Category: Statistics

United European Gastroenterol J. 2022 May 4. doi: 10.1002/ueg2.12231. Online ahead of print.

ABSTRACT

BACKGROUND: The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument has been developed to inform the methodology, reporting and appraisal of clinical practice guidelines. Evidence suggests that the quality of surgical guidelines can be improved, and the structure and content of AGREE II can be modified to help enhance the quality of guidelines of surgical interventions.

OBJECTIVE: To develop an extension of AGREE II specifically designed for guidelines of surgical interventions.

METHODS: In the tripartite Guideline Assessment Project (GAP) funded by United European Gastroenterology and the European Association for Endoscopic Surgery, (i) we assessed the quality of surgical guidelines and we identified factors associated with higher quality (GAP I); (ii) we applied correlation analysis, factor analysis and the item response theory to inform an adaption of AGREE II for the purposes of surgical guidelines (GAP II); and (iii) we developed an AGREE II extension for surgical interventions, informed by the results of GAP I, GAP II, and a Delphi process of stakeholders, including representation from interventional and surgical disciplines; the Guideline International Network (GIN); the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group; the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) initiative; and representation of surgical journal editors and patient/public.

RESULTS: We developed AGREE-S, an AGREE II extension for surgical interventions, which comprises 24 items organized in 6 domains; Scope and purpose, Stakeholders, Evidence synthesis, Development of recommendations, Editorial independence, and Implementation and update. The panel of stakeholders proposed 3 additional items: development of a guideline protocol, consideration of practice variability and surgical/interventional expertise in different settings, and specification of infrastructures required to implement the recommendations. Three of the existing items were amended, 7 items were rearranged among the domains, and one item was removed. The domain Rigour of Development was divided into domains on Evidence Synthesis and Development of Recommendations. The new domain Development of Recommendations incorporates items from the original AGREE II domain Clarity of Presentation.

CONCLUSION: AGREE-S is an evidence-based and stakeholder-informed extension of the AGREE II instrument, that can be used as a guide for the development and adaption of guidelines on surgical interventions.

PMID:35506366 | DOI:10.1002/ueg2.12231

Twin Res Hum Genet. 2022 May 4:1-16. doi: 10.1017/thg.2022.2. Online ahead of print.

ABSTRACT

Discordant monozygotic (MZ) twin methodologies are considered one of the foremost statistical approaches for estimating the influence of environmental factors on phenotypic variance. Limitations associated with the discordant MZ twin approach generates an inability to estimate particular relationships and adjust estimates for the confounding influence of gene-nonshared environment interactions. Recent advancements in molecular genetics, however, can provide the opportunity to address these limitations. The current study reviews an alternative technique, genetically adjusted propensity scores (GAPS) matching, that integrates observed genetic and environmental information to adjust for the confounding of these factors in nonkin individuals. Simulations and a real data example were used to compare the GAPS matching approach to the discordant MZ twin method. Although the results of the simulated comparisons demonstrated that the discordant MZ twin approach remains the more robust statistical technique to adjust for shared environmental and genetic factors, GAPS matching – under certain conditions – could represent a viable alternative when MZ twin samples are unavailable. Overall, the findings suggest that GAPS matching can potentially provide an alternative to the discordant MZ twin approach when limited variation exists between identical twin pairs. Moreover, the ability to adjust for gene-nonshared environment interactions represents a potential advancement associated with the GAPS approach. The limitations of the approach, as well as polygenic risk scores, are also discussed.

PMID:35506340 | DOI:10.1017/thg.2022.2

Hosp Pediatr. 2022 May 4:e2021006397. doi: 10.1542/hpeds.2021-006397. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe changes in neonatal use of acute care services during the coronavirus disease 2019 (COVID-19) pandemic. We hypothesized neonatal visits would decrease and the degree of decline would vary by condition.

METHODS: We conducted a retrospective cohort study of neonatal visits to the urgent cares, emergency departments, inpatient units, and intensive care units at a free-standing pediatric healthcare system during the COVID-19 pandemic and a comparator period. We included visits of infants presenting for acute care within the first 30 days of life. Transfers from a referring nursery, inpatient unit, or ICU were excluded. Data collected included demographics, patient characteristics, and visit characteristics. Descriptive statistics and χ2 tests were used for analyses and to determine statistically significant differences.

