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1.
Article in English | MEDLINE | ID: mdl-38957231

ABSTRACT

The Philippines' Republic Act 11332 (2020) mandates prisons, jails and detention centres to participate in disease surveillance, but currently no surveillance system exists in these facilities. This report aims to describe the piloting of an early warning disease surveillance system in 21 selected jails in Calabarzon from July to September 2021. Sites were selected based on congestion, proximity to health facilities and logistical capacity. Data sources, collection mechanisms and reporting tools were determined and health personnel were trained in the operation of the system. During the implementation period, the system detected 10 health events, with influenza-like illness and foodborne illness being the most common. Nine of these events were reported within 24 hours. The local health unit provided medications for clinical management and instructed jail nurses on infection prevention and control measures, including active case finding, the isolation of cases and the inspection of food handling. Twelve sites reported over 8 of the 10 weeks, with all sites reporting zero cases promptly. The challenges identified included insufficient workforce, slow internet speed and multitasking. It was concluded that the jail-based early warning surveillance system is feasible and functional, but the perceived benefits of jail management are crucial to the acceptability and ownership of the system. It is recommended to replicate the surveillance system in other penitentiaries nationwide.


Subject(s)
Jails , Population Surveillance , Humans , Philippines/epidemiology , Population Surveillance/methods , Jails/statistics & numerical data , Disease Outbreaks/prevention & control , Prisons/statistics & numerical data
3.
ESMO Open ; 9(5): 103007, 2024 May.
Article in English | MEDLINE | ID: mdl-38744101

ABSTRACT

BACKGROUND: Understanding stakeholders' perception of cure in prostate cancer (PC) is essential to preparing for effective communication about emerging treatments with curative intent. This study used artificial intelligence (AI) for landscape review and linguistic analysis of definition, context and value of cure among stakeholders in PC. MATERIALS AND METHODS: Subject-matter experts (SMEs) selected cure-related key words using Elicit, a semantic literature search engine, and extracted hits containing the key words from Medline, Sermo and Overton, representing academic researchers, health care providers (HCPs) and policymakers, respectively. NetBase Quid, a social media analytics and natural language processing tool, was used to carry out key word searches in social media (representing the general public). NetBase Quid analysed linguistics of key word-specific hit sets for key word count, geolocation and sentiments. SMEs qualitatively summarised key word-specific insights. Contextual terms frequently occurring with key words were identified and quantified. RESULTS: SMEs identified seven key words applicable to PC (number of acquired hits) across four platforms: Cure (12429), Survivor (6063), Remission (1904), Survivorship (1179), Curative intent (432), No evidence of disease (381) and Complete remission (83). Most commonly used key words were Cure by the general public and HCPs (11815 and 224 hits), Survivorship by academic researchers and Survivor by policymakers (378 hits each). All stakeholders discussed Cure and cure-related key words primarily in early-stage PC and associated them with positive sentiments. All stakeholders defined cure differently but communicated about it in relation to disease measurements (e.g. prostate-specific antigen) or surgery. Stakeholders preferred different terms when discussing cure in PC: Cure (academic researchers), Cure rates (HCPs), Potential cure and Survivor/Survivorship (policymakers) and Cure and Survivor (general public). CONCLUSION: This human-led, AI-assisted large-scale qualitative language-based research revealed that cure was commonly discussed by academic researchers, HCPs, policymakers and the general public, especially in early-stage PC. Stakeholders defined and contextualised cure in their communications differently and associated it with positive value.


Subject(s)
Artificial Intelligence , Prostatic Neoplasms , Social Media , Humans , Male , Prostatic Neoplasms/therapy , Linguistics/methods , Health Policy , Perception , Natural Language Processing
4.
Child Abuse Negl ; 153: 106844, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38761717

