher dropout. Only 5 (6%) countries achieved coverages with the final dose of more than 90%, 22 countries (21%) achieved coverages of 75% or higher while 35 (40%) had a final dose coverage of 50% or less. When expressed as world population coverage (i.e., weighted by population size), global coverage of the final HPV dose for 2019 is estimated at 15%. There is a long way to go to meet the 2030 elimination target of 90%. In the post-COVID era attention should be paid to maintain the pace of introductions, specially ensuring the most populous countries introduce, and further improving program performance globally.

Measuring Primary Care Across 35 OECD Countries.

PURPOSE: To examine the psychometric properties and scores of the Person-Centered Primary Care Measure (PCPCM) in 28 languages and 35 Organisation for Economic Co-operation and Development (OECD) countries. METHODS: Using a paid online sampling service, we requested age- and sex-representative samples of 360 adults in each country. We administered the Person-Centered Primary Care Measure-a previously validated 11-item, patient-reported measure that was developed using what patients and clinicians said is most important about primary care. We also assessed construct validity through associations with demographics, the Patient-Enablement Instrument, number of years the person had been with their primary care physician and practice, whether the patient thought the doctor knowing the results would improve their care, and whether it was hard to complete the survey. We assessed the psychometric properties of the PCPCM in each country and report the summative and item-specific PCPCM scores for each country. RESULTS: The PCPCM exhibited solid psychometric properties across all languages and countries, with Cronbach's alphas ranging from 0.88 to 0.95, and corrected item-total correlations ranging from 0.47 to 0.81, with the vast majority of countries ranging from the low 0.50s to the high 0.70s. Multiple analyses showed strong evidence of concurrent validity. With a potential range from a low of 1 to a high of 4, the overall mean score was 2.74, with a standard deviation of 0.19. Mean PCPCM scores ranged from the lowest in Sweden (2.28) to the highest in Turkey (3.08), with Germany ranking second (3.01), and the United States third (2.99). CONCLUSION: The internal consistency and concurrent validity of the PCPCM across multiple countries provides strong evidence of the coherence of the breadth of primary care functions that patients and clinicians say are important. The diversity of total and item-specific scores across countries provokes interesting hypotheses about the influence of each different country's policies, practices, demographics, and culture on primary care, and provides a strong impetus for further ecological and individual data analyses using the Person-Centered Primary Care Measure. Annals "Online First" article.

Working memory deficits in schizophrenia are associated with the rs34884856 variant and expression levels of the NR4A2 gene in a sample Mexican population: a case control study.

BACKGROUND: Cognitive functions represent useful endophenotypes to identify the association between genetic variants and schizophrenia. In this sense, the NR4A2 gene has been implicated in schizophrenia and cognition in different animal models and clinical trials. We hypothesized that the NR4A2 gene is associated with working memory performance in schizophrenia. This study aimed to analyze two variants and the expression levels of the NR4A2 gene with susceptibility to schizophrenia, as well as to evaluate whether possession of NR4A2 variants influence the possible correlation between gene expression and working memory performance in schizophrenia. METHODS: The current study included 187 schizophrenia patients and 227 controls genotyped for two of the most studied NR4A2 genetic variants in neurological and neuropsychiatric diseases. Genotyping was performed using High Resolution Melt and sequencing techniques. In addition, mRNA expression of NR4A2 was performed in peripheral mononuclear cells of 112 patients and 118 controls. A group of these participants, 54 patients and 87 controls, performed the working memory index of the WAIS III test. RESULTS: Both genotypic frequencies of the two variants and expression levels of the NR4A2 gene showed no significant difference when in patients versus controls. However, patients homozygous for the rs34884856 promoter variant showed a positive correlation between expression levels and auditory working memory. CONCLUSIONS: Our finding suggested that changes in expression levels of the NR4A2 gene could be associated with working memory in schizophrenia depending on patients' genotype in a sample from a Mexican population.

Mixotrophic growth regime as a strategy to develop microalgal bioprocess from nutrimental composition of tequila vinasses.

The selection of a suitable growth regime can increase the physiological performance of microalgae and improve bioprocess based on these microorganisms from agro-industrial residues. Thus, this study assessed the biotechnology capacity-biomass production, biochemical composition, and nutrient uptake-from tequila vinasses (TVs) as the nutrient source of three indigenous microalgae-Chlorella sp., Scenedesmus sp., and Chlamydomonas sp.-cultured under heterotrophic and mixotrophic conditions. The results demonstrated that under the mixotrophic regime, the three microalgae evaluated reached the highest nitrogen uptake, biomass production, and cell compound accumulation. Under this condition, Chlorella sp. and Scenedesmus sp. showed the highest nutrient uptake and biomass production, 1.7 ± 0.3 and 1.9 ± 0.3 g L-1, respectively; however, the biochemical composition, mainly carbohydrates and proteins, varied depending on the microalgal strain and its growth regime. Overall, our results demonstrated the biotechnological capacity of native microalgae from TVs, which may vary not only depending on the microalgal strain but also the culture strategy implemented and the characteristics of the residue used, highlighting-from a perspective of circular bio-economy-the feasibility of implementing microalgal bioprocess to reuse and valorize the nutrimental composition of TVs through biomass and high-valuable metabolite production, depicting a sustainable strategy for tequila agro-industry in Mexico.

