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1.
Lancet Oncol ; 25(10): e512-e519, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39362262

ABSTRACT

Patients with brain tumours are motivated to participate in clinical trials involving repeat tissue sampling. Normalising the use of neoadjuvant and staged surgical trials necessitates collaboration among patients, regulatory agencies, and researchers. Initial and repetitive tissue sampling plays a crucial role in enhancing our understanding of resistance mechanisms and vulnerabilities in brain tumour therapy. Standardising biopsy techniques and ensuring technical uniformity across institutions are vital for effective interinstitutional collaboration. Although liquid biopsy technologies hold promise, they are not yet ready to replace tissue analysis. Clear communication about the risks and benefits of biopsies is essential, particularly regarding potential postoperative deficits. Changes in mindset and neurosurgical culture are imperative to achieve much needed breakthroughs in the development of new, effective therapies for brain tumours.


Subject(s)
Brain Neoplasms , Drug Development , Glioma , Humans , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Glioma/drug therapy , Glioma/pathology , Antineoplastic Agents/therapeutic use
2.
APMIS ; 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39377522

ABSTRACT

Lyme borreliosis (LB), the most common tick-borne disease in Europe, is endemic to southern coastal Norway. LB commonly presents as erythema migrans, which can disseminate, resulting in more severe disease such as Lyme neuroborreliosis or arthritis. In Norway, public health LB surveillance is conducted via mandatory reporting of laboratory-confirmed disseminated cases. From 2012 to 2022, Norway's surveillance-reported incidence of laboratory-confirmed disseminated LB increased by 78%. Although surveillance provides estimates of the incidence of disseminated LB, this study sought to estimate the incidence of symptomatic LB to better understand Norway's LB disease burden. Two studies were identified that, when combined, estimated an LB seroprevalence of 6.8% in the general adult population in southern Norway. Utilizing data from these seroprevalence studies, public health surveillance, and results from literature searches indicating that 37% of seroconverted LB cases are symptomatic and that the duration of LB antibody detection ranges from 10 to 20 years, we estimated that there were 315-630 symptomatic LB cases per 100,000 adult population in five southern coastal counties in Norway in 2022 and 24-48 cases of symptomatic LB for every public health surveillance-reported LB case in adults in these five counties in Norway.

3.
Int J Infect Dis ; : 107242, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39306075

ABSTRACT

OBJECTIVES: To better understand the Lyme borreliosis (LB) burden in Europe, we aimed to estimate the incidence of symptomatic Borrelia burgdorferi sensu lato (Bbsl) infections after adjusting public health LB surveillance data for under-detection of symptomatic Bbsl infections. METHODS: Data from seroprevalence studies and estimates of the symptomatic proportion and duration of antibody detection in Bbsl-infected individuals, derived from reviews of the published literature, were used to adjust public health LB surveillance data to estimate the incidence of symptomatic Bbsl infection in nine European countries from 2018-2022. RESULTS: The prevalence of anti-Bbsl antibodies ranged from 2.3% in Romania to 9.4% in Germany. Under-detection multipliers varied across surveillance systems; using 10-year duration of antibody detection, multipliers were 2.4-10.5 in countries reporting all LB cases and 54.6-722.2 in countries reporting only Lyme neuroborreliosis cases. The incidence of symptomatic Bbsl infection adjusted for under-detection was highest in Finland, Germany, Norway, Poland, and Switzerland, intermediate in the Czech Republic and Denmark, and lowest in Ireland and Romania. CONCLUSIONS: Adjustment of LB surveillance for under-detection found a high incidence of symptomatic Bbsl infection in several European countries. Differences in LB surveillance systems should be considered when comparing surveillance data between countries and when estimating LB disease burden.

