Tag: pubmed

Pain Med. 2023 Sep 21:pnad128. doi: 10.1093/pm/pnad128. Online ahead of print.

ABSTRACT

OBJECTIVE: This case series retrospectively reviewed the outcomes in patients implanted with combined, synchronous dorsal root ganglion stimulation (DRGS) and spinal cord stimulation (SCS) connected to a single implantable pulse generator (IPG) in a tertiary referral neuromodulation centre in the United Kingdom.

MATERIALS AND METHODS: Twenty-six patients underwent a trial of DRGS+SCS for treating focal neuropathic pain between January 2016 and December 2019, with a follow-up in February 2022. A Transgrade approach was employed for DRGS. Patients were provided with three possible stimulation programmes: DRGS-only, SCS-only, or DRGS+SCS. Patients were assessed for pain intensity, patients’ global impression of change (PGIC), preferred lead(s) and complications.

RESULTS: Twenty patients were successful and went on for full implantation. The most common diagnosis was Complex Regional Pain Syndrome. After an average of 3.1 years follow-up, one patient was lost to follow-up, and two were non-responders. Of the remaining 17 patients, 16 (94%) continued to report a PGIC of 7. The average pain intensity at Baseline was 8.5 on an NRS scale of 0-10. At the last follow-up, the average NRS reduction overall was 78.9% with no statistical difference between those preferring DRGS+SCS (n = 9), SCS-only (n = 3) and DRGS-only (n = 5). The combination of DRGS+SCS was preferred by 53% at the last follow-up. There were no serious neurological complications.

CONCLUSION: This retrospective case series demonstrates the potential effectiveness of combined DRGS+SCS with sustained analgesia observed at an average follow-up of over three years. Implanting combined DRGS+SCS may provide programming flexibility and therapeutic alternatives.

PMID:37738574 | DOI:10.1093/pm/pnad128

Clin Infect Dis. 2023 Sep 21:ciad552. doi: 10.1093/cid/ciad552. Online ahead of print.

ABSTRACT

BACKGROUND: Widespread outbreaks of person-to-person transmission of hepatitis A virus (HAV), particularly among people who inject drugs (PWID), continue across the United States and globally. However, the herd immunity threshold and vaccination coverage required to prevent outbreaks is unknown. We aimed to use surveillance data and dynamic modeling to estimate herd immunity thresholds among PWID in 16 U.S. states.

METHODS: We used a previously published dynamic transmission model of HAV transmission, calibrated to surveillance data from outbreaks involving PWID in 16 states. Using state-level calibrated models, we estimated the basic reproduction number (R0) and herd immunity threshold for PWID in each state. We performed a meta-analysis of herd immunity thresholds to determine the critical vaccination coverage required to prevent most HAV outbreaks among PWID.

RESULTS: Estimates of R0 for HAV infection ranged from 2.2 (95% CI 1.9-2.5) for North Carolina to 5.0 (95% CI 4.5-5.6) for West Virginia. Corresponding herd immunity thresholds ranged from 55% (95% CI 47-61%) for North Carolina to 80% (95% CI 78-82%) for West Virginia. Based on the meta-analysis, we estimated a pooled herd immunity threshold of 64% (95% CI 61-68%, 90% prediction interval 52-76%) among PWID. Using the prediction interval upper bound (76%) and assuming 95% vaccine efficacy, we estimate a vaccination coverage of 80% could prevent most HAV outbreaks.

CONCLUSIONS: Hepatitis A vaccination programs in the United States may need to achieve vaccination coverage of at least 80% among PWID in order to prevent most HAV outbreaks among this population.

PMID:37738564 | DOI:10.1093/cid/ciad552

Mol Biol Evol. 2023 Sep 21:msad212. doi: 10.1093/molbev/msad212. Online ahead of print.

