Overdose prevention activities led by local public health departments, 2019-2023.

BACKGROUND: Drug overdose deaths in the United States increased to historic levels in recent years, with provisional estimates indicating more than 111,000 deaths in the 12 months ending July 2023. In 2019, the Centers for Disease Control and Prevention's Division of Overdose Prevention in collaboration with the National Association of City and County Health Officials, funded local health departments (LHDs) to work on overdose prevention activities. This paper aims to: 1) describe the overdose prevention activities that LHDs implemented during the four eighteen-month funding cycles; 2) identify programmatic successes and areas of opportunity for LHDs to consider when implementing future overdose prevention activities; and to 3) inform policy considerations and future overdose prevention programming at the local level. METHODS: We used programmatic data to identify overdose prevention activities implemented by 45 LHDs. Activities were double-coded according to the social-ecological model and the U.S. Department of Health and Human Services Overdose Prevention Strategies and Guiding Principles. We analyzed final codes to identify distribution and overlap of the Strategies and Guiding Principles across the social ecological model co-occurrences. RESULTS: Approximately 55.9% (n=123) of the 220 overdose prevention activities that were coded took place at the community level, 32.3% (n=71) at the individual level, 8.6% (n=19) at the relationship level, and 3.2% (n=7) at the policy level. Most of the activities were coded as coordination, collaboration, and integration (n=52, 23.6%), harm reduction (n=51, 23.1%), data and evidence (n=47, 21.4%) or reducing stigma (n=24, 10.9%). Few activities were related to primary prevention (n=14, 6.4%), equity (n=14, 6.4%), recovery support (n=11, 5.0%), and evidence-based treatment (n=7, 3.2%). CONCLUSIONS: Localities have primarily implemented activities focused on the community and individual levels, with most of these centered around coordination, collaboration, and integration; harm reduction; or data and evidence. This study identified gaps in overdose prevention for LHDs related to treatment and health equity and that more interventions should be implemented at the relationship and policy levels. Continuing these efforts is important as LHDs explore opportunities to enhance and expand their work in various strategy areas across the social ecology. Findings from this study may be used to inform localities as they design and implement future overdose prevention activities.

Alcohol and other drug use patterns and services in an integrated refugee settlement in Northern Zambia: a formative research study.

BACKGROUND: Evidence on patterns of alcohol and other drug (AOD) use and how to effectively deliver services to address AOD use in humanitarian settings is limited. This study aimed to qualitatively explore the patterns of AOD use among Congolese refugees in Mantapala Refugee Settlement and members of the surrounding host community and identify potential appropriate intervention and implementation approaches to address AOD use disorders among conflict-affected populations. METHODS: Fifty free listing interviews, 25 key informant interviews, and four focus group discussions were conducted among refugees, host community members, humanitarian implementing agency staff, and refugee incentive workers. These participants were selected based on their knowledge of AOD use and related problems in the settlement and the surrounding host community in northern Zambia. RESULTS: Cannabis and home-brewed alcohol were the substances that were perceived to be most commonly used and have the greatest impact on the community. Participants reported that self-medication, boredom, and relief of daily stressors associated with lack of housing, safety, and employment were reasons that people used AODs. Participants recommended that programming include components to address the underlying causes of AOD use, such as livelihood activities. Stigma due to the criminalization of and societal ideals and religious beliefs regarding AOD use was identified as a substantial barrier to accessing and seeking treatment. CONCLUSIONS: Our study's findings indicate the need for services to address AOD use in Mantapala Refugee Settlement. Interventions should consider the social and structural determinants of AOD use.

Sequencing systemic therapy in hormone-receptor positive metastatic breast cancer: a modern paradigm.

Deaths from metastatic breast cancer continue to be a leading cause of global cancer mortality among women. The pace of advances in the treatment of hormone-receptor positive metastatic breast cancer (HR+ MBC) has introduced nuance and complexity in choosing between available agents as patients and physicians explore options across lines of therapy. In this review, we explore the modern paradigm of treatment options and the sequential approach to HR+ MBC, as well as treatment options on the horizon, and the particular impact on survival outcomes and the associated adverse effects of those treatments. We discuss the diagnostic approach, first- and second-line management, as well as management of later-line endocrine-refractory HR+ MBC. Treatments discussed include cyclin-dependent kinase 4/6 inhibitors, antibody drug conjugates, and targeted therapies against phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit alpha (PIK3CA), estrogen receptor 1 (ESR1), and poly[ADP-ribose] polymerase (PARP), among others. Building from the initial diagnostic approach, we describe how to pragmatically layer options by appropriate line of therapy and personalized drivers of disease to aid in treatment decision making step-by-step. Combining sequential treatment options, evolving treatment options, and advanced genetic and genomic testing along with shared decision making between patients and physicians, this review aims to outline the key factors that ultimately drive the decisions for treatment in hormone-positive metastatic breast cancer.

