Category: Statistics

Int J Biostat. 2021 Sep 2. doi: 10.1515/ijb-2020-0046. Online ahead of print.

ABSTRACT

Interrupted time series (ITS) design is commonly used to evaluate the impact of interventions in healthcare settings. Segmented regression (SR) is the most commonly used statistical method and has been shown to be useful in practical applications involving ITS designs. Nevertheless, SR is prone to aggregation bias, which leads to imprecision and loss of power to detect clinically meaningful differences. The objective of this article is to present a weighted SR method, where variability across patients within the healthcare facility and across time points is incorporated through weights. We present the methodological framework, provide optimal weights associated with data at each time point and discuss relevant statistical inference. We conduct extensive simulations to evaluate performance of our method and provide comparative analysis with the traditional SR using established performance criteria such as bias, mean square error and statistical power. Illustrations using real data is also provided. In most simulation scenarios considered, the weighted SR method produced estimators that are uniformly more precise and relatively less biased compared to the traditional SR. The weighted approach also associated with higher statistical power in the scenarios considered. The performance difference is much larger for data with high variability across patients within healthcare facilities. The weighted method proposed here allows us to account for the heterogeneity in the patient population, leading to increased accuracy and power across all scenarios. We recommend researchers to carefully design their studies and determine their sample size by incorporating heterogeneity in the patient population.

PMID:34473922 | DOI:10.1515/ijb-2020-0046

Diabet Med. 2021 Sep 2:e14685. doi: 10.1111/dme.14685. Online ahead of print.

ABSTRACT

AIMS: This study aimed to evaluate the ability of HbA1c combined with glycated albumin (GA) or 1,5-anhydroglucitol (1,5-AG) to detect diabetes in residents of Jiangsu, China.

METHODS: The oral glucose tolerance test (OGTT) was performed on 2,184 people in Jiangsu. HbA1c, GA, 1,5-AG, and other serum biochemical parameters were measured. Receiver operating characteristic curves were plotted to determine the optimal thresholds of HbA1c, GA, and 1,5-AG according to the Youden index.

RESULTS: (1) The optimal thresholds of HbA1c, GA, and 1,5-AG for the screening of diabetes were ≥ 45 mmol/mol (6.3%), ≥ 13.0%, and ≤ 23.0 μg/ml, respectively. (2) The sensitivities of HbA1c combined with GA and 1,5-AG were both 85%, higher than that of HbA1c (70%, P < 0.001).

CONCLUSIONS: This study is suitable for cases where plasma glucose is unavailable. Among the residents of Jiangsu, HbA1c combined with GA or 1,5-AG can improve the sensitivity of diabetes screening, reduce the miss rate, and save the use of OGTT. GA and 1,5-AG are superior in individuals with mild glucose metabolism disorder. GA enhances the detection of diabetes in the nonobese, and 1,5-AG enhances the detection in those with hyperuricemia.

PMID:34473869 | DOI:10.1111/dme.14685

Int J Clin Pract. 2021 Sep 2:e14766. doi: 10.1111/ijcp.14766. Online ahead of print.

ABSTRACT

BACKGROUND: Iodinated contrast media (ICM) – frequently used compound in radiology. Non-immediate hypersensitivity reactions (HSR) appear when a patient leaves the department and usually are undocumented. True hypersensitivity in this group is rarely proved.

METHODS: Single-center 2014-2018 data was retrospectively analysed. HSR to ICM were classified and investigated according to the time of occurrence (immediate <1h, non-immediate >1h). ENDA questionnaire and skin tests (prick or intradermal test) were performed according to ENDA/EAACI recommendations.

RESULTS: 69 patients with a clinical history of HSR to ICM were identified, 72.46% were females (n=50). Average age was 56 (SD ± 13.16) years. Non-immediate HSR occurred in 28.99% (n=20) patients. The suspected culprit drugs were: iodixanol 20% (n=4), iopromide 5% (n=1), diatrizoate 10% (n=2), iohexol 10% (n=2). Among non-immediate HSR 96.00% (n=19) of patients had skin rashes. A statistically significant correlation was found between the clinical symptoms and the type of reaction (p-value < 0,05): isolated skin manifestations mostly occurred in non-immediate HSR 75.00% (n=15). Only 13.04% (n=9) of all the patients were proved to be allergic to a certain ICM after the proposed diagnostic workup.

