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Pharmacogenomic Polygenic Risk Scores (PRS) have emerged as a tool to address the polygenic nature of pharmacogenetic phenotypes, increasing the potential to predict drug response. Most pharmacogenomic PRS have been extrapolated from disease-associated variants identified by genome wide association studies (GWAS), although some have begun to utilize genetic variants from pharmacogenomic GWAS. As pharmacogenomic PRS hold the promise of enabling precision medicine, including stratified treatment approaches, it is important to assess the opportunities and challenges presented by the current data. This assessment will help determine how pharmacogenomic PRS can be advanced and transitioned into clinical use. In this review, we present a summary of recent evidence, evaluate the current status, and identify several challenges that have impeded the progress of pharmacogenomic PRS. These challenges include the reliance on extrapolations from disease genetics and limitations inherent to pharmacogenomics research such as low sample sizes, phenotyping inconsistencies, among others. We finally propose recommendations to overcome the challenges and facilitate the clinical implementation. These recommendations include standardizing methodologies for phenotyping, enhancing collaborative efforts, developing new statistical methods to capitalize on drug-specific genetic associations for PRS construction. Additional recommendations include enhancing the infrastructure that can integrate genomic data with clinical predictors, along with implementing user-friendly clinical decision tools, and patient education. Ethical and regulatory considerations should address issues related to patient privacy, informed consent and safe use of PRS. Despite these challenges, ongoing research and large-scale collaboration is likely to advance the field and realize the potential of pharmacogenomic PRS.
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Estudo de Associação Genômica Ampla , Herança Multifatorial , Farmacogenética , Medicina de Precisão , Humanos , Farmacogenética/métodos , Herança Multifatorial/genética , Medicina de Precisão/métodos , Fenótipo , Medição de Risco/métodos , Variantes Farmacogenômicos , Estratificação de Risco GenéticoRESUMO
OBJECTIVE: To describe primary care providers' (PCPs) perspectives on discussing COVID-19 vaccination with their patients. METHODS: All PCPs from 11 primary care clinics at 3 health systems were invited to participate. Focus groups were conducted between December 2021-January 2022, and were recorded and transcribed. Participants were asked about their experience communicating about the COVID-19 vaccine. Themes and subthemes were inductively identified using thematic analysis. RESULTS: 40 PCPs participated. All PCPs viewed discussing COVID-19 vaccination as high priority. Strategies for promoting COVID-19 vaccination included influencing what people think and feel, building trust and leveraging their relationship with patients, and practical strategies such as on-site vaccination. Most strategies aimed at influencing what people think and feel and leveraging relationships were viewed as generally ineffective. On-site vaccine availability was identified as the most influential factor. PCPs expressed frustration by their interactions with vaccine hesitant patients, leading them to truncate their communication with these patients. CONCLUSIONS: Despite using a broad range of strategies, most PCPs were unable to change the strongly held beliefs among the most vaccine hesitant patients that were often informed by misinformation and mistrust. PRACTICE IMPLICATIONS: Promising strategies for promoting vaccination include social/relational (expressing empathy) and practical (on-site COVID-19 vaccine availability).
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Vacinas contra COVID-19 , COVID-19 , Grupos Focais , Atenção Primária à Saúde , Pesquisa Qualitativa , SARS-CoV-2 , Hesitação Vacinal , Humanos , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Masculino , Feminino , Hesitação Vacinal/psicologia , Adulto , Pessoa de Meia-Idade , Atitude do Pessoal de Saúde , Vacinação/psicologia , Relações Médico-Paciente , Comunicação , Médicos de Atenção Primária/psicologia , ConfiançaRESUMO
Aim: Telemedicine has emerged as a potential solution to enhance postoperative follow-up care after dental implant surgery, offering the convenience of remote monitoring and reduced need for in-person visits. Materials and Methods: Participants were randomly assigned to either the telemedicine group (n = 15) or the in-person group (n = 15). In the telemedicine group, patients received remote follow-up care through virtual consultations, during which they could communicate their concerns and share images of the surgical site. The in-person group received standard in-person follow-up visits. Patient satisfaction was measured using a standardized survey, with responses collected on a Likert scale. Results: Telemedicine group exhibited comparable levels of patient satisfaction (mean satisfaction score ± standard deviation: 4.6 ± 0.3) to the in-person group (4.7 ± 0.2). Moreover, clinical outcomes, including wound healing assessment, were similar between the two groups. No significant differences were observed in the incidence of postoperative complications or the need for additional interventions. Conclusion: In conclusion, this pilot study demonstrates that telemedicine is an effective alternative to traditional in-person follow-up care for postoperative dental implant surgery patients. It offers comparable patient satisfaction and clinical outcomes while proving to be more cost-effective.
