Nevin Manimala

Cancer Med. 2024 Feb;13(3):e7024. doi: 10.1002/cam4.7024.

ABSTRACT

OBJECTIVES: The use of immune checkpoint inhibitors, particularly PD-1 inhibitors, has revolutionized the treatment of advanced tumors and shown significant improvements in patient survival rates. However, which PD-1 inhibitor is more effective and safer for a specific indication remains unclear. To address this problem, our study aimed to evaluate the effectiveness and safety of different PD-1 inhibitors in combination with chemotherapy as first-line therapy for individuals with advanced non-small-cell lung cancer (NSCLC) without driver genes in the real world.

MATERIALS AND METHODS: We conducted a retrospective study of individuals diagnosed with aNSCLC who received immune checkpoint inhibitors (ICIs) with modified PD-1 inhibitors, including Sintilimab, Toripalimab, Tislelizumab, Camrelizumab, or Pembrolizumab as first-line treatment between March 5th, 2016 and October 20th, 2022. We assessed demographic and clinical information and analyzed clinical response, survival outcomes, and safety profiles. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety.

RESULTS: As of the date cut-off on October 20th, 2022, the median follow-up time was 20.62 months. A total of 204 patients were enrolled in the study, including 56 (27.5%) patients receiving modified PD-1 inhibitors (Sintilimab, Toripalimab, Tislelizumab, or Camrelizumab) in combination with chemotherapy and 148 (72.5%) patients receiving Pembrolizumab in combination with chemotherapy. In the overall cohort, the median overall survival (OS) was 26.9 months (95%CI, 22.3-31.6), the median progression-free survival (PFS) was 8.4 months (95%CI, 6.9-9.8), and the objective response rate (ORR) and disease control rate (DCR) were 47.6% (95%CI, 29.9-43.6) and 84.3% (95%CI, 78.4-88.9). The mOS of modified PD-1 inhibitors group and Pembrolizumab group were 30.7 (95%CI, 17.3-44.4) months and 26.8 (95%CI, 22.2-31.4) months. The mPFS of two groups were 8.3(95%CI, 6.9-9.6) months and 8.8 (95%CI, 6.9-10.7) months, respectively. There was no statistical difference between the two groups in terms of OS or PFS. The ORR for the two groups was 48.2% (95%CI, 34.8-61.8) and 47.3% (95%CI, 39.1-5.6), respectively. However, due to the limited sample size, the difference was not statistically significant. On the other hand, the DCR tended to be higher in the Pembrolizumab group (86.5%; 95%CI, 79.7-91.4) compared to the modified PD-1 inhibitors group (78.6%; 95%CI, 65.2-87.9), and this difference was statistically significant (p = 0.006). In terms of safety, both groups exhibited favorable clinical safety profiles. The only two types of potentially immune-related adverse events reported were pneumonitis and reactive cutaneous capillary endothelial proliferation (RCCEP).

CONCLUSIONS: The modified PD-1 inhibitors showed comparable survival outcomes and manageable safety profiles in NSCLC compared to Pembrolizumab. Moreover, these inhibitors exhibited improved accessibility and economic outcomes compared to Pembrolizumab. While there were similarities in drug-related and immunotherapy-related adverse reactions between the modified PD-1 inhibitors and Pembrolizumab, there were some slight differences. Further prospective and retrospective studies would be necessary to validate these findings beyond the scope of the CTONG1901 study.

PMID:38400661 | DOI:10.1002/cam4.7024

Echocardiography. 2024 Feb;41(2):e15784. doi: 10.1111/echo.15784.

ABSTRACT

OBJECTIVE: We sought to evaluate the left atrial (LA) strain parameters of maintenance hemodialysis (MHD) patients before and after dialysis by two dimensional speckle tracking imaging (2D-STI), and to explore the effect of volume load change on LA function.

