Category: Statistics

Phytomedicine. 2022 Jun 15;104:154278. doi: 10.1016/j.phymed.2022.154278. Online ahead of print.

ABSTRACT

BACKGROUND: The Qilong capsule (QLC) is a Chinese patented medicine characterized by an equal emphasis on replenishing Qi and activating blood circulation. In 2000, China’s FDA approved the use of QLC for ischemic stroke (IS). However, there is not yet much high-quality evidence of the clinical effectiveness of QLC combined with conventional treatment (CT) for IS with Qi deficiency and blood stasis syndrome.

PURPOSE: In this study, we conducted a prospective, multicenter, non-randomized controlled trial at 7 hospitals in China to investigate the clinical effectiveness of QLC combined with CT for IS with Qi deficiency and blood stasis syndrome.

METHODS: Participants aged 35 to 80 years old diagnosed as IS with Qi deficiency and blood stasis syndrome in TCM were recruited. Participants were treated with QLC (intervention group) or non-QLC (control group). The intervention course of QLC was 12 weeks. All participants in two groups received standard treatment. All participants returned for in-person follow-up visits at the 12th week and 24th week. Primary outcome measures included a modified Rankin Scale (mRS), the National Institute of Health Stroke Scale (NIHSS), and the Barthel Index (BI). Secondary outcome measures included TCM syndromes (Qi deficiency syndrome score, blood stasis syndrome score), psychological index (self-rating depression scale, SDS; self-rating anxiety scale, SAS), blood lipid index, blood coagulation index, homocysteine, and favorable functional outcome (mRS 0 – 3). Multiple imputations were used for any missing data. Propensity score matching (PSM) was used to deal with any confounding factors (age, gender, scale score, etc.). Rank alignment transformation variance analysis (ART ANOVA) and generalized linear mixed model (GLMM) were introduced to improve the scientific and accuracy of repeated measurement data. All statistical calculations were carried out with R 3.6.1 statistical analysis software.

RESULTS: A total of 2468 participants were screened from November 2016 to January 2019. Finally, 2302 eligible participants were included in the analysis. There were 1260 participants in the intervention group (QLC group) and 1042 participants in the control group (non-QLC group). After PSM matching, sub-samples of 300 participants in the QLC group and 300 participants in the non-QLC group were finally formed. The final results of clinical effectiveness are the same results shared by the total samples and sub-samples after PSM. In the 24th week after treatment, QLC combined with CT proved to be significantly better than CT alone in reducing the scores of mRS (p < 0.05), NIHSS (p < 0.001), Qi deficiency syndrome (p < 0.01), and blood stasis syndrome (p < 0.001), SAS (p < 0.05), as well as in improving BI score (p < 0.05). The favourable functional outcome (mRS score of 0 to 3 at week 12) was statistically different between QLC and non-QLC group in the sub-samples (p < 0.01, 97% vs 91.7%). The results of the ART ANOVA showed that the improvement of mRS (p < 0.01), BI (p < 0.05) and NIHSS (p < 0.001) in QLC group was better than non-QLC group when the interaction effect was considered. The results of GLMM showed that the reduction of mRS and NIHSS scores of patients in the QLC group were better than those of the non-QLC group (p < 0.001). The BI score of the QLC group in the sub-samples after PSM increased more than the non-QLC group (p < 0.001). There was no evidence showing that QLC can cause serious adverse reactions (ADRs) in treating patients with IS.

CONCLUSION: QLC combined with CT was better than CT alone in reducing mRS score, NIHSS score, Qi deficiency syndrome score, blood stasis syndrome score, and SAS score, as well as improving BI score after treatment. Further high-quality RCTs are needed to confirm the positive results. The study protocol was embedded in a registry study that registered in the Clinical Trials USA Registry (registration No. NCT03174535).

PMID:35780589 | DOI:10.1016/j.phymed.2022.154278

Int J Drug Policy. 2022 Jun 29;107:103770. doi: 10.1016/j.drugpo.2022.103770. Online ahead of print.

ABSTRACT

BACKGROUND: Most states in the U.S. have enacted prescription opioid quantity limits to curb long-term opioid dependency. While several studies of these policies find reductions in subsequent prescriptions, others find mixed results in reducing overall opioid prescriptions and prescription length. Our objective was to examine three opioid restriction policies implemented in Louisiana Medicaid: (1) a 15-day quantity limit for opioid-naïve acute pain patients, (2) a subsequent further reduction to a 7-day quantity limit and a Morphine Milligram Equivalent Dosing (MME) limit of 120mg per day, and (3) a final reduction in daily MMEs to 90mg per day.

