Tag: pubmed

Pharm Stat. 2022 Nov 2. doi: 10.1002/pst.2271. Online ahead of print.

ABSTRACT

In randomized clinical trials, methods of pairwise comparisons such as the ‘Net Benefit’ or the ‘win ratio’ have recently gained much attention when interests lies in assessing the effect of a treatment as compared to a standard of care. Among other advantages, these methods are usually praised for delivering a treatment measure that can easily handle multiple outcomes of different nature, while keeping a meaningful interpretation for patients and clinicians. For time-to-event outcomes, a recent suggestion emerged in the literature for estimating these treatment measures by providing a natural handling of censored outcomes. However, this estimation procedure may lead to biased estimates when tails of survival functions cannot be reliably estimated using Kaplan-Meier estimators. The problem then extrapolates to the other outcomes incorporated in the pairwise comparison construction. In this work, we suggest to extend the procedure by the consideration of a hybrid survival function estimator that relies on an extreme value tail model through the Generalized Pareto distribution. We provide an estimator of treatment effect measures that notably improves on bias and remains easily apprehended for practical implementation. This is illustrated in an extensive simulation study as well as in an actual trial of a new cancer immunotherapy.

PMID:36321470 | DOI:10.1002/pst.2271

Med Phys. 2022 Nov 2. doi: 10.1002/mp.16029. Online ahead of print.

ABSTRACT

BACKGROUND: For proton therapy, a relative biological effectiveness (RBE) of 1.1 has broadly been applied clinically. However, as unexpected toxicities have been observed by the end of the proton tracks, variable RBE models have been proposed. Typically, the dose averaged linear energy transfer (LET_d ) has been used as an input variable for these models but the way the LET_d was defined, calculated or determined was not always consistent, potentially impacting the corresponding RBE value.

PURPOSE: This study compares consistently calculated LET_d with other quantities as input variables for a phenomenological RBE model and attempts to determine which quantity that can best predicts proton RBE. The comparison was performed within the frame of introducing a new model for the proton RBE.

METHODS: High-throughput experimental set-ups of in vitro cell survival studies for proton RBE determination are simulated using the SHIELD-HIT12A Monte Carlo particle transport code. Together with LET, z*² /β² , here called effective Q (Q_eff ), and Q are scored. Each quantity is calculated using the dose and track averaging methods, while the scoring includes all hadronic particles, all protons or only primaries. A phenomenological linear-quadratic based RBE model is subsequently applied to the in vitro data with the various beam quality descriptors used as input variables and the goodness of fit is determined and compared using a bootstrapping approach. Both linear and non-linear fit functions were tested.

RESULTS: Versions of Q_eff and Q outperform LET with a statistically significant margin, with the best non-linear and linear fit having a relative root-mean-square-error (RMSE) for RBE_2Gy ± one standard error of 1.55 ± 0.04 (Q_{eff, t, primary} ) and 2.84 ± 0.07 (Q_{eff, d, primary} ), respectively. For comparison, the corresponding best non-linear and linear fits for LET_{d, all protons} had a relative RMSE of 2.07 ± 0.06 and 3.39 ± 0.08, respectively. Applying Welch’s t-test for comparing the calculated RMSE of RBE_2Gy resulted in two-tailed p-values of <0.002 for all Q and Q_eff quantities compared to LET_{d, all protons} .

CONCLUSIONS: The study shows that Q or Q_eff could be better RBE descriptors that dose averaged LET. This article is protected by copyright. All rights reserved.

PMID:36321465 | DOI:10.1002/mp.16029

J Hum Nutr Diet. 2022 Nov 2. doi: 10.1111/jhn.13109. Online ahead of print.

ABSTRACT

BACKGROUND: Poor diet including inadequate vegetable intake is a leading risk factor for non-communicable disease. Culinary and nutrition education provided to trainee and practising health and education professionals is an emerging strategy to promote improved dietary intake, including vegetable consumption. We evaluated the impact and feasibility of an online culinary medicine and nutrition (CM/CN) short course for health, education and vegetable industry professionals. The course aimed to improve participants’ skills, and confidence to prepare vegetables, knowledge of evidence-based nutrition information, and recommendations for improving vegetable consumption and diet quality.

METHODS: A pre-post study consisting of two separate groups participating in two course rounds, recruited practising professionals (n = 30) working in health; community, adult and/or culinary education; and the vegetable industry. Evaluation assessed diet quality, vegetable consumption barriers, cooking and food skills confidence, nutrition knowledge and process measures.

RESULTS: Seventeen participants (68%) completed the program. Pre to post intervention statistically significant increases in vegetables (M1.3, SD2.2), fruit (M1.6, SD3.1), and breads and cereal (M1.1, SD1.7) intakes were observed. Statistically significant increases and large effect sizes for mean food skill confidence scores (M8.9, SD 15.4, Cohen’s d 0.56) and nutrition knowledge scores (M6.2, SD 15.4, Cohen’s d 0.83) were also observed pre to post intervention.

CONCLUSION: The short online course was feasible and improved diet quality, food skill confidence and nutrition knowledge. Online CM/CN education for practising professionals represents a promising area of research. Future research involving a larger study sample and more rigorous study design such as RCT is warranted. This article is protected by copyright. All rights reserved.