RESULTS: We identified 4439 neonatal acute care visits, of which 2677 occurred in the prepandemic period and 1762 in the COVID-19 pandemic period, representing a 34.2% decline. Urgent cares and emergency departments experienced the greatest decline in visits for infectious conditions (49%) and the proportion of these visits also significantly decreased. Similarly, the largest clinically significant declines in hospitalizations were for infectious and respiratory diagnoses (48% and 52%, respectively) and the proportions of these hospitalizations also significantly decreased. Despite a small decline in hospitalizations for jaundice, the proportion of jaundice hospitalizations significantly increased by 5.7% (P = .02).

CONCLUSIONS: The COVID-19 pandemic was associated with a significant reduction in neonatal visits across a spectrum of acute care settings. The impact on use varied by diagnosis with the most notable decline in visits for infectious conditions.

PMID:35506337 | DOI:10.1542/hpeds.2021-006397

Psychol Med. 2022 May 4:1-13. doi: 10.1017/S0033291722000356. Online ahead of print.

ABSTRACT

BACKGROUND: Lemborexant has demonstrated statistically significant improvements in sleep onset and sleep maintenance compared with placebo and zolpidem tartrate extended release, measured both objectively using polysomnography and subjectively using sleep diaries, in the phase 3 clinical trial SUNRISE 1. This study evaluated the cost-effectiveness of lemborexant compared with suvorexant, zolpidem immediate release (IR), and untreated insomnia.

METHODS: A decision-tree model was developed for falls, motor vehicle collisions, and workplace accidents associated with insomnia and insomnia treatments from a Japanese healthcare perspective and with a 6-month time horizon. The model extracted subjective sleep onset latency treatment responses and disutility values for non-responders from SUNRISE 1. Cost-effectiveness was assessed using incremental cost per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were conducted to evaluate the impact of parameter uncertainty on the results.

RESULTS: In the base-case analysis, the mean estimated QALYs for lemborexant, suvorexant, zolpidem-IR, and untreated insomnia were 0.4220, 0.4204, 0.4113, and 0.4163, and expected medical costs were JPY 34 034, JPY 38 371, JPY 38 139, and JPY 15 383, respectively. Lemborexant saved JPY 4337 and JPY 4105 compared with suvorexant or zolpidem-IR, respectively, while conferring QALY benefits. The incremental cost-effectiveness ratio (ICER) of lemborexant compared with that of untreated insomnia was JPY 3 220 975 /QALY. Lemborexant was dominant over suvorexant and zolpidem-IR and was cost-effective when compared with untreated insomnia. Sensitivity analyses supported the results’ robustness.

CONCLUSIONS: In a Japanese clinical practice setting, lemborexant may represent a better investment for treating insomnia in the healthcare system in Japan.

PMID:35506334 | DOI:10.1017/S0033291722000356

Nucl Med Commun. 2022 May 4. doi: 10.1097/MNM.0000000000001563. Online ahead of print.

ABSTRACT

OBJECTIVE: To systematically investigate the physiological distribution and benign lesion incidental uptake of Al18F-NOTA-FAPI-04 (18F-FAPI) in cancer patients to establish the normal uptake range in relevant organs and lesions.

METHODS: Twenty patients who underwent 18F-FAPI PET/CT imaging were retrospectively assessed. Organ and benign lesion tracer uptake was quantified based on standardized uptake values (SUVmax and SUVmean). We compared the variation in tracer uptake in certain organs between men and women, analyzed the possible reasons for diffuse uptake in the thyroid, and assessed tracer uptake variations in the uterus in different menstrual cycle phases. Incidental tracer uptake in benign lesions was also assessed.