METHODS: Seventy-six patients with end stage renal disease (ESRD) on hemodialysis (HD) were enrolled in the study protocol. The median duration of dialysis was 24.0 (7.5, 59.5) months. In addition, 30 healthy subjects were selected as control group. Comprehensive echocardiography was performed immediately before and after hemodialysis to compare the changes in left atrial function.

RESULTS: Regarding LA strain parameters in patients of pre-HD, the median (25th, 75th) LA reservoir, LA conduit, and LA contractile reserve were 28.0 (23.0, 34.5), -15.5 (-10.0, -21.5), -12.0 (-9.0, -16.0) respectively; the post-HD were 26.0 (21.0, 29.0), -12.0 (-9, -15.5), -12.5 (-9, -15.5) respectively; and controls were 43.0 (36.0, 48.0), -24.0 (-18.0, -32.0), -17.0 (-15.0, -22.0) respectively. The left atrial strain parameters before HD were lower than controls, the differences were statistically significant, the p-value were .000, .025, and .000, respectively. The reservoir function and conduit function of LA strain decreased after hemodialysis, the differences were statistically significant, the p-value were .003 and .006, respectively. Regarding the contraction of LA, the differences between pre- and post-HD were not statistically significant (p = .965).

CONCLUSION: Hemodialysis removes excess water in human body, while LVGLS and Doppler parameters are greatly affected by reduced preload. New echocardiographic parameters, such as left atrial strain, can quantitatively evaluate the changes in left atrial function before and after hemodialysis in ESRD patients, which can provide valuable information for the overall cardiac evaluation in this specific population.

PMID:38400659 | DOI:10.1111/echo.15784

Psychogeriatrics. 2024 Feb 24. doi: 10.1111/psyg.13098. Online ahead of print.

ABSTRACT

Primitive reflexes (PRs) are clinical signs that indicate diffuse cerebral dysfunction and frontal lesions. We aimed to present a comprehensive analysis of the prevalence and risk of PRs in patients with dementia. English-language articles published from January 1990 to April 2021 were searched in PubMed, ScienceDirect, Cochrane, and Web of Science with keywords. The titles and abstracts of the identified articles were screened to identify potentially relevant papers. Odds ratios and risk ratios were extracted with 95% confidence intervals and combined using the random-effects model after logarithmic transformation. The prevalence in dementia patients was also combined using the random-effects model. This meta-analysis involved 29 studies. The snout reflex (48% of cases) was the most prevalent. It was found that the risk of PRs in individuals with dementia was significantly elevated, ranging from 13.94 to 16.38 times higher than in healthy controls. The grasp reflex exhibited the highest risk for dementia. This meta-analysis showed that the prevalence and the risk of PRs is high in older patients with dementia. Therefore, PRs, especially the grasp reflex, should be carefully assessed as a part of routine physical examination in the diagnostic process for dementia.

PMID:38400649 | DOI:10.1111/psyg.13098

J Dent Educ. 2024 Feb 24. doi: 10.1002/jdd.13498. Online ahead of print.

ABSTRACT

PURPOSE: The annual teaching oral-systemic health (TOSH) virtual clinical simulation and case study activity exposes interprofessional teams of nurse practitioner, nurse midwifery, dental, medical, and pharmacy students to a virtual clinical simulation experience that uses oral-systemic health as a clinical exemplar for promoting interprofessional core competencies. The present study examines changes in participating students’ self-reported interprofessional competencies following participation in virtual TOSH from 2020 to 2022. These findings are also compared to those from in-person TOSH (2019) to examine the equivalence of student outcomes of both the in-person and virtual programs.

METHODS: A pre- and post-test evaluation design was used to examine the effectiveness of exposure to the TOSH program on self-reported attainment of interprofessional competencies for participating students using the interprofessional collaborative competency attainment scale.

RESULTS: Analysis of pre- and post-surveys demonstrated statistically significant improvement in students’ self-rated interprofessional experience competencies following the virtual TOSH program, which aligns with results from the in-person cohorts. Similar findings between the in-person and virtual cohorts indicated no statistically significant difference between the two formats.