CONCLUSIONS: One third of the hypersensitivity reactions investigated were classified as non-immediate type. Most of them manifested with isolated skin symptoms. The most frequent culprit drug encountered was iodixanol. The overall non-immediate hypersensitivity confirmation rate after diagnostic evaluation was only 15%.

PMID:34473887 | DOI:10.1111/ijcp.14766

Int Endod J. 2021 Sep 2. doi: 10.1111/iej.13625. Online ahead of print.

ABSTRACT

AIM: To compare the shaping ability of a heat-treated centric reciprocating file system (WaveOne Gold), a heat-treated eccentric rotary multi-file system (TRUShape 3D Conforming Files), and a heat-treated expandable one-file rotary system (XP-endo Shaper) extending its activation time, in preparing oval-shaped root canals in extracted mandibular molars by means of micro-computed tomography (micro-CT) analysis.

METHODOLOGY: Thirty moderately curved oval-shaped distal roots of mandibular molars were selected. The normality of canal length, curvature angle, volume, surface area, structure model index, and aspect ratio were confirmed. The samples were randomly divided into three groups (n = 10). Micro-CT scans were taken before and after canals were instrumented using WaveOne Gold (size 35, .06 taper), or TRUShape (size 30, .06v taper), both following the manufacturer’s instructions, or XP-endo Shaper following a new protocol with extended activation time. The mechanical preparation time for each sample was recorded. Pre- and postoperative images were analysed for the percentage of unprepared areas and the percentage of removed dentine. Data were compared between groups using the statistical analyses one-way ANOVA and Tukey tests (P < 0.05).

RESULTS: The percentage of unprepared canal areas was significantly higher with WaveOne Gold (% 11.5 ± 4.0) and TRUShape (% 12.4 ± 5.8) compared to XP-endo Shaper (% 5.2 ± 2.6) (P < 0.05). XP-endo Shaper removed significantly more dentine (3.3 ± 1.5 mm3) than WaveOne Gold (1.8 ± 0.8 mm3) and TRUShape (1.9 ± 0.8 mm3) (P < 0.05). No significant differences were seen for mechanical preparation time between WaveOne Gold (79 ± 31 s), TRUShape (104 ± 41 s) and XP-endo Shaper (71 ± 23 s) (P > 0.05).

CONCLUSIONS: The comparison of three recognized root canal filing systems has shown that, with similar preparation times, the XP-endo Shaper removed more dentine (mm3) leaving less unprepared area (%) than WaveOne Gold and TRUShape when preparing oval-shaped root canals of extracted mandibular molars.

PMID:34473842 | DOI:10.1111/iej.13625

Psychophysiology. 2021 Sep 2:e13933. doi: 10.1111/psyp.13933. Online ahead of print.

ABSTRACT

Non-invasive brain stimulation techniques, such as transcutaneous auricular vagus nerve stimulation (taVNS), have considerable potential for clinical use. Beneficial effects of taVNS have been demonstrated on symptoms in patients with mental or neurological disorders as well as transdiagnostic dimensions, including mood and motivation. However, since taVNS research is still an emerging field, the underlying neurophysiological processes are not yet fully understood, and the replicability of findings on biomarkers of taVNS effects has been questioned. The objective of this analysis was to synthesize the current evidence concerning the effects of taVNS on vagally mediated heart rate variability (vmHRV), a candidate biomarker that has, so far, received most attention in the field. We performed a living Bayesian random effects meta-analysis. To keep the synthesis of evidence transparent and up to date as new studies are being published, we developed a Shiny web app that regularly incorporates new results and enables users to modify study selection criteria to evaluate the robustness of the inference across potential confounds. Our analysis focuses on 16 single-blind studies comparing taVNS versus sham in healthy participants. The meta-analysis provides strong evidence for the null hypothesis (g = 0.014, CI_shortest = [-0.103, 0.132], BF₀₁ = 24.678), indicating that acute taVNS does not alter vmHRV compared to sham. To conclude, there is no support for the hypothesis that vmHRV is a robust biomarker for acute taVNS. By increasing transparency and timeliness, the concept of living meta-analyses can lead to transformational benefits in emerging fields such as non-invasive brain stimulation.

PMID:34473846 | DOI:10.1111/psyp.13933

Age Ageing. 2021 Aug 28:afab174. doi: 10.1093/ageing/afab174. Online ahead of print.

