Category: Statistics

J Clin Pharm Ther. 2022 Apr 6. doi: 10.1111/jcpt.13663. Online ahead of print.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: It is important to identify effective, easy-to-use and cost-effective non-pharmacological methods in the management of pain caused by medical interventions. The purpose of this study is to compare the effects of cold spray and ShotBlocker on pain in adults in reducing pain caused by intramuscular injection in the adult emergency department.

METHODS: This is a randomized controlled trial with two experimental groups, two placebo groups and a control group. The study was conducted on 195 adults who received diclofenac sodium injections. In the study, the injection procedure was performed by following the same injection protocol in all five groups. In the injection process, cold spray or ShotBlocker was used in the intervention groups based on the group, and cold spray with distilled water or the smooth surface of the ShotBlocker was used in the placebo groups. Following the injection, the pain caused by the injection was evaluated using the Visual Analog Scale.

RESULTS AND DISCUSSION: The study was completed with the remaining 195 patients. In the study, the average pain scores due to injection of the individuals in the cold spray group were lower than those of the control group (p < 0.05). There was no statistically significant difference between the pain score averages due to injection of the individuals in the ShotBlocker group and cold spray, control, ShotBlocker placebo and cold spray placebo groups.

WHAT IS NEW AND CONCLUSION: The routine use of a fast-acting, cost-effective and easy-to-use method, cold spray, to reduce pain in the intramuscular injection will be beneficial in increasing patient satisfaction and quality of care.

PMID:35385141 | DOI:10.1111/jcpt.13663

QJM. 2022 Apr 6:hcac093. doi: 10.1093/qjmed/hcac093. Online ahead of print.

ABSTRACT

BACKGROUND: Sudden infant death syndrome (SIDS) still remains one of the leading causes of infant death worldwide, especially in high-income countries. To date, however, there is no detailed information on the global health burden of SIDS.

AIMS: To characterize the global disease burden of SIDS and its trends from 1990 to 2019 and to compare the burden of SIDS according to the socio-demographic index (SDI).

DESIGN: Systematic analysis based on the Global Burden of Disease (GBD) 2019 data.

METHODS: Epidemiological data of 204 countries from 1990 to 2019 were collected via various methods including civil registration and vital statistics in the original GBD study. Estimates for mortality and disease burden of SIDS were modelled. Crude mortality and mortality rates per 100,000 population were analyzed. Disability-adjusted life years (DALYs) and DALY rates were also assessed.

RESULTS: In 2019, mortality rate of SIDS accounted for 20.98 [95% Uncertainty Interval (UI), 9.15 to 46.16] globally, which was a 51% decrease from 1990. SIDS was most prevalent in Western sub-Saharan Africa, High-income North America and Oceania in 2019. The burden of SIDS was higher in males than females consistently from 1990 to 2019. Higher SDI and income level was associated with lower burden of SIDS; further, countries with higher SDI and income had greater decreases in SIDS burden from 1990 to 2019.

CONCLUSIONS: The burden of SIDS has decreased drastically from 1990 to 2019. However, the improvements have occurred disproportionately between regions and SDI levels. Focused preventive efforts in under-resourced populations are needed.

PMID:35385121 | DOI:10.1093/qjmed/hcac093

Bioinformatics. 2022 Apr 6:btac212. doi: 10.1093/bioinformatics/btac212. Online ahead of print.

ABSTRACT

MOTIVATION: Allelic expression analysis aids in detection of cis-regulatory mechanisms of genetic variation which produce allelic imbalance (AI) in heterozygotes. Measuring AI in bulk data lacking time or spatial resolution has the limitation that cell-type-specific (CTS), spatial-, or time-dependent AI signals may be dampened or not detected.

RESULTS: We introduce a statistical method airpart for identifying differential CTS AI from single-cell RNA-sequencing (scRNA-seq) data, or other spatially- or time-resolved datasets. airpart outputs discrete partitions of data, pointing to groups of genes and cells under common mechanisms of cis-genetic regulation. In order to account for low counts in single-cell data, our method uses a Generalized Fused Lasso with Binomial likelihood for partitioning groups of cells by AI signal, and a hierarchical Bayesian model for AI statistical inference. In simulation, airpart accurately detected partitions of cell types by their AI and had lower RMSE of allelic ratio estimates than existing methods. In real data, airpart identified DAI patterns across cell states and could be used to define trends of AI signal over spatial or time axes.