METHODS: Using interrupted time series (ITS) models with Medicaid pharmacy claims data, we estimated changes in trends of opioid prescription fills associated with opioid restriction policies in Louisiana Medicaid. Outcomes of interest included average opioid prescription length, average MMEs per day, and the likelihood that an opioid-naïve beneficiary who received their first opioid prescription filled a second prescription within 30 or 60 days of their initial fill.

RESULTS: 15-day and 7-day opioid prescription quantity limits were associated with a 0.720 and a 0.401 day reduction in average opioid prescription lengths. 7-day limits were associated with a 2.7 and a 3.0 percentage point reduction in the likelihood of a second opioid prescription fill within 30 or 60 days of the initial fill. The 120mg per day MME limit was associated with a 0.80 MMEs per day reduction in average daily MMEs. Further restricting daily MMEs to 90mg per day had no statistically significant association with average daily MMEs.

CONCLUSION: These findings suggest that efforts to limit opioid exposure through the implementation of prescription quantity limits and MME restrictions in Louisiana’s Medicaid program were successful and are likely to be associated with a reduction in future opioid dependency among the state’s Medicaid population.

PMID:35780564 | DOI:10.1016/j.drugpo.2022.103770

Accid Anal Prev. 2022 Jun 30;174:106763. doi: 10.1016/j.aap.2022.106763. Online ahead of print.

ABSTRACT

Among all crashes involving cyclists, a motorist approaching from behind a cyclist on a shared lane is particularly dangerous and likely to result in serious injuries and fatalities. Previous research has highlighted that inadequate lateral distance and high vehicle speed are among the main contributing factors of crashes involving cars overtaking cyclists. A new advanced driver assistance system (ADAS) which supports drivers as they overtake cyclists was designed to avoid or, at least, mitigate crashes. In human-machine interface (HMI) design, the information was presented via multiple modalities with a multistage warning system. A combination of lateral clearance (LC) and time-to-danger (TTD) parameters was used as ADAS activation criterion. Experimentation was carried out using the medium-fidelity driving simulator at the Transportation Research Institute (IMOB) of Hasselt University in Belgium. Forty-eight drivers drove the two-lane rural experimental route two times, in baseline condition and with the ADAS activated, testing three overtaking events. Statistical tests showed that the proposed in-vehicle driving assistance system had a significant effect in increasing 1) the length of the passing phase, 2) the LC in the overtaking passing phase, and 3) the TTD along the overtaking maneuver. No effect of the ADAS system on vehicle speed was observed. Overall, the designed system is effective in improving car-cyclist overtaking behaviour in terms of both safety and cyclists’ mobility.

PMID:35780562 | DOI:10.1016/j.aap.2022.106763

Comput Methods Programs Biomed. 2022 May 25;223:106898. doi: 10.1016/j.cmpb.2022.106898. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Recent clinical data suggest that 75% of patients undergoing surgery are anxious, despite pharmacological measures to relieve anxiety. As an alternative to the administration of drugs, the scientific literature reports the relevant psychophysiological effects of auditory and visual stimulation in reducing preoperative anxiety. The main objective of this study is the development of a portable computer-controlled device for the simultaneous combined administration of audio-visual stimuli and the evaluation of this device through the collection and the statistical analysis of psychophysiological parameters strictly related to the state of anxiety.

METHODS: A new algorithmic approach for the real-time association of sounds and colours is proposed and implemented in a low-cost architectural platform. The combined administration of auditory and visual stimuli is tested on 220 subjects undergoing dental surgery; in particular, psychophysiological parameters are collected and evaluated in four experimental conditions, in order to demonstrate the efficacy of cross-modal stimulation (auditory and visual) compared to non-pharmacological treatments based on monomodal stimuli (auditory or visual).

RESULTS: Non-parametric statistical techniques applied to the recorded experimental data show that the experimental conditions considered significantly differ. Pairwise comparisons between experimental groups show that the combined administration of sounds and colors significantly reduces the level of anxiety, systolic blood pressure and heart rate to a greater extent than monomodal stimulation.

CONCLUSION: The study demonstrates the potential benefits of a device for the combined administration of auditory and visual stimuli. The developed device has proven effective in reducing preoperative anxiety levels, becoming a serious candidate for non-pharmacological therapies. The study also encourages a deeper investigation of models capable of better capturing the potential of cross-modal stimulation, maximizing the desired effects (relaxation, arousal) on patients awaiting specific medical treatments.

PMID:35780520 | DOI:10.1016/j.cmpb.2022.106898

Epidemics. 2022 Jun 22;40:100604. doi: 10.1016/j.epidem.2022.100604. Online ahead of print.

