Category: Statistics

Infect Chemother. 2021 Jun;53(2):221-237. doi: 10.3947/ic.2021.0016.

ABSTRACT

This study aims to assess anakinra’s safety and efficacy for treating severe coronavirus disease 2019 (COVID-19). Numerous electronic databases were searched and finally 15 studies with a total of 3,530 patients, 757 in the anakinra arm, 1,685 in the control arm were included. The pooled adjusted odds ratio (OR) for mortality in the treatment arm was 0.34 (95% confidence interval [CI], 0.21 – 0.54, I² = 48%), indicating a significant association between anakinra and mortality. A significant association was found regarding mechanical ventilation requirements in anakinra group compared to the control group OR, 0.68 (95% CI, 0.49 – 0.95, I² = 50%). For the safety of anakinra, we evaluated thromboembolism risk and liver transaminases elevation. Thromboembolism risk was OR, 1.59 (95% CI, 0.65 – 3.91, I² = 0%) and elevation in liver transaminases with OR was 1.35 (95% CI, 0.61 – 3.03, I² = 76%). Both were not statistically significant over the control group. Anakinra is beneficial in lowering mortality in COVID-19 patients. However, these non-significant differences in the safety profile between the anakinra and control groups may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra’s safety profile.

PMID:34216117 | DOI:10.3947/ic.2021.0016

Diabetes Metab Res Rev. 2021 Jul 3:e3482. doi: 10.1002/dmrr.3482. Online ahead of print.

ABSTRACT

AIMS: The study aimed to elucidate the effects of rare genetic variants on the risk of type 2 diabetes (T2D).

MATERIALS AND METHODS: Weighted burden analysis of rare variants was applied to a sample of 200,000 exome-sequenced participants in the UK Biobank project, of whom over 13,000 were identified as having T2D. Variant weights were allocated based on allele frequency and predicted effect, as informed by a previous analysis of hyperlipidaemia.

RESULTS: There was an exome-wide significant increased burden of rare, functional variants in three genes, GCK, HNF4A and GIGYF1. GIGYF1 has not previously been identified as a diabetes risk gene and its product appears to be involved in the modification of insulin signalling. A number of other genes did not attain exome-wide significance but were highly ranked and potentially of interest, including ALAD, PPARG, GYG1 and GHRL. Loss of function (LOF) variants were associated with T2D in GCK and GIGYF1 whereas nonsynonymous variants annotated as probably damaging were associated in GCK and HNF4A. Overall, fewer than 1% of T2D cases carried one of these variants. In HNF1A and HNF1B there was an excess of LOF variants among cases but the small numbers of these fell short of statistical significance.

CONCLUSIONS: Rare genetic variants make an identifiable contribution to T2D in a small number of cases but these may provide valuable insights into disease mechanisms. As larger samples become available it is likely that additional genetic factors will be identified. This research has been conducted using the UK Biobank Resource. This article is protected by copyright. All rights reserved.

PMID:34216101 | DOI:10.1002/dmrr.3482

Pain Pract. 2021 Jul 3. doi: 10.1111/papr.13055. Online ahead of print.

ABSTRACT

The objective of this prospective, multicenter study is to characterize responses to percutaneous medial branch peripheral nerve stimulation (PNS) to determine if results from earlier, smaller single-center studies and reports were generalizable when performed at a larger number and wider variety of centers in patients recalcitrant to non-surgical treatments. Participants with chronic axial low back pain were implanted with percutaneous PNS leads targeting the lumbar medial branch nerves for up to 60 days, after which the leads were removed. Participants were followed long-term for 12 months after the 2-month PNS treatment. Data collection is complete for visits through end of treatment with PNS (Primary Endpoint) and 6 months after lead removal (8 months after start of treatment), with some participant follow-up visits thereafter in progress. Clinically and statistically significant reductions in pain intensity, disability, and pain interference were reported by a majority of participants. Seventy-three percent of participants were successes for the Primary Endpoint, reporting clinically significant (≥30%) reductions in back pain intensity after the 2-month percutaneous PNS treatment (n=54/74). While prospective follow up is ongoing, among those who had already completed the long-term follow up visits (n=51), reductions in pain intensity, disability, and pain interference were sustained in a majority of participants through 14 months after the start of treatment. Given the minimally invasive, non-destructive nature of percutaneous PNS and the significant benefits experienced by participants who were recalcitrant to non-surgical treatments, percutaneous PNS may provide a promising first-line neurostimulation treatment option for patients with chronic axial back pain.

