Category: Statistics

J Prosthet Dent. 2022 May 5:S0022-3913(22)00220-7. doi: 10.1016/j.prosdent.2022.04.003. Online ahead of print.

ABSTRACT

STATEMENT OF PROBLEM: Sintering-based computer-aided metal manufacturing strategies have been proposed as an alternative to hard metal milling. While these fabrication methods have been evaluated in terms of marginal and internal discrepancies and bond strength to porcelain, limited information on metal frameworks is available regarding their flexural yield strength.

PURPOSE: The purpose of this in vitro study was to evaluate the flexural yield strength of 3-unit cobalt-chromium (Co-Cr) metal frameworks fabricated by hard metal milling (HMM), presintered soft metal milling (PSMM), and direct metal laser melting (DMLM) with 25-μm and 50-μm layer thicknesses.

MATERIAL AND METHODS: Three-unit master metal die models were prepared. A total of 40 metal frameworks (n=10) were fabricated by using HMM (group HM), PSMM (group PSM), and DMLM with 25-μm (group LM25) and 50-μm layer thicknesses (group LM50). Metal frameworks were cemented to the master die and then subjected to a 3-point bend test. The flexural yield force was used to calculate the flexural yield strength. The data were statistically analyzed (α=.05). One metal framework from each group was evaluated with scanning electron microscopy for microstructural analysis.

RESULTS: The group LM50 exhibited the lowest significant (P<.001) flexural yield strength values. The group HM exhibited higher flexural yield strength values than the other groups. No significant difference was found between the groups LM25 and PSM (P=.954) or between the groups PSM and HM (P=.111).

CONCLUSIONS: The fabrication method significantly affected the flexural yield strength of metal frameworks. Metal frameworks fabricated by DMLM with a 50-μm layer thickness exhibited considerably lower flexural yield strength values.

PMID:35527067 | DOI:10.1016/j.prosdent.2022.04.003

Am J Surg. 2022 Apr 30:S0002-9610(22)00296-3. doi: 10.1016/j.amjsurg.2022.04.034. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with limited health literacy (HL) have difficulty understanding written/verbal information. The quality of verbal communication is not well understood. Therefore, our aim was to characterize patient-surgeon conversations and identify opportunities for improvement.

METHODS: New colorectal patient-surgeon encounters were audio-recorded and transcribed. HL was measured. Primary outcomes were rates-of-speech, understandability of words, patient-reported understanding, and usage of medical jargon/statistics. Secondary outcomes included length-of-visit (LOV), conversation possession time, patient-surgeon exchanges, and speech interruptions.

RESULTS: Significant variations existed between surgeons in rates-of-speech and understandability of words (p < 0.05). Faster rates-of-speech were associated with significantly less understandable words (p < 0.05). Patient-reported understanding varied by HL and by surgeon. Conversation possession time and usage of medical jargon/statistics varied significantly by surgeon (p < 0.05) in addition to patient-surgeon exchanges and interruptions. Patients with limited HL had shorter LOV.

CONCLUSIONS: Significant variations exist in how surgeons talk to patients. Opportunities to improve verbal communication include slowing speech and using more understandable words.

PMID:35527045 | DOI:10.1016/j.amjsurg.2022.04.034

Fertil Steril. 2022 May 5:S0015-0282(22)00190-X. doi: 10.1016/j.fertnstert.2022.03.006. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the neurodevelopmental outcomes at 18-24 months of corrected age between preterm (<32 weeks of gestational age) infants with very low birth weight (VLBW) conceived with and without the assistance of in vitro fertilization (IVF).

DESIGN: Prospective cohort study.

SETTING: Not applicable.

PATIENT(S): In total, 4,940 infants with VLBW were born before 32 weeks of gestational age from January 2013 to December 2015.

INTERVENTION(S): In vitro fertilization.

