Tag: statistics

Eur J Cancer. 2021 Aug 6;155:127-135. doi: 10.1016/j.ejca.2021.06.034. Online ahead of print.

ABSTRACT

BACKGROUND: This study was designed to demonstrate the non-inferiority (NI) in overall survival (OS) of suspension of androgen deprivation therapy (ADT) versus maintenance and intermittent versus continuous docetaxel administration in metastatic castration-resistant prostate cancer (mCRPC) patients.

PATIENTS AND METHODS: mCRPC patients were randomised to first-line docetaxel with maintenance or suspension of ADT. Patients attaining a prostate-specific antigen (PSA) response after four chemotherapy cycles underwent second randomisation to receive continuous or intermittent docetaxel therapy. Six hundred patients were to be randomised to achieve 80% statistical power to demonstrate an NI hazard ratio (HR) of 1.25 of interruption versus maintenance of ADT.

RESULTS: The trial was prematurely closed when 198 participants were randomised. OS was similar in patients who continued (N = 96) versus those who interrupted (n = 102) ADT during docetaxel therapy (HR 0.98, 95% confidence interval [CI] 0.72-1.33] and those on a continuous (N = 35) versus an intermittent (N = 42) docetaxel schedule (HR 0.86, 95% CI 0.55-1.43). No difference in radiological progression-free survival, PSA response, or toxicity was observed between the study arms. The actual NI hazard margins of OS in Arms A and B patients were 1.33 and 1.43, respectively.

CONCLUSIONS: This trial enrolled one-third of the planned patients; this main weakness dramatically limits the interpretation of the results. ADT discontinuation and switching to an intermittent schedule did not seem to affect docetaxel efficacy. The absence of testosterone recovery in the majority of patients could have been a contributory factor. In men with mCRPC, ADT discontinuation should only be done with regular biochemical and clinical monitoring, with the option of quickly restarting ADT at disease progression.

PMID:34371442 | DOI:10.1016/j.ejca.2021.06.034

Sci Total Environ. 2021 Aug 2;799:149408. doi: 10.1016/j.scitotenv.2021.149408. Online ahead of print.

ABSTRACT

Rapid and accurate delineation of contaminated sediments in marine environments is critical for the effective assessment of site risks and the development of appropriate remedial action plans. In this study, a new application of the ultraviolet optical screening tool (UVOST) equipped with electrical conductivity measurement (UVOST-EC) is proposed to delineate a water-covered sediment contaminated with dioxins and furans in a decommissioned pulp and paper wastewater stabilization basin. Bench scale experiments are presented that were used to develop a UVOST-EC interpretation method for delineating between two different sediment types present in the basin: an anthropogenically derived organic rich contaminated sediment (“black sediment”) and a naturally occurring grey organic silt sediment with marine provenance (“grey sediment”). The method involves comparative analysis of fluorescence and electrical conductivity signatures between the two sediments. Results indicate that each sediment type presents unique “signatures” related to fluorescence and electrical signals which corresponds to variability in their physio-chemical structure. Almost 100 UVOST-EC tests performed at the study site were paired with ex situ physical gravity core measurements of the black sediment to test the accuracy of the UVOST-EC-based method. A statistical analysis at seven sample “cluster” sites (i.e. multiple sub-samples within a defined area) indicated that the mean of sediment thickness obtained by the UVOST-EC measurement technique at a given site were not significantly different (p = 0.05) from measurements derived from sediment gravity core measurements. The UVOST-EC-based sediment thickness delineation method reliably determined the thickness of the dioxin and furan contaminated sediments as compared to gravity core determination for the sediment in this study. Application of this approach to other studies should be assessed in a similar manner. The UVOST-EC method offers health and safety, cost, logistics, and data interpretation benefits.

PMID:34371404 | DOI:10.1016/j.scitotenv.2021.149408

ESMO Open. 2021 Aug 6;6(4):100229. doi: 10.1016/j.esmoop.2021.100229. Online ahead of print.

ABSTRACT

BACKGROUND: Licensed systemic treatment options for platinum-sensitive recurrent ovarian cancer are platinum-based chemotherapy and maintenance treatment with bevacizumab and poly (ADP-ribose) polymerase inhibitors. For platinum-resistant disease, several non-platinum options are available. We aimed to assess the clinical benefit of these treatments according to the European Society of Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS).