4.
JMIR Cancer ; 10: e56048, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39348891

ABSTRACT

BACKGROUND: Black/African American adults are underrepresented in oncology clinical trials in the United States, despite efforts at narrowing this disparity. OBJECTIVE: This study aims to explore differences in how Black/African American oncology patients perceive clinical trials to improve support for the clinical trial participation decision-making process. METHODS: As part of a larger randomized controlled trial, a total of 244 adult oncology patients receiving active treatment or follow-up care completed a cross-sectional baseline survey on sociodemographic characteristics, clinical trial knowledge, health literacy, perceptions of cancer clinical trials, patient activation, patient advocacy, health care self-efficacy, decisional conflict, and clinical trial intentions. Self-reported race was dichotomized into Black/African American and non-Black/African American. As appropriate, 2-tailed t tests and chi-square tests of independence were used to examine differences between groups. RESULTS: Black/African American participants had lower clinical trial knowledge (P=.006), lower health literacy (P<.001), and more medical mistrust (all P values <.05) than non-Black/African American participants. While intentions to participate in a clinical trial, if offered, did not vary between Black/African American and non-Black/African American participants, Black/African American participants indicated lower awareness of clinical trials, fewer benefits of clinical trials, and more uncertainty around clinical trial decision-making (all P values <.05). There were no differences for other variables. CONCLUSIONS: Despite no significant differences in intent to participate in a clinical trial if offered and high overall trust in individual health care providers among both groups, beliefs persist about barriers to and benefits of clinical trial participation among Black/African American patients. Findings highlight specific ways that education and resources about clinical trials could be tailored to better suit the informational and decision-making needs and preferences of Black/African American oncology patients.


Subject(s)
Black or African American , Neoplasms , Humans , Cross-Sectional Studies , Male , Female , Middle Aged , Neoplasms/therapy , Neoplasms/ethnology , Black or African American/psychology , Adult , Health Knowledge, Attitudes, Practice/ethnology , Clinical Trials as Topic , Healthcare Disparities/ethnology , Aged , Health Literacy , United States , Decision Making , Patient Participation/psychology
5.
Parasit Vectors ; 17(1): 378, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39238048

ABSTRACT

BACKGROUND: Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. Although public health surveillance for LB has been conducted in Romania since 2007, the extent of under-detection of Bbsl infections by LB surveillance has not been estimated. We therefore estimated the under-detection of symptomatic Bbsl infections by LB surveillance to better understand the LB burden in Romania. METHODS: The number of incident symptomatic Bbsl infections were estimated from a seroprevalence study conducted in six counties (population 2.3 M) and estimates of the symptomatic proportion and duration of persistence of anti-Bbsl immunoglobulin G (IgG) antibodies. The number of incident symptomatic Bbsl infections were compared with the number of surveillance-reported LB cases to derive an under-detection multiplier, and then the under-detection multiplier was applied to LB surveillance data to estimate the incidence of symptomatic Bbsl infection from 2018 to 2023. RESULTS: We estimate that there were 1968 individuals with incident symptomatic Bbsl infection in the six counties where the seroprevalence study was conducted in 2020, compared with the 187 surveillance-reported LB cases, resulting in an under-detection multiplier of 10.5 (i.e., for every surveillance-reported LB case, there were 10.5 symptomatic incident Bbsl infections). The incidence of symptomatic Bbsl infection in the six counties was 86.9/100,000 population in 2023, similar to the incidence in 2018-2020 (86.0) and higher than in 2021-2022 (40.3). CONCLUSIONS: There is a higher incidence of symptomatic Bbsl infection than is reported through public health surveillance for LB in Romania. Additional efforts are needed to strengthen disease prevention and address the important public health problem of LB.


Subject(s)
Antibodies, Bacterial , Borrelia burgdorferi Group , Lyme Disease , Romania/epidemiology , Humans , Lyme Disease/epidemiology , Incidence , Seroepidemiologic Studies , Borrelia burgdorferi Group/isolation & purification , Antibodies, Bacterial/blood , Immunoglobulin G/blood , Female , Male , Middle Aged , Adult , Adolescent
6.
Drugs Aging ; 2024 Sep 29.
Article in English | MEDLINE | ID: mdl-39342531

