Category: Statistics

Oncologist. 2021 Apr 29. doi: 10.1002/onco.13806. Online ahead of print.

ABSTRACT

BACKGROUND: Abemaciclib is a CDK4/6 inhibitor used to treat hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+, HER2-) advanced breast cancer (ABC). The prognostic value of patient-reported outcomes (PROs) have been minimally explored for treatment outcomes with CDK4/6 inhibitors. The performance of PROs compared to Eastern Cooperative Oncology Group Performance Status (ECOG-PS) is unknown.

MATERIAL AND METHODS: This study pooled data from single-arm trial, MONARCH 1, and randomized-trials, MONARCH 2 and 3. In total, 900 patients initiated abemaciclib and 384 comparator therapy. Pre-treatment PRO association with progression-free survival (PFS) was modelled using Cox proportional hazards regression. Prediction performance assessed via the C-statistic (c). PROs were recorded via the EORTC QLQ-C30.

RESULTS: Patient-reported physical function, pain, role function, fatigue and appetite loss were associated with PFS on univariable and adjusted analysis (P<0.05). Physical function (c=0.55) was most predictive, superior to ECOG-PS (c=0.54), with multivariable analysis indicating both provide independent information (P<0.02). In the pooled randomised arms of MONARCH 2 and 3, the PFS treatment benefit [HR (95% CI)] of abemaciclib (vs comparators) was 0.75 (0.57-1.0) for low physical function, compared to 0.48 (0.40-0.59) for intermediate/high (P[interaction] = 0.01).

CONCLUSION: PROs were identified as prognostic factors for PFS in patients initiating abemaciclib, with patient-reported physical function containing independent predictive information beyond ECOG-PS. Low physical function was associated with a decrease in the magnitude of PFS benefit from abemaciclib. PROs should be explored as prognostic, predictive and stratification factors for clinical use and research trials of CDK4/6 inhibitors.

IMPLICATIONS FOR PRACTICE: For the first time, pre-treatment patient-reported outcomes have been shown to be independent prognostic markers for progression-free survival (PFS) in patients diagnosed with HR+/HER2- advanced breast cancer treated with abemaciclib. Importantly, patients with low physical function had a smaller PFS benefit from abemaciclib (vs comparator) than patients with intermediate/high physical function. The present study demonstrates PROs as a simple, effective, inexpensive and independent prognostic marker for HR+/HER2- ABC patients treated with abemaciclib.

PMID:33914991 | DOI:10.1002/onco.13806

Int J Clin Pract. 2021 Apr 29:e14276. doi: 10.1111/ijcp.14276. Online ahead of print.

ABSTRACT

OBJECTIVES: Helicobacter pylori is a major cause of gastritis and a potential trigger of inflammatory disease. The effect of Helicobacter pylori infection on distal femoral cartilage has yet to be evaluated. The aim of this study was to evaluate femoral cartilage thickness in patients with helicobacter pylori infection and whether Helicobacter pylori infection affects femoral cartilage thickness.

METHODS: This cross-sectional study included 199 patients. To measure the thickness of femoral articular cartilage, 99 patients with Helicobacter pylori infections and 100 Helicobacter pylori negative controls were enrolled into two groups. The measurements were made using a linear probe ultrasonography with the patients in supine positions and their knees in maximum flexion. Demographic, clinical, endoscopic, and laboratory data were collected for all patients.

RESULTS: Both the right and left medial femoral condyles had thinner cartilage thickness in the Helicobacter pylori positive group than in the Helicobacter pylori negative group (p=0.016, p=0.036). For the intercondylar area and lateral femoral condyles, although the Helicobacter pylori positive patients had thinner femoral cartilage thickness than the Helicobacter pylori negative individuals for both extremities, this finding was not statistically significant (p>0.05).

CONCLUSION: Femoral cartilage was thinner in patients with Helicobacter pylori than patients without Helicobacter pylori for right and left medial femoral condyles. This study suggests that Helicobacter pylori infections may affect femoral cartilage thickness and potentially increase the risk of cartilage degeneration.

PMID:33914992 | DOI:10.1111/ijcp.14276

Int J Clin Pract. 2021 Apr 29:e14278. doi: 10.1111/ijcp.14278. Online ahead of print.