ABSTRACT

The time-varying reproduction number (R_t) can change rapidly over the course of a pandemic due to changing restrictions, behaviours, and levels of population immunity. Many methods exist that allow the estimation of R_t from case data. However, these are not easily adapted to point prevalence data nor can they infer R_t across periods of missing data. We developed a Bayesian P-spline model suitable for fitting to a wide range of epidemic time-series, including point-prevalence data. We demonstrate the utility of the model by fitting to periodic daily SARS-CoV-2 swab-positivity data in England from the first 7 rounds (May 2020-December 2020) of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Estimates of R_t over the period of two subsequent rounds (6-8 weeks) and single rounds (2-3 weeks) inferred using the Bayesian P-spline model were broadly consistent with estimates from a simple exponential model, with overlapping credible intervals. However, there were sometimes substantial differences in point estimates. The Bayesian P-spline model was further able to infer changes in R_t over shorter periods tracking a temporary increase above one during late-May 2020, a gradual increase in R_t over the summer of 2020 as restrictions were eased, and a reduction in R_t during England’s second national lockdown followed by an increase as the Alpha variant surged. The model is robust against both under-fitting and over-fitting and is able to interpolate between periods of available data; it is a particularly versatile model when growth rate can change over small timescales, as in the current SARS-CoV-2 pandemic. This work highlights the importance of pairing robust methods with representative samples to track pandemics.

PMID:35780515 | DOI:10.1016/j.epidem.2022.100604

Eur J Heart Fail. 2022 Jul 3. doi: 10.1002/ejhf.2602. Online ahead of print.

ABSTRACT

AIMS: Benzodiazepines have been used as safe anxiolytic drugs for decades and some authors have suggested they could be an alternative for morphine for treating acute cardiogenic pulmonary edema (ACPE). We compared the efficacy and safety of midazolam and morphine in patients with ACPE.

METHODS AND RESULTS: A randomized, multicenter, open-label, blinded endpoint clinical trial was performed in 7 Spanish emergency departments (EDs). Patients >18 years old clinically diagnosed with ACPE and with dyspnea and anxiety were randomized (1:1) at ED arrival to receive either intravenous midazolam or morphine. Efficacy was assessed by in-hospital all-cause mortality (primary endpoint). Safety was assessed through serious adverse event (SAE) reporting, and composite endpoint included 30-day mortality and SAE. Analyses were made on an intention-to-treat basis. The trial was stopped early after a planned interim analysis by the safety monitoring committee. At that time, 111 patients had been randomized: 55 to midazolam and 56 to morphine. There were no statistically significantly differences in primary endpoint (in-hospital mortality for midazolam/morphine 12.7%/17.9%, Risk Ratio[RR], 0.71; 95% confidence interval[CI], 0.29 to 1.74; P=0.60). SAE were less common with midazolam (18.2%/42.9%, RR, 0.42; 95%CI, 0.22 to 0.80; P=0.007), as were the composite safety endpoint (23.6%/44.6%, RR, 0.53; 95% CI, 0.30 to 0.92; P=0.03).

CONCLUSION: Although the number of patients was too small to draw final conclusions and there were no significant differences in mortality between midazolam and morphine, a significantly higher rate of SAEs was found in the morphine group.

PMID:35780488 | DOI:10.1002/ejhf.2602

Transpl Infect Dis. 2022 Jul 3. doi: 10.1111/tid.13898. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate epidemiology, risk-factors and outcomes of high-level cytomegalovirus (CMV) viremia in liver transplant recipients.

METHODS: Adult patients receiving a liver transplant between 1/1/2017-9/30/2020 were evaluated. Viral loads at UW Health Clinical Laboratories were required to allow for numerical comparison. Primary objective was incidence and outcomes of high-level (HL) CMV viremia (viral-load >100,000 IU/mL). Secondary objective was to elucidate risk factors to allow targeted interventions.