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This study addresses the durability and complications of zirconia dental implants through a prospective clinical investigation. Zirconia implants are increasingly utilized in dental implantation, and a comprehensive understanding of their long-term performance is essential. Background: Zirconia dental implants have gained attention due to their biocompatibility and aesthetics. However, research on their extended success and complication rates is limited. Materials and Methods: A prospective clinical study involved the placement of 30 zirconia dental implants in patients requiring tooth replacement. The implants were followed up for five years. Success was defined as the implant remaining stable and functional. Complications, including peri-implant mucositis and peri-implantitis, were monitored. Statistical analysis included descriptive statistics, Chi-square test, and P-values were set at P < 0.05. Results: The long-term success rate of zirconia dental implants was found to be 93.3%. Among the 30 implants, only 2 exhibited failure. The most common complication was peri-implant mucositis, occurring in 16.7% of implants. Notably, the incidence of peri-implantitis was limited, observed in 6.7% of implants. Statistical analysis showed significant associations between implant failure and smoking (P = 0.021). Conclusion: Zirconia dental implants demonstrated a high long-term success rate of 93.3% over five years. Peri-implant mucositis was the predominant complication, with a relatively low occurrence of peri-implantitis. The findings underscore the potential of zirconia implants for reliable dental implantation. Addressing modifiable risk factors, such as smoking, could further enhance implant success. Continued research is recommended to validate and expand upon these outcomes.
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BACKGROUND: Effective primary care necessitates follow-up actions by the patient beyond the visit. Prior research suggests room for improvement in patient adherence. OBJECTIVE: This study sought to understand patients' views on their primary care visits, the plans generated therein, and their self-reported adherence after 3 months. METHODS: As part of a large multisite cluster randomized pragmatic trial in 3 health care organizations, patients completed 2 surveys-the first within 7 days after the index primary care visit and another 3 months later. For this analysis of secondary outcomes, we combined the results across all study participants to understand patient adherence to care plans. We recorded patient characteristics and survey responses. Cross-tabulation and chi-square statistics were used to examine bivariate associations, adjusting for multiple comparisons when appropriate. We used multivariable logistic regression to assess how patients' intention to follow, agreement, and understanding of their plans impacted their plan adherence, allowing for differences in individual characteristics. Qualitative content analysis was conducted to characterize the patient's self-reported plans and reasons for adhering (or not) to the plan 3 months later. RESULTS: Of 2555 patients, most selected the top box option (9=definitely agree) that they felt they had a clear plan (n=2011, 78%), agreed with the plan (n=2049, 80%), and intended to follow the plan (n=2108, 83%) discussed with their provider at the primary care visit. The most common elements of the plans reported included reference to exercise (n=359, 14.1%), testing (laboratory, imaging, etc; n=328, 12.8%), diet (n=296, 11.6%), and initiation or adjustment of medications; (n=284, 11.1%). Patients who strongly agreed that they had a clear plan, agreed with the plan, and intended to follow the plan were all more likely to report plan completion 3 months later (P<.001) than those providing less positive ratings. Patients who reported plans related to following up with the primary care provider (P=.008) to initiate or adjust medications (P≤.001) and to have a specialist visit were more likely to report that they had completely followed the plan (P=.003). Adjusting for demographic variables, patients who indicated intent to follow their plan were more likely to follow-through 3 months later (P<.001). Patients' reasons for completely following the plan were mainly that the plan was clear (n=1114, 69.5%), consistent with what mattered (n=1060, 66.1%), and they were determined to carry through with the plan (n=887, 53.3%). The most common reasons for not following the plan were lack of time (n=217, 22.8%), having decided to try a different approach (n=105, 11%), and the COVID-19 pandemic impacted the plan (n=105, 11%). CONCLUSIONS: Patients' initial assessment of their plan as clear, their agreement with the plan, and their initial willingness to follow the plan were all strongly related to their self-reported completion of the plan 3 months later. Patients whose plans involved lifestyle changes were less likely to report that they had "completely" followed their plan. TRIAL REGISTRATION: ClinicalTrials.gov NCT03385512; https://clinicaltrials.gov/study/NCT03385512. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/30431.