MATERIALS AND METHODS: A PubMed search was carried out including all studies evaluating systemic treatment of recurrent epithelial ovarian cancer, from 1990 onwards. Randomised trials with an adequate comparator and design showing a statistically significant benefit of the study arm were independently scored by two blinded observers using the ESMO-MCBS.

RESULTS: A total of 1127 papers were identified, out of which 61 reported results of randomised trials of sufficient quality. Nineteen trials showed statistically significant results and the studied treatments were graded according to ESMO-MCBS. Only three treatments showed substantial benefit (score of 4 on a scale of 1-5) according to the ESMO-MCBS: platinum-based chemotherapy with paclitaxel in the platinum-sensitive setting and the addition of bevacizumab to chemotherapy in the platinum-resistant setting. The WEE1 inhibitor adavosertib (not licensed) also scores a 4, based on a recent small phase II study. Assessment of quality-of-life data and toxicity using the ESMO-MCBS showed to be complex, which should be taken into account in using this score for clinical decision making.

CONCLUSION: Only a few licensed systemic therapies for recurrent ovarian cancer show substantial clinical benefit based on ESMO-MCBS scores. Trials demonstrating overall survival benefit are sparse.

PMID:34371383 | DOI:10.1016/j.esmoop.2021.100229

Sex Med. 2021 Aug 6;9(5):100402. doi: 10.1016/j.esxm.2021.100402. Online ahead of print.

ABSTRACT

INTRODUCTION: Female sexual dysfunction (FSD) is a common public health issue. Most studies, especially in the sub-Saharan region are typically carried out in the older married female population, but the post-secondary education period is crucial for the development of the sexuality of young women. Poor awareness and management of FSD may lead to adverse physical and psychosocial complications later on in the lives of these women.

AIM: To determine the prevalence of the risk of having FSD and the factors associated with having FSD among sexually active students of the University of Buea.

METHODS: This was a cross-sectional study carried out in the University of Buea involving 405 sexually active students; 16 years of age and above. Quantitative data on sociodemographic, biological, interpersonal and psychosocial characteristics were collected. A validated Japanese modified version of the Female Sexual Function Index (FSFI-J) was used to assess the risk of having female sexual dysfunction. Data analysis involved descriptive statistics, binary and multivariate logistic analyses.

MAIN OUTCOME MEASURES: Prevalence of risk of having FSD and its associated factors among students of the University of Buea.

RESULTS: A total of 171 (42.0%) out of 405 students showed a risk of having at least one form of FSD. The commonest forms of dysfunction were problems of sexual pain (46.9%), orgasm (42.0%), desire (29.1%) and arousal (21.2%). Participants who were unmarried but in a relationship (P = .002) were less likely to experience FSD. Lower levels of education (first year [P = .005], second year [P = .001]), having a history of sexual assault (P = 0.012) and poor health (P = .012) were all independently associated with a higher risk of having FSD.

CONCLUSION: The prevalence of students at risk of having FSD was high with 4 out of every 10 students showing a risk of having at least one form. Lower levels of education, having a history of sexual assault and poor health were independent risk factors of FSD. Being unmarried but in a relationship was the sole protective factor against FSD. Halle-Ekane GE, Timti LF, Tanue EA, Ekukole CM, Yenshu EV. Prevalence and Associated Factors of Female Sexual Dysfunction Among Sexually Active Students of the University of Buea. Sex Med 2021;XX:XXXXXX.

PMID:34371387 | DOI:10.1016/j.esxm.2021.100402

J Trace Elem Med Biol. 2021 Aug 2;68:126833. doi: 10.1016/j.jtemb.2021.126833. Online ahead of print.

ABSTRACT

BACKGROUND: The present study focuses on the evaluation of potential relationships between trace elements and acute and chronic types of leukemia, via the determination of their levels in human blood serum.

METHODS: A total of 199 serum samples from a Greek cohort were examined, including both leukemia cases and controls. Elements’ analysis was carried out using inductively coupled plasma mass spectrometry (ICP-MS) and demographic features such as age, gender, smoking habits and area of residence were recorded and statistically treated applying Shapiro-Wilk, Kolmogorov-Smirnov, Mann Whitney and Kruskal Wallis tests (p < 0.05). Spearman correlation and principal component analysis (PCA) were also performed to investigate possible associations.