ABSTRACT

Molecular evolutionary rate variation is a key aspect of the evolution of many organisms that can be modelled using molecular clock models. For example, fixed local clocks revealed the role of episodic evolution in the emergence of SARS-CoV-2 variants of concern. Like all statistical models, however, the reliability of such inferences is contingent on an assessment of statistical evidence. We present a novel Bayesian phylogenetic approach for detecting episodic evolution. It consists of computing Bayes factors, as the ratio of posterior and prior odds of evolutionary rate increases, effectively quantifying support for the effect size. We conducted an extensive simulation study to illustrate the power of this method and benchmarked it to formal model comparison of a range of molecular clock models using (log) marginal likelihood estimation, and to inference under a random local clock model. Quantifying support for the effect size has higher sensitivity than formal model testing and is straight-forward to compute, because it only needs samples from the posterior and prior distribution. However, formal model testing has the advantage of accommodating a wide range molecular clock models. We also assessed the ability of an automated approach, known as the random local clock, where branches under episodic evolution may be detected without their a priori definition. In an empirical analysis of a data set of SARS-CoV-2 genomes, we find ‘very strong’ evidence for episodic evolution. Our results provide guidelines and practical methods for Bayesian detection of episodic evolution, as well as avenues for further research into this phenomenon.

PMID:37738550 | DOI:10.1093/molbev/msad212

JCO Glob Oncol. 2023 Sep;9:e2200397. doi: 10.1200/GO.22.00397.

ABSTRACT

PURPOSE: Timely radiation treatment (RT) is critical in cervical cancer treatment, but patients in low- and middle-income countries (LMICs) in sub-Saharan Africa often face barriers that delay care. Time to care was benchmarked in a multidisciplinary team (MDT) setting in Botswana.

METHODS: Time intervals between steps in care were recorded for 230 patients reviewed at MDT between January 2016 and July 2018. Associations between RT delay and overall survival (OS) were evaluated using Kaplan-Meier curves and multivariable Cox proportional hazards models.

RESULTS: For patients who received RT (n = 187; 81.3%), the median biopsy to pathology reporting interval was 25 (IQR, 19-36) days and was 57 (IQR, 28-68) days for patients who did not (P = .003). Intervals in care did not differ between patients who did and did not receive RT. Among treated patients, the uppermost quartile interval from pathology reporting to RT initiation was ≥111 days and that from RT simulation to initiation was ≥12 days. Among patients receiving a RT dose of ≥65 Gy (n = 100), the delay from RT simulation to initiation of >12 days was associated with worse median OS (2.0 v 4.6 years; P = .048); this association trended toward, although did not meet, statistical significance on multivariable analysis (hazard ratio, 2.35; 95% CI, 0.95 to 5.85; P = .07).

CONCLUSION: The MDT-coordinated care model allows for systematic benchmarking of the patient treatment cascade. Barriers to timely treatment exist for this cohort in Botswana, and RT delay may be associated with OS of patients receiving curative treatment. Interventions to accelerate the timing of the radiation oncology care cascade may improve clinical outcomes in this LMIC setting.

PMID:37738538 | DOI:10.1200/GO.22.00397

JCO Oncol Pract. 2023 Sep 22:OP2300309. doi: 10.1200/OP.23.00309. Online ahead of print.

ABSTRACT

PURPOSE: Biosimilars are clinically equivalent to branded products yet cost significantly less. Interchangeability is a US Food and Drug Administration (FDA) designation that allows generic drugs to be substituted for reference drugs at the pharmacy, without a physician’s consent. Currently, no oncologic biosimilar has FDA approval for interchangeability.

METHODS: Building on pharmacy auto-substitution processes with therapeutic interchange, Plan-Do-Study-Act methodology was used to automate conversions from reference biological products to Pharmacy and Therapeutics-/Physician-approved biosimilars. After establishing the baseline metrics, cycle 1 focused on full staff education (completed July 2020) with systematic pharmacy-driven biosimilar conversion initiated in September 2020 for rituximab, trastuzumab, and bevacizumab. Physician-initiated conversion of Neulasta biosimilar products was encouraged but not mandated. During cycle 2 (May 1, 2021-November 30, 2021), pharmacy-driven Neulasta biosimilar conversion was mandated. In cycle 3 (December 1, 2021-April 30, 2023), stakeholder education was reinforced and the sustainability of conversions was confirmed.

RESULTS: Systematic pharmacy-driven conversion to biosimilar products improved over cycles 1 and 2 from baseline: 1.8% to 90.3% for rituximab, 9.2% to 89.7% for trastuzumab, and 20.5% to 96.1% for bevacizumab. Physician-driven biosimilar conversion for Neulasta was lower at 12.7% through April 2021. Pharmacy-driven Neulasta biosimilar conversion was initiated during cycle 2, resulting in a conversion rate of 39.7%. The conversion rates remained sustainable through April 2023.

