Category: Statistics

J Intern Med. 2022 May 22. doi: 10.1111/joim.13523. Online ahead of print.

ABSTRACT

BACKGROUND: The Bacillus Calmette-Guérin (BCG) vaccine may confer cross-protection against viral diseases in adults. This study evaluated BCG vaccine cross-protection in adults with convalescent coronavirus disease 2019 (COVID-19).

METHOD: This was a multicenter, prospective, randomized, placebo-controlled, double-blind phase III study (ClinicalTrials.gov: NCT04369794).

SETTING: University Community Health Center and Municipal Outpatient Center in South America.

PATIENTS: A total of 378 adult patients with convalescent COVID-19 were included.

INTERVENTION: Single intradermal BCG vaccine (n = 183) and placebo (n = 195).

MEASUREMENTS: The primary outcome was clinical evolution. Other outcomes included adverse events and humoral immune responses for up to six months.

RESULTS: A significantly higher proportion of BCG patients with anosmia and ageusia recovered at the 6-week follow-up visit than placebo (anosmia: 83.1% vs. 68.7% healed, p = 0.043, number needed to treat [NNT] = 6.9; ageusia: 81.2% vs. 63.4% healed, p = 0.032, NNT = 5.6). BCG also prevented the appearance of ageusia in the following weeks: seven in 113 (6.2%) BCG recipients versus 19 in 126 (15.1%) placebos, p = 0.036, NNT = 11.2. BCG did not induce any severe or systemic adverse effects. The most common and expected adverse effects were local vaccine lesions, erythema (n = 152; 86.4%), and papules (n = 111; 63.1%). Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) humoral response measured by N protein immunoglobulin G (IgG) titer and seroneutralization by interacting with the angiotensin-converting enzyme 2 (ACE2) receptor suggest that the serum of BCG-injected patients may neutralize the virus at lower specificity; however, the results were not statistically significant.

CONCLUSION: BCG vaccine is safe and offers cross-protection against COVID-19 with potential humoral response modulation.

LIMITATIONS: No severely ill patients were included. This article is protected by copyright. All rights reserved.

PMID:35599154 | DOI:10.1111/joim.13523

Semergen. 2022 May 19:S1138-3593(22)00077-6. doi: 10.1016/j.semerg.2022.02.006. Online ahead of print.

ABSTRACT

This fourth in a series of five articles on systematic reviews demonstrates how to compile and summarize the results of the studies included in a review. The synthesis of the extracted data consists of tabulating the characteristics, and the quality of the included studies, with the effects or the magnitude of the associations found in them. Statistical methods can be used to explore the differences between studies and the reasons for the inconsistencies. The magnitude of this heterogeneity influences whether it is feasible to perform an overall or subgroup meta-analysis. Finally, information is provided both to assessment of clinical and methodological reasons for heterogeneity.

PMID:35599147 | DOI:10.1016/j.semerg.2022.02.006

J Cardiol. 2022 May 19:S0914-5087(22)00102-2. doi: 10.1016/j.jjcc.2022.04.011. Online ahead of print.

ABSTRACT

BACKGROUND: Current guidelines provide recommendation for transcatheter aortic-valve replacement (TAVR) in severe aortic stenosis without emphasis on valve systems. The comparative performances of balloon-expandable valves (BEV) and self-expanding valves (SEV) remain unclear. We aim to compare the early (30-day) and midterm (1-year) mortality and cardiovascular outcomes of BEV with SEV.

METHODS: PubMed, CENTRAL, and EMBASE were searched from inception to February 13, 2020 for randomized controlled trials (RCTs) and propensity-score matched (PSM) studies. Odds ratios (ORs) for binary outcomes and mean differences for continuous outcomes were pooled using random-effect models (DerSimonian-Laird method) with Hartung-Knapp-Sidik-Jonkman variance correction. Primary outcomes were early and midterm all-cause mortality.