RESULTS: Physiological 18F-FAPI uptake was observed in the urinary tract, biliary tract system, submandibular glands, pancreas, thyroid, uterus, intestine, prostate gland, parotid gland, myocardium, kidney cortex, and muscles, but not the brain, lungs, liver, spleen, colon, and breasts. The SUVmean for each organ was similar for women and men (all P > 0.05). Diffuse tracer uptake in the thyroid was caused by normal thyroid or thyroiditis; there were no statistically significant differences between them (SUVmax: t = -1.3, P = 0.25; SUVmean: t = -1.1, P = 0.31). There was a significant difference for uterus uptake among different menstrual cycle phases (SUVmax: F = 5.08, P = 0.04; SUVmean: F = 5.19, P = 0.04). Incidental benign lesion tracer uptake was observed in patients with esophagitis, thyroiditis, arthritis, fractures, and uterine fibroids.

CONCLUSION: This study provides a reference range for 18F-FAPI uptake in relevant organs and benign lesions. Benign lesion 18F-FAPI uptake may reduce 18F-FAPI PET/CT specificity.

PMID:35506283 | DOI:10.1097/MNM.0000000000001563

Cancer Epidemiol Biomarkers Prev. 2022 May 4;31(5):999-1005. doi: 10.1158/1055-9965.EPI-21-1165.

ABSTRACT

BACKGROUND: There is a growing body of evidence supporting the protective effect of statins on the risk of prostate cancer, in particular aggressive disease. Past research has mostly been conducted in North American cohorts of White men.

METHODS: In the multiethnic cohort (MEC), we investigated the association of prediagnostic statin use with the incidence and mortality of prostate cancer across five racial/ethnic groups (White, African American, Japanese American, Latino, and Native Hawaiian).

RESULTS: Among 31,062 male participants who completed a detailed medication questionnaire, 31.4% reported use of statins, 2,748 developed prostate cancer, and 261 died from the disease. After adjusting for potential confounders, prediagnostic statin use was associated with a 32% lower risk of fatal prostate cancer [95% confidence interval (CI) = 0.50-0.91], with the inverse association suggested consistently across the five racial/ethnic groups. Moreover, an 11% lower risk of aggressive prostate cancer (95% CI = 0.76-1.03) was observed in statin users than in nonusers. We found no statistically significant association between prediagnostic statin use and total prostate cancer or nonaggressive disease. Prediagnostic statin use was suggestively associated with a 19% reduction in prostate cancer-specific mortality (95% CI = 0.59-1.10) and an 8% reduction in all-cause mortality (95% CI = 0.79-1.07).

CONCLUSIONS: In the MEC, prediagnostic use of statin was associated with lower risks of aggressive forms of prostate cancer.

IMPACT: Our findings provide further support for the potential benefits of statins in reducing the risk and mortality of prostate cancer, especially aggressive disease.

PMID:35506249 | DOI:10.1158/1055-9965.EPI-21-1165

Biomarkers. 2022 May 4:1-29. doi: 10.1080/1354750X.2022.2071991. Online ahead of print.

ABSTRACT

The diagnosis of tuberculous meningitis (TBM) in children is often delayed due to diagnostic difficulties. New tools are urgently needed to improve the diagnosis of the disease in this vulnerable group. The present study aimed to validate the accuracy of recently identified host cerebrospinal (CSF) biomarkers as candidates for the diagnosis of TBM in children. We collected CSF samples from 87 children aged 3 months to 13 years, that were consecutively admitted at a tertiary hospital in Cape Town, South Africa, on suspicion of having TBM. We evaluated the concentrations of 67 selected host protein biomarkers using a multiplex platform. Previously identified 3-marker (VEGF-A + IFN-γ + MPO) and 4-marker (IFN-γ + MPO + ICAM-1 + IL-8) signatures diagnosed TBM with AUCs of 0.89 (95% CI, 0.81-0.97) and 0.87 (95% CI, 0.79-0.95) respectively; sensitivities of 80.6% (95% CI, 62.5-92.5%) and 81.6% (95% CI, 65.7-92.3%), and specificities of 86.8% (71.9-95.6%) and 83.7% (70.4-92.7%) respectively. Furthermore, a new combination between the analytes (CC4b + CC4 + procalcitonin + CCL1) showed promise, with an AUC of 0.98 (95% CI, 0.94-1.00). We have shown that the accuracies of previously identified candidate CSF biomarkers for childhood TBM was reproducible. Our findings augur well for the future development of a simple bedside test for the rapid diagnosis of TBM in children.

