Category: Statistics

J Pediatr Hematol Oncol. 2022 May 4. doi: 10.1097/MPH.0000000000002480. Online ahead of print.

ABSTRACT

Sarcomas with BCOR alteration are a heterogenous group characterized by changes including internal tandem duplications (ITDs) and recurring fusions with CCNB3, ZC3H7B, and other rare partners. With widespread genomic testing, these alterations are now associated with histologies such as Ewing-like sarcoma (BCOR::CCNB3), high-grade endometrial stromal sarcoma (ZC3H7B::BCOR), and clear cell sarcoma of kidney (BCOR-ITD). BCOR altered sarcomas of soft tissues and organs were identified through PubMed using keywords “Sarcoma (AND) BCOR” from 2005 through October 2021. Summary statistics and outcome data were calculated using STATA v12.1. Forty-one publications described 190 patients with BCOR altered soft tissue or organ sarcomas. BCOR-ITD was most common, followed by BCOR::CCNB3, ZC3H7B::BCOR. BCOR-ITD tumors occurred mainly in infants, BCOR::CCNB3 commonly occurred in adolescent young adults, and ZC3H7B::BCOR only in adults. The most common site for BCOR::CCNB3 fused tumors was extremity, BCOR-ITD kidney and ZC3H7B::BCOR uterus. Metastasis was rare in patients with BCOR::CCNB3. While most underwent resection and chemotherapy, few received radiation. Median follow-up of survivors was 24 months. Five year overall survival for patients with BCOR::CCNB3 fusions was 68% (95% confidence interval [CI]: 46%-83%). Patients with BCOR-ITD and ZC3H7B::BCOR had worse prognoses with 5 years overall survival of 35% (95% CI: 15%-56%) and 41% (95% CI: 11%-71%), respectively, demonstrating need for collaborative efforts identifying optimal treatments to improve outcomes.

PMID:35537005 | DOI:10.1097/MPH.0000000000002480

Cancer Res. 2022 May 10:canres.2395.2021. doi: 10.1158/0008-5472.CAN-21-2395. Online ahead of print.

ABSTRACT

Identifying biomarkers predictive of cancer cell response to drug treatment constitutes one of the main challenges in precision oncology. Recent large-scale cancer pharmacogenomic studies have opened new avenues of research to develop predictive biomarkers by profiling thousands of human cancer cell lines at the molecular level and screening them with hundreds of approved drugs and experimental chemical compounds. Many studies have leveraged these data to build predictive models of response using various statistical and machine learning methods. However, a common pitfall to these methods is the lack of interpretability as to how they make predictions, hindering the clinical translation of these models. To alleviate this issue, we used the recent logic modeling approach to develop a new machine learning pipeline that explores the space of bimodally expressed genes in multiple large in vitro pharmacogenomic studies and builds multivariate, nonlinear, yet interpretable logic-based models predictive of drug response. The performance of this approach was showcased in a compendium of the three largest in vitro pharmacogenomic data sets to build robust and interpretable models for 101 drugs that span 17 drug classes with high validation rates in independent datasets. These results along with in vivo and clinical validation, support a better translation of gene expression biomarkers between model systems using bimodal gene expression.

PMID:35536872 | DOI:10.1158/0008-5472.CAN-21-2395

PLoS Med. 2022 May 10;19(5):e1003993. doi: 10.1371/journal.pmed.1003993. eCollection 2022 May.

ABSTRACT

BACKGROUND: The effects of the Coronavirus Disease 2019 (COVID-19) pandemic in humanitarian contexts are not well understood. Specific vulnerabilities in such settings raised concerns about the ability to respond and maintain essential health services. This study describes the epidemiology of COVID-19 in Azraq and Zaatari refugee camps in Jordan (population: 37,932 and 79,034, respectively) and evaluates changes in routine health services during the COVID-19 pandemic.