MAIN OUTCOME MEASURE(S): Neuromotor or sensory disability (primary outcome) and developmental delay assessed using the Bayley Scales of Infant and Toddler Development (secondary outcome) at 18-24 months of corrected age.

RESULT(S): Of the 4,940 infants with VLBW enrolled, 2,818 surviving infants who were followed up for neurodevelopmental assessment at 18-24 months of corrected age were included in the study. Of these 2,818 infants, 630 (22.4%) were conceived with the assistance of IVF, and 2,188 (77.6%) were not. After adjustment for potential confounders, no statistically significant differences were found in the rate of neuromotor or sensory disability at 18-24 months of corrected age between infants conceived with and without the assistance of IVF. After excluding infants with neuromotor or sensory disability, the rate of developmental delay was also comparable between those conceived with and without the assistance of IVF.

CONCLUSION(S): This study showed comparable neurodevelopmental outcomes at 18-24 months of corrected age between preterm infants with VLBW conceived with and without the assistance of IVF.

PMID:35527036 | DOI:10.1016/j.fertnstert.2022.03.006

Am J Health Syst Pharm. 2022 May 8:zxac130. doi: 10.1093/ajhp/zxac130. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: To describe the perceptions of residency candidates, residency practitioners (current residents and preceptors), and residency program directors (RPDs) regarding a virtual interview process for pharmacy residency programs across multiple institutions.

METHODS: In May 2021, an anonymous web-based questionnaire characterizing perceptions of the virtual interview process used during the coronavirus disease 2019 (COVID-19) pandemic was distributed to residency candidates, residency practitioners, and RPDs across 13 institutions. Quantitative responses measured on a 5-point Likert scale were summarized with descriptive statistics, and open-ended questions were analyzed using thematic qualitative methods.

RESULTS: 236 residency candidates and 253 residency practitioners/RPDs completed the questionnaire, yielding response rates of 27.8% (236 of 848), and 38.1% (253 of 663), respectively. Overall, both groups perceived the virtual interview format positively. When asked whether virtual interviews should replace in-person interviews moving forward, 60.0% (18 of 30) of RPDs indicated they agreed or strongly agreed, whereas only 30.5% (61 of 200) of current preceptors/residents and 28.7% (66 of 230) of residency candidates agreed or strongly agreed. Thematic analysis of qualitative responses revealed that while virtual interviews were easier logistically, the lack of in-person interactions was a common concern for many stakeholders. Lastly, the majority (65.0%) of residency candidates reported greater than $1,000 in savings with virtual interviews.

CONCLUSION: Virtual interviews offered logistical and financial benefits. The majority of RPDs were in favor of offering virtual interviews to replace in-person interviews, whereas the majority of residency candidates and practitioners preferred on-site interviews. As restrictions persist with the ongoing pandemic, our results provide insight into best practices for virtual pharmacy residency interviews.

PMID:35526277 | DOI:10.1093/ajhp/zxac130

J Crohns Colitis. 2022 May 8:jjac066. doi: 10.1093/ecco-jcc/jjac066. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The Phase 3 study ENVISION I demonstrated efficacy and safety of adalimumab in pediatric patients with moderate to severe ulcerative colitis. The protocol-specified high dose adalimumab regimen was numerically more efficacious than the standard dose regimen. The objective of this work was to bridge a fixed dosing regimen to the protocol-specified high induction/high maintenance body weight-based dosing regimen studied in ENVISION I, using a pharmacometrics modeling and simulation approach.

METHODS: A stepwise strategy was implemented, including developing an adalimumab pediatric population pharmacokinetic model; using this model to determine a fixed dosing regimen in pediatric ulcerative colitis patients that achieves similar concentrations to those observed in ENVISION I patients; determining adalimumab exposure-response relationship using population pharmacokinetic/pharmacodynamic model and data from ENVISION I; simulating clinical remission rate in pediatric ulcerative colitis patients using the Markov exposure-response model and the dosing regimen determined to provide similar efficacy to that observed in ENVISION I.