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CONTEXT: Potentially inappropriate prescribing of medications in older adults, particular those with dementia, can lead to adverse drug events including falls and fractures, worsening cognitive impairment, emergency department visits, and hospitalizations. Educational mailings from health plans to patients and their providers to encourage deprescribing conversations may represent an effective, low-cost, "light touch", approach to reducing the burden of potentially inappropriate prescription use in older adults with dementia. OBJECTIVES: The objective of the Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer's Disease (D-PRESCRIBE-AD) trial is to evaluate the effect of a health plan based multi-faceted educational outreach intervention to community dwelling patients with dementia who are currently prescribed sedative/hypnotics, antipsychotics, or strong anticholinergics. METHODS: The D-PRESCRIBE-AD is an open-label pragmatic, prospective randomized controlled trial (RCT) comparing three arms: 1) educational mailing to both the health plan patient and their prescribing physician (patient plus physician arm, n = 4814); 2) educational mailing to prescribing physician only (physician only arm, n = 4814); and 3) usual care (n = 4814) among patients with dementia enrolled in two large United States based health plans. The primary outcome is the absence of any dispensing of the targeted potentially inappropriate prescription during the 6-month study observation period after a 3-month black out period following the mailing. Secondary outcomes include dose-reduction, polypharmacy, healthcare utilization, mortality and therapeutic switching within targeted drug classes. CONCLUSION: This large pragmatic RCT will contribute to the evidence base on promoting deprescribing of potentially inappropriate medications among older adults with dementia. If successful, such light touch, inexpensive and highly scalable interventions have the potential to reduce the burden of potentially inappropriate prescribing for patients with dementia. ClinicalTrials.gov Identifier: NCT05147428.
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Doença de Alzheimer , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Idoso , Prescrição Inadequada/prevenção & controle , Doença de Alzheimer/tratamento farmacológico , Cuidadores , Lista de Medicamentos Potencialmente Inapropriados , Polimedicação , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Bioaccumulation of Chlorpyrifos (CP) as pesticides due to their aggrandized use in agriculture has raised serious concern on the health of ecosystem and human beings. Moreover, their degraded products like 3,5,6-trichloro-2-pyridinol (TCP) has enhanced the distress due to their unpredictable biotoxicity. This study evaluates and deduce the comparative in vivo mechanistic biotoxicity of CP and TCP with zebrafish embryos through experimental and computational approach. Experimental cellular and molecular analysis showed higher induction of morphological abnormalities, oxidative stress and apoptosis in TCP exposed embryos compared to CP exposure due to upregulation of metabolic enzymes like Zhe1a, Sod1 and p53. Computational analysis excavated the differential discrepancies in intrinsic atomic interaction as a reason of disparity in biotoxicity of CP and TCP. The mechanistic differences were deduced due to the differential accumulation and internalisation leading to variable interaction with metabolic enzymes for oxidative stress and apoptosis causing physiological and morphological abnormalities. The study unravelled the information of in vivo toxicity at cellular and molecular level to advocate the attention of taking measures for management of CP as well as TCP for environmental and human health.