CONCLUSION: Pharmacy-driven auto-substitution of biosimilar products results in rapid and statistically significant biosimilar adoption. The pharmacy-based substitution approach was found to be far more effective than physician-driven substitution. Rapid conversion from branded products to FDA-approved biosimilar is feasible, measurable, and sustainable and can be scaled. Barriers to Neulasta conversion warrant further investigation.

PMID:37738533 | DOI:10.1200/OP.23.00309

Eur J Neurol. 2023 Sep 22. doi: 10.1111/ene.16064. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Essential tremor (ET) is one of the most common neurological disorders, but information on treatment pattern is still scant. The aim of this study was to describe the demographic and clinical characteristics, treatment patterns, and determinants of drug use in patients with newly diagnosed ET in France and the United Kingdom.

METHODS: Incident cases of ET diagnosed between January 1, 2015 and December 31, 2018 with 2 years of follow-up were identified by using The Health Improvement Network (THIN®) general practice database. During the follow-up, we assessed the daily prevalence of use and potential switches from first-line to second-line treatment or other lines of treatment. Logistic regression models were conducted to assess the effect of demographic and clinical characteristics on the likelihood of receiving ET treatment.

RESULTS: A total of 2957 and 3249 patients were selected in the United Kingdom and France, respectively. Among ET patients, drug use increased from 12 months to 1 month prior the date of index diagnosis (ID). After ID, nearly 40% of patients received at least one ET treatment, but during follow-up drug use decreased and at the end of the follow-up approximately 20% of patients were still on treatment. Among treated patients, ≤10% maintained the same treatment throughout the entire follow-up, nearly 20% switched, and 40%-75% interrupted any treatment. Results from the multivariate analysis revealed that, both in France and the United Kingdom, patients receiving multiple concomitant therapies and affected by psychiatric conditions were more likely to receive an ET medication.

CONCLUSION: This study shows that ET is an undertreated disease with a lower-than-expected number of patients receiving and maintaining pharmacological treatment. Misclassification of ET diagnosis should be acknowledged; thus, results require cautious interpretation.

PMID:37738526 | DOI:10.1111/ene.16064

S D Med. 2023 Sep;76(9):410.

ABSTRACT

INTRODUCTION: Stigma towards people struggling with depression is pervasive across society- even in health care. Many anti-stigma interventions have been tested across a variety of healthcare professionals in an attempt to decrease stigma levels. These interventions have generally elicited short-term change in stigma levels but failed to produce long-term destigmatization.

METHODS: This study sought to determine if literature could be used to decrease stigma levels and increase empathy/ kindness towards patients with depression in medical students at the University of South Dakota, Sanford School of Medicine. Students were administered a 51-question survey scored on a 6-point Likert scale designed largely from peer-reviewed surveys to measure stigma, empathy, and kindness levels towards patients with depression. Students then read a collection of autobiographical or semiautobiographical literature written by authors who had clinically diagnosed major depressive disorder (MDD). This literature was selected with the help of a medical student focus group. Immediately after reading this, students took the survey again. The survey was again administered one week later and 6 months later. A pre-intervention demographics questionnaire was administered to identify potential confounding variables, including personal experience with major depressive disorder and interest in psychiatry.

RESULTS: Twenty-five medical students completed all 3 phases. Statistical analysis comparing pre-intervention score to the three post-intervention composite scores were completed via one-tailed paired two-sample t-tests using Microsoft Excel software. The pre-intervention stigma score mean was 61.84. Although stigma scores did decrease from preintervention to all the post-intervention time points (immediate: 59.92, 1 week: 60.08, 6 months: 58.28), these differences were not statistically significant. Students who reported personal experience with MDD did not have a statistically significant drop in stigma; however, students who reported no personal experience with MDD did have a statistically significant decrease in stigma levels at 1-week post-intervention (mean=58.6, p=0.008) and 6-months post-intervention (mean=57.9; p=0.03) with a pre-intervention mean score was 66.2. The empathy pre-intervention mean score was 63.48. Empathy score changes were statistically significant at all three post-intervention time points (immediate: 66.62, 1 week: 66.92, 6 months: 67.24). The pre-intervention kindness score mean was 41.32. Kindness scores did not increase in a statistically significant manner at any of the post-intervention time points (immediate: 41.88, 1 week: 41.36, 6 months: 42.32).

