Nevin Manimala

Cephalalgia. 2022 Mar 25:3331024221089567. doi: 10.1177/03331024221089567. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine changes in the occurrence, severity, and symptoms of headache episodes in patients with chronic migraine following eptinezumab treatment.

METHODS: PROMISE-2 was a double-blind, placebo-controlled, parallel-group trial that randomized adults with chronic migraine to eptinezumab 100 mg, 300 mg, or placebo IV every 12 weeks for up to 24 weeks (2 infusions). Headache episodes (migraine and non-migraine) and their characteristics were reported in daily electronic diaries during the 28-day baseline and throughout the 24-week treatment period.

RESULTS: A total of 1072 patients were included in this post hoc analysis. Mean monthly headache days decreased by 8.9 (100 mg) and 9.7 (300 mg) compared to a 7.3 decrease in placebo over the first 4-week interval post initial dose and reductions were maintained throughout the 24-week treatment period. Mean monthly headache episodes also decreased by 8.4 (100 mg) and 9.0 (300 mg) compared to a decrease of 7.1 with placebo. The proportion of headache episodes that were migraine attacks decreased by 11.2% (100 mg), 12.4% (300 mg), and 3.9% (placebo), and among remaining headaches decreases in severe pain, nausea, phonophobia, photophobia, and physical activity limitations were numerically greater than placebo.

CONCLUSIONS: Patients with chronic migraine treated with eptinezumab decreased the monthly severity and frequency of headache days and episodes more than placebo. Beyond decreased headache frequency, patients treated with eptinezumab reported a reduction in the percent of remaining headache episodes that were migraine attacks, as well as a decrease in burdensome symptoms of headache episodes, indicating additional decreased headache severity after eptinezumab treatment.Trial registration: ClinicalTrials.gov Identifier: NCT02974153; registered November 23, 2016.

PMID:35332807 | DOI:10.1177/03331024221089567

Future Oncol. 2022 Mar 25. doi: 10.2217/fon-2021-1633. Online ahead of print.

ABSTRACT

Aim: To compare pembrolizumab with competing interventions for previously untreated, unresectable or metastatic microsatellite instability-high or mismatch repair-deficient colorectal cancer. Method: Trials were identified via a systematic literature review and synthesized using a Bayesian network meta-analysis with time-varying hazard ratios (HRs). Results: Using intention-to-treat data, HRs for overall survival were generally in favor of pembrolizumab but not statistically significant; however, statistical significance was reached versus all comparators by month 16 when accounting for crossover. Estimated HRs for progression-free survival significantly favored pembrolizumab versus all comparators by month 12. Pembrolizumab was also superior to all comparators in terms of grade ≥3 adverse events. Conclusion: These analyses suggest that pembrolizumab is a highly efficacious and safe treatment in this population.

PMID:35332802 | DOI:10.2217/fon-2021-1633

J Public Health Res. 2022 Mar 25;11(2). doi: 10.4081/jphr.2022.2748.

ABSTRACT

BACKGROUND: The outbreak of a novel coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19, raised worldwide concern. The present study investigates the association between anti-contagion policies and the spread of COVID-19 across the United States.

DESIGN AND METHODS: We selected the most frequently implemented COVID-19 anti-contagion policies in all the U.S. states issued from 29 February 2020. Accordingly, we modified an epidemiological model and combined it with a comprehensive statistical analysis to evaluate the policies’ individual and overall likely impact.

RESULTS: For the first time, a novel index, evaluates the associations between policy implementation and COVID-19 spread at both statewide and national levels. Our results indicate that governmental policies requiring mask use, businesses social distancing, and quarantining travelers may be most effective for controlling COVID-19 spread. Simultaneously, widespread orders like school closure and safer-at-home that can be particularly disruptive to the economy and social fabric of society may be unnecessary given their lack of association with reducing infection.

CONCLUSIONS: The absence of any COVID-19 vaccines during the first several months of its pandemic necessitated using governmental policies to help stop the spread of this disease. Our index showed the association between implemented policies and COVID-19 spread, highlighting the specific policies with the greatest association – mandatory quarantine upon entering a state, businesses implementing social distancing, and mandatory mask use – and those with less association like school closure and safer-at-home orders. This study provided evidence to inform policy choices for the current global crisis and future pandemics.