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Clorpirifos , Animais , Humanos , Clorpirifos/toxicidade , Clorpirifos/análise , Peixe-Zebra , Ecossistema , Piridonas/toxicidadeRESUMO
BACKGROUND AND AIM: Combined anticoagulant-antiplatelet therapy is often indicated in adults with cardiovascular disease and atrial fibrillation or venous thromboembolism. The study aim was to assess the comparative risk of bleeding between rivaroxaban and apixaban when combined with clopidogrel. METHODS: We conducted a retrospective cohort study of commercially insured US adults newly treated with a combination of rivaroxaban+clopidogrel or apixaban+clopidogrel (2015-2018) using Merative™ Marketscan Research Databases. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the treatment groups. Weighted Cox proportional hazards regression was used to estimate the risk of major bleeding. RESULTS: The study cohort included 2895 rivaroxaban+clopidogrel users and 3628 apixaban+clopidogrel users. The median (range) duration of follow up was 61 (73) days. Rivaroxaban+clopidogrel users had a similar risk of major bleeding compared with apixaban+clopidogrel users (IPTW incidence rate per 100 person-years 7.96 vs 7.38; IPTW hazard ratio [HR] 1.13 [95% CI 0.78-1.63]). In the subcohort of adults who were treated with DOAC or clopidogrel monotherapy prior to the combined therapy, the risk of major bleeding did not differ by the drug of monotherapy (IPTW HR for rivaroxaban+clopidogrel group: 0.66 [95% CI 0.33-1.32]; IPTW HR for apixaban+clopidogrel group: 1.10 [95% CI 0.55-2.23]) CONCLUSIONS: In our study of commercially insured US adults, the concomitant use of rivaroxaban+clopidogrel and apixaban+clopidogrel conferred a similar risk of major bleeding. DOAC versus clopidogrel monotherapy prior to the concomitant therapy did not influence the risk of major bleeding.
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Fibrilação Atrial , Acidente Vascular Cerebral , Adulto , Humanos , Inibidores do Fator Xa/efeitos adversos , Rivaroxabana/efeitos adversos , Clopidogrel/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Estudos Retrospectivos , Dabigatrana , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Anticoagulantes , Fibrilação Atrial/tratamento farmacológico , Piridonas , Administração OralRESUMO
OBJECTIVE: Bone stress injuries (BSIs) in trabecular-rich bone are associated with greater biological risk factors compared with cortical-rich bone. We hypothesized that female runners with high Female Athlete Triad (Triad)-related risk would be at greater risk for trabecular-rich BSIs than runners with low Triad-related risk. DESIGN: Prospective cohort study. SETTING: Two NCAA institutions. PARTICIPANTS: Female runners were followed prospectively for up to 5 years. INTERVENTION: The intervention consisted of team nutrition presentations focused on optimizing energy availability plus individualized nutrition sessions. Triad Cumulative Risk Assessment (CRA) categories were assigned yearly based on low-energy availability, menstrual status, age of menarche, low body mass index, low bone mineral density, and prior BSI. MAIN OUTCOME MEASURES: The outcome was the annual incidence of trabecular- and cortical-rich BSI. Generalized Estimating Equations (GEE, to account for the correlated nature of the observations) with a Poisson distribution and log link were used for statistical modeling. RESULTS: Cortical-rich BSI rates were higher than trabecular-rich BSI rates (0.32 vs 0.13 events per person-year). Female runners with high Triad-related risk had a significantly higher incidence rate ratio of trabecular-rich BSI (RR: 4.40, P = 0.025) and cortical-rich BSI (RR: 2.87, P = 0.025) than women with low Triad-related risk. Each 1-point increase in Triad CRA score was associated with a significant 26% increased risk of trabecular-rich BSI ( P = 0.0007) and a nonsignificant 14% increased risk of cortical-rich BSI ( P = 0.054). CONCLUSIONS: Increased Triad CRA scores were strongly associated with increased risk for trabecular-rich BSI. Incorporating Triad CRA scores in clinical care could guide BSI prevention.
