Category: Statistics

Lung Cancer. 2021 Nov 25;163:14-18. doi: 10.1016/j.lungcan.2021.11.010. Online ahead of print.

ABSTRACT

PURPOSE: Response Evaluation Criteria in Solid Tumors (RECIST) has limitations but remains the conventional approach for tumor assessments. We explored whether circulating tumor DNA (ctDNA) can be incorporated into RECIST to provide a more robust measure of tumor response in advanced EGFR-mutant NSCLC.

PATIENTS AND METHODS: In FASTACT-2, patients with advanced NSCLC received platinum/gemcitabine intercalated with erlotinib or placebo. EGFR mutation (tumor and plasma ctDNA) was detected using cobas v2. Patients selected for this hypothesis-generating analysis had EGFR mutations (on either tumor or plasma) at baseline and evaluable week 8 plasma EGFR. Week 8 ctDNA and radiologic response status were correlated with survival using landmark cox regression analyses.

RESULTS: Of the original 451 patients, 86 (19.1%) were eligible for this analysis. 73% (n = 63) had detectable ctDNA at baseline. At week 8, 40% (n = 34) had radiologic partial response (PR), 60% (n = 52) had stable disease (SD); 80% (n = 69) had a ctDNA response (undetectable ctDNA). In patients who had initial PR and undetectable ctDNA, 93% (28/30) had ongoing PR subsequently at week 16. The median duration of response was 14.9 months. In patients with SD and undetectable ctDNA at week 8, 28% had radiological PR at week 16. Amongst those with PR at week 8, survival outcomes for those with undetectable vs detectable ctDNA were not statistically significant (PFS HR 0.49, 95%CI 0.16-1.48, p = 0.21; OS HR 0.39, 95%CI 0.13-1.19, p = 0.10). Amongst those with SD at week 8, there was significantly longer survival for those with undetectable vs detectable ctDNA (PFS HR 0.27, 95% CI 0.13-0.57, p < 0.0001; OS HR 0.40, 95% CI 0.20-0.80, p = 0.009).

CONCLUSION: In patients with SD, undetectable ctDNA at week 8 correlated with survival improvement. Both radiologic and ctDNA responses are prognostic of PFS. Incorporation of ctDNA with RECIST may improve tumor response assessment in EGFR-mutant NSCLC.

PMID:34894454 | DOI:10.1016/j.lungcan.2021.11.010

Ophthalmic Physiol Opt. 2021 Dec 11. doi: 10.1111/opo.12931. Online ahead of print.

ABSTRACT

PURPOSE: To expand the SyntEyes keratoconus (KTC) model to assess the Visual Image Quality (VIQ) of sphero-cylindrical spectacle and rigid contact lens corrections as keratoconus progresses.

METHODS: The previously published SyntEyes KTC eye model to determine best sphero-cylindrical spectacle and rigid contact lens correction in keratoconic eyes was expanded to include the natural progression of keratoconus, thus allowing the assessment of corrected VIQ with disease progression.

RESULTS: As keratoconus progresses, the pattern of visual Strehl ratio (VSX) in correction space for spectacles alters from a typical hourglass into a shell pattern. The former would guide the subjective refraction towards the optimal correction while the latter is relatively insensitive to large dioptric steps. In 15 out of the 20 SyntEyes, the shell pattern eventually produces two foci on different sides of the correction space separated by a clinically significant dioptric difference with a similar, albeit lower VIQ. Wearing the best possible spectacle corrections provided an average gain of up to 3.5 lines of logMAR visual acuity compared to the uncorrected cases, which increased to 5.5 lines for the best rigid contact lens correction. Continuing to wear a spectacle correction as the disease progresses often leads to a VIQ that is almost as bad as the uncorrected case. Continuing to wear a rigid contact lens correction as the disease progresses maintains a relatively high level of VIQ, albeit in the low range for typically well-corrected normal eyes.

CONCLUSIONS: The results reflect the clinical experience that subjective refraction is difficult in highly-aberrated keratoconic eyes, the benefit of spectacle correction is short lived and that rigid contact lenses provide better and more stable VIQ with disease progression. Other aspects, such as the presence and behaviour of the second focus in some cases, remain to be confirmed clinically.

PMID:34894167 | DOI:10.1111/opo.12931

Int J Cancer. 2021 Dec 11. doi: 10.1002/ijc.33893. Online ahead of print.