RESULTS: 209 patients met inclusion criteria; 175 kept their graft for at least 240 days. Of these 9 patients developed HL CMV, 28 developed low-level (LL CMV, viral-load 250-100,000 IU/mL) and 138 did not develop CMV viremia. When comparing these 3 groups via classic statistical methods time from transplant to viremia was similar (HL 158 ± 77 days, LL 150 ± 76 days). Clinical factors were also similar with the exception of donor seropositivity (HL 87.5%, LL 70.4%, No CMV 49.6%, p = 0.025). HL CMV was significantly associated with graft loss (p < 0.0001) on Kaplan-Meier analysis; graft loss in the LL CMV group did not differ from the No CMV group (p = 0.96) To allow valid assessment of risk factors in the total study population (n = 209) models of time-varying covariates were used and Cox proportional hazards ratios were calculated. In this analysis HL CMV was associated with a significantly increased risk of graft loss (HR 5.6, p = 0.0016). When investigating risk factors associated with HL CMV, donor seropositivity significantly increased risk (HR 8.85, 95% CI 1.13-71.43, p = 0.038). Pre-transplant total bilirubin (HR 1.04, 95% CI 0.998-1.07, p = 0.06) trended towards significance. Recipient seronegativity, liver disease, clinical and allocation MELD, transplant surgery duration, age, sex, induction immunosuppression, and maintenance immunosuppression were not significantly associated with development of HL CMV.

CONCLUSION: HL CMV after liver transplant is uncommon but is associated with a significantly increased risk of graft loss that is not present in those patients who develop LL CMV or do not develop CMV viremia. Given these negative graft effects, CMV stewardship interventions targeting recipients of CMV seropositive allografts are warranted. Future larger scale studies evaluating the potential role of other factors in risk stratification are needed. This article is protected by copyright. All rights reserved.

PMID:35780512 | DOI:10.1111/tid.13898

Nutr Clin Pract. 2022 Jul 3. doi: 10.1002/ncp.10890. Online ahead of print.

ABSTRACT

BACKGROUND: Nutrition support is an essential part of critical care medicine. It is commonly accepted that for the critically ill patient, enteral nutrition (EN) is favored. For the patient who receives neuromuscular blockades, EN may be held, or initiation delayed, because of concerns for EN intolerance. We hypothesized there would be no difference in EN tolerance between groups receiving cisatracurium while receiving EN compared with those not receiving cisatracurium.

METHODS: This was a retrospective study that included 459 patients from a combined medical and surgical intensive care unit. There were 44 patients who received cisatracurium with EN and 415 who received EN alone. Data collected included gastric residual volume (GRV) and emesis occurrences, new-onset abdominal pain, new or worsening abdominal distention, and bowel ischemia.

RESULTS: There were more patients with new or worsening abdominal distention in the group receiving cisatracurium (31.82% vs 14.94%; P < 0.01) as well as occurrences of GRV > 300 ml (P < 0.01). There was no statistically significant difference between the groups regarding emesis, new-onset abdominal pain, or bowel ischemia.

CONCLUSION: Our findings suggest that it is acceptable to provide patients with EN who are receiving cisatracurium.

PMID:35780473 | DOI:10.1002/ncp.10890

Pharmaceut Med. 2022 Jul 3. doi: 10.1007/s40290-022-00435-x. Online ahead of print.

ABSTRACT

In the last decade there has been a significant increase in the literature discussing the use of benefit-risk methods in medical product (including devices) development. Government agencies, medical product industry groups, academia, and collaborative consortia have extensively discussed the advantages of structured benefit-risk assessments. However, the abundance of information has not resulted in a consistent way to utilize these findings in medical product development. Guidelines and papers on methods, even though well structured, have not led to a firm consensus on a clear and consistent approach. This paper summarizes the global landscape of benefit-risk considerations for product- or program-level decisions from available literature and regulatory guidance, providing the perspectives of three stakeholder groups-regulators, collaborative groups and consortia, and patients. The paper identifies key themes, potential impact on benefit-risk assessments, and significant future trends.

PMID:35780471 | DOI:10.1007/s40290-022-00435-x

Am J Epidemiol. 2022 Jul 2:kwac117. doi: 10.1093/aje/kwac117. Online ahead of print.

ABSTRACT

The early identification of clusters of persons with tuberculosis (TB) that will grow to become outbreaks creates an opportunity for intervention in preventing future TB cases. We used surveillance data (2009-2018) from the United States, statistically derived definitions of unexpected growth, and machine learning techniques to predict which clusters of genotype-matched TB cases are most likely to continue accumulating cases above expected growth within a 1-year follow-up period. We developed a model to predict which clusters are likely to grow on a training and testing dataset that was generalizable to a validation dataset. Our model shows that characteristics of clusters were more important than the social, demographic, and clinical characteristics of the patients in those clusters. For instance, the time between cases before unexpected growth was identified as the most important of our predictors. A faster accumulation of cases increased the probability of excess growth being predicted during the follow-up period. We demonstrated that combining the characteristics of clusters and cases with machine learning can add to existing tools to help prioritize which clusters may benefit most from public health interventions. For example, consideration of an entire cluster, not only an individual patient, may assist in interrupting ongoing transmission.

PMID:35780450 | DOI:10.1093/aje/kwac117