Tag: nevin manimala

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

BMC Psychiatry. 2023 Sep 22;23(1):691. doi: 10.1186/s12888-023-05172-2.

ABSTRACT

BACKGROUND: Prevalence of dementia illness, causing certain morbidity and mortality globally, places burden on global public health. This study primary goal was to assess future risks of dying from severe dementia, given specific return period, within selected group of regions or nations.

METHODS: Traditional statistical approaches do not have benefits of effectively handling large regional dimensionality, along with nonlinear cross-correlations between various regional observations. In order to produce reliable long-term projections of excessive dementia death rate risks, this study advocates novel bio-system reliability technique, that being particularly suited for multi-regional environmental, biological, and health systems.

DATA: Raw clinical data has been used as an input to the suggested population-based, bio-statistical technique using data from medical surveys and several centers.

RESULTS: Novel spatiotemporal health system reliability methodology has been developed and applied to dementia death rates raw clinical data. Suggested methodology shown to be capable of dealing efficiently with spatiotemporal clinical observations of multi-regional nature. Accurate disease risks multi-regional spatiotemporal prediction being done, relevant confidence intervals have been presented as well.

CONCLUSIONS: Based on available clinical survey dataset, the proposed approach may be applied in a variety of clinical public health applications. Confidence bands, given for predicted dementia-associated death rate levels with return periods of interest, have been reasonably narrow, indicating practical values of advocated prognostics.

PMID:37736716 | DOI:10.1186/s12888-023-05172-2

Trials. 2023 Sep 22;24(1):602. doi: 10.1186/s13063-023-07629-x.

ABSTRACT

BACKGROUND: Due to the growing gap between the demand and supply of therapeutic services for people suffering from depression, with this study, we are investigating the effectiveness and factors of influence of new approaches in group treatments for depression. Two previous studies have already identified bouldering psychotherapy (BPT) as an effective option. It combines psychotherapeutic interventions with action- and body-oriented bouldering exercises. Mental model therapy (MMT) is a new cognitive-behavioral approach for treating depression. It focuses on identifying cognitive distortions, biases in decision making, and false assumptions and aims to correct and replace them with useful mental models. We aim to investigate the effectiveness of the interventions compared with a control group (CG) and to assess the factors of influence in a mixed methods approach.

METHODS: The study is being conducted as a randomized controlled intervention trial. Adult participants with unipolar depression are being randomized into three groups (BPT, MMT, or CG), and the first two groups are undergoing a 10-week treatment phase. CG follows their individual standard treatment as usual. A priori power analysis revealed that about 120 people should be included to capture a moderate effect. The primary outcome of the study is depression rated with the Montgomery and Asberg Depression Rating Scale (MADRS) before (t0), directly after (t1), and 12 months after the intervention phase (t2). Data are being collected via questionnaires, computer-assisted video interviews, and physical examinations. The primary hypotheses will be statistically analyzed by mixed model ANOVAs to compare the three groups over time. For secondary outcomes, further multivariate methods (e.g., mixed model ANOVAs and regression analyses) will be conducted. Qualitative data will be evaluated on the basis of the qualitative thematic analysis.

DISCUSSION: This study is investigating psychological and physical effects of BPT and MMT and its factors of influence on outpatients suffering from depression compared with a CG in a highly naturalistic design. The study could therefore provide insight into the modes of action of group therapy for depression and help to establish new short-term group treatments. Methodological limitations of the study might be the clinical heterogeneity of the sample and confounding effects due to simultaneous individual psychotherapy.

TRIAL REGISTRATION: ISRCTN, ISRCTN12347878. Registered 28 March 2022, https://www.isrctn.com/ISRCTN12347878 .

PMID:37736688 | DOI:10.1186/s13063-023-07629-x

Biom J. 2023 Sep 21:e2200285. doi: 10.1002/bimj.202200285. Online ahead of print.

ABSTRACT

In many areas, applied researchers as well as practitioners have to choose between different solutions for a problem at hand; this calls for optimal decision rules to settle the choices involved. As a key example, one may think of the search for optimal treatment regimes (OTRs) in clinical research, that specify which treatment alternative should be administered to each patient under study. Motivated by the fact that the concept of optimality of decision rules in general and treatment regimes in particular has received so far relatively little attention and discussion, we will present a number of reflections on it, starting from the basics of any optimization problem. Specifically, we will analyze the search space and the to be optimized criterion function underlying the search of single decision point OTRs, along with the many choice aspects that show up in their specification. Special attention is paid to formal characteristics and properties as well as to substantive concerns and hypotheses that may guide these choices. We illustrate with a few empirical examples taken from the literature. Finally, we discuss how the presented reflections may help sharpen statistical thinking about optimality of decision rules for treatment assignment and to facilitate the dialogue between the statistical consultant and the applied researcher in search of an OTR.

PMID:37736675 | DOI:10.1002/bimj.202200285

J Sports Med Phys Fitness. 2023 Sep 22. doi: 10.23736/S0022-4707.23.14996-6. Online ahead of print.

ABSTRACT

BACKGROUND: Physical strength stimulation and, in general, physical activity induces brain plasticity (functional and structural adaptations) in different cerebral areas, benefiting executive function, cognition, attention and academic performance, which is usually estimated by measuring the Intelligent Quotient (IQ), and IQ is related to short-term memory, generally during school age. However, very little is known about the role of physical strength on short-term memory efficiency. Therefore, the primary aim of this study is to examine whether the level of physical strength can positively impact short-term memory efficiency in primary school children. Additionally, if this effect is observed, the secondary goal of this study is to determine whether the age of the participants plays a role in mediating and moderating this influence.

METHODS: Seventy-five children from a primary school in the metropolitan area of Turin were recruited for this study. Each subject performed the overhead medicine ball toss (backwards) test to assess physical strength and the Digit Span test from the Wechsler Intelligence Scale for Children (WISC) to evaluate short-term memory efficiency. Firstly, a simple mediation model was used to identify the possible impact of physical strength levels on short-term memory efficiency and the potential role of participants’ chronological age. Secondly, a moderation model was carried out to observe if age could moderate the impact of physical training on short-term memory efficiency and the different significance levels of the moderator. Significance was assumed at P<0.05.

RESULTS: The results showed a statistically significant direct effect of physical strength on short-term memory (Β=0.429, t<inf>(72)</inf>=3.247, P<0.01). On the contrary, age was not statistically significant (Β=0.167, t<inf>(72)</inf>=3.247, P=0.211). Furthermore, a significant interaction between strength and age was identified by the moderation model (β=-0.270, P<0.01). Specifically, the impact of physical strength levels on short-term memory increased for individuals who were above the mean age (β=0.755, P<0.001). but not for those under the mean age (β=0.215, P=0.153). This model explains 37.2% of the variance in memory (R²=0.372, F<inf>(3, 71)</inf>=14.031, P<0.001).

CONCLUSIONS: These findings suggest that physical strength can positively influence short-term memory. In addition, this impact is enhanced in older-age children. Thus, primary school programs should stimulate physical strength to help children develop cognitive abilities.

PMID:37736663 | DOI:10.23736/S0022-4707.23.14996-6