ABSTRACT

BACKGROUND: Older inpatients with dementia are at an increased risk of an adverse drug reaction (ADR) during hospitalization. OBJECTIVE: To quantify the prevalence of ADRs in older inpatients according to dementia status and ADR definition approach and to identify risk factors of ADRs during hospitalization. METHODS: This was a retrospective cohort study of 2000 inpatients aged ≥ 75 years admitted consecutively to six Sydney hospitals (1 July 2016 to 31 May 2017). Dementia was defined by diagnosis in electronic medical records. ADRs were defined according to two approaches: the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) and classification by a research pharmacist (subset cohort, n = 600). A binary logistic regression was conducted to determine risk factors of ADRs. RESULTS: Among 2000 patients, 25.9% (n = 517) were reported to have dementia. ADRs defined by ICD-10-AM were identified in 8.3% (n = 43) and 14.6% (n = 217) of inpatients with and without dementia respectively (p < 0.001). A total of 13.0% (n = 260) and 12.5% (n = 75) of patients had ADRs defined by ICD-10-AM and a research pharmacist, respectively. Key risk factors of ADRs were longer hospital stay [odds ratio (OR) 1.01, 95% confidence interval (CI) 1.01, 1.02) and a greater number of regular potentially inappropriate medicines (PIMs) on admission (OR 1.17, 95% CI 1.00, 1.38). CONCLUSIONS: ADRs were more prevalent among inpatients without dementia and when assessed by a research pharmacist. Our findings underline the need for improved ADR detection in older inpatients.

7.
J Vasc Surg Cases Innov Tech ; 10(6): 101029, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39319080

ABSTRACT

The use of inferior vena cava filters remains a valuable solution for patients with venous thromboembolism who have contraindications to anticoagulation therapy. Some of the most common complications associated with these devices include malposition or migration. In the present case report, we have described the case of a patient who had presented with an unretrievable, malpositioned filter with struts perforating her duodenum, aorta, and vertebral body. She subsequently underwent a two-surgeon endovascular procedure with complete extrication of the filter struts.

8.
ACS Synth Biol ; 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39302688

ABSTRACT

Terminal deoxynucleotidyl transferase (TdT) is a unique DNA polymerase capable of template-independent extension of DNA. TdT's de novo DNA synthesis ability has found utility in DNA recording, DNA data storage, oligonucleotide synthesis, and nucleic acid labeling, but TdT's intrinsic nucleotide biases limit its versatility in such applications. Here, we describe a multiplexed assay for profiling and engineering the bias and overall activity of TdT variants with high throughput. In our assay, a library of TdTs is encoded next to a CRISPR-Cas9 target site in HEK293T cells. Upon transfection of Cas9 and sgRNA, the target site is cut, allowing TdT to intercept the double-strand break and add nucleotides. Each resulting insertion is sequenced alongside the identity of the TdT variant that generated it. Using this assay, 25,623 unique TdT variants, constructed by site-saturation mutagenesis at strategic positions, were profiled. This resulted in the isolation of several altered-bias TdTs that expanded the capabilities of our TdT-based DNA recording system, Cell HistorY Recording by Ordered InsertioN (CHYRON), by increasing the information density of recording through an unbiased TdT and achieving dual-channel recording of two distinct inducers (hypoxia and Wnt) through two differently biased TdTs. Select TdT variants were also tested in vitro, revealing concordance between each variant's in vitro bias and the in vivo bias determined from the multiplexed high throughput assay. Overall, our work and the multiplex assay it features should support the continued development of TdT-based DNA recorders, in vitro applications of TdT, and further study of the biology of TdT.

10.
Vaccines (Basel) ; 12(8)2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39203981

ABSTRACT

Despite the availability of tick-borne encephalitis (TBE) vaccines, the incidence of TBE is increasing. To understand the historical patterns of infection, we conducted a global meta-analysis of studies before December 2023 reporting human antibody prevalence against TBEV (TBE virus) among general or high-risk population groups stratified by country, collection year, serological method, and vaccination status. Pooled data were compared within groups over time by random-effects modeling. In total, 2403 articles were retrieved; 130 articles published since 1959 were included. Data were extracted from 96 general populations (117,620 participants) and 71 high-risk populations (53,986 participants) across 33 countries. Germany had the most population groups (21), and Poland had the most participants (44,688). Seven serological methods were used; conventional IgG/IgM ELISAs were the most common (44%). Four studies (1.7%) used NS1-ELISA serology. Between 1956-1991 and 1992-2022, anti-TBEV seroprevalence remained at ~2.75% across all population groups from "high-risk" areas (p = 0.458) but decreased within general populations (1.7% to 1%; p = 0.001) and high-risk populations (5.1% to 1.3%; p < 0.001), possibly due to differences in the study methodologies between periods. This global summary explores how serological methods can be used to assess TBE vaccination coverage and potential exposure to TBEV or measure TBE burden and highlights the need for standardized methodology when conducting TBE seroprevalence studies to compare across populations.