CONCLUSION: A literature-based intervention significantly decreased stigma levels at the 1-week and 6-months postintervention time points in medical students who reported no personal experience with MDD. This intervention significantly increased empathy levels, irrespective of personal experience. It did not increase kindness levels. These results suggest that literature could be used as a long-term stigma reduction technique in medical students in the absence of personal experience with MDD. Additionally, it could be used to improve empathy levels in medical students, regardless of their personal experience with depression.

PMID:37738494

Arch Orthop Trauma Surg. 2023 Sep 22. doi: 10.1007/s00402-023-05057-9. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to optimize cement application techniques in fully cemented primary total knee arthroplasty (TKA) by comparing the effects of two different approaches: cement on bone surface (CoB) versus cement on bone surface and implant surface (CoBaI) on the short-term presence of radiolucent lines (RLL) as indicators of potential complications.

METHODS: In this monocentric study, a total of 379 fully cemented primary TKAs (318 patients) were included. The two study groups were differentiated by the technique of cement application: CoB group (cement applied only on bone surface) and CoBaI group (cement applied on both bone surface and implant surface). The presence of RLL or osteolysis was evaluated using the updated Knee Society Radiographic Evaluation System.

RESULTS: In the whole study population, RLL were present in 4.7% of cases, with a significantly higher incidence in the CoBaI group (10.5%) at the 4-week follow-up. At the 12-month follow-up, RLL were observed in 29.8% of TKAs in the CoBaI group, while the incidence was lower in the CoB group (24.0%) (not statistically significant). There were two revisions in each group, none of which were due to aseptic loosening.

CONCLUSION: The findings of this study suggest that the application of bone cement on bone surface only (CoB) may be more beneficial than applying it on both bone surface and implant surface (CoBaI) in terms of short-term presence of RLL in fully cemented primary TKA. Long-term results, especially with regard to aseptic loosening, will be of interest and may provide valuable guidance for future directions in bone cement applications in TKA.

PMID:37736767 | DOI:10.1007/s00402-023-05057-9

NPJ Syst Biol Appl. 2023 Sep 22;9(1):46. doi: 10.1038/s41540-023-00299-0.

ABSTRACT

Mechanistic models are commonly employed to describe signaling and gene regulatory kinetics in single cells and cell populations. Recent advances in single-cell technologies have produced multidimensional datasets where snapshots of copy numbers (or abundances) of a large number of proteins and mRNA are measured across time in single cells. The availability of such datasets presents an attractive scenario where mechanistic models are validated against experiments, and estimated model parameters enable quantitative predictions of signaling or gene regulatory kinetics. To empower the systems biology community to easily estimate parameters accurately from multidimensional single-cell data, we have merged a widely used rule-based modeling software package BioNetGen, which provides a user-friendly way to code for mechanistic models describing biochemical reactions, and the recently introduced CyGMM, that uses cell-to-cell differences to improve parameter estimation for such networks, into a single software package: BioNetGMMFit. BioNetGMMFit provides parameter estimates of the model, supplied by the user in the BioNetGen markup language (BNGL), which yield the best fit for the observed single-cell, time-stamped data of cellular components. Furthermore, for more precise estimates, our software generates confidence intervals around each model parameter. BioNetGMMFit is capable of fitting datasets of increasing cell population sizes for any mechanistic model specified in the BioNetGen markup language. By streamlining the process of developing mechanistic models for large single-cell datasets, BioNetGMMFit provides an easily-accessible modeling framework designed for scale and the broader biochemical signaling community.

PMID:37736766 | DOI:10.1038/s41540-023-00299-0

Syst Rev. 2023 Sep 22;12(1):170. doi: 10.1186/s13643-023-02281-7.

ABSTRACT

This paper presents a generalized registration form for systematic reviews that can be used when currently available forms are not adequate. The form is designed to be applicable across disciplines (i.e., psychology, economics, law, physics, or any other field) and across review types (i.e., scoping review, review of qualitative studies, meta-analysis, or any other type of review). That means that the reviewed records may include research reports as well as archive documents, case law, books, poems, etc. Items were selected and formulated to optimize broad applicability instead of specificity, forgoing some benefits afforded by a tighter focus. This PRISMA 2020 compliant form is a fallback for more specialized forms and can be used if no specialized form or registration platform is available. When accessing this form on the Open Science Framework website, users will therefore first be guided to specialized forms when they exist. In addition to this use case, the form can also serve as a starting point for creating registration forms that cater to specific fields or review types.

PMID:37736736 | DOI:10.1186/s13643-023-02281-7