ABSTRACT

BACKGROUND: the interrelatedness between social determinants of health impedes researchers to identify important social factors for health investment. A new approach is needed to quantify the aggregate effect of social factors and develop person- centred social interventions.

METHODS: participants ([n = 7,383], 54.5% female) were aged 65 years or above who complete an additional psychosocial questionnaire in the health and retirement study in 2006 or 2008. Social determinants of health encompassed five social domains: economic stability, neighbourhood and physical environment, education, community and social context, and healthcare system. We used the forward stepwise logistic regression to derive a polysocial score model for 5-year mortality. Indices of goodness-of-fit, discrimination and reclassification were used to assess model performance. We used logistic regression to identify the association between polysocial score and mortality. Subgroup analyses were conducted to examine sex- and race-specific association.

RESULTS: polysocial score was created using 14 social determinants of health. In the training cohort, the C-statistic was 0.71 for the reference model (only age, sex and race/ethnicity) and increased to 0.75 for the continuous and categorical polysocial score. Compared with the reference model, the integrated discrimination index for adding the continuous or categorical polysocial score was both 0.03 (P values < 0.001). Participants with an intermediate (odds ratio [OR] = 0.69; 95% confidence interval [CI], 0.51-0.82) or high (OR = 0.48; 95% CI, 0.38-0.60) polysocial score had lower odds of death than those in the low category in the fully adjusted model, respectively.

CONCLUSIONS: the polysocial approach may offer possible solutions to monitor social environments and suggestions for older people to improve their social status for specific health outcomes.

PMID:34473824 | DOI:10.1093/ageing/afab174

Clin Pharmacol Ther. 2021 Sep 2. doi: 10.1002/cpt.2412. Online ahead of print.

ABSTRACT

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 infection, is a severe acute respiratory syndrome with an underlying inflammatory state. We have previously demonstrated that acute inflammation modulates cytochromes P450 (CYP) activities in an isoform-specific manner. We therefore hypothesized that COVID-19 might also impact CYP activities, and thus aimed to evaluate the impact of acute inflammation in the context of SARS-CoV-2 infection on the six main human CYPs activity. This prospective observational study was conducted in 28 patients hospitalized at the Geneva University Hospitals (Switzerland) with a diagnosis of moderate to severe COVID-19. They received the Geneva phenotyping cocktail orally during the first 72h of hospitalization and after three months. Capillary blood samples were collected 2h after cocktail administration to assess the metabolic ratios (MRs) of CYP1A2, 2B6, 2C9, 2C19, 2D6 and 3A. CRP, IL-6 and TNF-α levels were also measured in blood. CYP1A2, CYP2C19, and CYP3A MRs decreased by 52.6% (p=0.0001), 74.7% (p=0.0006) and 22.8% (p=0.045), respectively, in COVID-19 patients. CYP2B6 and CYP2C9 MRs increased by 101.1% (p=0.009) and 55.8% (p=0.0006) respectively. CYP2D6 MRs variation did not reach statistical significance (p=0.072). As expected, COVID-19 was a good acute inflammation model as mean serum levels of CRP, IL-6 and TNF-α were significantly (p<0.001) higher during SARS-CoV-2 infection. CYP activities are modulated in an isoform-specific manner by SARS-CoV-2 infection. The pharmacokinetics of CYP substrates, whether used to treat the disease or as the usual treatment of patients, could be therefore clinically impacted.

PMID:34473836 | DOI:10.1002/cpt.2412

Age Ageing. 2021 Aug 28:afab169. doi: 10.1093/ageing/afab169. Online ahead of print.

ABSTRACT

OBJECTIVES: To reduce infections with Clostridioides difficile (CDI) in geriatric patients by interventions easily implementable in standard clinical care.

METHODS: Prevalence and incidence of CDI between January 2015 and February 2020 were analysed (n = 25,311 patients). Pre-intervention status was assessed from April 2016 to March 2017 (n = 4,922). Between May 2017 and August 2019, a monocentric interventional crossover study (n = 4,655) was conducted including standard care and three interventions: (A) sporicidal cleaning of hospital wards, (B) probiotics and (C) improvement in personal hygiene for CDI patients. This was followed by a multicentric comparison of the interventional bundle (A + B + C) between September 2019 and February 2020 (n = 2,593) with the pre-intervention phase. In 98 CDI cases and matched controls individual risk factors for the development of CDI were compared.