11.
Hip Pelvis ; 36(3): 218-222, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39210575

ABSTRACT

Purpose: Acetabular and femoral offset (FO) play an important role in total hip arthroplasty (THA). The Sundsvall method has been proposed to account for both FO and cup offset in one global hip offset measurement. In this study, we examine the agreement and inter-observer reliability of the Sundsvall method of hip offset measurement. Materials and Methods: Four hundred and ninety-nine THA patients at a single tertiary academic institution were retrospectively reviewed. Preoperative hip offset was measured on anteroposterior radiographs of the pelvis on the operative and contralateral side. Hip offset was also measured postoperatively on the operative side. Hip offset was measured using the Sundsvall method as the distance between the femoral axis and midline of the pelvis at the height of the lateral most point of the greater trochanter. All measurements were completed by two raters. Intra-class correlation coefficients (ICC) and Pearson's correlation coefficients were used to evaluate agreement and inter-observer reliability between two raters. Results: There was excellent agreement between raters for preoperative hip offset measurement with an ICC of 0.91 (confidence interval [CI] 0.90-0.93, P<0.01) and R=0.92. There was excellent agreement between raters for postoperative hip offset with an ICC of 0.93 (CI 0.92-0.94, P<0.01) and R=0.93. Conclusion: This study confirms the inter-observer agreement and reliability of the Sundsvall method of hip offset measurement. With its high agreement and reliability, the Sundsvall method is an easy and reliable way to measure hip offset that can be applied in future clinical and research settings.

12.
BMC Public Health ; 24(1): 2325, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39192313

ABSTRACT

BACKGROUND: In recent years, overdoses involving illicit cocaine, methamphetamine, and other stimulants have increased in the U.S. The unintentional consumption of stimulants containing illicit fentanyl is a major risk factor for overdoses, particularly in Massachusetts and Rhode Island. Understanding the drug use patterns and strategies used by people who use stimulants (PWUS) to prevent overdose is necessary to identify risk and protective factors for stimulant and opioid-involved overdoses. Mixed-methods research with people who distribute drugs (PWDD) can also provide critical information into the mechanisms through which fentanyl may enter the stimulant supply, and the testing of drug samples can further triangulate PWUS and PWDD perspectives regarding the potency and adulteration of the drug supply. These epidemiological methods can inform collaborative intervention development efforts with community leaders to identify feasible, acceptable, and scalable strategies to prevent fatal and non-fatal overdoses in high-risk communities. METHODS: Our overall objective is to reduce stimulant and opioid-involved overdoses in regions disproportionately affected by the overdose epidemic. To meet this long-term objective, we employ a multi-pronged approach to identify risk and protective factors for unintentional stimulant and opioid-involved overdoses among PWUS and use these findings to develop a package of locally tailored intervention strategies that can be swiftly implemented to prevent overdoses. Specifically, this study aims to [1] Carry out mixed-methods research with incarcerated and non-incarcerated people who use or distribute illicit stimulants to identify risk and protective factors for stimulant and opioid-involved overdoses; [2] Conduct drug checking to examine the presence and relative quantity of fentanyl and other adulterants in the stimulant supply; and [3] Convene a series of working groups with community stakeholders involved in primary and secondary overdose prevention in Massachusetts and Rhode Island to contextualize our mixed-methods findings and identify multilevel intervention strategies to prevent stimulant-involved overdoses. DISCUSSION: Completion of this study will yield a rich understanding of the social epidemiology of stimulant and opioid-involved overdoses in addition to community-derived intervention strategies that can be readily implemented and scaled to prevent such overdoses in two states disproportionately impacted by the opioid and overdose crises: Massachusetts and Rhode Island.


