Tag: statistics

Clin Pharmacokinet. 2021 Mar 22. doi: 10.1007/s40262-021-00989-0. Online ahead of print.

ABSTRACT

BACKGROUND: Two pharmacokinetic/pharmacodynamic studies were conducted to evaluate the potential drug-drug interaction between elagolix, an oral gonadotropin-releasing hormone receptor antagonist, and an oral contraceptive (ethinylestradiol [EE] 0.035 mg and norgestimate 0.18/0.215/0.25 mg) or progestin-only contraceptive (norethindrone 0.35 mg) in healthy premenopausal women.

METHODS: These phase I studies used a two-period, sequential design, where period 1 included treatment with oral contraceptives, followed by period 2 with contraceptives coadministered with elagolix 150 mg once daily.

RESULTS: In study 1, pharmacokinetic exposures for EE in period 2 increased by 30% and the norgestimate metabolites decreased by approximately 15% when coadministered with elagolix. Mean hormone exposure appeared lower for follicle-stimulating hormone (FSH; 31%), luteinizing hormone (LH; 38%), and estradiol (E2; 16%). The percentage of women with consecutive progesterone (P) concentrations above 5 nmol/L was similar in both periods. Norethindrone pharmacokinetic exposures were comparable in both periods. The hormone exposure for LH and FSH was similar, and mean E2 exposure was 32% lower in period 2. The percentage of subjects with consecutive ovulatory P concentrations was also similar in both periods (study 2). Safety and tolerability profiles were unremarkable in both studies.

CONCLUSIONS: Coadministration of elagolix 150 mg once daily with oral contraceptives containing EE and norgestimate, or norethindrone, resulted in small pharmacokinetic changes in the oral contraceptive components. Similar or lower FSH, LH, and E2 exposures were observed during coadministration, with ovulatory P concentrations also comparable in both periods. The pharmacodynamic profiles of the oral contraceptives were maintained when coadministered with elagolix.

PMID:33748934 | DOI:10.1007/s40262-021-00989-0

Br J Haematol. 2021 Mar 21. doi: 10.1111/bjh.17388. Online ahead of print.

ABSTRACT

Glucocorticoid treatment increases venous thromboembolism (VTE) risk. Whether this is due to the medication or the underlying disease, or affects the risk of VTE recurrence, has been difficult to determine. The aim of our present study was to quantify the risk for first and recurrent VTE associated with oral glucocorticoids use, considering the underlying disease. A total of 2547 patients with VTE from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study were linked to the Dutch Pharmaceutical Statistics register. The risk of first VTE during periods of exposure with oral glucocorticoids was estimated by the self-controlled case series method and that of recurrent VTE was examined in a cohort design. The incidence rate ratio (IRR) of first VTE in the period of glucocorticoid treatment was 3·51 [95% confidence interval (CI) 2·55-4·80]. This IRR was 2·53 (95% CI 1·10-5·72) in the week before treatment started, 5·28 (95% CI 2·89-9·53) in the first 7 days of treatment, remained elevated afterwards and decreased to 1·55 (95% CI 0·85-3·12) after 6 months, as compared to unexposed periods. The hazard ratio for recurrence was 2·72 (95% CI 1·64-4·78) in treatment periods as compared with no treatment. The increased risk of VTE associated with oral glucocorticoid treatment is due to a combined effect of the treatment and the underlying disease, remaining high during the first months of prescription.

PMID:33748963 | DOI:10.1111/bjh.17388

Community Dent Oral Epidemiol. 2021 Mar 21. doi: 10.1111/cdoe.12633. Online ahead of print.

ABSTRACT

OBJECTIVES: Evidence on serum arsenic and oral cancer risk was limited. We aimed to evaluate the association between serum arsenic and the risk of oral cancer in a southeast China population.

METHODS: Serum arsenic was determined for 325 oral cancer patients and 648 controls using inductively coupled plasma-mass spectrometry (ICP-MS). Logistic regression and restricted cubic spline were analysed the association between serum arsenic level and oral cancer risk, and crude and adjusted odds ratios (aOR) with 95% confidence interval (95% CI) were calculated. Factors adjusted for included age, gender, BMI, smoking, drinking, education, residence, marital status and dietary factors. Stratification analysis was further performed according to drinking, smoking and dietary characteristics.