ABSTRACT

AIM: In this study, we aimed to evaluate the anxiety and depression status of prostate cancer (PCa) patients whose planned operations in the urology clinic of our hospital, which is serving as a pandemic hospital in Turkey have been postponed due to the coronavirus disease 2019 pandemic.

METHODS: This survey study was conducted at urology clinic of Ankara City Hospital between March 1 and June 1, 2020 and included 24 male patients who agreed to answer the questionnaires (State-Trait Anxiety Inventory [STAI] I and II and Beck Depression Inventory [BDI]). Demographical and clinical data (age, time since diagnosis, total serum prostate specific antigen (PSA) levels, risk groups according to the D’Amico classification system, smoking, alcohol habitus, major surgical history, and comorbidities) of the patients were collected from hospital software.

RESULTS: The mean STAI-I score of the patients (46.7 ± 1.4 [44-49]) was significantly higher than their STAI-II score (41.7 ± 2.4 [39-47]) (p < 0.001). The negative correlation between the decrease in age and STAI-I score was found to be statistically significant (r = 0.439, p < 0.05). The mean BDI score of the patients was 4.3 ± 3.2 (0-13), which was compatible with mild depression. There was no statistically significant difference between the time elapsed from diagnosis, PSA levels, smoking and alcohol habitus, major surgical history and comorbidity status, and STAI-I, STAI-II, and BDI scores (p > 0.05).

CONCLUSION: Prostate cancer patients with postponed operations should be guided properly in order to manage their anxiety status especially young patients.

PMID:33914983 | DOI:10.1111/ijcp.14278

Glob Chang Biol. 2021 Apr 29. doi: 10.1111/gcb.15661. Online ahead of print.

ABSTRACT

While wetlands are the largest natural source of methane (CH₄ ) to the atmosphere, they represent a large source of uncertainty in the global CH₄ budget due to the complex biogeochemical controls on CH₄ dynamics. Here we present, to our knowledge, the first multi-site synthesis of how predictors of freshwater wetland CH₄ fluxes (FCH4) vary across wetland types at diel, multiday (synoptic), and seasonal time scales. We used several statistical approaches (correlation analysis, generalized additive modeling, mutual information, random forests) in a wavelet-based multiresolution framework to assess the importance of environmental predictors, nonlinearities and lags on FCH4 across 23 eddy covariance sites. Seasonally, soil and air temperature were dominant predictors of FCH4 at sites with smaller seasonal variation in water table depth (WTD). In contrast, WTD was the dominant predictor for wetlands with smaller variations in temperature (e.g., seasonal tropical/subtropical wetlands). Changes in seasonal FCH4 lagged fluctuations in WTD by ~17 ± 11 days, and lagged air and soil temperature by median values of 8 ± 16 and 5 ± 15 days, respectively. Temperature and WTD were also dominant predictors at the multiday scale. Atmospheric pressure (PA) was another important multiday scale predictor for peat dominated sites, with drops in PA coinciding with synchronous releases of CH₄ . At the diel scale, synchronous relationships with latent heat flux and vapor pressure deficit suggest that physical processes controlling evaporation and boundary layer mixing exert similar controls on CH₄ volatilization, and suggest the influence of pressurized ventilation in aerenchymatous vegetation. In addition, 1-4 hour lagged relationships with ecosystem photosynthesis indicate recent carbon substrates, such as root exudates, may also control FCH4. By addressing issues of scale, asynchrony, and nonlinearity, this work improves understanding of the predictors and timing of wetland FCH4 that can inform future studies and models, and help constrain wetland CH₄ emissions.

PMID:33914985 | DOI:10.1111/gcb.15661

J Eur Acad Dermatol Venereol. 2021 Apr 29. doi: 10.1111/jdv.17315. Online ahead of print.

ABSTRACT

BACKGROUND: In a European study on contact allergy in the general population, it has been hypothesized that the combination of contact allergy to a fragrance together with a history indicating dermatitis at exposure and thereafter subsequent avoidance of scented products implied a diagnosis of allergic contact dermatitis.

OBJECTIVES: The primary aim of this study was to validate this hypothesis/algorithm. The secondary aim was to investigate whether there was any association between the outcome of the ROAT and the patch test reactivity.