AVAILABILITY: The airpart package is available as an R/Bioconductor package at https://bioconductor.org/packages/airpart.

PMID:35385108 | DOI:10.1093/bioinformatics/btac212

Genetics. 2022 Apr 6:iyac050. doi: 10.1093/genetics/iyac050. Online ahead of print.

ABSTRACT

Genomic regions subject to purifying selection are more likely to carry disease causing mutations than regions not under selection. Cross species conservation is often used to identify such regions but with limited resolution to detect selection on short evolutionary timescales such as that occurring in only one species. In contrast, genetic intolerance looks for depletion of variation relative to expectation within a species, allowing species specific features to be identified. When estimating the intolerance of noncoding sequence, methods strongly leverage variant frequency distributions. As the expected distributions depend on ancestry, if not properly controlled for, ancestral population source may obfuscate signals of selection. We demonstrate that properly incorporating ancestry in intolerance estimation greatly improved variant classification. We provide a genome-wide intolerance map that is conditional on ancestry and likely to be particularly valuable for variant prioritization.

PMID:35385101 | DOI:10.1093/genetics/iyac050

JAMA Netw Open. 2022 Apr 1;5(4):e226250. doi: 10.1001/jamanetworkopen.2022.6250.

ABSTRACT

IMPORTANCE: Suicide rates are rising disproportionately in rural counties, a concerning pattern as the COVID-19 pandemic has intensified suicide risk factors in these regions and exacerbated barriers to mental health care access. Although telehealth has the potential to improve access to mental health care, telehealth’s effectiveness for suicide-related outcomes remains relatively unknown.

OBJECTIVE: To evaluate the association between the escalated distribution of the US Department of Veterans Affairs’ (VA’s) video-enabled tablets during the COVID-19 pandemic and rural veterans’ mental health service use and suicide-related outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included rural veterans who had at least 1 VA mental health care visit in calendar year 2019 and a subcohort of patients identified by the VA as high-risk for suicide. Event studies and difference-in-differences estimation were used to compare monthly mental health service utilization for patients who received VA tablets during COVID-19 with patients who were not issued tablets over 10 months before and after tablet shipment. Statistical analysis was performed from November 2021 to February 2022.

EXPOSURE: Receipt of a video-enabled tablet.

MAIN OUTCOMES AND MEASURES: Mental health service utilization outcomes included psychotherapy visits, medication management visits, and comprehensive suicide risk evaluations (CSREs) via video and total visits across all modalities (phone, video, and in-person). We also analyzed likelihood of emergency department (ED) visit, likelihood of suicide-related ED visit, and number of VA’s suicide behavior and overdose reports (SBORs).

RESULTS: The study cohort included 13 180 rural tablet recipients (11 617 [88%] men; 2161 [16%] Black; 301 [2%] Hispanic; 10 644 [80%] White; mean [SD] age, 61.2 [13.4] years) and 458 611 nonrecipients (406 545 [89%] men; 59 875 [13%] Black or African American; 16 778 [4%] Hispanic; 384 630 [83%] White; mean [SD] age, 58.0 [15.8] years). Tablets were associated with increases of 1.8 psychotherapy visits per year (monthly coefficient, 0.15; 95% CI, 0.13-0.17), 3.5 video psychotherapy visits per year (monthly coefficient, 0.29; 95% CI, 0.27-0.31), 0.7 video medication management visits per year (monthly coefficient, 0.06; 95% CI, 0.055-0.062), and 0.02 video CSREs per year (monthly coefficient, 0.002; 95% CI, 0.002-0.002). Tablets were associated with an overall 20% reduction in the likelihood of an ED visit (proportion change, -0.012; 95% CI, -0.014 to -0.010), a 36% reduction in the likelihood of suicide-related ED visit (proportion change, -0.0017; 95% CI, -0.0023 to -0.0013), and a 22% reduction in the likelihood of suicide behavior as indicated by SBORs (monthly coefficient, -0.0011; 95% CI, -0.0016 to -0.0005). These associations persisted for the subcohort of rural veterans the VA identifies as high-risk for suicide.