RESULTS: Serum arsenic level was lower in the case group (P₅₀ = 19.2μg/L, IQR = 11.6 ~ 26.4μg/L) than in the control group (P₅₀ = 30.2 μg/L, IQR = 25.0 ~ 36.4 μg/L). An inverse but nonlinear association was observed between arsenic level and oral cancer risk by restricted cubic spline. These with moderate serum arsenic levels had a lower risk of oral cancer than those with low levels (OR = 0.11; 95%CI: 0.07-0.18), after adjusting for demographic and dietary intake factors. We also kept serum arsenic as a continuous variable in a regression model, where a similar inverse association between arsenic and oral cancer was observed, with OR = 0.86 (95%CI: 0.84-0.88). Stratification analysis revealed no significant multiplicative interactions between serum arsenic and smoking, drinking or dietary intake.

CONCLUSION: Serum arsenic is inversely related to oral cancer risk. Relative to those with low levels of arsenic, people with moderate serum arsenic levels had a lower risk of oral cancer. If confirmed, serum arsenic level may be a useful predictive marker for oral cancer risk.

PMID:33748987 | DOI:10.1111/cdoe.12633

Environ Res. 2021 Mar 18:111023. doi: 10.1016/j.envres.2021.111023. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence is limited regarding the association between temperatures and health costs.

OBJECTIVES: We tried to investigate the association between temperatures and emergency department visits (EDVs) costs in China.

METHODS: Daily data on EDVs costs, weather, air pollution were collected from 17 sites in China during 2014-2018. A quasi-Poisson generalized additive regression with distributed lag nonlinear model was applied to assess the temperature-EDVs cost association. Random-effect meta-analysis was used to pool the estimates from each site. Attributable fractions and national attributable EDVs costs due to heat and cold were calculated.

RESULTS: Relative risk (RR) due to extreme heat over 0-7 lag days was 1.14 [95% confidence intervals (CI): 1.08-1.19] and 1.11 (95% CI: 1.07-1.16) for EDVs examination (including treatment) and medicine cost, respectively. People aged 18-44 and those with genitourinary diseases were at higher risk from heat. 0.72% of examination cost and 0.57% of medicine cost were attributed to extreme heat, costing 274 million Chinese Yuan annually. Moderate heat had lower RR but higher attributable fraction of EDVs costs. Exposure to extreme cold over 0-21 lag days increased the risk of medicine cost for people aged 18-44 [RR: 1.30 (95% CI: 1.10-1.55)] and those with respiratory diseases [RR: 1.56 (95% CI: 1.14-2.14)], but had non-statistically significant attributable fraction of the total EDVs cost.

CONCLUSIONS: Exposure to heat and cold resulted in remarkable health costs. More resources and preparedness are needed to tackle such a challenge as our climate is rapidly changing.

PMID:33745933 | DOI:10.1016/j.envres.2021.111023

Arthroscopy. 2021 Mar 18:S0749-8063(21)00227-9. doi: 10.1016/j.arthro.2021.03.005. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the accuracy of the Trampoline and Hook tests, used in the arthroscopic assessment of triangular fibrocartilage complex (TFCC) tears compared to arthroscopic direct visualization of the radiocarpal joint (RCJ) and of the distal radial ulnar joint (DRUJ).

METHODS: 135 patients (97 males, 38 females, mean age 43.5 years) were divided into 2 groups: A) 80 patients with chronic ulnar sided wrist pain and positive fovea sign and B) 55 patients with other complaints. TFCC was assessed by RCJ and DRUJ arthroscopy, by Trampoline and Hook tests to detect rupture of distal and proximal components of the TFCC. Accuracy, specificity, sensitivity and likelihood ratio of the two diagnostic methods were measured and compared, using RCJ and DRUJ arthroscopy as reference.

RESULTS: The Trampoline and the Hook test showed an overall accuracy of 70.37% and 86.67%, respectively. The accuracy of the Trampoline test was similar for distal (69%), proximal (66%) and complete (73%) TFCC tears. The Hook test was more accurate when evaluating proximal (97%) and complete (98%) tears, rather than distal lesions (75%). Sensitivity for Trampoline and Hook tests was 75.00% and 0.00% (p<0.001) for distal tears, and 78.85% and 100.00% (p<0.001), and 58.33% and 100.00% (p<0.001), for complete or isolated proximal tears, respectively. Specificity for Trampoline and Hook tests was 67.27% and 96.36% (p<0.001) respectively.