CONCLUSION: These findings demonstrate the success of TOSH in promoting attainment of interprofessional competencies among future health professionals. We encourage administrators and faculty who lead health professional programs to take advantage of using virtual simulations as an integral component of interprofessional oral health clinical experiences where students from different health professions learn from and about each other in assessing and treating patients across the lifespan.

PMID:38400648 | DOI:10.1002/jdd.13498

Int J Inj Contr Saf Promot. 2024 Feb 23:1-9. doi: 10.1080/17457300.2024.2319620. Online ahead of print.

ABSTRACT

Road traffic crashes (RTCs) are significantly high in Nigeria with serious social and health consequences. While existing studies on RTCs have mainly focused on the effect of socio-economic, environmental, human and mechanical factors to address the high rates, the relationship between road transport fares and RTCs has been glossed over in literature. Thus, this study examines the influence of road transport fares and other covariates on RTCs. Data on RTCs and the predictors between 2017 and 2022 were obtained from the records of the National Bureau of Statistics and the Federal Road Safety Corps. Spatial statistical techniques were used for the data analysis. RTCs vary across the country, and Northern Nigeria is the hot spot. Results from the spatial analysis show that road transport fares, population density, and illiteracy rate are significant predictors of RTCs. The study recommends striking a balance between fare affordability, the quality of service provided, and the implementation of effective transportation strategies.

PMID:38400629 | DOI:10.1080/17457300.2024.2319620

J Esthet Restor Dent. 2024 Feb 23. doi: 10.1111/jerd.13212. Online ahead of print.

ABSTRACT

OBJECTIVES: This study evaluated the clinical performance of bulk-fill resin composite systems with different viscosities in class II cavities.

MATERIALS AND METHODS: A total of 80 class II restorations were performed with a single operator in 50 patients using four different bulk-fill resin composite materials: Filtek™ Bulk Fill, Heated Filtek™ Bulk Fill, G-aenial™ BULK Injectable, and SonicFill3. A double-blinded randomized clinical trial was designed to evaluate the two-year clinical performance of the four bulk-fill composite resins using modified FDI criteria. Data were analyzed descriptively. Level of significance was set at 0.05. Differences between groups were tested using Wilcoxon-signed-rank and Mann-Whitney-U test as nonparametric tests.

RESULTS: Data were analyzed using Kruskal-Wallis, Mann-Whitney U, and Wilcoxon signed rank tests (p < 0.05). Eighty restorations were available for evaluation, with a survival function of 100%. No statistically significant differences were observed between the four groups regarding assessing esthetic, functional, and biological properties during different follow-up periods.

CONCLUSIONS: After 2 years of clinical follow-up, the bulk-fill composite systems with different viscosities seem to be esthetically, functionally, and biologically acceptable, with a promising clinical performance in class II cavities.

PMID:38400614 | DOI:10.1111/jerd.13212

J Fish Dis. 2024 Feb 23:e13933. doi: 10.1111/jfd.13933. Online ahead of print.

ABSTRACT

Nodular gill disease (NGD) is an emerging condition associated with amoeba trophozoites in freshwater salmonid farms. However, unambiguous identification of the pathogens still must be achieved. This study aimed to identify the amoeba species involved in periodic NGD outbreaks in two rainbow trout (Oncorhynchus mykiss) farms in Northeastern Italy. During four episodes (February-April 2023), 88 fish were euthanized, and their gills were evaluated by macroscopic, microscopic and histopathological examination. The macroscopic and microscopic severity of the lesions and the degree of amoebae infestation were scored and statistically evaluated. One gill arch from each animal was put on non-nutrient agar (NNA) Petri dishes for amoeba isolation, cultivation and subsequent identification with SSU rDNA sequencing. Histopathology confirmed moderate to severe lesions consistent with NGD and mild to moderate amoeba infestation. The presence of amoebae was significantly correlated with lesion severity. Light microscopy of cultured amoebae strains and SSU rDNA analysis revealed the presence of a previously characterized amoeba Naegleria sp. strain GERK and several new strains: two strains from Hartmannelidae, three vannelid amoebae from the genus Ripella and cercozoan amoeba Rosculus. Despite the uncertainty in NGD etiopathogenesis and amoebae pathogenic role, identifying known and new amoebae leans towards a possible multi-aetiological origin.