RESULTS: The results demonstrated significantly higher (p < 0.05) trace elements concentrations in cases’ serum compared to that of controls excluding Ba, with Cu (median concentration 1295 μg L^-1) being the most abundant in cases. Additionally, concentration of toxic Pb and Cd were found at seven and four fold higher concentrations in cases, respectively. Among the trace elements examined, only Rb (164 μg L^-1) was detected in higher concentrations in controls. Ba, Cd and Co presented the lowest concentrations (lower than 1 μg L^-1). PCA was performed for overall and classified data, indicating a stronger relation among the toxic As, Cd, Ni and Pb in cases than controls, particularly referring to smokers and industrial sites’ residents. Hematological parameters and factors such as age and gender did not present any significant outcome or correlation.

CONCLUSIONS: The findings from this pilot study suggest a potential relationship between metals and leukemia, especially concerning the toxic ones. Results from the employed source apportionment tools imply that smoking and atmospheric degradation may be positively related with higher metal serum levels in leukemia patients.

PMID:34371329 | DOI:10.1016/j.jtemb.2021.126833

Econ Hum Biol. 2021 Jul 24;43:101049. doi: 10.1016/j.ehb.2021.101049. Online ahead of print.

ABSTRACT

OBJECTIVE: To estimate whether becoming widowed had a significant effect on individual’s health status as well as on healthcare and non-healthcare resources use, compared to people who remained in a couple in Europe.

DATA AND METHOD: It was used the Survey of Health, Aging and Retirement in Europe from 2004 to 2015. The statistical technique used was genetic matching which analysed the differences in wellbeing, mental health, health status, risk of death, health care resources and long-term care utilization of people who have become widowed, comparing with people who remained married or with a partner. We considered shortterm and medium-term effects.

RESULTS: In the short term, those who became widowed had a worse wellbeing and mental health, in addition to a greater probability of receiving formal care and informal care from outside the household. There seems to be a significant effect in the use of formal and informal care from outside the household in the medium term.

CONCLUSIONS: The results might help to concentrate a major effort of any policy or strategy, not only in the field of health but also in the provision of long-term care, immediately after the negative shock occurs.

PMID:34371339 | DOI:10.1016/j.ehb.2021.101049

Lung Cancer. 2021 Jul 20;160:17-27. doi: 10.1016/j.lungcan.2021.07.008. Online ahead of print.

ABSTRACT

OBJECTIVES: Immune checkpoint inhibition after radiochemotherapy (RTCT) has become a new standard of care for locally advanced non-small cell lung cancer with programmed death-ligand 1 (PD-L1) expression. However, little is known about the prognostic role of immune response markers in this setting. We analysed PD-L1 expression and tumour infiltrating lymphocytes (TiLs) in tumour biopsies from the multicenter German Intergroup Lung Trial (GILT), which previously randomised patients with stage III NSCLC to RTCT with or without consolidation chemotherapy.

MATERIALS AND METHODS: We retrospectively analyzed tumour biopsies from patients treated in the GILT trial. PD-L1 expression was analysed using the Ventana SP263 assay and TiL score (low, intermediate, high) and pattern (excluded, inflamed, desert) were assessed. The primary endpoint of the biomarker analysis was PFS in patients with PD-L1 ≥ 1% vs. PD-L1 < 1% NSCLC. Secondary endpoints explored the prognostic relevance of additional PD-L1 expression levels and TiL score and pattern.

RESULTS: Biopsies were available from 92 patients treated with RTCT. Patients with available tumor tissue did not differ significantly from the whole study population. PD-L1 scores from 78 samples were available for analysis. There was no difference in PFS in the PD-L1 < 1% vs. PD-L1 ≥ 1% subgroups. TiL score was available in 66 patients. Patients with high TiL score showed favourable overall survival compared to the low TiL subgroup. This trend was most pronounced in those patients treated with consolidative chemotherapy.

CONCLUSION: In this analysis, PD-L1 expression did not correlate with PFS following RTCT. However, patients with TiLs > 10% were found to have longer overall survival, especially for those patients treated with consolidation chemotherapy after the end of RTCT. Further analyses to explore the prognostic and predictive relevance of TiLs in the context of consolidative checkpoint inhibition with durvalumab are required.

PMID:34371299 | DOI:10.1016/j.lungcan.2021.07.008

Microbiol Res. 2021 Jul 31;251:126836. doi: 10.1016/j.micres.2021.126836. Online ahead of print.