CONCLUSIONS: Trampoline and Hook tests can assure accurate diagnosis of peripheral TFCC tear. The Hook test shows higher specificity and sensitivity to recognize foveal TFCC tears. Values of positive likelihood ratio suggest a higher probability to detect foveal laceration of peripheral TFCC for the Hook test than for the Trampoline test. These findings suggest that DRUJ arthroscopy is not necessary to confirm foveal detachment of the TFCC, if the Hook test is positive.

PMID:33745938 | DOI:10.1016/j.arthro.2021.03.005

Clin Lung Cancer. 2021 Feb 19:S1525-7304(21)00032-2. doi: 10.1016/j.cllc.2021.02.009. Online ahead of print.

ABSTRACT

BACKGROUND: We conducted a 2-part study to evaluate the incorporation of veliparib, a PARP inhibitor, into chemoradiotherapy (CRT) for stage III non-small-cell lung cancer.

PATIENTS AND METHODS: In the phase I part, patients were treated successively at 3 dose levels of veliparib (40, 80, and 120 mg) twice daily during CRT. In the phase II part, patients were randomized to receive veliparib or placebo during thoracic radiotherapy with concurrent weekly carboplatin and paclitaxel, followed by 2 cycles of consolidation carboplatin and paclitaxel with veliparib or placebo. The study was prematurely discontinued owing to the emergence of adjuvant immunotherapy as standard of care.

RESULTS: Of 21 patients enrolled in phase I, 2 patients developed dose-limiting toxicities (DLTs): 1 grade 3 esophagitis with dysphagia (at 40 mg) and 1 grade 3 esophagitis with dehydration (at 80 mg). No DLTs were seen at veliparib dose of 120 mg twice daily, which was selected for the phase II part that enrolled 31 eligible patients. Progression-free survival (PFS) was not different between the 2 arms (P = .20). For the veliparib and placebo arms, response rates were 56% and 69%, PFS at 1 year 47% and 46%, and overall survival at 1 year 89% and 54%, respectively.

CONCLUSION: Veliparib with CRT was feasible and well tolerated. Efficacy could not accurately be determined because of early study closure. Nonetheless, there is enthusiasm for the evaluation of PARP inhibitors in lung cancer as predictive biomarkers are being developed and combinations with immunotherapy are attractive.

PMID:33745865 | DOI:10.1016/j.cllc.2021.02.009

J Acad Nutr Diet. 2021 Mar 18:S2212-2672(21)00103-9. doi: 10.1016/j.jand.2021.02.011. Online ahead of print.

ABSTRACT

BACKGROUND: Longitudinal studies have shown significant dose-response associations between dietary share of ultraprocessed foods and the incidence of several noncommunicable diseases and all-cause mortality. Several attributes of ultraprocessed foods are potential mechanisms for their link with health outcomes, including their typically unbalanced nutrient profile, high glycemic loads, high energy intake rate, and the presence of food additives, neoformed substances, and substances released by synthetic packaging materials. However, no studies have assessed the plausibility of reduced water intake as an additional association of diets rich in ultraprocessed foods.

OBJECTIVE: To assess the association between ultraprocessed food consumption and total water intake.

DESIGN: This cross-sectional secondary analysis used data from the National Health and Nutrition Examination Survey, cycles 2011 to 2016, in the United States.

PARTICIPANTS/SETTINGS: This study included 24,505 participants aged ≥1 year who completed the first 24-hour dietary recall interview.

MAIN OUTCOMES MEASURES: The main outcome evaluated was the mean of total water intake.

STATISTICAL ANALYSIS: Crude and adjusted linear regressions were applied to investigate the association between quintiles of the dietary share of ultraprocessed foods and the total water intake.

RESULTS: A significant linear reduction in the daily mean total water intake was observed across ultraprocessed food quintiles, amounting to 706 mL between the lower and the upper quintiles. Important increases across quintiles were observed for the intake of sugar-sweetened and artificially sweetened drinks, whereas important reductions occurred for unsweetened drinks, plain water, and water present in solid foods and dishes.