ABSTRACT

BACKGROUND: Empirical studies have demonstrated associations between ten original adverse childhood experiences (ACEs) and multiple health outcomes. Identifying expanded ACEs can capture the burden of other childhood adversities that may have important health implications. OBJECTIVE: We sought to identify childhood adversities that warrant consideration as expanded ACEs. We hypothesized that experiencing expanded and original ACEs would be associated with poorer adult health outcomes compared to experiencing original ACEs alone. PARTICIPANTS: The 11,545 respondents of the National Longitudinal Surveys (NLS) and Child and Young Adult Survey were 48.9 % female, 22.7 % Black, 15.8 % Hispanic, 36.1 % White, 1.7 % Asian/Native Hawaiian/Pacific Islander/Native American/Native Alaskan, and 7.5 % Other. METHODS: This study used regression trees and generalized linear models to identify if/which expanded ACEs interacted with original ACEs in association with six health outcomes. RESULTS: Four expanded ACEs-basic needs instability, lack of parental love and affection, community stressors, and mother's experience with physical abuse during childhood -significantly interacted with general health, depressive symptom severity, anxiety symptom severity, and violent crime victimization in adulthood (all p-values <0.005). Basic needs instability and/or lack of parental love and affection emerged as correlates across multiple outcomes. Experiencing lack of parental love and affection and original ACEs was associated with greater anxiety symptoms (p = 0.022). CONCLUSIONS: This is the first study to use supervised machine learning to investigate interaction effects among original ACEs and expanded ACEs. Two expanded ACEs emerged as predictors for three adult health outcomes and warrant further consideration in ACEs assessments.


Subject(s)
Adverse Childhood Experiences , Humans , Female , Male , Adverse Childhood Experiences/statistics & numerical data , Adult , Longitudinal Studies , Child , Young Adult , Adolescent , Health Status , Regression Analysis , Depression/epidemiology , Crime Victims/statistics & numerical data , Crime Victims/psychology , Anxiety/epidemiology , United States/epidemiology , Adult Survivors of Child Abuse/psychology , Adult Survivors of Child Abuse/statistics & numerical data
5.
Nature ; 630(8015): 158-165, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38693268

ABSTRACT

The liver has a unique ability to regenerate1,2; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option3-5. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2+ migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration. Interrogation of necrotic wound closure and hepatocyte proliferation across multiple timepoints following APAP-induced liver injury in mice demonstrates that wound closure precedes hepatocyte proliferation. Four-dimensional intravital imaging of APAP-induced mouse liver injury identifies motile hepatocytes at the edge of the necrotic area, enabling collective migration of the hepatocyte sheet to effect wound closure. Depletion of hepatocyte ANXA2 reduces hepatocyte growth factor-induced human and mouse hepatocyte migration in vitro, and abrogates necrotic wound closure following APAP-induced mouse liver injury. Together, our work dissects unanticipated aspects of liver regeneration, demonstrating an uncoupling of wound closure and hepatocyte proliferation and uncovering a novel migratory hepatocyte subpopulation that mediates wound closure following liver injury. Therapies designed to promote rapid reconstitution of normal hepatic microarchitecture and reparation of the gut-liver barrier may advance new areas of therapeutic discovery in regenerative medicine.


Subject(s)
Liver Failure, Acute , Liver Regeneration , Animals , Female , Humans , Male , Mice , Acetaminophen/pharmacology , Cell Lineage , Cell Movement/drug effects , Cell Proliferation/drug effects , Chemical and Drug Induced Liver Injury/pathology , Disease Models, Animal , Hepatocyte Growth Factor/metabolism , Hepatocyte Growth Factor/pharmacology , Hepatocytes/cytology , Hepatocytes/drug effects , Hepatocytes/metabolism , Hepatocytes/pathology , Liver/cytology , Liver/drug effects , Liver/pathology , Liver Failure, Acute/pathology , Liver Failure, Acute/chemically induced , Liver Regeneration/drug effects , Mice, Inbred C57BL , Necrosis/chemically induced , Regenerative Medicine , Single-Cell Gene Expression Analysis , Wound Healing
6.
Trop Med Health ; 52(1): 32, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38650044

ABSTRACT

Schistosomiasis, a neglected tropical disease, caused by blood flukes belonging to the genus Schistosoma; it persists as a public health problem in selected regions throughout Africa, South America, and Asia. Schistosoma mekongi, a zoonotic schistosome species endemic to the Mekong River in Laos and Cambodia, is one of the significant causes of human schistosomiasis along with S. japonicum, S. mansoni, S. haematobium and S. intercalatum. Since its discovery, S. mekongi infection has been highly prevalent in communities along the Mekong River. Although surveillance and control measures have shown success in recent years, more robust diagnostic tools are still needed to establish more efficient control and prevention strategies to achieve and sustain an elimination status. Diagnosis of S. mekongi infection still relies on copro-parasitological techniques, commonly made by Kato-Katz stool examination. Serological techniques such as enzyme-linked immunosorbent assay (ELISA) may also be applicable but in a limited setting. Targeted molecular and serological tools specific to the species, on the other hand, have been limited. This is due, in part, to the limited research and studies on the molecular biology of S. mekongi since genome information of this species has not yet been released. In this review, current advances, and gaps and limitations in the molecular and immunological diagnosis of S. mekongi are discussed.