Subject(s)
Drug Overdose , Humans , Drug Overdose/prevention & control , Drug Overdose/epidemiology , Rhode Island/epidemiology , Central Nervous System Stimulants/analysis , Massachusetts/epidemiology , Risk Factors , Fentanyl/poisoning , Fentanyl/analysis
13.
Adv Drug Alcohol Res ; 4: 12197, 2024.
Article in English | MEDLINE | ID: mdl-39040943

ABSTRACT

Introduction: The Health Belief Model (HBM) has been successfully applied to understanding adherence to COVID-19 prevention practices. It has not, however, been used to understand behavior in people who use drugs (PWUD). The aim of this study was to use the HBM to better understand COVID-19 perceptions among PWUD and understand how resiliency affects those perceptions. Materials and methods: A cross-sectional survey was completed from September to December 2021 with PWUD (n = 75) who utilize services at a large harm reduction organization in Philadelphia. Segmentation analysis was done using a k-means clustering approach. Two clusters emerged based on perceived COVID-19 personal impact and resiliency (Less COVID impact/High resilience (NoCOV/HR) and High COVID impact/Low resilience (COV/LR). Differences in responses by cluster to perceptions of COVID-19 and individual pandemic response grouped by HBM constructs were assessed using Student's t-test and chi squares. Results: Significant differences in HBM constructs were seen between clusters. Those in the COV/LR cluster were more likely to think they were susceptible to getting COVID-19 and less likely to believe they knew how to protect themselves. The NoCOV/HR cluster believed they were able to protect themselves from COVID-19 and that they were able to easily understand messages about protecting themselves. Conclusion: Understanding how PWUD conceptualize disease threat and using HBM can better inform interventions to improve future pandemic response. Findings suggest that resilience is key to protecting PWUD from future infectious disease outbreaks. Interventions aimed at increasing resiliency among PWUD may improve preventative behavior and decrease disease burden in this vulnerable population.

14.
Med Dosim ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38849262

ABSTRACT

Bolus electron conformal therapy (BECT) in the treatment of cancers of the head and neck is often limited by an inability to reduce dosimetric hot spots resulting from surface irregularity or tissue heterogeneity. We examined the potential benefits of using intensity modulation for electron therapy (IM-BECT) to reduce hotspots in patients undergoing electron beam therapy for superficial cancers of the head and neck (HN). Twenty patients with HN cancer previously treated with BECT were identified. Each case included the treatment targets and a primary organ at risk (OAR) that were defined by the radiation oncologist. A target +2 cm rind structure was created for analysis of the dose deposition in areas surrounding the target volume as a measure of conformality. Each patient plan was transferred into the novel IM-BECT planning software and each case was recomputed as per the original parameters. Next, each case was replanned with the inclusion of intensity modulation, as well as a new custom conformal bolus that was redesigned for optimized range compensation when paired with an intensity modulator. The plans were then normalized to prescription dose and compared for target coverage/dose and OAR dose. For patients who had a hotspot of 125% or greater, the hotspot was on average reduced by 13.1% with IM-BECT. For IM-BECT, the average primary OAR means dose and target+2cm rind mean dose increased slightly by 10.6% and 6.4%, respectively (primary OAR mean [p = 0.0001], and Target+2cm rind mean [p = 0.0001], paired t-test). IM-BECT is an effective method of reducing hotspots in patients with superficial HN cancer. Improvements came at the expense of slight increases in dose to the underlying tissues. This retrospective planning study represents the first example of IM-BECT to actual HN patient cases. Expanding the role of IM-BECT in other disease sites could potentially compared to conventional BECT.

15.
Anaerobe ; 88: 102878, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38909713

ABSTRACT

Clostridioides difficile infection (CDI) is an important cause of morbidity and mortality worldwide. Data from public health surveillance systems are important for estimating country-level CDI burden. CDI surveillance can be population-based or hospital-based. Population-based surveillance results in overall estimates of CDI incidence (cases per 100,000 population-per-year), and hospital-based surveillance results in estimates of hospital-based CDI incidence (cases per 10,000 patient-days) or CDI admission rates (cases per 1,000 admissions). We sought to better understand temporal trends in CDI incidence reported in publicly available surveillance data worldwide and describe varying surveillance methods. We identified 13 countries in Europe, North America, and Oceania with publicly available population-based and/or hospital-based CDI surveillance data in online reports and/or dashboards. Additional countries in Europe, in particular, also conduct hospital-based CDI surveillance. Inconsistent CDI case definitions and surveillance approaches between countries limit the interpretability of multi-country comparisons. Nonetheless, publicly available CDI surveillance data enabled us to compare CDI incidence among countries with population-based and/or hospital-based surveillance systems and to describe trends in CDI incidence within countries over time. The highest CDI incidence is in the United States. While there have been recent declines in CDI incidence in all countries, the CDI burden remains high, and the need persists for CDI prevention strategies in communities and healthcare settings.