PMID:35332753 | DOI:10.4081/jphr.2022.2748

Sichuan Da Xue Xue Bao Yi Xue Ban. 2022 Mar;53(2):321-326. doi: 10.12182/20220360206.

ABSTRACT

OBJECTIVE: To explore the treatment outcome of the strategy of early extubation and then switching to non-invasive mechanical ventilation in children with acute respiratory failure, and the safety and feasibility of using the strategy to replace traditional methods.

METHODS: A total of 102 children, aged between 1 month to 14 years old, who had acute respiratory failure and were admitted to the pediatric ICU of West China Second University Hospital, Sichuan University between January 2019 and December 2020 were enrolled and randomly assigned to treatment group 1 (n=55) and treatment group 2 (n=47). In addition, 53 children who had the same condition in the 12 month prior to the beginning of the study were included in the control group. In the two treatment groups, the patients were extubated first, and then weaned off the ventilator. In group 1, when the patient met the invasive-non-invasive switching criteria, the tracheal tube was pulled out and non-invasive bi-level positive airway pressure (BiPAP) ventilation was used for respiratory support. In group 2, high-flow nasal cannula (HFNC) oxygen therapy was used for respiratory support. The traditional progressive weaning method was adopted for the control group (extubing and weaning were performed at the same time). The incidence of ventilator-associated pneumonia (VAP) during the period of tracheal intubation was compared and the mortality of the two groups was evaluated from the point when the patients were recruited. At the time of extubation in the treatment groups and extubation plus weaning in the control group, the pressure support levels, or PC above PEEP, intubation time, sequential time (between 2 treatment groups only), weaning failure rate, and the incidence of laryngeal edema and nasal pressure ulcer were compared.

RESULTS: The subjects of the study were predominantly infants (93 cases, 60%) and young children (31 cases, 20%). Among the 155 cases, 82 (53%) were male. There was no statistical difference in age distribution or gender among the groups. There was no significant difference in the clinical indicators among the three groups before tracheal intubation. At the time of extubation, the PC above PEEP in the two treatment groups was higher than that in the control group, and higher in group 1 than that of group 2, the difference being statistically significant (P<0.05). The intubation time of the two treatment groups was shorter than that of the control group, and shorter in group 1 than that of group 2 (P<0.05). The sequential time of group 2 was shorter than that of group 1 (P<0.05). The extubation failure rate and the incidence of VAP in the two treatment groups were lower than those in the control group, and there was no statistically significant difference between the two treatment groups. The incidence of nasal pressure ulcers in group 1 was higher than that in the other two groups (P<0.05). There was 1 death in treatment group 1, and no deaths in treatment group 2 or the control group. There was no significant difference in mortality or the incidence of laryngeal edema after extubation in the three groups.

CONCLUSION: Early extubation and then switching to non-invasive mechanical ventilation can be well tolerated by the patients, and can be used in clinical practice as an effective weaning method for children with acute respiratory failure.

PMID:35332737 | DOI:10.12182/20220360206

Sichuan Da Xue Xue Bao Yi Xue Ban. 2022 Mar;53(2):256-262. doi: 10.12182/20220360504.

ABSTRACT

OBJECTIVE: To study the effects of CD47-targted immunotherapy on the oral-gut microbiota of immune-competent mice.

METHODS: A peritoneal metastatic colon cancer model was constructed in immune-competent mice. Anti-CD47 monoclonal antibody was intraperitoneally administered to the mice in the treatment group, while PBS was administered to mice in the control group. Tumor growth was documented with small animal live imaging technology. 16S rRNA sequencing technology was used to analyze the composition and diversity of oral-gut microbiota.

RESULTS: The alpha diversity of oral microbes in the anti-CD47 monoclonal antibody treatment group decreased, and the difference was statistically significant. There was no significant change in the alpha diversity of gut microbes. Differential species analysis showed significantly decreased abundance of Staphylococcus, Jeotgalicoccus, and Sporosarcina in the oral microbiota of mice in the treatment group compared to that of mice in the control group. The abundance of Bacteroides in the gut microbiota was significantly higher in the treatment group.