ABSTRACT

The increases observed in incidence and survival of oropharyngeal squamous cell carcinoma (OPSCC) have been attributed to human papillomavirus (HPV) infection, but the survival-impact of specific genotypes is poorly understood. We investigated the potential influence of HPV genotypes on survival in HPV-positive (HPV+) OPSCC. All patients with HPV+/p16+ OPSCC and available genotype data within the period 2011-2017 in Eastern Denmark were included. Descriptive statistics on clinical and tumor data, as well as overall survival (OS) and recurrence-free survival (RFS) with Cox hazard models and Kaplan-Meier plots were performed. Overall, 769 HPV+/p16+ OPSCC patients were included of which genotype HPV16 accounted for 86% (n=662). Compared to high-risk non-HPV16 genotypes (HR non-HPV16), HPV16 patients were younger at diagnosis (median years, 60 vs. 64), had a higher male to female ratio (3.7:1 vs. 2.1:1), and lower performance scores of <1 (90%, n=559, vs. 81%, n=74). Regarding 5-year OS and RFS, no difference was observed between HPV16 and HR non-HPV16 patients. Subgrouping the HR non-HPV16 group into HPV33 (n=57), HPV35 (n=26) and “other genotypes” (n=24) a significantly worse OS in the “other genotypes” group (hazard rate: 2.33, p=0.027) was shown. With similar survival results between HPV16 and non-HPV16 genotypes, genotyping in OPSCC is interesting from an epidemiological point of view as well as in vaccination programs, but not a necessary addition in prognostication of HPV+/p16+ OPSCC.

PMID:34894151 | DOI:10.1002/ijc.33893

Laryngoscope. 2021 Dec 11. doi: 10.1002/lary.29965. Online ahead of print.

ABSTRACT

INTRODUCTION: Lipoinjection is one of the available treatments for unilateral vocal fold paralysis.

OBJECTIVE: To evaluate lipoinjection predictability, and analyze the differences in safety and efficacy of the different techniques.

STUDY DESIGN: Systematic review and meta-analysis.

METHODS AND RESULTS: A systematic review on Medline, Cochrane, and Scopus databases included 49 articles analyzing the data of 1,166 patients, concerning technical details and voice parameters changes. Lipoinjection used a mean volume of 1.3 mL, 95% confidence interval (CI) (0.92, 1.69)-average overcorrection of 30%. Meta-analysis of pre- and postoperative voice parameters’ means showed a significant improvement at 6 months of mean phonation time (preoperative: 5.12, 95% CI [4.48, 5.76]-6 months: 10.46, 95% CI [9.18, 11.75]), Jitter (preoperative: 2.71, 95% CI [2.08, 3.33])-6 months: 1.37, 95% CI [1.05, 1.70]), Shimmer (preoperative: 4.55, 95% CI [3.04, 6.07]-6 months: 2.57, 95% CI [1.69, 3.45]), grade (preoperative: 2.15, 95% CI [1.73, 2.57]-6 months: 0.12, 95% CI [0.97, 1.43]), breathiness (preoperative: 2.012, 95% CI [1.48, 2.55]-6 months: 0.99, 95% CI [0.58, 1.40]), and asthenia (preoperative: 1.90, 95% CI [1.33, 2.47]-6 months: 0.75, 95% CI [0.17, 1.33]) of GRBAS (Grade, Roughness, Breathiness, Asthenia and Strain), and Voice Handicap Index-30 (preoperative: 72.06, 95% CI [54.35, 89.76]-6 months: 26.24, 95% CI [19.58, 32.90]). Subgroup analysis by harvesting technique concluded in no statistically significant difference between them. Few complications were reported. Reintervention was only required for 86 patients.

CONCLUSION: Lipoinjection seems a safe therapeutic option for unilateral vocal fold paralysis, with available data showing an efficacy lasting 6 months to 1 year. Laryngoscope, 2021.

PMID:34894158 | DOI:10.1002/lary.29965

J Burn Care Res. 2021 Nov 19:irab227. doi: 10.1093/jbcr/irab227. Online ahead of print.