Testing a Screening, Brief Intervention, and Referral to Treatment Intervention Approach for Addressing Unhealthy Alcohol and Other Drug Use in Humanitarian Settings: Protocol of the Ukuundapwa Chapamo Randomised Controlled Trial.

Refugees and other displaced persons are exposed to many risk factors for unhealthy alcohol and other drug (AOD) use and concomitant mental health problems. Evidence-based services for AOD use and mental health comorbidities are rarely available in humanitarian settings. In high income countries, screening, brief intervention and referral to treatment (SBIRT) systems can provide appropriate care for AOD use but have rarely been used in low- and middle-income countries and to our knowledge never tested in a humanitarian setting. This paper describes the protocol for a randomised controlled trial to compare the effectiveness of an SBIRT system featuring the Common Elements Treatment Approach (CETA) to treatment as usual in reducing unhealthy AOD use and mental health comorbidities among refugees from the Democratic Republic of the Congo and host community members in an integrated settlement in northern Zambia. The trial is an individually randomised, single-blind, parallel design with outcomes assessed at 6-months (primary) and 12-months post-baseline. Participants are Congolese refugees and Zambians in the host community, 15 years of age or older with unhealthy alcohol use. Outcomes are: unhealthy alcohol use (primary), other drug use, depression, anxiety and traumatic stress. The trial will explore SBIRT acceptability, appropriateness, cost-effectiveness, feasibility, and reach.

Priorities for addressing substance use disorder in humanitarian settings.

BACKGROUND: Populations affected by humanitarian emergencies are vulnerable to substance (alcohol and other drug) use disorders, yet treatment and prevention services are scarce. Delivering substance use disorder treatment services in humanitarian settings is hampered by limited guidance around the preparation, implementation, and evaluation of substance use disorder treatment programs. This study aims to identify and prioritize key gaps and opportunities for addressing substance use disorder in humanitarian settings. METHODS: UNODC convened a consultation meeting (n = 110) in coordination with UNHCR and WHO and administered an online survey (n = 34) to, thirteen program administrators and policymakers, eleven service providers, nine researchers, and one person with lived experience to explore best practices and challenges to addressing substance use disorder in diverse populations and contexts. Participants presented best practices for addressing substance use disorder, identified and ranked challenges and opportunities for improving the delivery of substance use disorder treatment interventions, and provided recommendations for guidelines that would facilitate the delivery of substance use disorder treatment services in humanitarian emergencies. RESULTS: Participants agreed on key principles for delivering substance use disorder treatment in humanitarian settings that centered on community engagement and building trust, integrated service delivery models, reducing stigma, considering culture and context in service delivery, and an ethical 'do no harm' approach. Specific gaps in knowledge that precluded the delivery of appropriate substance use disorder treatment include limited knowledge of the burden and patterns of substance use in humanitarian settings, the effectiveness of substance use disorder treatment services in humanitarian settings, and strategies for adapting and implementing interventions for a given population and humanitarian context. Participants emphasized the need to strengthen awareness and commitment related to the burden of substance use disorder treatment interventions among communities, practitioners, and policymakers in humanitarian settings. CONCLUSIONS: Results from this consultation process highlight existing gaps in knowledge related to the epidemiology and treatment of substance use disorders in humanitarian emergencies. Epidemiological, intervention, and implementation research as well as operational guidance are needed to fill these gaps and improve access to substance use treatment services in humanitarian settings.

Ethics Reporting Practices in Aging Research From the Arab Region.

Objectives: This study aims to assess the extent of ethics reporting practices in aging research from Arab countries. Methods: A systematic scoping review of research on aging in 22 Arab countries from seven databases (1994-2013) identified 637 publications warranting institutional ethical approval and 612 publications warranting informed consent. We used multivariable regression analysis to examine variations by time, place, and study characteristics. Results: Only 36.6% of articles reported approval from a Research Ethics Committee and 38.7% reported informed consent. Reporting of ethical research practices increased significantly over time and as research collaborations and journal impact factor increased, and when sampling frame included institutionalized participants. In contrast, failure to report ethical research practices was significantly more common in non-English articles and those that did not report a funding source. Discussion: Despite gains across time, reporting of ethical research practices remains suboptimal in the Arab region. Further guidelines and capacity building are needed.

Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer.