CONCLUSION: CD47-targted immunotherapy has a rather significant impact on the diversity of oral microbiota in mice, but does not have significant impact on the species diversity of gut microbiota.

PMID:35332726 | DOI:10.12182/20220360504

Clin Exp Dent Res. 2022 Mar 25. doi: 10.1002/cre2.561. Online ahead of print.

ABSTRACT

OBJECTIVES: The present study aims to describe the relationship between upper first molar roots and maxillary sinus, for the first time with a truly three-dimensional approach.

METHODS: From a retrospective cone-beam computed tomography (CBCT) sample of the upper jaw, a total of 105 upper first molars in contact with maxillary sinus from 74 patients (male 24, female 50, mean age 42) were included in the present study. Segmentation of the upper first molar and maxillary sinus in CBCT was performed utilizing a semiautomatic livewire segmentation tool in MeVisLab v.3.1. The segmentations were analyzed in 3-matic Medical 20.0 for root volume and the contact area between upper first molar roots and maxillary sinus. Analysis of variance test was applied to detect statistically significant differences between the roots.

RESULTS: The palatal root had the largest contact area with maxillary sinus 27.8 ± 21.4 mm² (20% of the root area) followed by the mesiobuccal 20.5 ± 17.9 mm² (17% of the root area) and distobuccal root 13.7 ± 12 mm² (14% of the root area). A significant difference in the contact area of the different roots of the upper first molar was seen.

CONCLUSIONS: This study showed that 70% of the upper first molars were in contact with the maxillary sinus. The palatal root had on average a fifth of its root surface in contact with the sinus, while for mesiobuccal this was a sixth of its root surface and distobuccal roots this was somewhat less. The true 3D relationship could help to better understand maxillary anatomy in relation to occurring pathologies and treatment planning in this area.

PMID:35332695 | DOI:10.1002/cre2.561

Pharm Stat. 2022 Mar 24. doi: 10.1002/pst.2209. Online ahead of print.

ABSTRACT

An immunotherapy trial often uses the phase I/II design to identify the optimal biological dose, which monitors the efficacy and toxicity outcomes simultaneously in a single trial. The progression-free survival rate is often used as the efficacy outcome in phase I/II immunotherapy trials. As a result, patients developing disease progression in phase I/II immunotherapy trials are generally seriously ill and are often treated off the trial for ethical consideration. Consequently, the happening of disease progression will terminate the toxicity event but not vice versa, so the issue of the semi-competing risks arises. Moreover, this issue can become more intractable with the late-onset outcomes, which happens when a relatively long follow-up time is required to ascertain progression-free survival. This paper proposes a novel Bayesian adaptive phase I/II design accounting for semi-competing risks outcomes for immunotherapy trials, referred to as the dose-finding design accounting for semi-competing risks outcomes for immunotherapy trials (SCI) design. To tackle the issue of the semi-competing risks in the presence of late-onset outcomes, we re-construct the likelihood function based on each patient’s actual follow-up time and develop a data augmentation method to efficiently draw posterior samples from a series of Beta-binomial distributions. We propose a concise curve-free dose-finding algorithm to adaptively identify the optimal biological dose using accumulated data without making any parametric dose-response assumptions. Numerical studies show that the proposed SCI design yields good operating characteristics in dose selection, patient allocation, and trial duration.

PMID:35332674 | DOI:10.1002/pst.2209

J Appl Clin Med Phys. 2022 Mar 25:e13595. doi: 10.1002/acm2.13595. Online ahead of print.

ABSTRACT

PURPOSE: Dose computation using cone beam computed tomography (CBCT) images is inaccurate for the purpose of adaptive treatment planning. The main goal of this study is to assess the dosimetric accuracy of synthetic computed tomography (CT)-based calculation for adaptive planning in the upper abdominal region. We hypothesized that deep learning-based synthetically generated CT images will produce comparable results to a deformed CT (CTdef) in terms of dose calculation, while displaying a more accurate representation of the daily anatomy and therefore superior dosimetric accuracy.

METHODS: We have implemented a cycle-consistent generative adversarial networks (CycleGANs) architecture to synthesize CT images from the daily acquired CBCT image with minimal error. CBCT and CT images from 17 liver stereotactic body radiation therapy (SBRT) patients were used to train, test, and validate the algorithm.

