Tag: statistics

J Manag Care Spec Pharm. 2021 Dec 16:1-10. doi: 10.18553/jmcp.2021.21310. Online ahead of print.

ABSTRACT

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in the United States. Several anaplastic lymphoma kinase (ALK) rearrangement inhibitors have been approved for the treatment of metastatic ALK-positive nonsmall cell lung cancer (NSCLC). Effective disease management requires an understanding of how these treatments are used in clinical practice, since low treatment adherence and/or early discontinuation have been associated with poor patient outcomes. Owing to the recency of approvals, real-world data on the use of ALK inhibitors in patients with ALKpositive NSCLC are currently limited; this represents a notable gap in our understanding of ALK treatment use. OBJECTIVE: To assess real-world adherence and persistence with ALK inhibitors in patients with ALK-positive NSCLC. METHODS: This retrospective observational study used US commercial claims for patients aged at least 18 years with lung cancer receiving ALK inhibitors (alectinib, brigatinib, ceritinib, crizotinib) between July 1, 2015, and December 31, 2018. Patients’ first and any subsequent ALK inhibitor uses were categorized into ALK inhibitor-naive and ALK inhibitor-pretreated cohorts, respectively. Adherence was measured by medication possession ratio and persistence by time from treatment initiation to discontinuation (earliest of a treatment switch or greater than a 60-day gap). Descriptive statistics were used to summarize patient characteristics. Cohort comparisons were made using chi-square tests and t-tests. Persistence and time to next ALK inhibitor were analyzed using Kaplan-Meier methods and the log-rank test. Poisson and Cox regression models of adherence and persistence, respectively, were applied to compare ALK inhibitors. RESULTS: We identified 1,482 patients treated with alectinib (n = 445) or crizotinib (n = 1,037) in the ALK inhibitor-naive cohort; 604, 142, and 134 patients received alectinib, brigatinib, or ceritinib in the ALK inhibitor-pretreated cohort. Adherence during the treatment period (95%-97%) and the proportion of patients with a medication possession ratio of at least 0.8 (92%-95%) were similar for all ALK inhibitors. In the ALK inhibitor-naive cohort, median time to treatment discontinuation with alectinib and crizotinib was 27.1 and 8.8 months, respectively; patients receiving alectinib were 46% less likely to discontinue than patients receiving crizotinib (adjusted hazard ratio [aHR] [95% CI]: 0.54 [0.44-0.65]; P < 0.0001). In the ALK inhibitor-pretreated cohort, the discontinuation risk for alectinib was 64% lower than for ceritinib (aHR [95% CI]: 0.36 [0.27-0.49]; P < 0.0001) and 34% lower than for brigatinib (aHR [95% CI]: 0.66 [0.42-1.02]; P = 0.062). CONCLUSIONS: To our knowledge, this study is the first to address a current research gap by assessing real-world adherence and persistence with ALK inhibitors among patients with ALK-positive NSCLC in real-world clinical practice. Alectinib was associated with longer real-world persistence than other ALK inhibitors, despite similar adherence. Further research with more patients and longer follow-up is needed to link persistence to real-world clinical outcomes. DISCLOSURES: This study was funded by Genentech Inc. Ganti has received research support from Takeda and has provided consulting services to Genentech Inc., AstraZeneca, Flagship Biosciences, Cardinal Health, BioGene, Mirati Therapeutics, Blueprint Medicines, and G1 Therapeutics. Lin, Wong, and Ogale are employees of Genentech Inc. and may own stock in F. Hoffmann-La Roche. Yang was employed by Genentech Inc. at the time of this study. Part of the study findings were presented as a poster at the NCCN 2020 Virtual Annual Conference, April 9, 2020.

PMID:34913728 | DOI:10.18553/jmcp.2021.21310

Cancer Med. 2021 Dec 16. doi: 10.1002/cam4.4484. Online ahead of print.

ABSTRACT

BACKGROUND: Current guidelines recommend endoscopic surveillance for Barrett oesophagus (BE), but the value of surveillance is still debated. Using a combination of primary care, secondary care and cancer registry datasets, we examined the impact of a prior BE diagnosis, clinical and risk factors on survival from oesophageal cancer and adenocarcinoma.