Subject(s)
Clostridioides difficile , Clostridium Infections , Public Health Surveillance , Clostridium Infections/epidemiology , Clostridium Infections/microbiology , Humans , Incidence , Clostridioides difficile/isolation & purification , Europe/epidemiology , North America/epidemiology , Global Health , Oceania/epidemiology
16.
J Subst Use Addict Treat ; 165: 209442, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38889880

ABSTRACT

BACKGROUND & AIMS: Anxiety and substance use disorders are highly comorbid and represent two of the leading causes of disease burden globally. Psychosocial interventions are important treatment options for people with co-occurring anxiety and substance use (A-SUD). To date, few reviews have assessed the efficacy of psychosocial treatments for patients with A-SUD. This systematic review and meta-analysis aims to synthesize this literature and assess the efficacy of psychosocial interventions among patients with A-SUD. METHODS: We searched all relevant records published until March 2023 in Medline, EMBASE, PsycINFO, CINAHL and Google Scholar. Two authors extracted and reconciled relevant data and assessed risk of bias. Random effects models were used to calculate effect sizes using Hedges' g for post treatment and follow-up time points. Main outcomes of the review were anxiety, alcohol use, and use of other substances. We examined effects on depression as a secondary outcome since it commonly co-occurs with A-SUD. RESULTS: Psychosocial interventions for co-occurring A-SUD showed moderate effects on anxiety (g = 0.44), alcohol (Hedges' g = 0.29), and other substance use (g = 0.38) at post intervention. Large effects were observed on depression (g = 0.88) at post intervention with high heterogeneity. These effects were maintained at follow-up for anxiety (Hedges' g = 0.38), other substances (g = 0.44), and depression (g = 0.50). Moderation analyses for demographic factors, intervention characteristics, community level factors, anxiety reduction, and alcohol use reduction, were non-significant. CONCLUSIONS: The current meta-analysis investigated the effects of psychosocial interventions on patients with anxiety and co-occurring SUD. The analyses indicated promising moderate-sized effects of treatment on anxiety, alcohol, all other drug use, and depression. The findings point to important avenues for psychosocial treatment while highlighting critical gaps in knowledge to be addressed in future research.


Subject(s)
Anxiety , Psychosocial Intervention , Substance-Related Disorders , Humans , Anxiety/therapy , Anxiety/epidemiology , Anxiety/psychology , Comorbidity , Depression/therapy , Depression/epidemiology , Depression/psychology , Psychosocial Intervention/methods , Substance-Related Disorders/psychology , Substance-Related Disorders/therapy , Substance-Related Disorders/epidemiology
17.
World Neurosurg ; 189: e294-e299, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38871283

ABSTRACT

BACKGROUND: There has been limited investigation into how social determinants of health impact treatment outcomes in patients with trigeminal neuralgia (TN). We aimed to investigate how social determinants of health may alter the course of clinical care for patients with TN. METHODS: The electronic medical record was queried for patients with a diagnosis of TN comanaged by neurosurgeons and other facial pain specialists at our medical center. Area Deprivation Index served as a proxy for socioeconomic status (SES). Multivariable linear regression models were performed using RStudio to assess the impact of social determinants on the time to neurosurgical referral and surgical intervention. RESULTS: A total of 229 patients (mean age 50 years, 74% female) were included. Of these, 135 (60%) patients underwent a neurosurgical procedure after referral, the most common being microvascular decompression (n = 84, 62%) (Table 1). Most of the patients were white (76.3%) and insured by Medicare (51.8%), followed by private insurance (38.6%). Age and sex were significant predictors of time to neurosurgical referral after symptom onset, as older patients (P < 0.01, Figure 3) and females (P = 0.02) tended to have a greater delay between symptom onset and specialist referral. Race, SES, and insurance status were not significantly associated with time-to-referral or time-to-treatment. CONCLUSION: This study found that older and female patients with TN had a longer time from symptom onset to specialist referral. Based on these data, there is no association between race, SES, and insurance status with time-to-referral or time-to-treatment in patients with TN.