PMID:38400598 | DOI:10.1111/jfd.13933

Stat Methods Med Res. 2024 Feb 23:9622802241229284. doi: 10.1177/09622802241229284. Online ahead of print.

ABSTRACT

The mixture of a distribution of responses from untreated patients and a shift of that distribution is a useful model for the responses from a group of treated patients. The mixture model accounts for the fact that not all the patients in the treated group will respond to the treatment and consequently their responses follow the same distribution as the responses from untreated patients. The treatment effect in this context consists of both the fraction of the treated patients that are responders and the magnitude of the shift in the distribution for the responders. In this article, we introduce inference based on a pseudo-likelihood approach and compare it with an existing method of moment approach. An extensive simulation study is used to compare robust performance of the two approaches regarding point estimation, confidence regions, and confidence intervals. The methods are demonstrated on an illustrative blood pressure data set.

PMID:38400596 | DOI:10.1177/09622802241229284

Ecology. 2024 Feb 23:e4240. doi: 10.1002/ecy.4240. Online ahead of print.

ABSTRACT

In response to external changes, ecosystems can undergo catastrophic transitions. Early warning indicators aim to predict such transitions based on the phenomenon of critical slowing down at bifurcation points found under a constant environment. When an explicit rate of environmental change is considered, catastrophic transitions can become distinct phenomena from bifurcations, and result from a delayed response to noncatastrophic bifurcations. We use a trophic metacommunity model where transitions in time series and bifurcations of the system are distinct phenomena. We calculate early warning indicators from the time series of the continually changing system and show that they predict not the bifurcation of the underlying system but the actual catastrophic transition driven by the explicit rate of change. Predictions based on the bifurcation structure could miss catastrophic transitions that can still be captured by early warning signals calculated from time series. Our results expand the repertoire of mechanistic models used to anticipate catastrophic transitions to nonequilibrium ecological systems exposed to a constant rate of environmental change.

PMID:38400588 | DOI:10.1002/ecy.4240

Stat Methods Med Res. 2024 Feb 23:9622802241232124. doi: 10.1177/09622802241232124. Online ahead of print.

ABSTRACT

Sequential multiple assignment randomized trial design is becoming increasingly used in the field of precision medicine. This design allows comparisons of sequences of adaptive interventions tailored to the individual patient. Superiority testing is usually the initial goal in order to determine which embedded adaptive intervention yields the best primary outcome on average. When direct superiority is not evident, yet an adaptive intervention poses other benefits, then non-inferiority testing is warranted. Non-inferiority testing in the sequential multiple assignment randomized trial setup is rather new and involves the specification of non-inferiority margin and other important assumptions that are often unverifiable internally. These challenges are not specific to sequential multiple assignment randomized trial and apply to two-arm non-inferiority trials that do not include a standard-of-care (or placebo) arm. To address some of these challenges, three-arm non-inferiority trials that include the standard-of-care arm are proposed. However, methods developed so far for three-arm non-inferiority trials are not sequential multiple assignment randomized trial-specific. This is because apart from embedded adaptive interventions, sequential multiple assignment randomized trial typically does not include a third standard-of-care arm. In this article, we consider a three-arm sequential multiple assignment randomized trial from an National Institutes of Health-funded study of symptom management strategies among people undergoing cancer treatment. Motivated by that example, we propose a novel data analytic method for non-inferiority testing in the framework of three-arm sequential multiple assignment randomized trial for the first time. Sample size and power considerations are discussed through extensive simulation studies to elucidate our method.

PMID:38400576 | DOI:10.1177/09622802241232124