METHODS: Retrospective cohort study of patients aged 50 and above diagnosed with malignant oesophageal cancer between 1993 and 2014 using Clinical Practice Research Datalink (CPRD). All prior BE diagnoses and endoscopies were identified from CPRD and Hospital Episode Statistics. Histology information was obtained from linked cancer registry data. We used flexible parametric models to estimate excess hazard ratios (EHRs) for relative survival. We simulated the potential impact of lead-time by adding random lead-times from a variety of distributions to all those with prior BE.

RESULTS: Among our oesophageal cancer (n = 7503) and adenocarcinoma (n = 1476) cohorts only small percentages, 3.4% and 5.3%, respectively, had a prior BE diagnosis. Two-year relative survival was better among patients with BE: 48.0% (95% CI 41.9-54.9) compared to 25.2% (24.3-26.2) without. Patients with BE had a better prognosis (EHR = 0.53, 0.41-0.68). Survival was higher even if patients with BE had fewer than two endoscopies (50.0%; 43.6-57.3). A survival benefit was still observed after lead-time adjustment, with a 20% absolute difference in 2-year survival using a 5 year mean sojourn time.

CONCLUSIONS: Patients with a prior BE diagnosis had a survival advantage. This was not fully explained by surveillance endoscopies.

PMID:34913599 | DOI:10.1002/cam4.4484

Microsc Res Tech. 2021 Dec 16. doi: 10.1002/jemt.24028. Online ahead of print.

ABSTRACT

This study compares the effect of different mouthwashes that have been recommended during the Coronavirus disease 2019 (COVID-19) pandemic on shear bond strength (SBS) of universal adhesive to enamel in regards to self-etch (SE) and etch-and-rinse (ER) modes. Flat enamel surfaces were obtained from 100 sound human maxillary central incisors. They were randomly allocated to five groups according to the different mouthwashes (no mouthwash/control [Ctrl], 0.2% chlorhexidine 1.5% hydrogen peroxide [H₂ O₂ ], 0.2% povidone-iodine [PVP-I], Listerine [L]), and adhesive application modes (ER and SE) (n = 10). After the application of a universal adhesive (single bond universal), composite resin (Filtek Z250) was bonded by a cylinder-shaped mold (height: 2 mm, diameter: 2.4 mm). They were subjected to SBS test using a universal testing machine (AGS-X, Shimadzu Corp.) (crosshead speed: 1 mm/min). The resin-enamel interfaces were observed with a scanning electron microscope (SEM). The semiquantitative chemical microanalyses were performed with energy-dispersive spectroscopy (EDS). The data were statistically analyzed by two-way analysis of variance and Bonferroni test (p < .05). In SE mode, Group Ctrl revealed significantly higher SBS than all mouthwash groups (p < .05). In ER mode, Group Ctrl showed significantly higher SBS than H₂ O₂ and PVP-I groups (p < .05). ER mode caused significantly higher SBS than SE mode in all mouthwash groups (p < .05). The SEM observations highlighted that Group Ctrl had a regular and intact hybrid layer with resin tag formation while the H₂ O₂ and PVP-I groups exhibited a thin hybrid layer in both modes. EDS analysis indicated that in SE mode, all mouthwash groups presented increased O content compared to Group Ctrl. H₂ O₂ and PVP-I that were suggested for preprocedural use during the COVID-19 pandemic, reduced the enamel bond strength of the universal adhesive in ER mode.

PMID:34913536 | DOI:10.1002/jemt.24028

Colorectal Dis. 2021 Dec 16. doi: 10.1111/codi.16020. Online ahead of print.

NO ABSTRACT

PMID:34913581 | DOI:10.1111/codi.16020

Environ Toxicol Chem. 2021 Dec 16. doi: 10.1002/etc.5273. Online ahead of print.