ABSTRACT

Burn injuries are among the most traumatic incidences which could be associated with substantial morbidity and mortality. The incidence of these injuries differs based on population socioeconomic characteristics. In this study, we aim to evaluate the distribution of burn injuries based on socioeconomic and causative factors. Relative features from the targeted population were obtained and evaluated. Data were extracted in August 2019 and statistical analysis of the data was conducted from February 2020 to April 2020. This cross-sectional record-based study was conducted from 2008 to 2016 in a main referral center for burn injuries in the southern Iran. Participants included burn survivors and burn patients who were registered as outpatients or inpatients. A total of 4919 burn cases with a mean age of 31.91 ± 17.33, including 2926 (59.5%) males and 1993 (40.5%) females was reported. The majority of our cases had an educational level of under diploma (40.72%). A significant correlation between age, gender, and percentage of burn with the level of education was recorded (P < .001). The most frequent cause of burn injuries was flame with 2537 (51.9%) cases. The most susceptible population to burn injuries were reported to be poorly educated individuals, which emphasizes the preventive role of education.

PMID:34894143 | DOI:10.1093/jbcr/irab227

J Chromatogr Sci. 2021 Dec 11:bmab131. doi: 10.1093/chromsci/bmab131. Online ahead of print.

ABSTRACT

An isocratic reversed-phase high performance liquid chromatographic method has been developed and validated to simultaneously determine nicotinic acid, pravastatin sodium, rosuvastatin calcium, atorvastatin calcium, pitavastatin calcium, lovastatin sodium and simvastatin sodium in focus on counterfeit drug detection. Thin-layer chromatography, nuclear magnetic resonance and mass spectrometry have been additionally performed to verify the identification of adulterants of counterfeit herbal medicines. Chromatographic separation was carried out on Inertsil® ODS-3 C18 (4.6 × 150 mm, 5 μm) with isocratic mobile phase elution containing a mixture of acetonitrile: methanol: 25 mM potassium dihydrogen phosphate buffer, pH 2.86 adjusted with 0.1 M o-phosphoric acid (48: 30: 22, v/v/v), at a flow rate of 1 mL/min and with UV detection at 238 nm. The design of experiment methodology, Plackett-Burman and Box-Behnken designs, was used to screen and optimize the mobile phase composition. The validation of the method was also carried out under the International Conference on Harmonization guidelines. The developed method was sensitive, accurate, simple, economical and highly robust, in addition to the comprehensiveness and novelty of this method for separating the seven drugs. The results were statistically compared with the reference methods used Student’s t-test and variance ratio F-test at P < 0.05.

PMID:34894146 | DOI:10.1093/chromsci/bmab131

Physiol Rep. 2021 Dec;9(23):e15141. doi: 10.14814/phy2.15141.

ABSTRACT

We conducted a meta-analysis to synthesize the best available evidence comparing cardiac biventricular structure and function using cardiac magnetic resonance imaging (CMR) and transthoracic echocardiography (TTE) in elite female athletes and healthy controls (HC). Chronic exposure to exercise may induce cardiac chamber enlargement as a means to augment stroke volume, a condition known as the “athlete’s heart.” These changes have not been clearly characterized in female athletes. Multiple databases were searched from inception to June 18, 2019. Outcomes of interest included left ventricular (LV) and right ventricular (RV) dimensional, volumetric, mass, and functional assessments in female athletes. Most values were indexed to body surface area. The final search yielded 22 studies, including 1000 female athletes from endurance, strength, and mixed athletic disciplines. CMR-derived LV end-diastolic volume (LVEDV) and RV end-diastolic volume (RVEDV) were greater in endurance athletes (EA) versus HC (17.0% and 18.5%, respectively; both p < 0.001). Similarly, TTE-derived LVEDV and RVEDV were greater in EA versus HC (16.8% and 28.0%, respectively; both p < 0.001). Both LVEF and RVEF were lower in EA versus HC, with the most pronounced difference observed in RVEF via TTE (9%) (p < 0.001). LV stroke volume was greater in EA versus HC via both CMR (18.5%) and TTE (13.2%) (both p < 0.05). Few studies reported data for the mixed athlete (MA) population and even fewer studies reported data for strength athletes (SA), therefore a limited analysis was performed on MA and no analysis was performed on SA. This evidence-synthesis review demonstrates the RV may be more susceptible to ventricular enlargement. General changes in LV and RV structure and function in female EA mirrored changes observed in male counterparts. Further studies are needed to determine if potential adverse outcomes occur secondary to these changes.