RESULTS: Both developed population pharmacokinetic and pharmacokinetic/pharmacodynamic models adequately described the observed data. Adalimumab exposure was identified as a significant predictor of clinical remission at Week 8 based on logistic regression (p <0.01). Simulated efficacy suggested that the fixed dosing regimen performs similarly to the more efficacious dosing regimen used in ENVISION I by providing comparable clinical remission per Partial Mayo Score response rates over time. No relationship between adalimumab exposure and adverse events was identified.

CONCLUSIONS: The population pharmacokinetic/pharmacodynamic model supports the appropriateness of the use of fixed dosing regimen in the pediatric ulcerative colitis population.

PMID:35526272 | DOI:10.1093/ecco-jcc/jjac066

Mol Biol Rep. 2022 May 8. doi: 10.1007/s11033-022-07397-y. Online ahead of print.

ABSTRACT

BACKGROUND: Celiac disease (CeD) and inflammatory bowel disease (IBD) are accompanied by impaired immune responses. To study the immune regulation of these diseases, we evaluated the expression levels of pro-inflammatory (IL-8 and IL-17 A) and anti-inflammatory (IL-10) cytokines in intestinal biopsy specimens of CeD and IBD patients in comparison to healthy subjects.

METHODS AND RESULTS: Intestinal biopsies were collected from 33 patients with IBD, 47 patients with CeD, and 20 healthy individuals. Total RNA was extracted and mRNA expression levels of IL-8, IL-17 A and IL-10 were assessed by qPCR. P-value < 0.05 was considered statistically significant. The expression levels of IL-8 and IL-17 A were higher in biopsies of IBD (UC and CD) and CeD patients compared to the control group (P < 0.05). IBD patients (UC and CD) had higher IL-8 intestinal level than CeD patients (P < 0.0001 and P = 0.0007, respectively). The expression of IL-10 was significantly down-regulated in intestinal biopsies of CeD and IBD patients compared with controls (P < 0.001). In addition, the expression level of this cytokine was significantly lower in IBD patients (P < 0.001 for UC patients and P < 0.0001 for CD patients) than CeD group.

CONCLUSIONS: The three selected pro- and anti-inflammatory cytokines showed a similar expression pattern in both IBD and CeD patients. As IBD and CeD are immune-mediated disorders and are accompanied by inflammatory events, the understanding of the similarities and differences among them can help researchers to find out useful candidate therapeutic protocols. We suggest that larger cohort studies be organized to achieve more insights into this regulation.

PMID:35526253 | DOI:10.1007/s11033-022-07397-y

Biometrics. 2022 May 8. doi: 10.1111/biom.13690. Online ahead of print.

ABSTRACT

Identifying a biomarker or treatment-dose threshold that marks a specified level of risk is an important problem, especially in clinical trials. In view of this goal, we consider a covariate-adjusted threshold-based interventional estimand, which happens to equal the binary treatment-specific mean estimand from the causal inference literature obtained by dichotomizing the continuous biomarker or treatment as above or below a threshold. The unadjusted version of this estimand was considered in Donovan et al. (2019). Expanding upon Stitelmen et al. (2010), we show that this estimand, under conditions, identifies the expected outcome of a stochastic intervention that sets the treatment dose of all participants above the threshold. We propose a novel nonparametric efficient estimator for the covariate-adjusted threshold-response function for the case of informative outcome missingness, which utilizes machine learning and Targeted Minimum-Loss Estimation (TMLE). We prove the estimator is efficient and characterize its asymptotic distribution and robustness properties. Construction of simultaneous 95% confidence bands for the threshold-specific estimand across a set of thresholds is discussed. In the supplementary information, we discuss how to adjust our estimator when the biomarker is missing-at-random, as occurs in clinical trials with biased sampling designs, using inverse-probability-weighting. Efficiency and bias-reduction of the proposed estimator are assessed in simulations. The methods are employed to estimate neutralizing antibody thresholds for virologically confirmed dengue risk in the CYD14 and CYD15 dengue vaccine trials. This article is protected by copyright. All rights reserved.