METHODS: 109 subjects with and without contact allergy to fragrance mix II (FM II) were recruited. Volunteers from 6 European dermatology clinics participated in the study including a patch test and a ROAT.

RESULTS: 24 positive ROAT reactions were noted in total including 20 of those 32 with contact allergy to FM II. None of the volunteers reacted to the vehicle (p<0.001). More individuals with a positive algorithm had positive ROATs when compared with those with a negative algorithm. However, the difference was not statistically significant (p=0.12). The lower the patch test concentration eliciting a positive test reaction, the more likely was a positive ROAT and the more likely that the positive ROAT appeared early during the investigative period.

CONCLUSIONS: The algorithm used in this study was not validated but it was indicated in this ROAT setup. The stronger the patch test reactivity the more likely was a positive ROAT and the more likely it was that the positive ROAT appeared early during the application period.

PMID:33914959 | DOI:10.1111/jdv.17315

J Eur Acad Dermatol Venereol. 2021 Apr 29. doi: 10.1111/jdv.17312. Online ahead of print.

ABSTRACT

BACKGROUND: Aquagenic Wrinkling of the Palms (AWP) is an excessive and early palmar wrinkling occurring after Brief Immersion to Water (BIW), and has been reported as a frequent finding among Cystic Fibrosis (CF) patients.

OBJECTIVES: To evaluate and assess the diagnostic performance of BIW test as an initial screening tool for CF diagnosis.

METHODS: We measured AWP in CF patients, CF-heterozygotes (CF-het) and normal controls. The AWP parameters of palmar wrinkling, oedema, papules, pruritus and pain were assessed at 3, 7, 11 mins after a BIW test was performed for all the participants. Statistical analyses explored the progression of AWP in time for the three groups and assessed the diagnostic performance of BIW test as a diagnostic screening tool for CF.

RESULTS: A total of 250 individuals (100 CF patients, their 50 CF-het parents, 100 healthy controls) were included in the analysis. The average age in years (mean±SD) was 10.4 ± 4.0 for CF, 35.9 ± 6.1 for CF-het and 10.5 ± 4.0 for Controls. The rate of positives for AWP at 3 minutes among CF patients, CF-het and controls was 68%, 8% and 0% respectively (p< 0.01). Kaplan Meier analysis showed a clear trend towards earlier appearance of all five parameters in the direction Controls < hetCF < CF (p values < 0.01). The best diagnostic performance in detecting between CF patients and non-CF was achieved by the presence of papules and wrinkling at 7 min (sensitivity/specificity: 94.0%/98.3% and 100.0%/92.0%, respectively).

CONCLUSIONS: A strong association between AWP and CF was detected. AWP after BIW could be elicited easily and possibly can be used as an initial screening tool to assess if an individual with symptoms and signs that raise the likelihood of CF is a CF patient.

PMID:33914973 | DOI:10.1111/jdv.17312

J Eur Acad Dermatol Venereol. 2021 Apr 29. doi: 10.1111/jdv.17324. Online ahead of print.

ABSTRACT

BACKGROUND: In the era of precision medicine, identification of possible predictive factors of clinical response to treatment is fundamental. This need is particularly strong for anogenital warts (AGW), because there are several treatment modalities with different clearance and recurrence rates. However, data regarding the effect of mental health parameters on response to treatment in patients with AGW are lacking.

OBJECTIVES: The purpose of the present study was to evaluate the association between patients’ mental health parameters and AGW treatment outcomes.

METHODS: This was a single-centre, prospective study that included newly diagnosed male patients with AGW. At their initial visit, all patients completed the State-Trait Anxiety Inventory (STAI), the Symptom Checklist-90-Revised (SCL-90-R), and the Eysenck Personality Questionnaire (EPQ) questionnaires, which evaluate anxiety, psychopathological manifestations, and personality traits, respectively. All patients received cryotherapy until clearance of lesions and were followed up for 18 months for detection of recurrences.

RESULTS: The study included 167 male patients. The mean number of days for AGW clearance was 89+/-65. During the 18-month follow up, 28 % of participants showed a recurrence, after a mean number of 150+/-132 days. No statistically significant association was detected between questionnaires scores and a) time needed for AGW clearance, b) time until 1^st recurrence, and c) number of recurrences.