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Densidade Óssea , Osso e Ossos , Humanos , Feminino , Estudos Prospectivos , Fatores de Risco , Medição de Risco , Índice de Massa CorporalRESUMO
BACKGROUND: There are unique opportunities related to the design and conduct of pragmatic trials embedded in health insurance plans, which have longitudinal data on member/patient demographics, dates of coverage, and reimbursed medical care, including prescription drug dispensings, vaccine administrations, behavioral healthcare encounters, and some laboratory results. Such trials can be large and efficient, using these data to identify trial-eligible patients and to ascertain outcomes. METHODS: We use our experience primarily with the National Institutes of Health Pragmatic Trials Collaboratory Distributed Research Network, which comprises health plans that participate in the US Food & Drug Administration's Sentinel System, to describe lessons learned from the conduct and planning of embedded pragmatic trials. RESULTS: Information is available for research on more than 75 million people with commercial or Medicare Advantage health plans. We describe three studies that have used or plan to use the Network, as well as a single health plan study, from which we glean our lessons learned. CONCLUSIONS: Studies that are conducted in health plans provide much-needed evidence to drive clinically meaningful changes in care. However, there are many unique aspects of these trials that must be considered in the planning, implementation, and analytic phases. The type of trial best suited for studies embedded in health plans will be those that require large sample sizes, simple interventions that could be disseminated through health plans, and where data available to the health plan can be leveraged. These trials hold potential for substantial long-term impact on our ability to generate evidence to improve care and population health.
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Medicare , Projetos de Pesquisa , Idoso , Humanos , National Institutes of Health (U.S.) , Tamanho da Amostra , Estados Unidos , Ensaios Clínicos Pragmáticos como AssuntoRESUMO
PURPOSE OF REVIEW: Several drugs cause nephrotoxicity and accelerate progression of chronic kidney disease (CKD). The objective of this review is to summarize recent evidence on drugs that either increase the risk of nephrotoxicity, progression of CKD or drug induced harm in patients with CKD. RECENT FINDINGS: Bisphosphonates and hypnotics increase the progression of CKD, whereas denosumab does not accelerate progression of CKD. Tenofovir disoproxil fumarate (TDF) increases the risk of renal tubular toxicity and adverse effects on bone, but Tenofovir alafenamide (TAF) and Tenofovir amibufenamide (TMF) have favorable safety profile on the kidneys and bones. Although no dosage adjustment is needed for Oral Nirmatrelvir/Ritonavir in patients with mild renal impairment and coronavirus disease 2019, the dosage is reduced to twice daily in those with moderate renal impairment. It is not recommended in patients with severe renal impairment. The prescribing information does not recommend use of remdesevir below glomerular filtration rate (eGFR) < 30âml/min but recent studies suggest that remdesevir may be safe and effective in patients with varying levels of CKD severity. Molnupiravir does not require dose adjustment in patients with CKD. SUMMARY: Several medications increase the risk of development of acute kidney injury or progression of CKD. Close attention is needed to select the appropriate dose or safer alternatives to reduce the risk of drug-induced harm in patients with CKD.
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COVID-19 , Insuficiência Renal Crônica , Insuficiência Renal , Humanos , Tenofovir/efeitos adversos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/induzido quimicamente , Adenina/efeitos adversos , RimRESUMO
Objectives: We evaluated the effect of a nutrition education intervention on bone stress injury (BSI) incidence among female distance runners at two NCAA Division I institutions. Methods: Historical BSI rates were measured retrospectively (2010-2013); runners were then followed prospectively in pilot (2013-2016) and intervention (2016-2020) phases. The primary aim was to compare BSI rates in the historical and intervention phases. Pilot phase data are included only for descriptive purposes. The intervention comprised team nutrition presentations focused on optimising energy availability plus individualised nutrition sessions for runners with elevated Female Athlete Triad risk. Annual BSI rates were calculated using a generalised estimating equation Poisson regression model adjusted for age and institution. Post hoc analyses were stratified by institution and BSI type (trabecular-rich or cortical-rich). Results: The historical phase included 56 runners and 90.2 person-years; the intervention phase included 78 runners and 137.3 person-years. Overall BSI rates were not reduced from the historical (0.52 events per person-year) to the intervention (0.43 events per person-year) phase. Post hoc analyses demonstrated trabecular-rich BSI rates dropped significantly from 0.18 to 0.10 events per person-year from the historical to intervention phase (p=0.047). There was a significant interaction between phase and institution (p=0.009). At Institution 1, the overall BSI rate dropped from 0.63 to 0.27 events per person-year from the historical to intervention phase (p=0.041), whereas no decline was observed at Institution 2. Conclusion: Our findings suggest that a nutrition intervention emphasising energy availability may preferentially impact trabecular-rich BSI and depend on team environment, culture and resources.