PMID:36321462 | DOI:10.1111/jhn.13109

Int J Technol Assess Health Care. 2022 Nov 2;38(1):e79. doi: 10.1017/S0266462322000605.

ABSTRACT

Advances in the digitization of health systems and expedited regulatory approvals of innovative treatments have led to increased potential for the use of real-world data (RWD) to generate real-world evidence (RWE) to complement evidence from clinical trials. However, health technology assessment (HTA) bodies and payers have concerns about the ability to generate RWE of sufficient quality to be pivotal evidence of relative treatment effectiveness. Consequently, there is a growing need for HTA bodies and payers to develop guidance for the industry and other stakeholders about the use of RWD/RWE to support access, reimbursement, and pricing. We therefore sought to (i) understand barriers to the use of RWD/RWE by HTA bodies and payers; (ii) review potential solutions in the form of published guidance; and (iii) review findings with selected HTA/payer bodies. Four themes considered key to shaping the generation of robust RWE for HTA bodies and payers were identified as: (i) data (availability, governance, and quality); (ii) methodology (design and analytics); (iii) trust (transparency and reproducibility); and (iv) policy and partnerships. A range of guidance documents were found from trusted sources that could address these themes. These were discussed with HTA experts. This commentary summarizes the potential guidance solutions available to help resolve issues faced by HTA decision-makers in the adoption of RWD/RWE. It shows that there is alignment among stakeholders about the areas that need improvement in the development of RWE and that the key priority to move forward is better collaboration to make data usable for multiple purposes.

PMID:36321447 | DOI:10.1017/S0266462322000605

J Dig Dis. 2022 Nov 2. doi: 10.1111/1751-2980.13142. Online ahead of print.

ABSTRACT

AIMS: Guidelines suggest bismuth-containing quadruple (BQT) or concomitant regimens (CT) as first line therapy in our geographic area. Both schedules contain metronidazole.

METHODS: We recruited naïve subjects with H. pylori infection in the period January 2020-December 2021, receiving either CT or BQT. Before therapy, patients collected a fecal sample using the THD fecal test device. H. pylori DNA was extracted and mutations rdxA/frxA and A2143G in genes for metronidazole and clarithromycin resistance were respectively investigated using RT-PCR with high resolution melting curve.

RESULTS: Ninety-six patients were enrolled: 29 received BQT and 67 CT. The overall eradication rate was 94.8%, in detail 100% for BQT and 92.5% for CT, respectively. Metronidazole resistance was found in 18 subjects (18.8%), while clarithromycin resistance in 19 (19.8%). All 18 patients with metronidazole resistance experienced eradication. Five had assumed BQT and 13 CT. The eradication rate in metronidazole-sensitive strains was 93.6%. Of these, 24 received BQT with 100% success, and 54 had CT with 5 failures (success 90.7%). Two failing patients were resistant to clarithromycin, and the remaining 3 were susceptible to both clarithromycin and metronidazole. We did not observe any statistical significance in the eradication rate between metronidazole-resistant and sensitive strains (100% versus 93.6%, respectively, p = 0.58).

CONCLUSIONS: Our results suggest that metronidazole resistance does not influence the eradication rate of BQT and CT regimens in our geographical area, even if such result needs to confirmed in a larger sample.

PMID:36321440 | DOI:10.1111/1751-2980.13142

Biol Lett. 2022 Nov;18(11):20220309. doi: 10.1098/rsbl.2022.0309. Epub 2022 Nov 2.

ABSTRACT

The strength of species interactions may have profound effects on population dynamics. Empirical estimates of interaction strength are often based on the assumption that the interaction strengths are constant. Barents Sea (BS) cod and capelin are two fish populations for which such an interaction has been acknowledged and used, under the assumption of constant interaction strength, when studying their population dynamics. However, species interactions can often be nonlinear in marine ecosystems and might profoundly change our understanding of food chains. Analysing long-term time series data comprising a survey over 37 years in the Arcto-boreal BS, using a state-space modelling framework, we demonstrate that the effect of capelin on cod is not linear but shifts depending on capelin abundance: while capelin is beneficial for cod populations at high abundance; below the threshold, it becomes less important for cod. Our analysis therefore shows the importance of investigating nonlinearity in species interactions and may contribute to an improved understanding on species assemblages.

PMID:36321432 | DOI:10.1098/rsbl.2022.0309

J Appl Gerontol. 2022 Nov 2:7334648221137060. doi: 10.1177/07334648221137060. Online ahead of print.

ABSTRACT

Medicare implemented Bundled Payments for Care Improvement (BPCI) Model 3 in 2013, in which participating skilled nursing facilities (SNFs) were accountable for episode costs. We performed comparative interrupted time series analyses to evaluate associations between SNF BPCI participation and nurse staffing levels, using Medicare claims, resident assessments, and facility-level and market-level files of 2010-2017. For persistent-participating SNFs, BPCI was associated with improved certified nursing assistant (CNA) staffing levels (differential change = .03 hours, p = .025). However, BPCI was not related to changes in registered nurse (RN) and all licensed nurse hours, and nurse skill mix. Among drop-out SNFs, BPCI was associated with increased RN staffing levels (differential change = .02 hours, p = .009), leading to a higher nurse skill ratio (0.51 percentage points, p = .016) than control SNFs. Bundled payments for care improvement had no impact on CNA and all licensed nurse staffing levels. In conclusion, BPCI was associated with statistically significant but small increases in nurse staffing levels.