CONCLUSION: If confirmed, our findings indicate that we may not need to modify our AGW treatment plan according to a patient’s mental health profile.

PMID:33914981 | DOI:10.1111/jdv.17324

Biometrics. 2021 Apr 29. doi: 10.1111/biom.13483. Online ahead of print.

ABSTRACT

A prominent threat to causal inference about peer effects in social science studies is the presence of homophily bias, that is, social influence between friends and families is entangled with common characteristics or underlying similarities that form close connections. Analysis of social study data has suggested that certain health conditions such as obesity and psychological states including happiness and loneliness can spread between friends and relatives. However, such analyses of peer effects or contagion effects have come under criticism because homophily bias may compromise the causal statement. We develop a regression-based approach which leverages a negative control exposure for identification and estimation of contagion effects on additive or multiplicative scales, in the presence of homophily bias. We apply our methods to evaluate the peer effect of obesity in Framingham Offspring Study. This article is protected by copyright. All rights reserved.

PMID:33914905 | DOI:10.1111/biom.13483

J Oral Rehabil. 2021 Apr 29. doi: 10.1111/joor.13177. Online ahead of print.

ABSTRACT

BACKGROUND: Discomfort encountered during oral processing may cause food avoidance and increase the risk of malnutrition in older adults. The aim of the present survey was to explore the relationships between oral health and the oral discomfort experienced while eating in senior people.

MATERIALS AND METHODS: In a cross-sectional study, oral discomfort was assessed in a sample of 119 independently-living participants aged between 35 and 81 years. Statistical analyses were used to identify categorical variables associated with food-related oral discomfort, including age, oral health-related quality of life (OHQoL), saliva secretion, occluding support, oral diseases, and denture use.

RESULTS: Food-related oral discomfort concerned 28.5% of the participants. Within the sample study, the risk of experiencing food-related oral discomfort was increased for participants perceiving average (OR= 7.968, CI95%= 2.603-24.381, p=0.000) or poor OHQoL (OR= 17.109, CI95%= 4.398-66.552, p=0.000), and presenting strictly fewer than 7 occlusal functional units (OFUs) (OR=3.396, CI95%= 1.206-9.561, p=0.020). Textured foods including fibrous (66.6%), heterogenous (60.6%) and grainy foods (42.4%) were mostly cited as food-related oral discomfort trigger factors. Within the 66-80 years group, participants having 0-6 OFUs were four times more likely to experience oral discomfort related to fibrous foods than participants having more than 7 OFUs (OR=4.812, CI95%=1.192-19.415, p=0.024). Within this group, participants having their teeth replaced by denture were also four times more likely to develop oral discomfort related to foods with heterogeneous textures (OR=4.714, CI95%=1.030-21.562, p=0.045) and grainy foods (OR=7.285, CI95%=1.308-40.568, p=0.023) than non-denture wearers.

CONCLUSION: Poor oral health conditions may generate oral discomfort with foods in the elderly especially with fibrous, heterogenous and grainy textures, and thus affect mealtime experience.

PMID:33914929 | DOI:10.1111/joor.13177

Genome Biol Evol. 2021 Apr 29:evab089. doi: 10.1093/gbe/evab089. Online ahead of print.

ABSTRACT

Codon bias is common to all organisms and is the result of mutation, drift, and selection. Selection for the efficiency and accuracy of translation is well recognized as a factor shaping the codon usage. In contrast, fewer studies report the control of the rate of translation as an additional selective pressure influencing the codon usage of an organism. Experimental molecular evolution using RNA virus populations is a powerful tool for the identification of mechanisms underlying the codon bias. Indeed, the role of deoptimized codons on the co-translational folding has been proven in the capsids of two fecal-orally transmitted picornaviruses, poliovirus and the hepatitis A virus, emphasizing the role of the frequency of codons in determining the phenotype. However, most studies on virus codon usage rely only on computational analyses, and experimental studies should be encouraged to clearly define the role of selection on codon evolution.

PMID:33914886 | DOI:10.1093/gbe/evab089