7.
Sci Adv ; 10(9): eadk3074, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38416824

ABSTRACT

Cancer cells program fibroblasts into cancer associated fibroblasts (CAFs) in a two-step manner. First, cancer cells secrete exosomes to program quiescent fibroblasts into activated CAFs. Second, cancer cells maintain the CAF phenotype via activation of signal transduction pathways. We rationalized that inhibiting this two-step process can normalize CAFs into quiescent fibroblasts and augment the efficacy of immunotherapy. We show that cancer cell-targeted nanoliposomes that inhibit sequential steps of exosome biogenesis and release from lung cancer cells block the differentiation of lung fibroblasts into CAFs. In parallel, we demonstrate that CAF-targeted nanoliposomes that block two distinct nodes in fibroblast growth factor receptor (FGFR)-Wnt/ß-catenin signaling pathway can reverse activate CAFs into quiescent fibroblasts. Co-administration of both nanoliposomes significantly improves the infiltration of cytotoxic T cells and enhances the antitumor efficacy of αPD-L1 in immunocompetent lung cancer-bearing mice. Simultaneously blocking the tumoral exosome-mediated activation of fibroblasts and FGFR-Wnt/ß-catenin signaling constitutes a promising approach to augment immunotherapy.


Subject(s)
Exosomes , Lung Neoplasms , Animals , Mice , Exosomes/metabolism , Cell Proliferation/genetics , Fibroblasts/metabolism , Lung Neoplasms/genetics , Phenotype , Immunotherapy , Cell Line, Tumor
8.
Am J Prev Med ; 66(6): 963-970, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38309671

ABSTRACT

INTRODUCTION: Recent research has indicated an association between both poverty and income inequality and firearm homicides. Increased minimum wages may serve as a strategy for reducing firearm violence by increasing economic security among workers earning low wages and reducing the number of families living in poverty. This study aimed to examine the association between state minimum wage and firearm homicides in the U.S. between 2000 and 2020. METHODS: State minimum wage, obtained from Temple's Law Atlas and augmented by legal research, was conceptualized using the Kaitz Index. State-level homicide counts were obtained from 2000 to 2020 multiple-cause-of death mortality data from the National Vital Statistics System. Log-linear regressions were conducted to model the associations between state minimum wage and firearm homicides, stratifying by demographic groups. Analyses were conducted in 2023. RESULTS: A 1% point increase in a state's Kaitz Index was associated with a 1.3% (95% CI: -2.1% to -0.5%) decrease in a state's firearm homicide rate. When interacted with quartile of firearm ownership, the Kaitz Index was associated with decreases in firearm homicide in all except the lowest quartile. These findings were largely consistent across stratifications. CONCLUSIONS: Changing a state's minimum wage, whereby a full-time minimum wage worker's salary is closer to a state's median income, may be an option for reducing firearm homicides.


Subject(s)
Firearms , Homicide , Salaries and Fringe Benefits , Humans , Homicide/statistics & numerical data , Homicide/trends , Firearms/statistics & numerical data , Firearms/legislation & jurisprudence , Firearms/economics , United States/epidemiology , Salaries and Fringe Benefits/statistics & numerical data , Salaries and Fringe Benefits/trends , Male , Female , Adult , Middle Aged , Poverty/statistics & numerical data , Young Adult , Adolescent , Income/statistics & numerical data
9.
Ir J Med Sci ; 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38376642