RESULTS: We included 3 RCTs (1418 patients) and 12 PSM studies (36,540 patients). Compared with SEV, BEV was associated with significantly lower mortality at 30 days (OR 0.76, 95% CI 0.67-0.85, p < 0.001, I2 = 0) and 1 year (OR 0.87, 95% CI 0.77-0.99, p = 0.04, I2 = 20.4%) in PSM studies, but not RCTs with insufficient power. Similar findings were found in subgroups analysis based on valve generations and SEV types. The 30-day and 1-year cardiovascular mortality, 30-day incidences of moderate to severe paravalvular leak, procedural contrast agent volume, and procedure time were lower, but transvalvular pressure gradient was higher in BEV than SEV in PSM studies. The 30-day incidences of permanent pacemaker implantation (PPI), acute kidney injury, stroke, major bleeding, major vascular complications, and rehospitalization were not statistically different between BEV and SEV. Early-generation SEV was associated with a higher 30-day PPI risk than corresponding BEV comparators. PPI risk was lower in ACURATE neo (Boston Scientific, Natick, MA) but higher in Evolut R SEV (Medtronic Inc., Minneapolis, MN), both compared with SAPIEN 3 BEV (Edwards Lifesciences, Irvine, CA).

CONCLUSIONS: PSM studies suggest lower early and midterm mortality in BEV than SEV, but the contribution of unmeasured confounders cannot be excluded. Results from adequately powered RCTs with long-term follow-up are critically needed to confirm these findings.

PMID:35599108 | DOI:10.1016/j.jjcc.2022.04.011

J Foot Ankle Surg. 2022 Apr 29:S1067-2516(22)00115-6. doi: 10.1053/j.jfas.2022.04.005. Online ahead of print.

ABSTRACT

Adult acquired flat foot deformity (AAFD) is a progressive, tri-planar deformity involving collapse of the medial longitudinal arch, valgus deformity of the rear foot, and abduction of the mid-foot on the rear foot. There are a wide variety of surgical treatment options for this deformity, including lateral column lengthening (LCL) which results in tri-planar correction of AAFD. We retrospectively reviewed weightbearing preoperative radiographs and weight-bearing 6-week postoperative radiographs of 34 patients with stage II AAFD who underwent LCL (with and without concurrent procedures) with a minimum of 1-year of follow up. Outcomes, including complications and postoperative differences in 6 types of angle measurements were evaluated. Radiographic evaluation showed statistically significant differences in preoperative and postoperative measures in the following angles: calcaneal inclination, Meary’s, Simmons, talocalcaneal, and metatarsus adductus (each p ≤ .05). Postoperative Engel’s angle difference did not reach statistical significance (p = .07). Paired t tests showed TN coverage angles increased greater with LCL plus a Cotton osteotomy as compared to isolated LCL. Additionally, there was no significant difference in TN coverage angle based on LCL graft size (p = .20). Furthermore, the distance of the osteotomy from the calcaneocuboid joint on anteroposterior and lateral radiographs did not significantly predict TN coverage angle change. Our study suggests that LCL corrects AAFD in three planes while decreasing the metatarsus adductus angle. LCL appears to be more effective when performed with a Cotton osteotomy. Wedge size (6 mm, 8 mm, 10 mm) and osteotomy location did not demonstrate a relationship with postoperative TN coverage angle or incidence of lateral column overload.

PMID:35599073 | DOI:10.1053/j.jfas.2022.04.005

Physiotherapy. 2022 May 19:S0031-9406(21)00389-8. doi: 10.1016/j.physio.2021.12.003. Online ahead of print.

NO ABSTRACT

PMID:35599069 | DOI:10.1016/j.physio.2021.12.003

Brief Bioinform. 2022 May 23:bbac179. doi: 10.1093/bib/bbac179. Online ahead of print.