CONCLUSIONS AND RELEVANCE: This cohort study of rural US veterans with a history of mental health care use found that receipt of a video-enabled tablet was associated with increased use of mental health care via video, increased psychotherapy visits (across all modalities), and reduced suicide behavior and ED visits. These findings suggest that the VA and other health systems should consider leveraging video-enabled tablets for improving access to mental health care via telehealth and for preventing suicides among rural residents.

PMID:35385088 | DOI:10.1001/jamanetworkopen.2022.6250

Biostatistics. 2022 Apr 6:kxac007. doi: 10.1093/biostatistics/kxac007. Online ahead of print.

ABSTRACT

Considerable statistical work done on dynamic treatment regimes (DTRs) is in the frequentist paradigm, but Bayesian methods may have much to offer in this setting as they allow for the appropriate representation and propagation of uncertainty, including at the individual level. In this work, we extend the use of recently developed Bayesian methods for Marginal Structural Models to arrive at inference of DTRs. We do this (i) by linking the observational world with a world in which all patients are randomized to a DTR, thereby allowing for causal inference and then (ii) by maximizing a posterior predictive utility, where the posterior distribution has been obtained from nonparametric prior assumptions on the observational world data-generating process. Our approach relies on Bayesian semiparametric inference, where inference about a finite-dimensional parameter is made all while working within an infinite-dimensional space of distributions. We further study Bayesian inference of DTRs in the double robust setting by using posterior predictive inference and the nonparametric Bayesian bootstrap. The proposed methods allow for uncertainty quantification at the individual level, thereby enabling personalized decision-making. We examine the performance of these methods via simulation and demonstrate their utility by exploring whether to adapt HIV therapy to a measure of patients’ liver health, in order to minimize liver scarring.

PMID:35385100 | DOI:10.1093/biostatistics/kxac007

JAMA Surg. 2022 Apr 6:e220135. doi: 10.1001/jamasurg.2022.0135. Online ahead of print.

ABSTRACT

IMPORTANCE: In 2014, Maryland initiated the global budget revenue (GBR) model, placing caps on total hospital expenditures across all care sites. The GBR program aims to reduce unnecessary utilization while maintaining or improving care quality. To date, there has been limited examination of program effects on cancer care.

OBJECTIVE: To compare changes in spending, clinical outcomes, and acute care utilization through 4 years of the GBR program among Medicare beneficiaries who undergo cancer-directed surgery in Maryland vs matched control states.

DESIGN, SETTING, AND PARTICIPANTS: Drawing from a matched pool of hospitals in Maryland (n = 35) and 24 control states with a similar timing of Medicaid expansion (n = 101), we identified Medicare beneficiaries from Maryland and control states who underwent any cancer-directed surgery from 2011 through 2018. Using difference-in-differences analysis, we compared changes in outcomes from before (2011-2013) to after (2015-2018) GBR implementation between patients treated in Maryland and control states. We also performed a subgroup analysis among patients who underwent major surgical procedures that are usually performed in the inpatient setting (cystectomy, esophagectomy, gastrectomy, colorectal resection, nephrectomy, pancreatectomy, and lung resection).

MAIN OUTCOMES AND MEASURES: Thirty-day episode spending, mortality, readmissions, and emergency department (ED) visits.

RESULTS: Relative to Medicare beneficiaries undergoing cancer surgery in control states (n = 4737; 3323 [70.1%] female; 571 [12.1%] dual-eligible; mean [SD] age 74.9 [6.5] years), patients in Maryland (n = 20 320; 14 068 [69.2%] female; 1705 [8.4%] dual-eligible; mean [SD] age 74.9 [6.5] years) had a statistically significant reduction of 2.2 percentage points (95% CI, -4.3 to -0.1) in the 30-day readmission rate. We found no statistically significant changes in 30-day spending, mortality, or ED visits. We report no significant results in the subgroup analysis of patients undergoing major surgical procedures.