ABSTRACT

BACKGROUND: Proximal humeral fractures are a common injury accounting for a significant workload across orthopaedic departments. Though often managed non-operatively, surgical management is indicated for a proportion of patients. AIMS: The aim of this study is to examine the trends in the management of proximal humeral fractures within Ireland over the past 13 years. METHODS: A retrospective review of Irish Hospital In-Patient Enquiry (HIPE) data was performed between January 2009 and December 2022. Information regarding demographics including age and gender, along with procedure type were collated after patients with proximal humerus fractures, were identified using relevant ICD 10 codes. RESULTS: Demographic details remained stable with females and those within the 55-69 year age bracket accounting for the highest proportion of patients. The mean annual number of procedures performed across the study period was 365 (273-508), with an increase from 288 cases in 2009 to 441 in 2022. Open reduction and internal fixation were the most common procedures accounting for 76.4% of cases. There has been a rising usage of total shoulder arthroplasty for fixation with an increase from < 5 cases in 2016 to 84 in 2022. A decrease in the usage of hemiarthroplasty and closed reduction internal fixation was also observed. CONCLUSIONS: There has been an increasing volume of operatively managed proximal humeral fractures in Ireland, which sustained despite the 2015 publication of the highly publicised PROPHER trial. The increasing utilisation of total shoulder arthroplasty in acute trauma management is notable and necessitates appropriate training for trauma theatre personnel.

10.
Inj Prev ; 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38182408

ABSTRACT

BACKGROUND: Children in households experiencing poverty are disproportionately exposed to maltreatment. Income support policies have been associated with reductions in child abuse and neglect. The advance child tax credit (CTC) payments may reduce child maltreatment by improving the economic security of some families. No national studies have examined the association between advance CTC payments and child abuse and neglect. This study examines the association between the advance CTC payments and child abuse and neglect-related contacts to the Childhelp National Child Abuse Hotline. METHODS: A time series study of contacts to the Childhelp National Child Abuse Hotline between January 2019 and December 2022 was used to examine the association between the payments and hotline contacts. An interrupted time series (ITS) exploiting the variation in the advance CTC payments was estimated using fixed effects. RESULTS: The CTC advance payments were associated with an immediate 13.8% (95% CI -17.5% to -10.0%) decrease in contacts to the hotline in the ITS model. Following the expiration of the advance CTC payments, there was a significant and gradual 0.1% (95% CI +0.0% to +0.2%) daily increase in contacts. Sensitivity analyses found significant reductions in contacts following each payment, however, the reductions were associated with the last three of the six total payments. CONCLUSION: These findings suggest the advance CTC payments may reduce child abuse and neglect-related hotline contacts and continue to build the evidence base for associations between income-support policies and reductions in child abuse and neglect.

11.
J Vet Med Sci ; 86(1): 35-38, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38008465

ABSTRACT

Goat production is an important source of livelihood and food. Goats may serve as reservoir of surra affecting livestock production. Here, forty-two free-roaming goats from Cavite, Philippines were screened using two primer sets, Trypanosoma brucei minisatellite chromosome for initial detection and the internal transcribed spacer 1 (ITS-1) to determine phylogeny. Initial PCR detection showed that 19/42 (45%) goats were positive, much higher than the rate previously reported in goats from Cebu (34%). The infectivity rate was higher in male (56%) than in female (42%) and the rate was higher in young ≤1 year old (100%) than in adult >1 year old (43%). Phylogenetic analysis of the ITS-1 sequences between T. evansi goat samples and other isolates indicate potential interspecies transmission.


Subject(s)
Goat Diseases , Trypanosoma , Trypanosomiasis , Female , Male , Animals , Goats , Philippines/epidemiology , Phylogeny , DNA, Protozoan/genetics , Trypanosoma/genetics , Trypanosomiasis/epidemiology , Trypanosomiasis/veterinary , Goat Diseases/epidemiology , Goat Diseases/diagnosis
13.
Support Care Cancer ; 31(10): 570, 2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37698629

ABSTRACT

PURPOSE: To describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway. METHODS: Participants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary). RESULTS: 99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy. The chemotherapy group had poorer QoL; FACT-B total score mean differences were 8.53 (95% CI: 3.42 to 13.64), 5.38 (95% CI: 0.17 to 10.58) and 8.00 (95% CI: 2.76 to 13.24) at 6, 9 and 12 months, respectively. The odds of psychological morbidity (GHQ12 >4) were 5.5-fold greater for those treated with chemotherapy. Financial and caring burdens (PRRS) were worse for this group (mean difference in change at 9 months 3.25 (95% CI: 0.42 to 6.07)). GSE and GHQ-12 scores impacted FACT-B total scores, indicating QoL decline for those with high baseline psychological morbidity. Chemotherapy patients or those with high psychological morbidity or were unable to carry out normal activities had the highest service costs. Over the 12 months, 68.2% participants phoned/emailed breast care nurses, and 53.3% visited a hospital breast clinician. CONCLUSION: The data suggest that chemotherapy patients and/or those with heightened psychological morbidity might benefit from closer monitoring and/or supportive interventions whilst on the SSM/PIFU pathway. Reduced access due to COVID-19 could have affected service use.