RESULTS: The synthetically generated images showed increased signal-to-noise ratio, contrast resolution, and reduced root mean square error, mean absolute error, noise, and artifact severity. Superior edge matching, sharpness, and preservation of anatomical structures from the CBCT images were observed for the synthetic images when compared to the CTdef registration method. Three verification plans (CBCT, CTdef, and synthetic) were created from the original treatment plan and dose volume histogram (DVH) statistics were calculated. The synthetic-based calculation shows comparatively similar results to the CTdef-based calculation with a maximum mean deviation of 1.5%.

CONCLUSIONS: Our findings show that CycleGANs can produce reliable synthetic images for the adaptive delivery framework. Dose calculations can be performed on synthetic images with minimal error. Additionally, enhanced image quality should translate into better daily alignment, increasing treatment delivery accuracy.

PMID:35332646 | DOI:10.1002/acm2.13595

Psychogeriatrics. 2022 Mar 24. doi: 10.1111/psyg.12827. Online ahead of print.

ABSTRACT

BACKGROUND: Late-life depression is a geriatric syndrome which should be taken seriously. Many clinical scales have been developed for the screening of geriatric depression. Most of these have been validated at different times and in diverse populations. A five-question version of the Geriatric Depression Scale (GDS-5) was developed in 1997. This test has been validated and used in different populations. In the present study, we plan to validate the GDS-5 for the Turkish elderly population.

METHODS: Patients aged 60 years and older who applied to the Geriatrics Clinic of our hospital between November 2018 and November 2019 were included in the study. We compared the effectiveness of Yesavage Geriatric Depression Scale-30 (YGDS-30) and GDS-5 in screening depression, based on Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) depression criteria.

RESULTS: Four hundred participants were included in the study. A significant positive correlation was found between the DSM-5 scale and the GDS-5 scale (rho = 0.726, P <0.001). According to DSM-5, YGDS-30 and GDS-5, 112 participants (28%), 154 patients (%38.5) and 199 patients (%49.8) were diagnosed with depression respectively. When the cut-off value was taken as ≥2, the sensitivity, specificity, positive predictive and negative predictive values for the GDS-5 scale were determined as 96%, 68%, 54%, and 98%, respectively. We obtained these diagnostic measures with 95% confidence intervals.

CONCLUSION: This study demonstrated the validity and reliability of the GDS-5 for Turkish elderly populations. This five-question scale will be significant in daily use to screen for depression in elderly individuals with multiple problems.

PMID:35332628 | DOI:10.1111/psyg.12827

Physiother Res Int. 2022 Mar 24:e1947. doi: 10.1002/pri.1947. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the recovery of physical function, health related quality of life (HRQoL), and pain for people following hip fracture for the initial 12 months, and to examine whether postoperative outcome measures of physical function, HRQoL, and pain can predict physical function at 3 and 12 months.

DESIGN: A prospective single-center observational study, as part of the HIPFRAC trial.

SETTINGS: One hospital with two associated municipalities in Norway.

SUBJECTS: 207 participants with hip fracture included in the study (140 participants transferred to a short-term nursing home placement and 67 transferred directly home at discharge from hospital).

METHOD: Outcome measures were Short Physical Performance Battery (SPPB), Timed Up & Go (TUG), Stair climbing test (SC), Numeric Rating Scale (NRS) for pain at rest and in activity, and EQ-5D-5L index and health score. Data were analysed by repeated measures of variance and multivariate regression analyses.

RESULTS: There were statistically significant improvements in physical function (SPPB total score and TUG), NRS-pain in activity, and HRQoL (EQ-5D-5L) from hospital discharge to 3-month follow-up for the whole cohort and the two groups (p < 0.001). However, the largest improvements occurred within the first 3 months. Further statistically significant improvements occurred between 3 and 12 months (p < 0.05). The strongest predictors of physical function at 3 and 12 months post-fracture were physical function (SPPB) at hospital discharge and pre-fracture requirement of a walking aid.

CONCLUSION: The recovery of physical function, HRQoL, and pain in participants after hip fracture indicates gradual improvements during the initial 12-month follow-up, with the largest improvements within the first 3 months.

PMID:35332627 | DOI:10.1002/pri.1947