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Background: Ultimate goal of BMP is to extirpate the pulp tissue completely, microorganisms, debris & shaping the canal which preserves the original course of the canal to receive an obturating material. Due to various morphological challenges present in deciduous root canal, there is high demand of an improved quality & design of file system with less working length to prevent undesirable complication & reduce treatment time. Aim: To evaluate & inter-compare the dentin thickness and instrumentation time in root dentin of deciduous teeth after BMP in Hand, Rotary & Reciprocation motion with single-file systems. Material and Methods: 60 extracted primary single rooted teeth with un-resorbed roots were included in the study. Teeth were divided into three groups consisting of 20 teeth in each group. In Group-1 Root canal preparation was done with pediatric Hand files, In Group-2 with pediatric Single-file system in rotary motion and in Group-3 with pediatric Single-file system in reciprocating motion. Teeth were scanned before & after preparation with CBCT. Segments were analyzed for dentin thickness at 3mm,5mm and 7mm respectively. Instrumentation time was recorded by an assistant. Results: Mean instrumentation time of Rotary was least as compared to Reciprocation & Hand respectively, instrumentation time taken by hand filing was significantly higher. Reciprocating filing helps in better dentin debridement at apical and the middle third and no difference was found at the coronal third among all three groups. Conclusions: Reciprocating filing helps in better dentin debridement and rotary instrumentation requires least time for canal preparation. Key words:Hand Files, Rotary Files, Reciprocating motion, CBCT.
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OBJECTIVES: COVID-19 vaccines are widely available, but uptake is suboptimal. To develop strategies to increase vaccination rates, we sought to (1) characterize adults initially hesitant to be vaccinated for COVID-19 who later received the vaccine and (2) identify factors associated with their vaccination decision. METHODS: In January 2021, we conducted an online survey of US adults via Prolific that assessed vaccination intent, COVID-19-related knowledge and attitudes, and demographic characteristics. In May 2021, we recontacted respondents to assess vaccination status and factors influencing their vaccination decision. We used χ2 statistics and t tests to examine associations between respondents' vaccination status and their characteristics, knowledge, and attitudes. We analyzed reasons for vaccination using thematic analysis. RESULTS: Of 756 initially vaccine-hesitant respondents, 529 (70.0%) completed the follow-up survey. Nearly half of those initially not sure about vaccination (47.3%, 112 of 237) were vaccinated at follow-up, while 21.2% (62 of 292) of those initially planning not to be vaccinated were vaccinated at follow-up. Of those initially not sure, higher educational attainment, greater knowledge of COVID-19, and a doctor's recommendation were associated with vaccination. Of those initially intending not to be vaccinated, male sex, Democratic political affiliation, receipt of an influenza shot within 5 years, being more worried about COVID-19, and having greater COVID-19 knowledge were associated with increased likelihood of being vaccinated. Of 167 respondents who gave reasons for vaccination, protecting oneself and others (59.9%), practical issues (29.9%), social influences (17.4%), and vaccine safety (13.8%) were the main reasons. CONCLUSION: Providing information on the protective value of vaccination, implementing rules that make remaining unvaccinated burdensome, making vaccination easy, and providing social support may influence vaccine-hesitant adults to accept vaccination.