Subject(s)
Breast Neoplasms , COVID-19 , Porcine Reproductive and Respiratory Syndrome , Self-Management , Swine , Animals , Humans , Female , Breast Neoplasms/drug therapy , Quality of Life
14.
bioRxiv ; 2023 May 31.
Article in English | MEDLINE | ID: mdl-37398072

ABSTRACT

Lipid bilayer provides a two-dimensional hydrophobic solvent milieu for membrane proteins in cells. Although the native bilayer is widely recognized as an optimal environment for folding and function of membrane proteins, the underlying physical basis remains elusive. Here, employing the intramembrane protease GlpG of Escherichia coli as a model, we elucidate how the bilayer stabilizes a membrane protein and engages the protein's residue interaction network compared to the nonnative hydrophobic medium, micelles. We find that the bilayer enhances GlpG stability by promoting residue burial in the protein interior compared to micelles. Strikingly, while the cooperative residue interactions cluster into multiple distinct regions in micelles, the whole packed regions of the protein act as a single cooperative unit in the bilayer. Molecular dynamics (MD) simulation indicates that lipids less efficiently solvate GlpG than detergents. Thus, the bilayerinduced enhancement of stability and cooperativity likely stems from the dominant intraprotein interactions outcompeting the weak lipid solvation. Our findings reveal a foundational mechanism in the folding, function, and quality control of membrane proteins. The enhanced cooperativity benefits function facilitating propagation of local structural perturbation across the membrane. However, the same phenomenon can render the proteins' conformational integrity vulnerable to missense mutations causing conformational diseases1,2.

15.
Support Care Cancer ; 31(8): 459, 2023 Jul 11.
Article in English | MEDLINE | ID: mdl-37432501

ABSTRACT

PURPOSE: To determine the experiences, information, support needs and quality of life of women in the UK living with metastatic breast cancer (MBC) to provide content for educational materials. METHODS: An online survey, hosted for 3 months on a UK MBC charity website, comprised sections covering issues such as communication about MBC treatment and management, helpful and less helpful things that healthcare professionals, family and friends did or said and completion of the Patient Roles and Responsibilities Scale (PRRS). RESULTS: A total of 143 patients participated; 48/143(33%) presented de novo; 54/143(38%) had been living with MBC > 2 years. PRRS analysis revealed that MBC imposed a serious impact upon most respondents' own caring abilities and social lives. A majority 98/139 (71%) wished they had known more about MBC before their diagnosis; 63/134(47%) indicated that they still did not fully understand their illness; merely 78/139(56%) had access to a specialist nurse and only 69/135(51%) had been offered any additional support. Respondents reported little consideration given to their lifestyle/culture during consultations and inconsistent information, support services, continuity of care or access to clinical trials. They commented upon things health care professionals/friends and family did or said that were useful and cited other behaviours that were especially unhelpful. CONCLUSIONS: MBC exerted a deleterious impact upon patients' activities of daily living which were exacerbated in part by significant gaps in support, communication and information. IMPLICATIONS FOR CANCER SURVIVORS: LIMBER results are informing the content of educational materials currently being developed for patients' formal and informal carers.