CONCLUSIONS AND RELEVANCE: Global budget revenue was not associated with changes in expenditures, ED utilization, or clinical outcomes after cancer-directed surgery through 4 years. There was a modest decline in 30-day readmissions. Specialty-specific definitions of care quality and better alignment across the entire care delivery value chain (ie, physician incentives) may be strategies that could improve delivery of high-value care for beneficiaries undergoing cancer surgery.

PMID:35385085 | DOI:10.1001/jamasurg.2022.0135

JAMA Surg. 2022 Apr 6. doi: 10.1001/jamasurg.2022.0713. Online ahead of print.

ABSTRACT

IMPORTANCE: More than half of patients who undergo knee replacement surgery report substantial acute postoperative pain.

OBJECTIVE: To evaluate the efficacy and cost-effectiveness of periarticular liposomal bupivacaine for recovery and pain management after knee replacement.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, patient-blinded, pragmatic, randomized clinical superiority trial involved 533 participants at 11 institutions within the National Health Service in England. Adults undergoing primary unilateral knee replacement for symptomatic end-stage osteoarthritis were enrolled between March 29, 2018, and February 29, 2020, and followed up for 1 year after surgery. Follow-up was completed March 1, 2021. A per-protocol analysis for each coprimary outcome was performed in addition to the main intention-to-treat analysis.

INTERVENTIONS: Two hundred sixty-six milligrams of liposomal bupivacaine admixed with 100 mg of bupivacaine hydrochloride compared with 100 mg of bupivacaine hydrochloride alone (control) administered by periarticular injection at the time of surgery.

MAIN OUTCOME AND MEASURES: The coprimary outcomes were Quality of Recovery 40 (QoR-40) score at 72 hours and pain visual analog scale (VAS) score area under the curve (AUC) from 6 to 72 hours. Secondary outcomes included QoR-40 and mean pain VAS at days 0 (evening of surgery), 1, 2, and 3; cumulative opioid consumption for 72 hours; functional outcomes and quality of life at 6 weeks, 6 months, and 1 year; and cost-effectiveness for 1 year. Adverse events and serious adverse events up to 12 months after randomization were also assessed.

RESULTS: Among the 533 participants included in the analysis, the mean (SD) age was 69.0 (9.7) years; 287 patients were women (53.8%) and 246 were men (46.2%). Baseline characteristics were balanced between study groups. There was no difference between the liposomal bupivacaine and control groups in QoR-40 score at 72 hours (adjusted mean difference, 0.54 [97.5% CI, -2.05 to 3.13]; P = .64) or the pain VAS score AUC at 6 to 72 hours (-21.5 [97.5% CI, -46.8 to 3.8]; P = .06). Analyses of pain VAS and QoR-40 scores demonstrated only 1 statistically significant difference, with the liposomal bupivacaine arm having lower pain scores the evening of surgery (adjusted difference -0.54 [97.5% CI, -1.07 to -0.02]; P = .02). No difference in cumulative opioid consumption and functional outcomes was detected. Liposomal bupivacaine was not cost-effective compared with the control treatment. No difference in adverse or serious adverse events was found between the liposomal bupivacaine and control groups.

CONCLUSIONS AND RELEVANCE: This study found no difference in postoperative recovery or pain associated with the use of periarticular liposomal bupivacaine compared with bupivacaine hydrochloride alone in patients who underwent knee replacement surgery.

TRIAL REGISTRATION: isrctn.com Identifier: ISRCTN54191675.

PMID:35385072 | DOI:10.1001/jamasurg.2022.0713

Eur J Cardiothorac Surg. 2022 Apr 6:ezac125. doi: 10.1093/ejcts/ezac125. Online ahead of print.

ABSTRACT

OBJECTIVES: We evaluate the mid-term results of mitral valve (MV) repair with patch augmentation of the posterior leaflet in secondary mitral regurgitation.

METHODS: Patients were included after diagnosis of a severe symptomatic secondary MV insufficiency with grade III and IV according to the Carpentier classification IIIb. Indication for a patch augmentation technique was a dilatation of the left ventricle leading to a displacement of the papillary muscles, causing restricted leaflet motion and a marked leaflet tenting height. Data were collected prospectively between December 2011 and March 2020.