PURPOSE: Based on improvement in pathologic complete response (pCR) in the NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP (docetaxel + HP), FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-THP, and TCHP (docetaxel, carboplatin + HP). However, in the United States, doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing neoadjuvant AC-THP with AC-TH or TCHP. Here we report outcomes for patients with localized HER2+ breast cancer treated with pertuzumab-containing neoadjuvant regimens and AC-TH. METHODS: We reviewed clinicopathological characteristics of patients with HER2+ breast cancer (Stage I-III) treated with either a neoadjuvant pertuzumab-containing regimen or dose-dense (dd) AC-TH, from 2011 to 2016 at a large academic medical institution and two affiliated community sites. pCR was defined as ypT0/is ypN0. Fisher's exact test and logistic regression analysis were used for statistical analysis. RESULTS: In this study (N = 121), pCR was numerically higher with pertuzumab-based regimens, including ddAC-THP (60%), TCHP (63%), THP (55%), as compared with ddAC-TH (46%). THP resulted in significantly less cycle delays due to toxicity compared to the other regimens (p = 0.02). THP also resulted in the least dose reductions, lowest rate of hospitalization, and lowest rate of treatment discontinuation. CONCLUSIONS: Pertuzumab-based regimens, including THP, resulted in higher pCR rates as compared to ddAC-TH, with the THP regimen associated with the best tolerability among patients with localized HER2+ breast cancer. Given the various neoadjuvant regimens, additional studies are needed to determine optimal treatment sequencing and escalation/de-escalation strategies to personalize neoadjuvant regimens for localized HER2+ breast cancer.

Phylogenomic Data Yield New and Robust Insights into the Phylogeny and Evolution of Weevils.

The phylogeny and evolution of weevils (the beetle superfamily Curculionoidea) has been extensively studied, but many relationships, especially in the large family Curculionidae (true weevils; > 50,000 species), remain uncertain. We used phylogenomic methods to obtain DNA sequences from 522 protein-coding genes for representatives of all families of weevils and all subfamilies of Curculionidae. Most of our phylogenomic results had strong statistical support, and the inferred relationships were generally congruent with those reported in previous studies, but with some interesting exceptions. Notably, the backbone relationships of the weevil phylogeny were consistently strongly supported, and the former Nemonychidae (pine flower snout beetles) were polyphyletic, with the subfamily Cimberidinae (here elevated to Cimberididae) placed as sister group of all other weevils. The clade comprising the sister families Brentidae (straight-snouted weevils) and Curculionidae was maximally supported and the composition of both families was firmly established. The contributions of substitution modeling, codon usage and/or mutational bias to differences between trees reconstructed from amino acid and nucleotide sequences were explored. A reconstructed timetree for weevils is consistent with a Mesozoic radiation of gymnosperm-associated taxa to form most extant families and diversification of Curculionidae alongside flowering plants-first monocots, then other groups-beginning in the Cretaceous.

Pathologic Complete Response After Neoadjuvant Chemotherapy and Long-Term Outcomes Among Young Women With Breast Cancer.

Purpose: Breast cancer in young women is associated with an aggressive tumor biology and higher risk of recurrence. Pathologic complete response (pCR) after neoadjuvant therapy has been shown to be a surrogate marker for disease-free survival (DFS) and overall survival (OS), but the association between pCR and survival outcomes in young women with breast cancer is not well described. Methods: This study included women aged ≤40 years at diagnosis who received neoadjuvant chemotherapy (NAC) for stage II-III invasive breast cancer between 1998 and 2014 at Massachusetts General Hospital. Outcomes were compared between patients who achieved pCR (ypT0/is, ypN0) and those with residual disease. Results: A total of 170 young women were included in the analytical data set, of which 53 (31.2%) achieved pCR after NAC. The 5-year DFS rate for patients with and without pCR was 91% versus 60%, respectively (P<.01), and the OS rate was 95% versus 75%, respectively (P<.01). Among patients with pCR, no difference was seen in OS irrespective of baseline clinical stage (P=.6), but among patients with residual disease after NAC, a significant difference in OS based on baseline clinical stage was observed (P<.001). Conclusions: Our results suggest pCR after NAC is strongly associated with significantly improved DFS and OS in young women with breast cancer, and perhaps even more so than baseline stage. However, the significantly higher mortality for patients who did not attain pCR highlights the need for better therapies, and the neoadjuvant trial design could potentially serve as an efficient method for rapid triage and escalation/de-escalation of therapies to improve outcomes for young women with breast cancer.