PMID:34216103 | DOI:10.1111/papr.13055

Clin Transl Sci. 2021 Jul 3. doi: 10.1111/cts.13088. Online ahead of print.

ABSTRACT

Sepsis-induced metabolic dysfunction contributes to organ failure and death. L-carnitine has shown promise for septic shock, but a recent phase II study of patients with vasopressor-dependent septic shock demonstrated a non-significant reduction in mortality. We undertook a pharmacometabolomics study of these patients (n = 250) to identify metabolic profiles predictive of a 90-day mortality benefit from L-carnitine. The independent predictive value of each pretreatment metabolite concentration, adjusted for L-carnitine dose, on 90-day mortality was determined by logistic regression. A grid-search analysis maximizing the Z-statistic from a binomial proportion test identified specific metabolite threshold levels that discriminated L-carnitine responsive patients. Threshold concentrations were further assessed by hazard ratio and Kaplan-Meier estimate. Accounting for L-carnitine treatment and dose, 11 ¹ H-NMR metabolites and 12 acylcarnitines were independent predictors of 90-day mortality. Based on the grid-search analysis numerous acylcarnitines and valine were identified as candidate metabolites of drug response. Acetylcarnitine emerged as highly viable for the prediction of an L-carnitine mortality benefit due to its abundance and biological relevance. Using its most statistically significant threshold concentration, patients with pretreatment acetylcarnitine greater than or equal to 35 µM were less likely to die at 90 days if treated with L-carnitine (18 g) versus placebo (p = 0.01 by log rank test). Metabolomics also identified independent predictors of 90-day sepsis mortality. Our proof-of-concept approach shows how pharmacometabolomics could be useful for tackling the heterogeneity of sepsis and informing clinical trial design. In addition, metabolomics can help understand mechanisms of sepsis heterogeneity and variable drug response, because sepsis induces alterations in numerous metabolite concentrations.

PMID:34216108 | DOI:10.1111/cts.13088

J Aquat Anim Health. 2021 Jul 2. doi: 10.1002/aah.10130. Online ahead of print.

ABSTRACT

In this case study, phage therapy was applied to treat a multidrug-resistant case of septicemic cutaneous ulcerative disease (SCUD) caused by Citrobacter freundii in a loggerhead sea turtle Caretta caretta. Phages were applied topically, intravenously, into the carapace, and into the exhibit water using various phage cocktails specific to the causative agent over an 8-month period. This was performed in conjunction with antimicrobial therapy. The animal was monitored through weekly cultures, photographs, and complete blood cell counts, as well as immune assays (phagocytosis, plasma lysozyme and superoxide dismutase activity, and plasma electrophoresis profiles). The animal, in comparison to an untreated, unaffected control, had elevated antibody titers to the administered phages, which persisted for at least 35 weeks. Although cultures were clear of C. freundii after phage treatment, the infection did return over time and immune assays confirmed deficiencies when compared to a healthy loggerhead sea turtle. Immune parameters with statistically significant changes over the study period included the following: decreased phagocytosis, increased alpha- and gamma-globulin protein components, and an increased albumin : globulin ratio. When C. freundii appeared again, the multidrug-resistant status had reverted back to normal susceptibility patterns. Although not completely known whether it was another subspecies of bacteria, the therapy did resolve the multidrug-resistant challenge. Phage therapy in combination with antimicrobial agents may be an effective treatment for sea turtles with normally functioning immune systems or less-severe infections. Additional research is needed to better understand and quantify sea turtle immunology.

PMID:34216060 | DOI:10.1002/aah.10130

Health Econ. 2021 Jul 2. doi: 10.1002/hec.4372. Online ahead of print.

ABSTRACT

Prior to the Affordable Care Act (ACA), insurance companies could charge higher premiums, or outright deny coverage, to people with preexisting health problems. But the ACA’s “guaranteed issue” provision forbids such price discrimination and denials of coverage. This paper seeks to determine whether, after implementation of the ACA, nongroup private insurance plans have experienced adverse selection. Our empirical approach employs a copula-based hurdle regression model, with dependence modeled as a function of dimensions along which adverse selection might occur. Our main finding is that, after implementation of the ACA, nongroup insurance enrollees with preexisting health problems do not appear to exhibit adverse selection. This finding suggests that the ACA’s mandate that everyone acquire coverage might have attracted enough healthy enrollees to offset any adverse selection.

