Category: Statistics

Eur J Nutr. 2021 Apr 14. doi: 10.1007/s00394-021-02556-6. Online ahead of print.

ABSTRACT

PURPOSE: The burden of non-communicable diseases (NCDs) has increased in China. However, the contribution of dietary risks to the NCD burden has not been evaluated. This study aimed to estimate the burden of ischemic heart disease (IHD) and colorectal cancer (CRC) attributable to a diet low in fiber in China from 1990 to 2017.

METHODS: China data from the Global Burden of Disease Study (GBD) 2017 were used to assess the age-, sex-, and province-specific mortality and disability-adjusted life-years (DALYs) of IHD and CRC related to a diet low in fiber.

RESULTS: In 2017, a diet low in fiber contributed 170,143 [95% uncertainty interval (UI): 99,623-256,806] IHD deaths and 25,561 (95% UI: 13,726-39,215) CRC deaths, with the population attributable fractions (PAFs) were 9.7 and 13.7%, respectively. Males had higher risk-attributable mortality and DALY rates for IHD and CRC than females. An upward trend with age in rates of mortality and DALY was observed. All-age risk-attributable mortality and DALY rates increased significantly by 111.4 and 53.2% for IHD, and 94.4 and 59.6% for CRC from 1990 to 2017, respectively; however, the corresponding age-standardized rates for IHD and CRC showed relatively stable trends. Heilongjiang, Xinjiang, and Inner Mongolia were ranked as the top three provinces in terms of total risk-attributable NCD burden in 2017.

CONCLUSIONS: China has a large and growing NCD burden attributable to a diet low in fiber. Greater priority in disease prevention and control should be given to male and older adults throughout China, particularly in some western provinces.

PMID:33852070 | DOI:10.1007/s00394-021-02556-6

Breast Cancer Res Treat. 2021 Apr 14. doi: 10.1007/s10549-021-06221-8. Online ahead of print.

ABSTRACT

PURPOSE: To compare efficacy and safety of capecitabine and lapatinib with or without IMC-A12 (cituxumumab) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab.

PATIENTS AND METHODS: Following an initial safety run-in cohort, patients were randomized 1:2 to Arm A (capecitabine and lapatinib) or to Arm B (capecitabine, lapatinib, and cituxumumab). Given the frequency of non-hematologic grade ≥ 3 adverse events in those receiving the three-drug combination in the safety cohort, lapatinib and capecitabine doses were reduced in Arm B only. The primary objective was to determine if the addition of cituxumumab to capecitabine and lapatinib improved progression-free survival (PFS) compared with capecitabine and lapatinib. Secondary objectives included a comparison between arms of other clinical endpoints, safety, change in overall quality of life (QOL) and self-assessed fatigue, rash, diarrhea, and hand-foot syndrome.

RESULTS: From July 2008 to March 2012, 68 patients (out of 142 planned) were enrolled and 63 were evaluable, including 8 for the safety run-in and 55 for the randomized cohort. Study enrollment was stopped early due to slow accrual. The addition of cituxumumab to capecitabine and lapatinib did not improve PFS (HR 0.93, 95% CI: 0.52-1.64). Furthermore, no difference in objective response rate or overall survival (OS) was observed. No difference between arms was observed in grade ≥ 3 adverse events, overall QOL change from baseline after 4 cycles of treatment.

CONCLUSION: The addition of cituxumumab to lapatinib and capecitabine did not improve PFS or OS compared with lapatinib and capecitabine in patients with HER2-positive MBC.

CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT00684983.

PMID:33852121 | DOI:10.1007/s10549-021-06221-8

Eur J Nucl Med Mol Imaging. 2021 Apr 14. doi: 10.1007/s00259-021-05354-8. Online ahead of print.

ABSTRACT

PURPOSE: Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemical recurrence post prostatectomy to detect local recurrence and metastatic disease at low PSA levels. The aim of this study was to assess patterns of disease detection, predictive factors and safety using [¹⁸F]DCFPyL PET/CT versus diagnostic CT in patients being considered for salvage radiotherapy with biochemical recurrence post prostatectomy.

METHODS: We conducted a prospective trial recruiting 100 patients with detectable PSA post prostatectomy (PSA 0.2-2.0 ng/mL) and referred for salvage radiotherapy from August 2018 to July 2020. All patients underwent a PSMA PET/CT using the [¹⁸F]DCFPyL tracer and a diagnostic CT. The detection rates of [¹⁸F]DCFPyL PET/CT vs diagnostic CT were compared and patterns of disease are reported. Clinical patient and tumour characteristics were analysed for predictive utility. Thirty-day post-scan safety is reported.