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COVID-19 , Vacinas contra Influenza , Adulto , Masculino , Humanos , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação , Estudos LongitudinaisRESUMO
INTRODUCTION: Electronic health record (EHR) or medical claims-based algorithms (i.e., operational definitions) can be used to define safety outcomes using real-world data. However, existing tools do not allow researchers and decision-makers to adequately appraise whether a particular algorithm is fit for purpose (FFP) to support regulatory decisions on drug safety surveillance. Our objective was to develop a tool to enable regulatory decision-makers and other stakeholders to appraise whether a given algorithm is FFP for a specific decision context. METHODS: We drafted a set of 77 generic items informed by regulatory guidance documents, existing instruments, and publications. The outcome of ischemic stroke served as an exemplar to inform the development of draft items. The items were designed to be outcome independent. We conducted a three-round online Delphi panel to develop and refine the tool and achieve consensus on items (> 70% agreement) among panel participants composed of regulators, researchers from pharmaceutical organizations, academic clinicians, methodologists, pharmacoepidemiologists, and cardiologists. We conducted a qualitative analysis of panel responses. Five pairs of reviewers independently evaluated two ischemic stroke algorithm validation studies to test its application. We developed a user guide, with explanation and elaboration for each item, guidance on essential and additional elements for user responses, and an illustrative example of a complete assessment. Furthermore, we conducted a 2-h online stakeholder panel of 16 participants from regulatory agencies, academic institutions, and industry. We solicited input on key factors for an FFP assessment, their general reaction to the Algorithm CErtaInty Tool (ACE-IT), limitations of the tool, and its potential use. RESULTS: The expert panel reviewed and made changes to the initial list of 77 items. The panel achieved consensus on 38 items, and the final version of the ACE-IT includes 34 items after removal of duplicate items. Applying the tool to two ischemic stroke algorithms demonstrated challenges in its application and identified shared concepts addressed by more than one item. The ACE-IT was viewed positively by the majority of stakeholders. They identified that the tool could serve as an educational resource as well as an information-sharing platform. The time required to complete the assessment was identified as an important limitation. We consolidated items with shared concepts and added a preliminary screen section and a summary assessment box based on their input. The final version of the ACE-IT is a 34-item tool for assessing whether algorithm validation studies on safety outcomes are FFP. It comprises the domains of internal validity (24 items), external validity (seven items), and ethical conduct and reporting of the validation study (three items). The internal validity domain includes sections on objectives, data sources, population, outcomes, design and setting, statistical methods, reference standard, accuracy, and strengths and limitations. The external validity domain includes items that assess the generalizability to a proposed target study. The domain on ethics and transparency includes items on ethical conduct and reporting of the validation study. CONCLUSION: The ACE-IT supports a structured, transparent, and flexible approach for decision-makers to appraise whether electronic health record or medical claims-based algorithms for safety outcomes are FFP for a specific decision context. Reliability and validity testing using a larger sample of participants in other therapeutic areas and further modifications to reduce the time needed to complete the assessment are needed to fully evaluate its utility for regulatory decision-making.
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Algoritmos , Registros Eletrônicos de Saúde , Humanos , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To test the impact of varied physician recommendations on COVID-19 vaccine hesitancy. METHODS: We conducted a vignette-based experimental survey on Prolific, an online research platform. COVID-19 vaccine hesitant, adult panel members were assigned to one of five messages that varied by recommendation style (participatory vs explicit) and strategy (acknowledgement of concerns; comparison to the flu shot; statement that millions of people have already received it; emphasis on protecting others). Vaccine hesitancy was re-assessed with the question, "Would you get vaccinated at this visit?". RESULTS: Of the 752 participants, 60.1% were female, 43.4% Black, 23.6% Latino, and 33.0% White; mean age was 35.6 years. Overall, 33.1% of the initially "not sure" and 13.1% of the initially "no" participants became less hesitant following any recommendation. Among the "not sure" participants, 20.3% of those who received a participatory recommendation became less hesitant compared with 34.3%- 39.5% for the explicit recommendations. The "protect others" message was most effective among initially "no" participants; 19.8% become less hesitant, compared to 8.7% for the participatory recommendation. CONCLUSION: A physician recommendation may reduce COVID-19 vaccine hesitancy. PRACTICE IMPLICATIONS: An explicit recommendation and "protect others" message appear to be important elements of a physician recommendation for COVID-19 vaccination.