ABSTRACT

The post-ecdysial mineralization in crustaceans involves the deposition of carbonate salts, such as calcium carbonate, to the organic matrix. Due to the resemblance between Pb²⁺ and Ca²⁺ , this study was carried out to investigate whether Pb is incorporated into the new shell during post-ecdysial mineralization using the blue crab, Callinectes sapidus, as the model crustacean. It was hypothesized that injected Pb would be deposited in the shell via calcium transporters in the epidermis during the mineralization process. Post-ecdysial blue crabs were injected with two doses of 5 µg Pb/g wet weight each in lead acetate and then Pb, Ca and Mg content were analyzed in the exoskeleton, while only Pb bioaccumulation was quantified for the hepatopancreas, gills, muscles, and hemolymph. Results showed a statistically non-significant increase in exoskeletal Pb content in Pb-treated crabs compared to control, suggesting that exoskeletal Pb may not be a sensitive proxy for aquatic Pb pollution. There was a significant decrease in Ca content in Pb-treated crabs, suggesting that Pb hindered the deposition of Ca to crab exoskeleton, thereby obstructing calcification. A trend of decrease in exoskeletal Mg was also observed in Pb-treated crabs. There was a significant increase in Pb content found in the gills, hepatopancreas, muscle, and hemolymph in Pb-treated crabs. The rank of the Pb level amongst three soft tissues in a decreasing order is: hepatopancreas > gill > muscle. This study is the first to present evidence that Pb disrupts post-ecdysial exoskeletal calcification in a crustacean. This article is protected by copyright. All rights reserved.

PMID:34913519 | DOI:10.1002/etc.5273

Gerodontology. 2021 Dec 16. doi: 10.1111/ger.12612. Online ahead of print.

ABSTRACT

INTRODUCTION: Malnutrition and risk of malnutrition continues to be a common finding in elders, yet its association with oral function in hospitalised patients remains unclear.

MATERIAL AND METHODS: Patients aged 70 years or over who had been hospitalised for non-acute rehabilitation were recruited. Nutritional risk was screened using the Mini-Nutritional Assessment Short Form (MNA-SF) and Nutritional Risk Screening (NRS) scores. Malnutrition was assessed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria. All participants underwent the oral hypofunction test battery, evaluating oral hygiene, oral dryness, occlusal force, tongue-lip motor function, tongue pressure, masticatory and swallowing function. Statistical analyses comprised Mann-Whitney or Kruskal-Wallis tests. Bivariate associations between categorical variables were tested using the Pearson chi-square test; for continuous variables, the Spearman correlation was calculated. A P-value < .05 was considered statistically significant.

RESULTS: Sixty patients aged a mean 82.5 ± 7.0 years participated. Some 88.3% were diagnosed with oral hypofunction, and this was more common in older patients (P = .020). Analysing the 7 oral hypofunction tests as an interval variable (NiOF) revealed additional correlations with number of teeth (ρ = 0.477) as well as the nutritional risk, evaluated by the MNA-SF (ρ = -0.284) and NRS (ρ = 0.317) scores. NiOF scores were higher among denture wearers (P = .003). GLIM did not confirm the correlation with NiOF. Biomarkers such as serum albumin and CRP were not associated with the NiOF score.

CONCLUSION: In this sample, the association between oral function and nutritional state is more obvious in nutritional risk scores than in the malnutrition diagnosis by GLIM.

PMID:34913521 | DOI:10.1111/ger.12612

Artif Organs. 2021 Dec 16. doi: 10.1111/aor.14136. Online ahead of print.

ABSTRACT

Around 5% of coronavirus disease 2019 (COVID-19) patients develop critical disease, with severe pneumonia and acute respiratory distress syndrome (ARDS). In these cases, extracorporeal membrane oxygenation (ECMO) may be considered when conventional therapy fails. This study aimed to describe the clinical characteristics and in-hospital outcomes of COVID-19 patients with ARDS refractory to lung-protective ventilation and prone positioning on ECMO support, as well as to review the available literature on ECMO use and COVID-19 patients’ outcome. Patients from this case series were selected from the Brazilian COVID-19 Registry. From the 7646 patients included in the registry, only eight received ECMO support (0.1%), in four hospitals. The median age of the entire sample was 59 (interquartile range 54.2-64.4) years old and 87.5% were male. Hypertension (50.0%), diabetes mellitus (50.0%) and obesity (37.5%) were the most frequent comorbidities. The indications for ECMO were PaO₂ /FiO₂ ratio <80 mm Hg for more than 6 h or PaO₂ /FiO₂ ratio <60 mm Hg for more than 3 h. The mortality rate was 87.5%. In conclusion, in this case series of COVID-19 patients with ARDS refractory to conventional therapy who received ECMO support, a very high mortality was observed. Our findings are not different from previous studies including a small number of patients; however, there is a huge difference from Extracorporeal Life Support Organization results, which encourages us to keep looking for improvement.

PMID:34913492 | DOI:10.1111/aor.14136

J Ultrasound Med. 2021 Dec 16. doi: 10.1002/jum.15917. Online ahead of print.