RESULTS: Of 100 patients recruited, 98 were suitable for analysis with a median PSA of 0.32 ng/mL. [¹⁸F]DCFPyL PET/CT was positive 46.4% and equivocal 5.2%, compared to 15.5% positivity for diagnostic CT. Local recurrence was detected on [¹⁸F]DCFPyL PET/CT in 28.5%, nodal disease in 27.5% and bony metastases in 6.1% of patients. Both ISUP grade group (p < 0.001) and pre-scan PSA (p = 0.029) were significant predictors of [¹⁸F]DCFPyL PET/CT positivity, and logistic regression generated probabilities combining the two showed improved prediction rates. No significant safety events were reported post [¹⁸F]DCFPyL administration.

CONCLUSIONS: [¹⁸F]DCFPyL PET/CT increases detection of disease in patients with biochemical recurrence post prostatectomy compared to diagnostic CT. Patients being considered for salvage radiotherapy with a PSA >0.2 ng/mL should be considered for [¹⁸F]DCFPyL PET/CT scan.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number: ACTRN12618001530213 ( http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375932&isReview=true ).

PMID:33852051 | DOI:10.1007/s00259-021-05354-8

Surg Endosc. 2021 Apr 14. doi: 10.1007/s00464-021-08433-x. Online ahead of print.

ABSTRACT

BACKGROUND: Endoscopic submucosal dissection (ESD) for remnant gastric cancer (RGC) after distal gastrectomy (DG) is considered technically challenging due to the narrow working space, and severe fibrosis and staples from the previous surgery. Technical difficulties of ESD for RGC after DG have not been thoroughly investigated. This study aimed to develop and validate a risk-scoring system for assessing the technical difficulty of ESD for RGC after DG in a large multicenter cohort.

METHODS: We investigated patients who underwent ESD for RGC after DG in 10 institutions between April 2008 and March 2018. A difficult case was defined as ESD lasting ≥ 120 min, involving piecemeal resection, or the occurrence of perforation during the procedure. A risk-scoring system for the technical difficulty of the procedure was developed based on multiple logistic regression analyses, and its performance was internally validated using bootstrapping.

RESULTS: A total of 197 consecutive patients with 201 lesions were analyzed. There were 90 and 111 difficult and non-difficult cases, respectively. The scoring model consisted of four independent risk factors and points of risk scores were assigned for each as follows: tumor size > 20 mm: 2 points; anastomosis site: 2 points; suture line: 1 point; and non-expert endoscopist: 2 points. The C-statistics of the scoring system for technical difficulty was 0.72.

CONCLUSIONS: We developed a validated risk-scoring model for predicting the technical difficulty of ESD for RGC after DG that can contribute to its safer and more reliable performance.

PMID:33852062 | DOI:10.1007/s00464-021-08433-x

J Orofac Orthop. 2021 Apr 14. doi: 10.1007/s00056-021-00292-4. Online ahead of print.

ABSTRACT

PURPOSE: Main goal of the study was the identification and quantitative analysis of monomer elution from materials commonly used in fixed orthodontic therapy. Studies have shown severe health effects of monomers including cytotoxic, allergenic or mutagenic potential and endocrine changes. This in vitro study focusses primarily on five resins which are usually processed intraorally and remain in the oral cavity long-term.

METHODS: We tested the elution of monomers from specimens (7.5 mm × 1.5 mm) immersed in artificial saliva at body temperature (37 °C) for 30 min to 5 weeks. The used method is in accordance with DIN EN ISO 10993-13. The five tested materials were BrackFix® (Voco GmbH, Cuxhaven, Germany), Triad®Gel (DeguDent GmbH, Hanau, Germany), and Transbond™ XT, LR and Plus (3M Unitek, Monrovia, CA, USA). All aliquots were analyzed using high performance liquid chromatography (HPLC). Data were statistically analyzed.

RESULTS: All five analyzed materials eluted substances over a period of 5 weeks. Identified substances included bisphenol A (BPA), triethylene glycol dimethacrylate (TEGDMA) and urethane dimethacrylate (UDMA). BPA eluted from Transbond™ Plus, XT, LR and BrackFix®. The cumulated mean values after 35 days ranged from 16.04 to 64.83 ppm, depending on the material. TEGDMA eluted with a mean of 688.61 ppm from Transbond™ LR. UDMA with a mean of 1682.00 ppm from Triad®Gel. For each material the highest concentrations of all these substances were found in the first elution period. Other substances that were not equivocally identified or of low concentration also eluted.