Reporting of paclitaxel-induced peripheral neuropathy symptoms to clinicians among women with breast cancer: a qualitative study.

PURPOSE: Cases of chemotherapy-induced peripheral neuropathy (CIPN) under-reporting have been sporadically described in the literature, but no studies have focused on actively examining this behavior. Our primary aim was to identify women who purposefully under-reported CIPN, along with reasons for doing so. A secondary aim was to explore factors enabling or hindering communication of CIPN to clinicians. METHODS: Semi-structured interviews were conducted with women with breast cancer who had received paclitaxel in a prospective observational study. The interview guide was developed based on factors hypothesized to influence side effect disclosure to clinicians. Interviews were recorded, transcribed verbatim, and thematically content analyzed. RESULTS: Thirty-four women were interviewed. Three main themes emerged from the analysis: (1) enablers of CIPN reporting (e.g., positive relationship with the oncology team, sufficient appointment time, existence of alternative communication channels to office visits, expectation of CIPN as a side effect); (2) deterrents to CIPN reporting (e.g., perception of need to complete the full course of therapy, fear of treatment discontinuation, lack of knowledge of long-term consequences of CIPN); and (3) balancing survival versus functional impairment due to CIPN. Women prioritized efficacy over CIPN until physical functioning was meaningfully affected. No patients reported purposeful CIPN under-reporting, but three women admitted having considered doing so. CONCLUSIONS: Despite the lack of evidence of CIPN withholding, women considered both the effectiveness and the toxicity of paclitaxel treatment, as well as beliefs about treatment and long-term consequences of CIPN and relationship with the oncology team, when deciding whether to report CIPN symptoms.

A New Comprehensive Measure of High-Value Aspects of Primary Care.

PURPOSE: To develop and evaluate a concise measure of primary care that is grounded in the experience of patients, clinicians, and health care payers. METHODS: We asked crowd-sourced samples of 412 patients, 525 primary care clinicians, and 85 health care payers to describe what provides value in primary care, then asked 70 primary care and health services experts in a 2½ day international conference to provide additional insights. A multidisciplinary team conducted a qualitative analysis of the combined data to develop a parsimonious set of patient-reported items. We evaluated items using factor analysis, Rasch modeling, and association analyses among 2 online samples and 4 clinical samples from diverse patient populations. RESULTS: The resulting person-centered primary care measure parsimoniously represents the broad scope of primary care, with 11 domains each represented by a single item: accessibility, advocacy, community context, comprehensiveness, continuity, coordination, family context, goal-oriented care, health promotion, integration, and relationship. Principal axes factor analysis identified a single factor. Factor loadings and corrected item-total correlations were >0.6 in online samples (n = 2,229) and >0.5 in clinical samples (n = 323). Factor scores were fairly normally distributed in online patient samples, and skewed toward higher ratings in point-of-care patient samples. Rasch models showed a broad spread of person and item scores, acceptable item-fit statistics, and little item redundancy. Preliminary concurrent validity analyses supported hypothesized associations. CONCLUSIONS: The person-centered primary care measure reliably, comprehensively, and parsimoniously assesses the aspects of care thought to represent high-value primary care by patients, clinicians, and payers. The measure is ready for further validation and outcome analyses, and for use in focusing attention on what matters about primary care, while reducing measurement burden.

Assessing electronic immunization registries: the Pan American Health Organization experience.

OBJECTIVE: To develop a methodology to assess electronic immunization registries (EIRs) in low- and middle-income countries (LMICs) in Latin America and the Caribbean. METHODS: A team from the Immunization Unit at the Pan American Health Organization (PAHO) reviewed existing methodologies to evaluate health information systems, particularly the Performance of Routine Information System Management (PRISM) framework and methodologies used to assess information systems. In 2014, the PAHO team convened a small working group to develop an evaluation approach to be added to the existing World Health Organization immunization data quality self-assessment (DQS) tool. The resulting DQS with an added EIR component was named "DQS Plus." The DQS Plus methodology was used in Panama in May 2014 and in Honduras in November 2015. RESULTS: The DQS Plus tool proved feasible and easy to implement in Panama and Honduras, including by not adding much time or resources to those needed for a usual DQS. The information obtained from the DQS Plus assessment was practical and helped provide health authorities with recommendations to update and improve their EIR, strengthen the use of the registry, and enhance the data the assessment produced, at all levels of the health system. These recommendations are currently being implemented in the two countries. CONCLUSIONS: The DQS Plus proved to be a practical and useful approach for assessing an EIR in an LMIC and generating actionable recommendations. Further work on defining operational and related EIR functional standards in LMICs will help develop an improved EIR assessment tool for Latin America and the Caribbean, and potentially elsewhere.