PMID:35506251 | DOI:10.1080/1354750X.2022.2071991

J Cosmet Dermatol. 2022 May 4. doi: 10.1111/jocd.15039. Online ahead of print.

ABSTRACT

BACKGROUND: Early detection of psoriasis is still an open discussion. Psoriatic lesions are characterized by red/scaly plaques affecting different body-sites.

OBJECTIVES: To evaluate the levels of Programmed cell death protein-1(PD-1) and Angiopoietins-2(Ang-2) in serum,lesional and perilesional of psoriatic patients and correlating them with controls and disease severity.

SUBJECTS AND METHODS: Serum samples were obtained from 40 participants subdivided equally into psoriatic and healthy controls, 4mm punch_biopsy equally from lesional and perilesional skin of individuals. PD-1/ANG-2 ELISA kits were used for determining the serum and tissue levels among groups.

RESULTS: Serum and tissue levels of PD-1 and Ang-2 were overexpressed in psoriatic patients compared to controls. There was a statistical difference between patients and controls in level of PD-1(serum and tissue) with p-value 0.006 and 0.0001 respectively. There was a statistical difference between both groups for ANG-2(serum and tissue) with p-value 0.03 and 0.0001 respectively. There were positive correlations between PASI score and PD-1 in tissue (r=0.467, p=0.038). Also, positive correlation between the level of PD-1 in serum and tissue (r=0.369,p=0.019), the serum levels of PD-1 and ANG-2 (r=0.78,p>0.0001), PD-1 and Ang-2 in tissue (r=0.583,p=0.0001) were detected.

CONCLUSION: PD-1 and ANG-2 can be highly recommended to determine the severity of psoriasis.

PMID:35506216 | DOI:10.1111/jocd.15039

J R Soc Interface. 2022 May;19(190):20210781. doi: 10.1098/rsif.2021.0781. Epub 2022 May 4.

ABSTRACT

Face masks do not completely prevent transmission of respiratory infections, but masked individuals are likely to inhale fewer infectious particles. If smaller infectious doses tend to yield milder infections, yet ultimately induce similar levels of immunity, then masking could reduce the prevalence of severe disease even if the total number of infections is unaffected. It has been suggested that this effect of masking is analogous to the pre-vaccination practice of variolation for smallpox, whereby susceptible individuals were intentionally infected with small doses of live virus (and often acquired immunity without severe disease). We present a simple epidemiological model in which mask-induced variolation causes milder infections, potentially with lower transmission rate and/or different duration. We derive relationships between the effectiveness of mask-induced variolation and important epidemiological metrics (the basic reproduction number and initial epidemic growth rate, and the peak prevalence, attack rate and equilibrium prevalence of severe infections). We illustrate our results using parameter estimates for the original SARS-CoV-2 wild-type virus, as well as the Alpha, Delta and Omicron variants. Our results suggest that if variolation is a genuine side-effect of masking, then the importance of face masks as a tool for reducing healthcare burdens from COVID-19 may be under-appreciated.

PMID:35506215 | DOI:10.1098/rsif.2021.0781

J R Soc Interface. 2022 May;19(190):20220041. doi: 10.1098/rsif.2022.0041. Epub 2022 May 4.

ABSTRACT

The establishment of young organisms in harsh environments often requires a window of opportunity (WoO). That is, a short time window in which environmental conditions drop long enough below the hostile average level, giving the organism time to develop tolerance and transition into stable existence. It has been suggested that this kind of establishment dynamics is a noise-induced transition between two alternate states. Understanding how temporal variability (i.e. noise) in environmental conditions affects establishment of organisms is therefore key, yet not well understood or included explicitly in the WoO framework. In this paper, we develop a coherent theoretical framework for understanding when the WoO open or close based on simple dichotomous environmental variation. We reveal that understanding of the intrinsic timescales of both the developing organism and the environment is fundamental to predict if organisms can or cannot establish. These insights have allowed us to develop statistical laws for predicting establishment probabilities based on the period and variance of the fluctuations in naturally variable environments. Based on this framework, we now get a clear understanding of how changes in the timing and magnitude of climate variability or management can mediate establishment chances.

PMID:35506213 | DOI:10.1098/rsif.2022.0041