CONCLUSION: Using the described method, it is possible to qualitatively and quantitatively determine the in vitro elution of monomers from orthodontic materials. The concentrations of the substances identified were below the current maximum recommended intake. However, a cumulative effect and low-dose effects should be considered for both patients and dental professionals, especially for young patients. Measures to reduce exposure patients and practitioners are suggested.

PMID:33852039 | DOI:10.1007/s00056-021-00292-4

Eur Radiol. 2021 Apr 14. doi: 10.1007/s00330-021-07918-6. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop an objective quantitative method to characterize and visualize meningioma-brain adhesion using MR elastography (MRE)-based slip interface imaging (SII).

METHODS: This retrospective study included 47 meningiomas (training dataset: n = 35; testing dataset: n = 12) with MRE/SII examinations. Normalized octahedral shear strain (NOSS) values were calculated from the acquired MRE displacement data. The change in NOSS at the tumor boundary (ΔNOSS_bdy) was computed, from which a 3D ΔNOSS_bdy map of the tumor surface was created and the probability distribution of ΔNOSS_bdy over the entire tumor surface was calculated. Statistical features were calculated from the probability histogram. After eliminating highly correlated features, the capability of the remaining feature for tumor adhesion classification was assessed using a one-way ANOVA and ROC analysis.

RESULTS: The magnitude and location of the tumor adhesion can be visualized by the reconstructed 3D ΔNOSS_bdy surface map. The entropy of the ΔNOSS_bdy histogram was significantly different between adherent tumors and partially/completely non-adherent tumors in both the training (AUC: 0.971) and testing datasets (AUC: 0.900). Based on the cutoff values obtained from the training set, the ΔNOSS_bdy entropy in the testing dataset yielded an accuracy of 0.83 for distinguishing adherent versus partially/non-adherent tumors, and 0.67 for distinguishing non-adherent versus completely/partially adherent tumors.

CONCLUSIONS: SII-derived ΔNOSS_bdy values are useful for quantification and classification of meningioma-brain adhesion. The reconstructed 3D ΔNOSS_bdy surface map presents the state and location of tumor adhesion in a “clinician-friendly” manner, and can identify meningiomas with a high risk of adhesion to adjacent brain parenchyma.

KEY POINTS: • MR elastography (MRE)-based slip interface imaging shows promise as an objective tool to preoperatively discriminate meningiomas with a high risk of intraoperative adhesion. • Measurement of the change of shear strain at meningioma boundaries can provide quantitative metrics depicting the state of adhesion at the tumor-brain interface. • The surface map of tumor adhesion shows promise in assisting precise adhesion localization, using a comprehensible, “clinician-friendly” 3D visualization.

PMID:33852045 | DOI:10.1007/s00330-021-07918-6

Eur Radiol. 2021 Apr 14. doi: 10.1007/s00330-021-07943-5. Online ahead of print.

ABSTRACT

OBJECTIVES: Quantum noise is a random process in X-ray-based imaging systems. We addressed and measured the uncertainty of radiomics features against this quantum noise in computed tomography (CT) images.

METHODS: A clinical multi-detector CT scanner, two homogeneous phantom sets, and four heterogeneous samples were used. A solid tumor tissue removed from a male BALB/c mouse was included. We the placed phantom sets on the CT scanning table and repeated 20 acquisitions with identical imaging settings. Regions of interest were delineated for feature extraction. Statistical quantities-average, standard deviation, and percentage uncertainty-were calculated from these 20 repeated scans. Percentage uncertainty was used to measure and quantify feature stability against quantum noise. Twelve radiomics features were measured. Random noise was added to study the robustness of machine learning classifiers against feature uncertainty.

RESULTS: We found the ranges of percentage uncertainties from homogeneous soft tissue phantoms, homogeneous bone phantoms, and solid tumor tissue to be 0.01-2138%, 0.02-15%, and 0.18-16%, respectively. Overall, it was found that the CT features ShortRunHighGrayLevelEmpha (SRHGE) (0.01-0.18%), ShortRunLowGrayLevelEmpha (SRLGE) (0.01-0.41%), LowGrayLevelRunEmpha (LGRE) (0.01-0.39%), and LongRunLowGrayLevelEmpha (LRLGE) (0.02-0.66%) were the most stable features against the inherent quantum noise. The most unstable features were cluster shade (1-2138%) and max probability (1-16%). The impact of random noise to the prediction accuracy by different machine learning classifiers was found to be between 0 and 12%.