PMID:36321398 | DOI:10.1177/07334648221137060

Psychol Med. 2022 Nov 2:1-9. doi: 10.1017/S003329172200321X. Online ahead of print.

ABSTRACT

BACKGROUND: Abnormal auditory processing of deviant stimuli, as reflected by mismatch negativity (MMN), is often reported in schizophrenia (SCZ). At present, it is still under debate whether this dysfunctional response is specific to the full-blown SCZ diagnosis or rather a marker of psychosis in general. The present study tested MMN in patients with SCZ, bipolar disorder (BD), first episode of psychosis (FEP), and in people at clinical high risk for psychosis (CHR).

METHODS: Source-based MEG activity evoked during a passive auditory oddball task was recorded from 135 patients grouped according to diagnosis (SCZ, BD, FEP, and CHR) and 135 healthy controls also divided into four subgroups, age- and gender-matched with diagnostic subgroups. The magnetic MMN (mMMN) was analyzed as event-related field (ERF), Theta power, and Theta inter-trial phase coherence (ITPC).

RESULTS: The clinical group as a whole showed reduced mMMN ERF amplitude, Theta power, and Theta ITPC, without any statistically significant interaction between diagnosis and mMMN reductions. The mMMN subgroup contrasts showed lower ERF amplitude in all the diagnostic subgroups. In the analysis of Theta frequency, SCZ showed significant power and ITPC reductions, while only indications of diminished ITPC were observed in CHR, but no significant decreases characterized BD and FEP.

CONCLUSIONS: Significant mMMN alterations in people experiencing psychosis, also for diagnoses other than SCZ, suggest that this neurophysiological response may be a feature shared across psychotic disorders. Additionally, reduced Theta ITPC may be associated with risk for psychosis.

PMID:36321391 | DOI:10.1017/S003329172200321X

J Periodontal Res. 2022 Nov 2. doi: 10.1111/jre.13066. Online ahead of print.

ABSTRACT

Selective outcome reporting (SOR) is a type of bias that can compromise the validity of results and affect evidence-based practice. SOR can overestimate the effect of an intervention and lead to conclusions that a treatment is effective when it is not. This study aimed to investigate the prevalence of SOR in publications of RCTs on nonsurgical periodontal therapy (NSPT) and to verify associated factors. The protocols were searched and selected on the www.clinicaltrials.gov platform up to January 16, 2022. Corresponding publications were identified, and data extraction and discrepancy analysis were performed. The risk of bias was assessed according to the RoB2 tool. One hundred forty-five studies (174 publications) were included. The prevalence of SOR was 49.7% and was unclear in nearly one third of studies (27.6%). Only 31.7% of the primary outcomes were completely described in the publications. The overall risk of bias was high in 60% of the included studies. SOR was associated with statistical significance (p < .001), and multiple publications of the same study (p = .005). Our study demonstrated the high prevalence of SOR, highlighting the need to improve the quality of reporting of RCTs on NSPT studies.

PMID:36321390 | DOI:10.1111/jre.13066

J Ultrasound Med. 2022 Nov 2. doi: 10.1002/jum.16122. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this meta-analysis was to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) and high-resolution magnetic resonance imaging (HR-MRI) in patients with carotid vulnerable plaques.

METHODS: A systematic review was conducted in PubMed, Embase, Cochrane Library, and Web of Science using the search terms carotid artery, atherosclerotic plaque, CEUS, contrast-enhanced ultrasound, HR-MRI, and high-resolution magnetic resonance. Studies published since the establishment of the library until December 2021 were retrieved. The statistical analyses were performed with Meta-DiSc version 1.4. Beyond that, the potential sources of heterogeneity for CEUS and HR-MRI were explored.

RESULTS: Nine articles were included in this study. For CEUS, the pooled sensitivity and specificity for detecting carotid vulnerable plaques 91% (95% confidence interval [CI]: 84%, 95%) and 67% (95% CI: 54%, 79%), respectively. For HR-MRI, the pooled sensitivity and specificity were 78% (95% CI: 72%, 83%) and 65% (95% CI, 56%, 73%), respectively. The area under the summary receiver operating characteristic curve for CEUS and HR-MRI were 0.9218 and 0.8129, respectively. However, the difference in diagnostic accuracy between CEUS and HR-MRI diagnostic accuracy was not statistically significant.

CONCLUSIONS: The study shows that the sensitivity of CEUS was higher than that of HR-MRI, and the specificity was similar to HR-MRI. CEUS and HR-MRI provide a similar diagnostic yield in detecting a vulnerable plaque. Thus, CEUS may be a useful tool for the diagnosis of carotid vulnerable plaques.

PMID:36321389 | DOI:10.1002/jum.16122