ABSTRACT

The concern regarding the emergence of phytopathogens strains which are resistant to conventional agrochemicals has given support to the search for alternatives on the use of chemical pesticides in agriculture. In this context, microorganisms are considered as promising sources of useful natural compounds and actinobacteria are particularly relevant since they are known to produce several bioactive metabolites. The objective of this work was to investigate the production of secondary metabolites with antifungal activity by a strain of the actinobacteria Streptomyces lunalinharesii (A54A) under axenic conditions and in co-cultivation with the phytopathogen Rhizoctonia solani. Tests to evaluate antifungal activity of the extracts indicated the presence of diffusable molecules capable of inhibiting the growth of R. solani produced by S. lunalinharesii, especially when in the presence of the fungus during fermentation. Metabolomic analyzes allowed the putative annotation of the bioactive compounds desferrioxamine E and anisomycin, in addition to the evaluation of the metabolic profile of the isolate when grown in axenic mode and in co-cultivation, while statistical analyzes enabled the comparison of such profiles and the identification of metabolites produced in greater relative quantities in the elicitation condition. Such methodologies provided the selection of unknown features with high bioactive potential for dereplication, and several metabolites of S. lunalinharesii possibly represent novel compounds.

PMID:34371303 | DOI:10.1016/j.micres.2021.126836

Tuberculosis (Edinb). 2021 Aug 5;130:102118. doi: 10.1016/j.tube.2021.102118. Online ahead of print.

ABSTRACT

BACKGROUND: There is an urgent need for new, accurate, rapid, and affordable tuberculosis (TB) diagnostic tests. The aim of the present study was to use mass spectrometry to identify new preliminary candidate TB diagnostic protein biomarkers in saliva obtained from individuals with TB, and patients with other respiratory diseases (ORD).

METHODS: Saliva samples were collected from 22 individuals who self-presented with symptoms suggestive of TB as part of a larger TB biomarker project. Purified salivary proteins were subjected to tryptic digestion peptides were analyzed using a QExactive Orbitrap Mass Spectrometer. Data are available via ProteomeXchange with identifier PXD027294. Identified proteins were subjected to gene ontology and ingenuity pathway analysis for functional enrichment analysis.

RESULTS: 26 of the 652 identified proteins significantly discriminated individuals with TB from those with ORD after Benjamini Hochberg correction (5% FDR), with five of these proteins diagnosing TB with an AUC ≥ 0.80. A 5-protein biosignature comprising of P01011, Q8NCW5, P28072, A0A2Q2TTZ9, and Q99574 diagnosed TB with an AUC of 1.00 (95% CI, 1.00-1.00), sensitivity of 100% (95% CI, 76.2-100%) and specificity of 90.9% (95% CI, 58.7-99.8%) after leave-one-out cross validation.

CONCLUSIONS: We identified novel candidate salivary protein biomarkers and biosignatures with strong potential as TB diagnostic candidates. Our results are preliminary and require validation in larger studies.

PMID:34371310 | DOI:10.1016/j.tube.2021.102118

Mult Scler Relat Disord. 2021 Aug 2;55:103185. doi: 10.1016/j.msard.2021.103185. Online ahead of print.

ABSTRACT

BACKGROUND: We previously reported that the single nucleotide polymorphism (SNP) rs9282860 in serine threonine kinase 11 (STK11) gene which codes for liver kinase B1 (LKB1) has higher prevalence in White relapsing-remitting multiple sclerosis (RRMS) patients than controls. However it is not known if this SNP is a risk factor for MS in other populations.

METHODS: We assessed the prevalence of the STK11 SNP in samples collected from African American (AA) persons with MS (PwMS) and controls at multiple Veterans Affairs (VA) Medical Centers and from a network of academic MS centers. Genotyping was carried out using a specific Taqman assay. Comparisons of SNP frequencies were made using Fisher’s exact test to determine significance and odds ratios. Group means were compared by appropriate t-tests based on normality and variance using SPSS V27.

RESULTS: There were no significant differences in average age at first symptom onset, age at diagnosis, disease duration, or disease severity between RRMS patients recruited from VAMCs versus non-VAMCs. The SNP was more prevalent in AA than White PwMS, however only in secondary progressive MS (SPMS) patients was that difference statistically significant. AA SPMS patients had higher STK11 SNP prevalence than controls; and in that cohort the SNP was associated with older age at symptom onset and at diagnosis.

CONCLUSIONS: The results suggest that the STK11 SNP represents a risk factor for SPMS in AA patients, and can influence both early (onset) and later (conversion to SPMSS) events.

PMID:34371271 | DOI:10.1016/j.msard.2021.103185