Subject(s)
Healthcare Disparities , Neurosurgical Procedures , Referral and Consultation , Trigeminal Neuralgia , Humans , Trigeminal Neuralgia/surgery , Female , Male , Middle Aged , Healthcare Disparities/statistics & numerical data , Adult , Neurosurgical Procedures/statistics & numerical data , Aged , Referral and Consultation/statistics & numerical data , Microvascular Decompression Surgery , Retrospective Studies , Time-to-Treatment/statistics & numerical data , Social Determinants of Health
18.
bioRxiv ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38915690

ABSTRACT

Terminal deoxynucleotidyl transferase (TdT) is a unique DNA polymerase capable of template-independent extension of DNA with random nucleotides. TdT's de novo DNA synthesis ability has found utility in DNA recording, DNA data storage, oligonucleotide synthesis, and nucleic acid labeling, but TdT's intrinsic nucleotide biases limit its versatility in such applications. Here, we describe a multiplexed assay for profiling and engineering the bias and overall activity of TdT variants in high throughput. In our assay, a library of TdTs is encoded next to a CRISPR-Cas9 target site in HEK293T cells. Upon transfection of Cas9 and sgRNA, the target site is cut, allowing TdT to intercept the double strand break and add nucleotides. Each resulting insertion is sequenced alongside the identity of the TdT variant that generated it. Using this assay, 25,623 unique TdT variants, constructed by site-saturation mutagenesis at strategic positions, were profiled. This resulted in the isolation of several altered-bias TdTs that expanded the capabilities of our TdT-based DNA recording system, Cell History Recording by Ordered Insertion (CHYRON), by increasing the information density of recording through an unbiased TdT and achieving dual-channel recording of two distinct inducers (hypoxia and Wnt) through two differently biased TdTs. Select TdT variants were also tested in vitro , revealing concordance between each variant's in vitro bias and the in vivo bias determined from the multiplexed high throughput assay. Overall, our work, and the multiplex assay it features, should support the continued development of TdT-based DNA recorders, in vitro applications of TdT, and further study of the biology of TdT.

19.
J Arthroplasty ; 39(10): 2525-2528, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38851407

ABSTRACT

BACKGROUND: Acetabular and femoral offset play an important role in total hip arthroplasty (THA) for postoperative stability and biomechanical function. However, it is unknown whether offset impacts patient-reported outcomes (PROs). This study evaluated patients undergoing direct anterior (DA) THA with the hypothesis that patients who have a decrease in hip offset postoperatively would have lower physical function scores and higher pain interference. METHODS: There were 499 patients who underwent DA THA at a single tertiary academic institution who were retrospectively evaluated. Preoperative and postoperative hip offset was measured by 2 reviewers using the Sundsvall method on standing anteroposterior pelvis radiographs. Postoperative changes in hip offset were categorized as increased (> 5 mm), matched (within 5 mm of the preoperative offset measurement), or decreased ( >5 mm). Postoperative PROs with a minimum 1-year follow-up were recorded. A one-way analysis of variance was utilized to compare postoperative pain and PROs between groups. RESULTS: Patients who had decreased offset had the lowest mean postoperative physical function scores at 39.4 (8.0), followed by the increased offset group at 42.2 (10.4) and the matched offset group at 42.8 (9.8) (P < .01). There were significant differences in postoperative physical function scores between matched offset (42.8) and decreased offset (39.4) groups (P < .01), as well as between increased offset (42.2) and decreased offset (39.4) groups (P = .04). There was no difference between matched and increased offset cohorts. CONCLUSIONS: Our data suggests that reducing hip offset may result in worse physical function scores compared to those who have matched or increased hip offset. This should be considered intraoperatively, and efforts should be made to avoid reduced offset even in the presence of hip stability.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Joint , Patient Reported Outcome Measures , Humans , Female , Male , Middle Aged , Retrospective Studies , Aged , Hip Joint/surgery , Hip Joint/diagnostic imaging , Hip Joint/physiopathology , Acetabulum/surgery , Acetabulum/diagnostic imaging , Hip Prosthesis , Femur/surgery , Femur/diagnostic imaging , Treatment Outcome , Adult
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