Subject(s)
Breast Neoplasms , Porcine Reproductive and Respiratory Syndrome , Swine , Animals , Humans , Female , Quality of Life , Activities of Daily Living , Breast Neoplasms/therapy , United Kingdom
16.
Drug Des Devel Ther ; 17: 1211-1231, 2023.
Article in English | MEDLINE | ID: mdl-37113467

ABSTRACT

Introduction: Researchers aim for new heights in wound healing to produce wound dressings with unique features. Natural, synthetic, biodegradable, and biocompatible polymers especially in the nanoscale are being employed to support and provide efficient wound management. Economical and environmentally friendly sustainable wound management alternatives are becoming an urgent issue to meet future needs. Nanofibrous mats possess unique properties for ideal wound healing. They mimic the physical structure of the natural extracellular matrix (ECM), promote hemostasis, and gas permeation. Their interconnected nanoporosity prevents wound dehydration and microbial infiltration. Purpose: To prepare and evaluate a novel verapamil HCl-loaded environmentally friendly composite, with biopolymer-based electrospun nanofibers suitable for application as wound dressings providing adequate wound healing with no scar formation. Methods: Composite nanofibers were prepared by electrospinning of a blend of the natural biocompatible polymers, sodium alginate (SA) or zein (Z) together with polyvinyl alcohol (PVA). Composite nanofibers were characterized in terms of morphology, diameter, drug entrapment efficiency, and release. In vivo study of the therapeutic efficacy of verapamil HCl-loaded nanofibers on a Sprague Dawley rat model with dermal burn wound was investigated in terms of percent wound closure, and presence of scars. Results: Combining PVA with SA or Z improved the electrospinnability and properties of the developed nanofibers. Verapamil HCl-loaded composite nanofibers showed good pharmaceutical attributes favorable for wound healing including, fiber diameter ∼150 nm, high entrapment efficiency (∼80-100%) and biphasic controlled drug release for 24 h. In vivo study demonstrated promising potentials for wound healing without scaring. Conclusion: The developed nanofibrous mats combined the beneficial properties of the biopolymers and verapamil HCl to provide an increased functionality by exploiting the unique advantages of nanofibers in wound healing at a small dose proved to be insufficient in case of the conventional dosage form.


Subject(s)
Burns , Nanofibers , Rats , Animals , Cicatrix/drug therapy , Nanofibers/chemistry , Nanofibers/therapeutic use , Rats, Sprague-Dawley , Wound Healing , Polyvinyl Alcohol/chemistry , Biopolymers/therapeutic use , Burns/drug therapy
17.
Ann Oncol ; 34(5): 477-485, 2023 05.
Article in English | MEDLINE | ID: mdl-36858151

ABSTRACT

BACKGROUND: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. PATIENTS AND METHODS: Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. RESULTS: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. CONCLUSIONS: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.


Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Androgen Antagonists/therapeutic use , Androgens/therapeutic use , Castration
18.
JAMA Netw Open ; 6(3): e233413, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36930150

ABSTRACT

Importance: Firearm homicides are a major public health concern; lack of timely mortality data presents considerable challenges to effective response. Near real-time data sources offer potential for more timely estimation of firearm homicides. Objective: To estimate near real-time burden of weekly and annual firearm homicides in the US. Design, Setting, and Participants: In this prognostic study, anonymous, longitudinal time series data were obtained from multiple data sources, including Google and YouTube search trends related to firearms (2014-2019), emergency department visits for firearm injuries (National Syndromic Surveillance Program, 2014-2019), emergency medical service activations for firearm-related injuries (biospatial, 2014-2019), and National Domestic Violence Hotline contacts flagged with the keyword firearm (2016-2019). Data analysis was performed from September 2021 to September 2022. Main Outcomes and Measures: Weekly estimates of US firearm homicides were calculated using a 2-phase pipeline, first fitting optimal machine learning models for each data stream and then combining the best individual models into a stacked ensemble model. Model accuracy was assessed by comparing predictions of firearm homicides in 2019 to actual firearm homicides identified by National Vital Statistics System death certificates. Results were also compared with a SARIMA (seasonal autoregressive integrated moving average) model, a common method to forecast injury mortality. Results: Both individual and ensemble models yielded highly accurate estimates of firearm homicides. Individual models' mean error for weekly estimates of firearm homicides (root mean square error) varied from 24.95 for emergency department visits to 31.29 for SARIMA forecasting. Ensemble models combining data sources had lower weekly mean error and higher annual accuracy than individual data sources: the all-source ensemble model had a weekly root mean square error of 24.46 deaths and full-year accuracy of 99.74%, predicting the total number of firearm homicides in 2019 within 38 deaths for the entire year (compared with 95.48% accuracy and 652 deaths for the SARIMA model). The model decreased the time lag of reporting weekly firearm homicides from 7 to 8 months to approximately 6 weeks. Conclusions and Relevance: In this prognostic study of diverse secondary data on machine learning, ensemble modeling produced accurate near real-time estimates of weekly and annual firearm homicides and substantially decreased data source time lags. Ensemble model forecasts can accelerate public health practitioners' and policy makers' ability to respond to unanticipated shifts in firearm homicides.