PMID:34216065 | DOI:10.1002/hec.4372

Perspect Psychiatr Care. 2021 Jul 2. doi: 10.1111/ppc.12898. Online ahead of print.

ABSTRACT

PURPOSE: This study was carried out to determine the effect of mindfulness levels on the life satisfaction of nursing students.

DESIGN AND METHODS: A descriptive correlational study was conducted on 333 nursing students enrolled at a state university in Turkey.

FINDINGS: The statistical analysis of the data indicated that students’ mindfulness levels had a significantly positive impact on their satisfaction with life.

IMPLICATIONS FOR PRACTICE: Activities that include exercises, meditation and training geared to raise the level of mindfulness can also be beneficial in terms of increasing satisfaction with life.

PMID:34216042 | DOI:10.1111/ppc.12898

Int J Geriatr Psychiatry. 2021 Jul 3. doi: 10.1002/gps.5596. Online ahead of print.

ABSTRACT

OBJECTIVES: The Covid-19 pandemic has had a significant impact on older adults mental health care. Our study aimed to explore staff perspectives on key challenges and innovations in order to help inform the delivery of older adults mental health care in subsequent waves of the pandemic.

METHODS: A mixed methods online questionnaire developed by NIHR Mental Health Policy Research Unit (PRU) was used to gather staff perspectives on their challenges at work, problems faced by service users and their carers, and sources of help and support. Descriptive statistics were used for quantitative analysis and descriptive content analysis for qualitative analysis.

RESULTS: 158 participants, working in either community or inpatient settings, and from a range of professional disciplines, were included. For inpatient staff, a significant challenge was infection control. In the community, staff identified a lack of access to physical and social care as well as reduced contact with friends and families as being challenges for patients. Remote working was seen as a positive innovation along with Covid-19 related guidance from various sources and peer support.

CONCLUSION: Our study, with a focus on staff and patient well-being, helps to inform service development for future waves of the pandemic. We discuss measures to improve infection control in inpatient settings, the role of voluntary organisations in supporting socially isolated community patients, the need for better integration of physical and mental health services at an organisational level, and the importance of training staff to support patients and their families with end of life planning. This article is protected by copyright. All rights reserved.

PMID:34216045 | DOI:10.1002/gps.5596

J Dent Educ. 2021 Jul 2. doi: 10.1002/jdd.12736. Online ahead of print.

ABSTRACT

PURPOSE/OBJECTIVES: To assess student perceptions on learning dental anatomy using natural extracted teeth, 3D printed models, 3D virtual models, and augmented reality (AR) technology. METHODS: Eighty first-year dental students enrolled in the dental anatomy course were instructed to examine four stations. The stations included four versions of a mandibular first molar: an extracted natural tooth, a 3D printed model, a 3D virtual model, and a model displayed on a novel AR device. After examining all stations, the students were asked to complete an electronic survey. Bivariate analysis was performed to determine whether students’ perceptions are related to their demographic characteristics and technological experience with computer use, 3D modeling, and video games. RESULTS: Seventy students completed the survey (87.5% response rate). Students rated natural teeth to have the highest educational value, the 3D printed tooth to be the most accessible, and the AR application to be the most interesting modality. Students who played little to no video games were more likely to rate AR as high educational value (48.8% vs. 10.3%; p < 0.001), while students with little 3D modeling experience were more likely to rate high accessibility of the 3D Model (78.1% vs. 48.3%; p < 0.001). No statistically significant associations between the perceptions and students’ demographic characteristics or use of computer were noted.

CONCLUSION: The natural extracted tooth was rated highest in educational value, while the 3D printed model was rated easiest to use, and the AR model was the most interesting to the students.

PMID:34216032 | DOI:10.1002/jdd.12736

Stat Med. 2021 Jul 2. doi: 10.1002/sim.9127. Online ahead of print.

ABSTRACT

We propose a ridge-penalized adaptive Mantel test (AdaMant) for evaluating the association of two high-dimensional sets of features. By introducing a ridge penalty, AdaMant tests the association across many metrics simultaneously. We demonstrate how ridge penalization bridges Euclidean and Mahalanobis distances and their corresponding linear models from the perspective of association measurement and testing. This result is not only theoretically interesting but also has important implications in penalized hypothesis testing, especially in high-dimensional settings such as imaging genetics. Applying the proposed method to an imaging genetic study of visual working memory in healthy adults, we identified interesting associations of brain connectivity (measured by electroencephalogram coherence) with selected genetic features.

PMID:34216035 | DOI:10.1002/sim.9127