PMID:35526218 | DOI:10.1111/biom.13690

JMIR Form Res. 2022 May 8. doi: 10.2196/37302. Online ahead of print.

ABSTRACT

BACKGROUND: Digital applications are commonly used to support mental health and well-being. However, successfully retaining and engaging users to complete digital interventions is challenging, and comorbidities such as chronic pain further reduce user engagement. Digital conversational agents may improve user engagement by applying engagement principles that have been implemented within in-person care settings.

OBJECTIVE: To evaluate user retention and engagement with an artificial intelligence (AI)-led digital mental health application (app) that is customized for individuals managing mental health symptoms and coexisting chronic pain (Wysa for Chronic Pain).

METHODS: In this ancillary survival analysis of a clinical trial, participants included 51 adults who presented to a tertiary care center for chronic musculoskeletal pain, who endorsed coexisting symptoms of depression and/or anxiety (PROMIS Depression and/or Anxiety score ≥ 55), and initiated onboarding to an 8-week subscription of Wysa for Chronic Pain. The study outcomes were user retention, defined as revisiting the app each week and the last day of engagement, and user engagement, defined by the number of sessions the user completed.

RESULTS: Users engaged in a cumulative mean of 33.3 sessions during the eight-week study period. The survival analysis depicted a median user retention period (i.e., time to complete disengagement) of 51 days, with the usage of a morning check-in feature statistically significant in its relationship with a longer retention period (p = .001).

CONCLUSIONS: Our findings suggest that the user retention and engagement with a CBT-based conversational agent which is built for users with chronic pain is higher than standard industry metrics. These results have clear implications for addressing issues of suboptimal engagement of digital health interventions and improving access to care for chronic pain. Future work should use these findings to inform the design of evidence-based interventions for individuals with chronic pain and to enhance user retention and engagement of digital health interventions more broadly.

CLINICALTRIAL: NCT04640090, Clinicaltrials.gov.

PMID:35526201 | DOI:10.2196/37302

Hum Reprod Update. 2022 May 8:dmac016. doi: 10.1093/humupd/dmac016. Online ahead of print.

ABSTRACT

BACKGROUND: The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates.

OBJECTIVE AND RATIONALE: The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men.

SEARCH METHODS: A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated.

OUTCOMES: A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias.

WIDER IMPLICATIONS: This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings.

PMID:35526153 | DOI:10.1093/humupd/dmac016

Int J Epidemiol. 2022 May 8:dyac078. doi: 10.1093/ije/dyac078. Online ahead of print.

ABSTRACT

Nearly all diseases are caused by different combinations of exposures. Yet, most epidemiological studies focus on estimating the effect of a single exposure on a health outcome. We present the Causes of Outcome Learning approach (CoOL), which seeks to discover combinations of exposures that lead to an increased risk of a specific outcome in parts of the population. The approach allows for exposures acting alone and in synergy with others. The road map of CoOL involves (i) a pre-computational phase used to define a causal model; (ii) a computational phase with three steps, namely (a) fitting a non-negative model on an additive scale, (b) decomposing risk contributions and (c) clustering individuals based on the risk contributions into subgroups; and (iii) a post-computational phase on hypothesis development, validation and triangulation using new data before eventually updating the causal model. The computational phase uses a tailored neural network for the non-negative model on an additive scale and layer-wise relevance propagation for the risk decomposition through this model. We demonstrate the approach on simulated and real-life data using the R package ‘CoOL’. The presentation focuses on binary exposures and outcomes but can also be extended to other measurement types. This approach encourages and enables researchers to identify combinations of exposures as potential causes of the health outcome of interest. Expanding our ability to discover complex causes could eventually result in more effective, targeted and informed interventions prioritized for their public health impact.

PMID:35526156 | DOI:10.1093/ije/dyac078