RESULTS: Time series analyses of CDI cases revealed a reduction in the prevalence of CDI in all three participating centres prior to the multicentric intervention phase. In the monocentric phase, no effect of individual interventions on CDI prevalence was identified. However, an aggregated analysis of CDI cases comparing the pre-intervention and the multicentric phase revealed a significant reduction in CDI prevalence. Risk factors for the development of CDI included use of antibiotics, anticoagulants, previous stay in long-term care facilities, prior hospital admissions, cardiac and renal failure, malnutrition and anaemia.

CONCLUSIONS: The observed reduction in CDI may be attributed to heightened awareness of the study objectives and specific staff training. Individual interventions did not appear to reduce CDI prevalence. A further randomised trial would be necessary to confirm whether the bundle of interventions is truly effective.

PMID:34473822 | DOI:10.1093/ageing/afab169

PLoS One. 2021 Sep 2;16(9):e0257040. doi: 10.1371/journal.pone.0257040. eCollection 2021.

ABSTRACT

OBJECTIVES: To study abnormality of spirometry, six-minute walk distance, and chest radiograph among patients recovered from Coronavirus Disease 2019 (COVID-19).

METHODS AND STUDY DESIGN: A prospective cohort study was conducted in 87 COVID-19 confirmed cases who recovered and discharged from a medical school hospital in Thailand. At the follow-up visit on day 60 after onset of symptoms, patients underwent an evaluation by spirometry (FVC, FEV1, FEV1/FVC, FEF25-75, and PEF), a six-minute-walk test (6MWT), and a chest radiograph.

RESULTS: There were 35 men and 52 women, with a mean age of 39.6±11.8 years and the mean body mass index (BMI) was 23.8±4.3 kg/m2. Of all, 45 cases had mild symptoms; 35 had non-severe pneumonia, and 7 had severe pneumonia. Abnormality in spirometry was observed in 15 cases (17.2%), with 8% of restrictive defect and 9.2% of obstructive defect. Among the patients with an abnormal spirometry, the majority of the cases were in the severe pneumonia group (71.4%), compared with 15.6% in the non-severe pneumonia group, and 10.2% in the mild symptom group (p = 0.001). The mean six-minute-walk distance (6MWD) in the mild symptom and non-severe pneumonia groups was 538±56.8 and 527.5±53.5 meters, respectively. Although the severe pneumonia group tended to have a shorter mean 6-min walking distance, but this was not statistically significant (p = 0.118). Twelve patients (13.8%) had abnormal chest radiographs that showed residual fibrosis. This abnormality was more common in the severe pneumonia group (85.7%) and in others (7.5%) (p<0.001).

CONCLUSIONS: Abnormal spirometry was noted in 17.2% of COVID-19 survivors with both restrictive and obstructive defects. Severe COVID-19 pneumonia patients had higher prevalence rates of abnormal spirometry and residual fibrosis on the chest radiographs when compared to patients in the mild symptom and non-severe pneumonia groups.

PMID:34473811 | DOI:10.1371/journal.pone.0257040

PLoS One. 2021 Sep 2;16(9):e0256956. doi: 10.1371/journal.pone.0256956. eCollection 2021.

ABSTRACT

This study investigates the topology and dynamics of collaboration networks that exist between inventors and their patent co-authors for patents granted by the USPTO from 2007-2019 (2,241,201 patents and 1,879,037 inventors). We study changes in the configurations of different technology fields via the power-law, small-world, preferential attachment, shrinking diameter, densification law, and gelling point hypotheses. Similar to the existing literature, we obtain mixed results. Based on network statistics, we argue that the sudden rise of large networks in six technology sectors can be understood as a phase transition in which small, isolated networks form one giant component. In two other technology sectors, such a transition occurred much later and much less dramatically. The examination of inventor networks over time reveals the increased complexity of all technology sectors, regardless of the individual characteristics of the network. Therefore, we introduce ideas associated with the technological diversification of inventors to complement our analysis, and we find evidence that inventors tend to diversify into new fields that are less mature. This behavior appears to be correlated with the compliance of some of the expected network rules and has implications for the emerging patterns among the different collaboration networks under consideration here.

PMID:34473792 | DOI:10.1371/journal.pone.0256956