METHODS AND FINDINGS: We calculate the descriptive statistics of COVID-19 cases in the United Nations High Commissioner for Refugees (UNHCR)’s linelist and adjusted odds ratios (aORs) for selected outcomes. We evaluate the changes in health services using monthly routine data from UNHCR’s health information system (HIS; January 2018 to March 2021) and apply interrupted time series analysis with a generalized additive model and negative binomial (NB) distribution, accounting for long-term trends and seasonality, reporting results as incidence rate ratios (IRRs). COVID-19 cases were first reported on September 8 and September 13, 2020 in Azraq and Zaatari camps, respectively, 6 months after the first case in Jordan. Incidence rates (IRs) were lower in camps than neighboring governorates (by 37.6% in Azraq (IRR: 0.624, 95% confidence interval [CI]: [0.584 to 0.666], p-value: <0.001) and 40.2% in Zaatari (IRR: 0.598, 95% CI: [0.570, 0.629], p-value: <0.001)) and lower than Jordan (by 59.7% in Azraq (IRR: 0.403, 95% CI: [0.378 to 0.430], p-value: <0.001) and by 63.3% in Zaatari (IRR: 0.367, 95% CI: [0.350 to 0.385], p-value: <0.001)). Characteristics of cases and risk factors for negative disease outcomes were consistent with increasing COVID-19 evidence. The following health services reported an immediate decline during the first year of COVID-19: healthcare utilization (by 32% in Azraq (IRR: 0.680, 95% CI [0.549 to 0.843], p-value < 0.001) and by 24.2% in Zaatari (IRR: 0.758, 95% CI [0.577 to 0.995], p-value = 0.046)); consultations for respiratory tract infections (RTIs; by 25.1% in Azraq (IRR: 0.749, 95% CI: [0.596 to 0.940], p-value = 0.013 and by 37.5% in Zaatari (IRR: 0.625, 95% CI: [0.461 to 0.849], p-value = 0.003)); and family planning (new and repeat family planning consultations decreased by 47.4% in Azraq (IRR: 0.526, 95% CI: [0.376 to 0.736], p-value = <0.001) and 47.6% in Zaatari (IRR: 0.524, 95% CI: [0.312 to 0.878], p-value = 0.014)). Maternal and child health services as well as noncommunicable diseases did not show major changes compared to pre-COVID-19 period. Conducting interrupted time series analyses in volatile settings such refugee camps can be challenging as it may be difficult to meet some analytical assumptions and to mitigate threats to validity. The main limitation of this study relates therefore to possible unmeasured confounding.

CONCLUSIONS: COVID-19 transmission was lower in camps than outside of camps. Refugees may have been affected from external transmission, rather than driving it. Various types of health services were affected differently, but disruptions appear to have been limited in the 2 camps compared to other noncamp settings. These insights into Jordan’s refugee camps during the first year of the COVID-19 pandemic set the stage for follow-up research to investigate how infection susceptibility evolved over time, as well as which mitigation strategies were more successful and accepted.

PMID:35536871 | DOI:10.1371/journal.pmed.1003993

PLoS Negl Trop Dis. 2022 May 10;16(5):e0010392. doi: 10.1371/journal.pntd.0010392. Online ahead of print.