CONCLUSIONS: Twelve features were used for uncertainty measurements. The upper and lower bounds of percentage uncertainties were determined. The quantum noise effect on machine learning classifiers is model dependent.

KEY POINTS: • Quantum noise is a random process and is intrinsic to X-ray-based imaging systems. This inherent quantum noise creates unpredictable fluctuations in the gray-level intensities of image pixels. Extra cautions and further validations are strongly recommended when unstable radiomics features are selected by a predictive model for disease classification or treatment outcome prognosis. • We addressed and used the statistical quantity of percentage uncertainty to measure the uncertainty of radiomics features against the inherent quantum noise in computed tomography (CT) images. • A clinical multi-detector CT scanner, two homogeneous phantom sets, and four heterogeneous samples were used in the stability measurement. A solid tumor tissue removed from a male BALB/c mouse was included in the heterogeneous sample.

PMID:33852047 | DOI:10.1007/s00330-021-07943-5

JAMA Psychiatry. 2021 Apr 14. doi: 10.1001/jamapsychiatry.2021.0154. Online ahead of print.

ABSTRACT

IMPORTANCE: Nurses are the largest component of the US health care workforce. Recent research suggests that nurses may be at high risk for suicide; however, few studies on this topic exist.

OBJECTIVES: To estimate the national incidence of suicide among nurses and examine characteristics of nurse suicides compared with physicians and the general population.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used US data from 159 372 suicides reported in the National Violent Death Reporting System from 2007 to 2018. With the use of workforce denominators, sex-specific suicide incidence estimates were generated among nurses, physicians, and the general population (age, ≥30 years). Associations between clinician type and method of suicide and results of toxicology examination at death were calculated, adjusted for sociodemographic characteristics. Statistical analysis was performed from October 16, 2020, to January 10, 2021.

EXPOSURE: Occupation as a nurse or physician.

MAIN OUTCOME AND MEASURES: Suicide incidence and characteristics associated with suicides.

RESULTS: A total of 2374 suicides among nurses (1912 women [80.5%]; mean [SD] age, 52.8 [11.8] years), 857 suicides among physicians (723 men [84.4%]; mean [SD] age, 59.8 [15.3] years), and 156 141 suicides in the general population (121 483 men [77.8%]; mean [SD] age, 53.1 [14.7] years) were identified. Overall, suicide was more common among nurses compared with the general population (sex-adjusted incidence in 2017-2018, 23.8 per 100 000 vs 20.1 per 100 000; relative risk, 1.18 [95% CI, 1.03-1.36]). Among women in 2017-2018, the suicide incidence among nurses was 17.1 per 100 000 (506 among 2 966 048) vs 8.6 per 100 000 (8879 among 103 731 387) in the general female population (relative risk, 1.99 [95% CI, 1.82-2.18]). In absolute terms, being a female nurse was associated with an additional 8.5 suicides per 100 000 (95% CI, 7.0-10.0 per 100 000) compared with the general population of women. By sex, physician suicide rates were not statistically different from the general population other than among female physicians in 2011-2012 (11.7 per 100 000 [95% CI, 6.6-16.8 per 100 000] female physicians vs 7.5 per 100 000 [95% CI, 7.2-7.7 per 100 000] general population; P = .04). In terms of the characteristics of suicides, clinicians were more likely to use poisoning than the general population; for example, 24.9% (95% CI, 23.5%-26.4%) of nurses used poisoning compared with 16.8% (95% CI, 16.6%-17.0%) of the general suicide population. The presence of antidepressants, benzodiazepines, barbiturates, and opiates was more common among clinician suicides than suicides in the general population.

CONCLUSION AND RELEVANCE: This study suggests that, in the US, the risk of suicide compared with the general population was significantly greater for nurses but not for physicians. Further research is needed to assess whether interventions would be associated with benefit in reducing suicide risk among nurses.

PMID:33851982 | DOI:10.1001/jamapsychiatry.2021.0154

JAMA Netw Open. 2021 Apr 1;4(4):e215902. doi: 10.1001/jamanetworkopen.2021.5902.

ABSTRACT

IMPORTANCE: Psychiatric emergency department (ED) visits may be avoidable if individuals have access to adequate outpatient care, but the extent to which individuals use the ED itself as a key point of access is largely unknown.