ABSTRACT

OBJECTIVES: Increased ovarian stromal area (SA), stromal-to-ovarian area ratio (S/A), and echogenicity (SEcho) on ultrasonography have been proposed as diagnostic markers for polycystic ovary syndrome. Although several methods to evaluate the stroma exist, their reproducibility has not been defined which limits clinical utility. This study aimed to determine the interrater reliability and agreement of methods to evaluate SA, S/A, and SEcho.

METHODS: Five raters tested 3 methods to obtain SA and S/A, and one to obtain SEcho on 30 ovarian cineloops under two imaging conditions, simulating real-time (free-choice) or offline (fixed-frame) imaging. For SA, Method 1 subtracted follicular area from the ovarian area, Method 2 involved outlining the periphery of the stroma, and Method 3 represented a hybrid approach in which central follicles were subtracted from the outlined stroma. SEcho was scored on a subjective 3-tiered scale. Intraclass correlation coefficients (ICCs) and the coefficient of variation were determined for SA and S/A, and Fleiss’ kappa agreement statistics (κ) were determined for SEcho.

RESULTS: Interrater reliability of SA was superior using Method 1 (ICC = 0.558 and ICC = 0.705) versus Method 2 (ICC = 0.522 and ICC = 0.230) or Method 3 (ICC = 0.429 and ICC = 0.305) under free-choice and fixed-frame imaging conditions, respectively. Interrater reliability of S/A was also moderate to poor across methods. SEcho was also not reliably assessed across raters (κ = <0.500).

CONCLUSIONS: Ultrasonographic assessments of the ovarian stroma were associated with moderate to poor reproducibility. Indirect estimates of the ovarian stroma (Method 1) could be optimized to yield a reproducible approach, clarifying the clinical relevance of the stroma.

PMID:34913507 | DOI:10.1002/jum.15917

Fam Process. 2021 Dec 16. doi: 10.1111/famp.12736. Online ahead of print.

ABSTRACT

This article reports results of a study that assessed the efficacy of multiple family therapy (MFT) for helping children of depressed parent(s), using a quasi-randomized controlled trial design. In total, 76 children participated in the study, with 51 children were assigned to the experimental group (EG) and 25 to the comparison group (CG). The EG children and their parents completed the three-month MFT program, while the CG children and their parents attended two psychoeducational talks scheduled at the same time as the MFT. A group × Time repeated measure ANCOVA did not discern the intervention types having any effect on children’s lives in the post-treatment phase or at the three-month follow-up. However, the MFT brought some promising positive changes in the EG children’s perceived social support, both overall and that from the father and other family members at three-month follow-up; compared to the CG children, the EG children also attached more importance to the support from their mothers in the post-treatment phase and that from other family members at the three-month follow-up. The results implied the potential efficacy of the MFT in facilitating an increase in the overall social support of children of depressed parents and their positive interactions with both the healthy and the depressed parent and other family members. Owing to multiple statistical limitations, caution is required while interpreting the results. A larger sample and a more sophisticated research design were suggested for future studies examining the efficacy and therapeutic mechanism of the MFT.

PMID:34913487 | DOI:10.1111/famp.12736

Dan Med J. 2022 Dec 15;69(1):A05210397.

ABSTRACT

INTRODUCTION: In penile cancer, both disease and treatment may be mutilating. We examined life satisfaction in three separate groups; at penile cancer diagnosis and one and two years later.

METHODS: From 1 January 2013 to 31 December2015, Danish penile cancer patients completed the Life-Satisfaction Questionnaire-11 (LISAT-11) at diagnosis and after one year and after two years. Responders scored 11 domains of life on a six-point scale. We analysed the scores and compared scores with those of a Swedish control cohort from the literature with patients in the same age group.

RESULTS: A total of 157 individual penile cancer patients completed the LISAT-11 checklist at one point in the trajectory and were considered for this study. We observed trends towards less life satisfaction in the years after diagnosis and with increasingly mutilating surgical treatment. The differences were not statistically significant. A difference was observed between the proportion of responders scoring “satisfied” on activities of daily living between penile cancer patients and a healthy control cohort, with a higher score being recorded for the healthy controls. No other LISAT-11 domains were scored significantly different between penile cancer patients and controls.

CONCLUSIONS: Danish responders with penile cancer are less satisfied than a Swedish control cohort within the self-care domain.

FUNDING: none.

TRIAL REGISTRATION: not relevant.

PMID:34913430