ABSTRACT

Sex-biased gene flow has been common in the demographic history of modern humans. However, the lack of sophisticated methods for delineating the detailed sex-biased admixture process prevents insights into complex admixture history and thus our understanding of the evolutionary mechanisms of genetic diversity. Here, we present a novel algorithm, MultiWaverX, for modeling complex admixture history with sex-biased gene flow. Systematic simulations showed that MultiWaverX is a powerful tool for modeling complex admixture history and inferring sex-biased gene flow. Application of MultiWaverX to empirical data of 17 typical admixed populations in America, Central Asia, and the Middle East revealed sex-biased admixture histories that were largely consistent with the historical records. Notably, fine-scale admixture process reconstruction enabled us to recognize latent sex-biased gene flow in certain populations that would likely be overlooked by much of the routine analysis with commonly used methods. An outstanding example in the real world is the Kazakh population that experienced complex admixture with sex-biased gene flow but in which the overall signature has been canceled due to biased gene flow from an opposite direction.

PMID:35598333 | DOI:10.1093/bib/bbac179

Dermatol Ther. 2022 May 22:e15593. doi: 10.1111/dth.15593. Online ahead of print.

ABSTRACT

BACKGROUND: Pustular psoriasis of pregnancy (PPP) can lead to life-threatening complications.

OBJECTIVES: To report clinical and genetic spectrum, prognostic factors and management options.

METHODS: We designed a retrospective study including 8 PPP patients. We collected clinical data, and performed genetic and statistical analysis to identify factors associated with fetal complications, resistance to treatment and post-partum flare extension. A systematic review of the literature was also carried out.

RESULTS: Eight Tunisian patients, with a mean age of 23±3.3 years, were included. They presented 14 flares (F) during pregnancies and 1 flare after delivery. Additional GPP flares outside pregnancy periods were noted in 2/8 of patients. The mean duration of PPP flares was 16.66±7.8 weeks. The first flare occurred at a gestational age of 26±5 weeks. Only 2/8 studied patients presented a homozygous mutation c.80T>C (p.L27P) in IL36RN gene. Used treatments were: Topical steroids (n=12F), systemic steroids (n=5F), Ciclosporin (n=1F), UVB (n=1F) and Acitretin (in post-partum n=6F). Complications were: oligoamnios (n=2), intra-uterine growth retardation (n=1), fetal death in utero (n=1), prematurity (n=3), low weight at birth (n=2). A significant association was found between: i- occurrence of fetal complications and early gestational age at the onset (p=0.036), ii- resistance to topical steroids and body surface affected area (p=0.008), iii- presence of mutation c.80T>C in PPP flares and low serum levels of calcium (p=0.01). Our systematic review of the literature identified 39 patients with 41 flares of PPP. Only 7/39 patients presented a causative mutation in IL36RN and CARD14 genes.

CONCLUSION: PPP is characterized by a phenotypic heterogeneity and can be associated to IL36RN mutations. Its early onset can be associated with fetal complications. Systemic steroids and cyclosporine remain the most used therapies. This article is protected by copyright. All rights reserved.

PMID:35598320 | DOI:10.1111/dth.15593

Brief Bioinform. 2022 May 23:bbac171. doi: 10.1093/bib/bbac171. Online ahead of print.

ABSTRACT

Many statistical methods for pathway analysis have been used to identify pathways associated with the disease along with biological factors such as genes and proteins. However, most pathway analysis methods neglect the complex nonlinear relationship between biological factors and pathways. In this study, we propose a Deep-learning pathway analysis using Hierarchical structured CoMponent models (DeepHisCoM) that utilize deep learning to consider a nonlinear complex contribution of biological factors to pathways by constructing a multilayered model which accounts for hierarchical biological structure. Through simulation studies, DeepHisCoM was shown to have a higher power in the nonlinear pathway effect and comparable power for the linear pathway effect when compared to the conventional pathway methods. Application to hepatocellular carcinoma (HCC) omics datasets, including metabolomic, transcriptomic and metagenomic datasets, demonstrated that DeepHisCoM successfully identified three well-known pathways that are highly associated with HCC, such as lysine degradation, valine, leucine and isoleucine biosynthesis and phenylalanine, tyrosine and tryptophan. Application to the coronavirus disease-2019 (COVID-19) single-nucleotide polymorphism (SNP) dataset also showed that DeepHisCoM identified four pathways that are highly associated with the severity of COVID-19, such as mitogen-activated protein kinase (MAPK) signaling pathway, gonadotropin-releasing hormone (GnRH) signaling pathway, hypertrophic cardiomyopathy and dilated cardiomyopathy. Codes are available at https://github.com/chanwoo-park-official/DeepHisCoM.