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COVID-19 , Médicos , Adulto , Feminino , Humanos , Masculino , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Intenção , VacinaçãoRESUMO
Introduction: Older adults with Alzheimer's disease and related dementias (ADRD) are at increased risk of harm due to prescribing of potentially inappropriate medications. Encouraging patients and caregivers to talk with their providers about potentially inappropriate medications could stimulate deprescribing. Our objective was to explore whether mailing educational materials to patients with ADRD might activate patients or caregivers to initiate a conversation with their provider about potentially inappropriate medications. Methods: We conducted semi-structured interviews with patients with ADRD, caregivers of patients with ADRD, and healthcare providers. All participants were shown educational materials referencing potentially inappropriate medications and suggestions to promote deprescribing. Interviews explored reactions to the materials, the idea of patients and caregivers initiating a conversation about deprescribing, and the deprescribing process. Interview transcripts were analyzed using inductive thematic analysis. Results: We conducted a total of 27 interviews: 9 with caregivers only, 2 with patients only, 3 with patient-caregiver dyads, and 13 with providers. Patients and caregivers reported that if a medication might cause harm, it would motivate them to talk to their provider about the medication. Trust in the provider could facilitate or inhibit such conversations; conversations would be more likely if there were prior positive experiences asking questions of the provider. Providers were receptive to patients and caregivers initiating conversations about their medications, as they valued deprescribing as part of their clinical practice and welcome informed patients and caregivers as participants in decision-making about medication. Conclusion: Mailing educational materials about potentially inappropriate medications to community-dwelling patients with ADRD may promote deprescribing conversations. Ongoing pragmatic trials will determine whether such interventions stimulate deprescribing conversations and achieve reductions in prescribing of inappropriate medications. Plain Language Summary: Encouraging patients with Alzheimer's disease to talk with their providers about medications that may cause harm Introduction: Older adults with Alzheimer's disease and related dementias (ADRD) are sometimes prescribed medications that may cause harm, especially when taken for extended periods of time. Patients and their caregivers may not know about the risks. Doctors know of the risks but may not address them due to competing priorities or other challenges in providing care to these patients with complex needs. Encouraging the patient or their caregiver to talk to their doctor about their medications might help to reduce the use of medications that are not beneficial. This study's goal was to explore whether sending educational materials to patients with ADRD might encourage patients or caregivers to ask their doctor about their medications.Methods: We interviewed patients with ADRD, caregivers, and doctors. We showed them educational materials that suggested patients and their caregivers talk to their doctor about reducing or stopping medications that may be harmful. We asked for reactions to the materials and to the idea of talking to the doctor about stopping the medication.Results: We conducted 27 interviews: 9 with caregivers only, 2 with patients only, 3 with patient-caregiver dyads, and 12 with doctors. Patients and caregivers said learning that a medication might cause harm would motivate them to talk to their doctor about the medication. Trust in their doctor was important. Some patients and caregivers were comfortable asking questions about medications, while others were reluctant to challenge the doctor. Doctors were open to patients and caregivers asking about medications and felt it was important that patients not take medications that are not needed.Conclusion: Sending educational materials to patients with ADRD and caregivers may encourage them to talk with their doctors about stopping or reducing medications. Studies are needed to learn whether such materials lead to reductions in prescribing of potential harmful medications.
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The ecotoxicological effect of after-usage released TiO2 nanoparticles in aquatic resources has been a major concern owing to their production and utilization in different applications. Addressing the issue, this study investigates the detailed in vivo molecular toxicity of TiO2 nanoparticles with Paramecium caudatum. TiO2 nanoparticles were synthesized at a lab scale using high energy ball milling technique; characterized for their physicochemical properties and investigated for their ecotoxicological impact on oxidative stress, steatosis, and apoptosis of cells through different biochemical analysis, flow cytometry, and fluorescent microscopy. TiO2 nanoparticles; TiO2 (N15); of size 36 ± 12 nm were synthesized with a zeta potential of - 20.2 ± 8.8 mV and bandgap of 4.6 ± 0.3 eV and exhibited a blue shift in UV-spectrum. Compared to the Bulk TiO2, the TiO2 (N15) exhibited higher cytotoxicity with a 24 h LC50 of 202.4 µg/ml with P. Caudatum. The mechanism was elucidated as the size and charge-dependent internalization of nanoparticles leading to abnormal physiological metabolism in oxidative stress, steatosis, and apoptosis because of their influential effect on the activity of metabolic proteins like SOD, GSH, MDA, and catalase. The study emphasized the controlled usage TiO2 nanoparticles in daily activity with a concern for ecological and biomedical aspects.