PMID:34894105 | DOI:10.14814/phy2.15141

Influenza Other Respir Viruses. 2021 Dec 10. doi: 10.1111/irv.12936. Online ahead of print.

ABSTRACT

BACKGROUND: Human respiratory syncytial virus (RSV) is one of the leading causes of respiratory infections, especially in infants and young children. Previous RSV sequencing studies have primarily focused on partial sequencing of G gene (200-300 nucleotides) for genotype characterization or diagnostics. However, the genotype assignment with G gene has not recapitulated the phylogenetic signal of other genes, and there is no consensus on RSV genotype definition.

METHODS: We conducted maximum likelihood phylogenetic analysis with 10 RSV individual genes and whole-genome sequence (WGS) that are published in GenBank. RSV genotypes were determined by using phylogenetic analysis and pair-wise node distances.

RESULTS: In this study, we first statistically examined the phylogenetic incongruence, rate variation for each RSV gene sequence and WGS. We then proposed a new RSV genotyping system based on a comparative analysis of WGS and the temporal distribution of strains. We also provide an RSV classification tool to perform RSV genotype assignment and a publicly accessible up-to-date instance of Nextstrain where the phylogenetic relationship of all genotypes can be explored.

CONCLUSIONS: This revised RSV genotyping system will provide important information for disease surveillance, epidemiology, and vaccine development.

PMID:34894077 | DOI:10.1111/irv.12936

Nurs Open. 2021 Dec 10. doi: 10.1002/nop2.1133. Online ahead of print.

ABSTRACT

BACKGROUND: Diabetes is a serious medical condition that may cause blindness, renal failure and amputation of the lower limbs, stroke and myocardial infarction. The global incidence of diabetes increases continuously. The self-management of diabetes can be problematic and burdensome, especially if employed individuals choose not to reveal their illness. The workplace has been highlighted as an important element that may impact how employed individuals, diagnosed with diabetes and managed their illness.

AIM: To describe the influence of diabetes disclosure on the cognitive, physical ability and diabetes self-management of employed adults with diabetes in Saudi Arabia.

DESIGN: A descriptive correlational study.

METHODS: This study used a self-administered questionnaire, including the Checklist Individual Strength and Perceived Diabetes Self-Management Scale, for data collection. The sample size was 250 employed adults with diabetes. The data were analysed using descriptive statistics, Spearman’s correlation coefficient and bivariate analysis.

RESULTS: A significant correlation was found between diabetes self-management and support from co-workers (r = .55, p < .05), and the employees who received more support from their co-workers were able to perform diabetes self-management. The results also indicate that employees who received support at their workplace reported improved concentration, motivation and activity (r = .41, p < .05).

CONCLUSION: It is essential for top management and policymakers to implement supportive programmes in the workplace, and considering a constant, not rotating, work schedule.

PMID:34894099 | DOI:10.1002/nop2.1133

J Cell Mol Med. 2021 Dec 10. doi: 10.1111/jcmm.17093. Online ahead of print.

ABSTRACT

Metastasis contributes to treatment failure in nasopharyngeal carcinoma (NPC) patients. Our study aimed at elucidating the role of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in NPC metastasis and the underlying mechanism involved. IGF2BP3 expression in NPC was determined by bioinformatics, quantitative polymerase chain reaction and immunohistochemistry analyses. The biological function of IGF2BP3 was investigated by using in vitro and in vivo studies. In this study, IGF2BP3 mRNA and protein levels were elevated in NPC tissues. In addition, IGF2BP3 exerted an oncogenic role by promoting epithelial-mesenchymal transition (EMT), thereby inducing NPC cell migration and invasion. Further studies revealed that IGF2BP3 regulated the expression of key regulators of EMT by activating AKT/mTOR signalling, thus stimulating NPC cell migration and invasion. Remarkably, targeting IGF2BP3 delayed NPC metastasis through attenuating p-AKT and vimentin expression and inducing E-cadherin expression in vivo. Moreover, IGF2BP3 protein levels positively correlated with distant metastasis after initial treatment. Importantly, IGF2BP3 expression served as an independent prognostic factor in predicting the overall survival and distant metastasis-free survival of NPC patients. This work identifies IGF2BP3 as a novel prognostic marker and a new target for NPC treatment.

PMID:34894048 | DOI:10.1111/jcmm.17093