PMID:35598329 | DOI:10.1093/bib/bbac171

Eur J Pain. 2022 May 22. doi: 10.1002/ejp.1978. Online ahead of print.

ABSTRACT

BACKGROUND: Multisite musculoskeletal pain is common and disabling. This study aimed to prospectively investigate distribution of musculoskeletal pain anatomically, and explore risk factors for increases/reductions in the number of painful sites.

METHODS: Using data from participants working in 45 occupational groups in 18 countries, we explored changes in reporting pain at 10 anatomical sites on two occasions 14 months apart. We used descriptive statistics to explore consistency over time in the number of painful sites, and their anatomical distribution. Baseline risk factors for increases/reductions by ≥3 painful sites were explored by random intercept logistic regression that adjusted for baseline number of painful sites.

RESULTS: Amongst 8,927 workers, only 20% reported no pain at either time point, and 16% reported ≥3 painful sites both times. After 14 months, the anatomical distribution of pain often changed but there was only an average increase of 0.17 painful sites. Some 14% workers reported a change in painful sites by ≥ 3. Risk factors for an increase of ≥ 3 painful sites included female sex, lower educational attainment, having a physically demanding job, and adverse beliefs about the work-relatedness of musculoskeletal pain. Also predictive were: older age, somatising tendency, and poorer mental health (each of which was also associated with lower odds of reductions of ≥ 3 painful sites).

CONCLUSIONS: Longitudinally, the number of reported painful sites was relatively stable but the anatomical distribution varied considerably. These findings suggest an important role for central pain sensitisation mechanisms, rather than localised risk factors, among working adults.

PMID:35598315 | DOI:10.1002/ejp.1978

Cancer Med. 2022 May 22. doi: 10.1002/cam4.4839. Online ahead of print.

ABSTRACT

OBJECTIVES: Microinvasive breast cancer (MIBC) is a special type of breast cancer with a relatively low prevalence, of which the understanding remains controversial. In this article, we aimed to clarify the clinicopathological characteristics and prognosis of MIBC in the setting of different molecular subtypes and give feasible suggestions on clinical practice in MIBC.

METHODS: This study utilized the data from Surveillance, Epidemiology, and End Results (SEER) database. Patients were divided into subgroups based on the molecular subtypes, of which the clinicopathological characteristics were further undergone comparative analyses. Kaplan-Meier method and Cox proportional hazard regression analysis were employed to determine the prognosis of the subtypes, and to explore the prognostic factors. Patients were randomly assigned in a 7:3 ratio to the training and validation cohorts. The independent risk variables were then adopted to generate a nomogram to predict the 3- and 5-year survival probability.

RESULTS: A total of 4301 MIBC patients between 2010 and 2016 were obtained from the SEER database, which were subsequently separated into HR+/HER2- (n = 2598), HR+/HER2+ (n = 723), HR-/HER2+ (n = 633), and HR-/HER2- (n = 347) groups. The HR+/HER2+ group showed the best overall survival (OS) (81.28 months, 95% CI 80.45-82.11) compared with other groups (p = 0.0089). The application of radiotherapy in HR+/HER2- and HR+/HER2+ MIBC patients brought out additional survival benefit compared with those without radiotherapy (p < 0.0001 and p = 0.024, respectively). The prognosis among four subgroups with or without chemotherapy showed no statistical difference. Based on the curated nomogram, the high-score group exhibited a better OS compared with patients from the low-score group.

CONCLUSIONS: Profound heterogeneity was detected among different molecular subtypes in MIBC patients, of which HR+/HER2+ subtype presented the best prognosis. For HR-positive MIBC patients, increasing survival benefits could be retrieved from radiotherapy. Chemotherapy was not recommended for patients with MIBC. Individual-based protocols were introduced based on the nomogram which warranted further validation.

PMID:35598300 | DOI:10.1002/cam4.4839