CONCLUSIONS: Reduced total water intake and an imbalance between sources of water that favors energy-dense and nutrient-poor sources were associated with increased consumption of ultraprocessed food, suggesting that decreased total water consumption might be a negative outcome of diets rich in ultraprocessed foods. This relationship should be further investigated in longitudinal or clinical trials.

PMID:33745880 | DOI:10.1016/j.jand.2021.02.011

Environ Res. 2021 Mar 18:111018. doi: 10.1016/j.envres.2021.111018. Online ahead of print.

ABSTRACT

The SARS-CoV-2 virus pandemic (COVID-19) has caused 2.25 million deaths worldwide by February 3, 2021 (JHU, 2021) and still causing severe health and economic disruptions with increasing rates. This study investigates the impact of lockdown measures on ambient air pollution and its association with human mobility in 81 cities of Turkey. We conducted a countrywide analysis using PM₁₀ and SO₂ measurement data by the Turkish Ministry of Environment and Urbanization and mobility data derived from cellular device movement by Google. We observed the most significant change in April 2020. PM₁₀ and SO₂ concentrations were lower in 67% and 59% of the cities, respectively in April 2020 compared to the previous five years (2015-2019). The correlation results show that Restaurant/Café, Transit, and Workplaces mobility is significantly correlated with PM₁₀ and SO₂ concentration levels in Turkey. This study is the first step of a long-term investigation to understand the air quality impacts on population susceptibility to COVID-19.

PMID:33745929 | DOI:10.1016/j.envres.2021.111018

Environ Res. 2021 Mar 18:111045. doi: 10.1016/j.envres.2021.111045. Online ahead of print.

ABSTRACT

This study aimed to characterise spatial-temporal distribution of noise complaints across urban areas with different densities and to analyse the associations between urban morphology and noise complaints. Taking New York City as the study area, crowdsourced noise complaints and urban morphology datasets from the city government’s open data source were statistically analysed. The results suggest that between boroughs the characteristics of noise complaints are different, in terms of their spatial-temporal distribution, their relation to road transport network, land use, and building morphology. Noise complaints were clustered around the highest density area (Manhattan). The rate of noise complaints showed a year-on-year increase, peaking in autumn and spring. The rate of noise complaints is higher in areas with higher densities and roads that are 20-40m wide, closer to road crossings, and in enclosed blocks. The relationships between noise complaints and urban morphology are weaker in high-density boroughs than in other boroughs.

PMID:33745930 | DOI:10.1016/j.envres.2021.111045

J Clin Densitom. 2021 Feb 28:S1094-6950(21)00018-4. doi: 10.1016/j.jocd.2021.02.004. Online ahead of print.

ABSTRACT

We describe a multicenter study using the European Spine Phantom (ESP) to compare the accuracy, linearity and precision of QCT measurements of spine vBMD between different brands of scanner, different models of the same brand and identical units of the same model. Ten scans of the same ESP with repositioning were performed on forty CT scanners from five manufacturers in different hospitals across China, all calibrated with the Mindways QCT system. The three ESP vertebral bodies simulating low (L1), medium (L2) and high (L3) vBMD and their average (L1-3 vBMD) were compared with phantom values. Linearity was assessed using the standard error of the estimate derived from linear regression. Precision errors were expressed as the standard deviation of the ten measurements on each scanner. Median (IQR) vBMD over all forty CT scanners compared with phantom values were: L1: 52.2 (49.9-56.4) vs 51.0; L2: 104.4 (101.2-108.6) vs 102.2; L3: 201.4 (195.0-204.9) vs 200.4; L1-3: 119.3 (116.6-123.2) vs 117.9 mg/cm³. Statistically significant differences in L1-3 vBMD were found between different brands (p= 0.005) and between different models of the same brand and identical units of the same model (both p< 0.001). Cross-calibration using linear regression gave a good fit for all forty systems with a median standard error of the estimate of 1.7 mg/cm³. The median precision error for L1-3 vBMD was 0.61 mg/cm³. Statistically significant differences in spine vBMD measurements between different scanners reinforce the importance of cross-calibration in multi-center studies. Cross-calibration can be reliably performed using linear regression equations.

PMID:33745832 | DOI:10.1016/j.jocd.2021.02.004