RESULTS: In total, 174 patients (mean age: 65 ± 12 years) received an MV repair with patch augmentation of the posterior leaflet and a true-sized remodelling annuloplasty (mean size 30.8 mm). Causes of the MV incompetence were dilatative cardiomyopathy in 126 patients and ischaemic myocardial disease in 48 patients. Concomitant bypass surgery was performed in 28 patients, and the tricuspid valve was repaired in 68 patients. The mean follow-up was 40 ± 28.2 months. There was no 30-day mortality. In-hospital mortality was 1.2% (n = 2); late mortality was 10.9% (n = 19). At 8 years, overall survival was 62.48%, freedom from moderate or severe recurrent mitral regurgitation was 91.9% and freedom from reoperation due to MV insufficiency was 97.1%.

CONCLUSIONS: Augmentation of the posterior MV leaflet in addition to remodelling annuloplasty is a safe and reproducible mitral reconstruction technique that renders sustainable MV competence.

PMID:35385074 | DOI:10.1093/ejcts/ezac125

JAMA Psychiatry. 2022 Apr 6. doi: 10.1001/jamapsychiatry.2022.0465. Online ahead of print.

ABSTRACT

IMPORTANCE: Neurocognitive impairments exist in children at familial high risk (FHR) of schizophrenia and bipolar disorder. Studies on preadolescent developmental courses of neurocognition are important to describe shared and distinct neurodevelopmental pathways in these groups.

OBJECTIVE: To assess the development in specific neurocognitive functions from age 7 to 11 years in children at FHR of schizophrenia or bipolar disorder compared with children in a population-based control (PBC) group.

DESIGN, SETTING, AND PARTICIPANTS: The Danish High Risk and Resilience Study is a prospective, longitudinal, cohort study that collected data from January 1, 2013, to January 31, 2016 (phase 1), and from March 1, 2017, to June 30, 2020 (phase 2). Data were collected at 2 university hospitals in Denmark, and participants included 520 children at FHR of schizophrenia or bipolar disorder along with a PBC group matched with the group of children at FHR of schizophrenia by age, sex, and municipality.

EXPOSURES: Parental schizophrenia, bipolar disorder, or neither.

MAIN OUTCOMES AND MEASURES: Neurocognitive functioning was assessed with validated tests of intelligence, processing speed, attention, memory, verbal fluency, and executive functioning. Multilevel mixed-effects linear regression models with maximum likelihood estimation were used to estimate neurocognitive development from age 7 to 11 years.

RESULTS: At 4-year follow-up, a total of 451 children (mean [SD] age; 11.9 [0.2] years; 208 girls [46.1%]) underwent neurocognitive testing. There were a total of 170 children at FHR of schizophrenia (mean [SD] age, 12.0 [0.3]; 81 girls [47.7%]), 103 children at FHR of bipolar disorder (mean [SD] age, 11.9 [0.2] years; 45 girls [43.7%]), and 178 children in the PBC group (mean [SD] age, 11.9 [0.2] years; 82 girls [46.1%]). At either age 7 or 11 years or at both assessments, 520 children participated in the neurocognitive assessment and were therefore included in the analyses. When correcting for multiple comparisons, no statistically significant time × group interactions were observed across the 3 groups. Compared with the PBC group at 4-year follow-up, children at FHR of schizophrenia showed significant neurocognitive impairment in 7 of 24 neurocognitive measures (29.2%; Cohen d range, 0.29-0.37). Compared with children at FHR of bipolar disorder, children at FHR of schizophrenia had significant neurocognitive impairment in 5 of 24 measures (20.8%; Cohen d range, 0.29-0.38). Children at FHR of bipolar disorder and those in the PBC group did not differ significantly.

CONCLUSIONS AND RELEVANCE: In this cohort study, findings suggest that neurocognitive maturation was comparable across groups of children at FHR of schizophrenia or bipolar disorder compared with PBCs from age 7 to 11 years. Compared with the PBC group, children at FHR of schizophrenia demonstrated widespread, stable, neurocognitive impairments during this period, whereas children at FHR of bipolar disorder showed no neurocognitive impairments, which may indicate distinct neurodevelopmental pathways in children at FHR of schizophrenia and bipolar disorder.

PMID:35385060 | DOI:10.1001/jamapsychiatry.2022.0465