[Effect of dental arch length decrease during orthodontic treatment in the upper airway development. A review]. / Impact de la diminution du périmètre des arcades dentaires lors d'une prise en charge orthodontique dans le développement des voies aériennes supérieures. Une revue de la littérature.

INTRODUCTION: A possible relation between an upper airway space decrease and the development of obstructive sleep apnea syndrom explains the importance to know the effect of the modification of dental arch length on the upper airway during orthodontic treatment. OBJECTIVES: The aim of this article is to expose recent knowledge about upper airway development and dental arch length decrease factors, to determine the influence of this decrease on upper airway development. METHODS: A review was done to determine the upper airway normal development, to define dental arch to specify if an ideal position of dental arch on apical base exists. All of the length dental arch decrease factors during orthodontic treatment (dental extraction, dental agenesis and dental malpositions) and their upper airway resounding were searched. RESULTS: Some authors found a diminution of upper airway space after premolars extractions while others didn't found this diminution after extractions premolars when incisor retraction is finished. A decrease of transversal maxillary diameter and nasal cavity may be due to absence of permanent teeth. CONCLUSION: The effect of dental arch length decrease during orthodontic treatment in the upper airway development was not scientifically proved. However we had to be vigilant and adapt our orthodontic treatment case by case to avoid an upper airway modification.

Genome of the Asian longhorned beetle (Anoplophora glabripennis), a globally significant invasive species, reveals key functional and evolutionary innovations at the beetle-plant interface.

BACKGROUND: Relatively little is known about the genomic basis and evolution of wood-feeding in beetles. We undertook genome sequencing and annotation, gene expression assays, studies of plant cell wall degrading enzymes, and other functional and comparative studies of the Asian longhorned beetle, Anoplophora glabripennis, a globally significant invasive species capable of inflicting severe feeding damage on many important tree species. Complementary studies of genes encoding enzymes involved in digestion of woody plant tissues or detoxification of plant allelochemicals were undertaken with the genomes of 14 additional insects, including the newly sequenced emerald ash borer and bull-headed dung beetle. RESULTS: The Asian longhorned beetle genome encodes a uniquely diverse arsenal of enzymes that can degrade the main polysaccharide networks in plant cell walls, detoxify plant allelochemicals, and otherwise facilitate feeding on woody plants. It has the metabolic plasticity needed to feed on diverse plant species, contributing to its highly invasive nature. Large expansions of chemosensory genes involved in the reception of pheromones and plant kairomones are consistent with the complexity of chemical cues it uses to find host plants and mates. CONCLUSIONS: Amplification and functional divergence of genes associated with specialized feeding on plants, including genes originally obtained via horizontal gene transfer from fungi and bacteria, contributed to the addition, expansion, and enhancement of the metabolic repertoire of the Asian longhorned beetle, certain other phytophagous beetles, and to a lesser degree, other phytophagous insects. Our results thus begin to establish a genomic basis for the evolutionary success of beetles on plants.

Saline Flush Test: Can Bedside Sonography Replace Conventional Radiography for Confirmation of Above-the-Diaphragm Central Venous Catheter Placement?

OBJECTIVES: Resuscitation often requires rapid vascular access via central venous catheters. Chest radiography is the reference standard to confirm central venous catheter placement and exclude complications. However, radiographs are often untimely. The purpose of this study was to determine whether dynamic sonographic visualization of a saline flush in the right side of the heart after central venous catheter placement could serve as a more rapid confirmatory study for above-the-diaphragm catheter placement. METHODS: A consecutive prospective enrollment study was conducted in the emergency departments of 2 major tertiary care centers. Adult patients of the study investigators who required an above-the-diaphragm central venous catheter were enrolled during the study period. Patients had a catheter placed with sonographic guidance. After placement of the catheter, thoracic sonography was performed. The times for visualization of the saline flush in the right ventricle and sonographic exclusion of ipsilateral pneumothorax were recorded. Chest radiography was performed per standard practice. RESULTS: Eighty-one patients were enrolled; 13 were excluded. The mean catheter confirmation time by sonography was 8.80 minutes (95% confidence interval, 7.46-10.14 minutes). The mean catheter confirmation time by chest radiograph availability for viewing was 45.78 minutes (95% confidence interval, 37.03-54.54 minutes). Mean sonographic confirmation occurred 36.98 minutes sooner than radiography (P< .001). No discrepancy existed between sonographic and radiographic confirmation. CONCLUSIONS: Confirmation of central venous catheter placement by dynamic sonographic visualization of a saline flush with exclusion of pneumothorax is an accurate, safe, and more efficient method than confirmation by chest radiography. It allows the central line to be used immediately, expediting patient care.