Subject(s)
Homicide , Models, Statistical , Wounds, Gunshot , Humans , Firearms , Homicide/statistics & numerical data , Machine Learning , United States/epidemiology , Wounds, Gunshot/mortality , Reproducibility of Results , Forecasting/methods
19.
MMWR Morb Mortal Wkly Rep ; 72(13): 333-337, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-36995967

ABSTRACT

During the COVID-19 pandemic, the U.S. firearm homicide rate increased by nearly 35%, and the firearm suicide rate remained high during 2019-2020 (1). Provisional mortality data from the National Vital Statistics System indicate that rates continued to increase in 2021: the rates of firearm homicide and firearm suicide in 2021 were the highest recorded since 1993 and 1990, respectively (2). Firearm injuries treated in emergency departments (EDs), the primary setting for the immediate medical treatment of such injuries, gradually increased during 2018-2019 (3); however, more recent patterns of ED visits for firearm injuries, particularly during the COVID-19 pandemic, are unknown. Using data from the National Syndromic Surveillance Program (NSSP),* CDC examined changes in ED visits for initial firearm injury encounters during January 2019-December 2022, by year, patient sex, and age group. Increases in the overall weekly number of firearm injury ED visits were detected at certain periods during the COVID-19 pandemic. One such period during which there was a gradual increase was March 2020, which coincided with both the declaration of COVID-19 as a national emergency† and a pronounced decrease in the total number of ED visits. Another increase in firearm injury ED visits occurred in late May 2020, concurrent with a period marked by public outcry related to social injustice and structural racism (4), changes in state-level COVID-19-specific prevention strategies,§ decreased engagement in COVID-19 mitigation behaviors (5), and reported increases in some types of crime (4). Compared with 2019, the average number of weekly ED visits for firearm injury was 37% higher in 2020, 36% higher in 2021, and 20% higher in 2022. A comprehensive approach is needed to prevent and respond to firearm injuries in communities, including strategies that engage community and street outreach programs, implement hospital-based violence prevention programs, improve community physical environments, enhance secure storage of firearms, and strengthen social and economic supports.


Subject(s)
COVID-19 , Firearms , Wounds, Gunshot , Humans , United States/epidemiology , COVID-19/epidemiology , Pandemics , Wounds, Gunshot/epidemiology , Wounds, Gunshot/therapy , Emergency Service, Hospital
20.
Biology (Basel) ; 12(2)2023 Feb 09.
Article in English | MEDLINE | ID: mdl-36829557

ABSTRACT

Probiotics may have the potential to protect against breast cancer, partly through systemic immunomodulatory action and active impact upon intestinal microbiota. Given a few clinical studies on their curative role, we conducted a systematic review of the potential effects of probiotics in breast cancer patients and survivors of breast cancer, aiming to support further clinical studies. A literature search was performed using PubMed, Embase, and the CENTRAL databases from inception through to March 2022. A total of eight randomized clinical trials were identified from thirteen articles published between 2004 and 2022. We evaluated quality-of-life measures, observed bacterial species and diversity indices, probiotic-related metabolites, inflammatory biomarkers, and other responses in breast cancer patients and survivors. Results were synthesized qualitatively and quantitatively using random-effects meta-analysis. Different probiotics supplements utilized included Lactobacillus species alone (Lacto), with or without estriol; probiotic combinations of Lactobacillus with Bifidobacterium (ProLB), with or without prebiotic fructooligosaccharides (FOS); ProLB plus Streptococcus and FOS (ProLBS + FOS); and ProLB plus Enterococcus (ProLBE). We found that use of ProLBS with FOS in breast cancer patients and use of ProLBE in survivors of breast cancer show potential benefits in countering obesity and dyslipidemia. ProLBS with FOS use decreases pro-inflammatory TNF-α in breast cancer survivors and improves quality of life in those with breast-cancer-associated lymphedema. Supplementing probiotics capsules (109 CFU) with a prebiotic and using an intake duration of 10 weeks could provide a better approach than probiotics alone.

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