OBJECTIVE: To describe the extent to which the ED is a first point of contact for mental health care among adults, and identify key factors associated with this outcome.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted from 2010 to 2018 in Ontario, Canada. Using health care administrative data, all individuals aged 16 years and older with an incident psychiatric ED visit were included. Statistical analysis was performed from September 2019 to February 2021.

MAIN OUTCOMES AND MEASURES: The primary outcome was no outpatient mental health or addictions contact in the 2 years preceding the incident ED visit. The study also measured predisposing (age, sex, immigrant status, comorbidity), enabling (neighborhood income, rurality, continuity of primary care), and need factors (diagnosis from incident ED visit) associated with the so-called first-contact ED visits, generating adjusted odds ratios (aORs) and 95% CIs.

RESULTS: The cohort included 659 084 patients who visited the ED. Among these patients, 340 354 were female individuals (51.6%), and the mean (SD) age was 39.1 (18.5) years. The incident ED visit was a first contact for 298 924 individuals (45.4%). Patients who had increased odds of first-contact ED visits included older individuals (aged 65-84 years vs 16-24 years; aOR, 1.13; 95% CI, 1.12-1.14), male individuals (aOR, 1.14; 95% CI, 1.13-1.15), immigrants (eg, economic class immigrant vs nonimmigrant status: aOR, 1.20; 95% CI, 1.18-1.21), rural residents (aOR, 1.21; 95% CI, 1.20-1.21), and in those with minimal primary care (aOR, 1.68; 95% CI, 1.67-1.69). All diagnoses had a higher likelihood of first-contact ED visits than mood disorders, particularly substance and alcohol use disorders (aOR, 1.66; 95% CI, 1.65-1.68).

CONCLUSIONS AND RELEVANCE: This study’s results suggest that nearly half of incident psychiatric ED visits were first-contact visits, which may be avoidable. Targeted efforts to improve outpatient access should focus on populations with risk factors for first-contact ED presentations, including men, older adults, rural residents, those with poor primary care connectivity, and those with substance-related diagnoses.

PMID:33852001 | DOI:10.1001/jamanetworkopen.2021.5902

JAMA Netw Open. 2021 Apr 1;4(4):e215832. doi: 10.1001/jamanetworkopen.2021.5832.

ABSTRACT

IMPORTANCE: Bruising caused by physical abuse is the most common antecedent injury to be overlooked or misdiagnosed as nonabusive before an abuse-related fatality or near-fatality in a young child. Bruising occurs from both nonabuse and abuse, but differences identified by a clinical decision rule may allow improved and earlier recognition of the abused child.

OBJECTIVE: To refine and validate a previously derived bruising clinical decision rule (BCDR), the TEN-4 (bruising to torso, ear, or neck or any bruising on an infant <4.99 months of age), for identifying children at risk of having been physically abused.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cross-sectional study was conducted from December 1, 2011, to March 31, 2016, at emergency departments of 5 urban children’s hospitals. Children younger than 4 years with bruising were identified through deliberate examination. Statistical analysis was completed in June 2020.

EXPOSURES: Bruising characteristics in 34 discrete body regions, patterned bruising, cumulative bruise counts, and patient’s age. The BCDR was refined and validated based on these variables using binary recursive partitioning analysis.

MAIN OUTCOMES AND MEASURES: Injury from abusive vs nonabusive trauma was determined by the consensus judgment of a multidisciplinary expert panel.

RESULTS: A total of 21 123 children were consecutively screened for bruising, and 2161 patients (mean [SD] age, 2.1 [1.1] years; 1296 [60%] male; 1785 [83%] White; 1484 [69%] non-Hispanic/Latino) were enrolled. The expert panel achieved consensus on 2123 patients (98%), classifying 410 (19%) as abuse and 1713 (79%) as nonabuse. A classification tree was fit to refine the rule and validated via bootstrap resampling. The resulting BCDR was 95.6% (95% CI, 93.0%-97.3%) sensitive and 87.1% (95% CI, 85.4%-88.6%) specific for distinguishing abuse from nonabusive trauma based on body region bruised (torso, ear, neck, frenulum, angle of jaw, cheeks [fleshy], eyelids, and subconjunctivae), bruising anywhere on an infant 4.99 months and younger, or patterned bruising (TEN-4-FACESp).

CONCLUSIONS AND RELEVANCE: In this study, an affirmative finding for any of the 3 BCDR TEN-4-FACESp components in children younger than 4 years indicated a potential risk for abuse; these results warrant further evaluation. Clinical application of this tool has the potential to improve recognition of abuse in young children with bruising.

PMID:33852003 | DOI:10.1001/jamanetworkopen.2021.5832