ABSTRACT

Q fever and brucellosis are zoonoses that cause fever and other systemic clinical signs in humans; their occurrences are neglected and the differential diagnosis for some diseases is disregarded. This study aimed to investigate the seropositivity for Coxiella burnetii and Brucella spp. antibodies in patients suspected of dengue from 38 municipalities in the state of São Paulo, Brazil. The samples (n = 604) were obtained by convenience from the Adolfo Lutz Institute serum bank. Sera were subjected to an indirect immunofluorescence assay (IFA) using in-house and commercial diagnostic protocols to evaluate C. burnetii positivity. For Brucella spp., sera were subjected to rapid plate serum agglutination with buffered acidified antigen (AAT), slow tube serum agglutination (SAL), and 2-mercaptoethanol (2-ME) techniques. Associations and statistical inferences of the results were performed by logistic regression according to the clinical and demographic variables collected from the patients. Statistical analyses were performed using Statistical Analysis Software (SAS) and associations were considered when p value was <0.05. In all, 129 patients showed positive results for Q fever, indicating a seropositivity of 21.4% (95% CI 18.15-24.85). Patients with 14-20 days of symptoms had 2.12 (95% CI 1.34-3.35) times more chances of being seropositive for Q fever than patients with 7-13 days, and patients with 21-27 days of fever had 2.62 (95% CI 1.27-5.41) times more chances of being seropositive for Q fever than patients with 7-13 days. For the other variables analyzed, there were no significant associations between the groups. No positivity for brucellosis was observed. This is the most comprehensive study of people seropositive for Q fever in São Paulo state and provides additional data for the medical community in Brazil. It is suggested that Q fever may be an important differential diagnosis of febrile illnesses in the region, demanding the government’s attention and investment in health.

PMID:35536865 | DOI:10.1371/journal.pntd.0010392

PLoS One. 2022 May 10;17(5):e0268136. doi: 10.1371/journal.pone.0268136. eCollection 2022.

ABSTRACT

Prosthetic foot stiffness plays a key role in the functional mobility of lower limb prosthesis users. However, limited objective data exists to guide selection of the optimal prosthetic foot stiffness category for a given individual. Clinicians often must rely solely on manufacturer recommendations, which are typically based on the intended user’s weight and general activity level. Availability of comparable forefoot and heel stiffness data would allow for a better understanding of differences between different commercial prosthetic feet, and also between feet of different stiffness categories and foot sizes. Therefore, this study compared forefoot and heel linear stiffness properties across manufacturer-designated stiffness categories and foot sizes. Mechanical testing was completed for five types of commercial prosthetic feet across a range of stiffness categories and three foot-sizes. Data were collected for 56 prosthetic feet, in total. Testing at two discrete angles was conducted to isolate loading of the heel and forefoot components, respectively. Each prosthetic foot was loaded for six cycles while force and displacement data were collected. Forefoot and heel measured stiffness were both significantly associated with stiffness category (p = .001). There was no evidence that the relationships between stiffness category and measured stiffness differed by foot size (stiffness category by size interaction p = .80). However, there were inconsistencies between the expected and measured stiffness changes across stiffness categories (i.e., magnitude of stiffness changes varied substantially between consecutive stiffness categories of the same feet). While statistical results support that, on average, measured stiffness is positively correlated with stiffness category, force-displacement data suggest substantial variation in measured stiffness across consecutive categories. Published objective mechanical property data for commercial prosthetic feet would likely therefore be helpful to clinicians during prescription.

PMID:35536854 | DOI:10.1371/journal.pone.0268136

PLoS One. 2022 May 10;17(5):e0268032. doi: 10.1371/journal.pone.0268032. eCollection 2022.

ABSTRACT

While interest in antimicrobial stewardship programmes (ASPs) is growing in most low- and middle-income countries (LMICs), there is a paucity of information on their adoption or implementation in Africa, particularly Uganda. The study assessed the presence and characteristics of ASPs, implemented antimicrobial stewardship (AMS) strategies and the challenges to their implementation in hospitals in Uganda. We conducted a cross-sectional study among heads of infection prevention committees (IPCs) in regional referral hospitals, general hospitals, and private-not-for-profit (PNFP) hospitals from November 2019 to February 2020. An interviewer-administered questionnaire was used to collect data. We analysed data using descriptive statistics. A total of 32 heads of IPCs were enrolled in the study. Of these, eight were from regional referral hospitals, 21 were from general hospitals, and three were from PNFPs. Most heads of IPC were pharmacists (17/32, 53.1%) with a mean age and standard deviation (sd) of 36.1 (±1.1) years. A formal ASP was adopted or implemented in 14 out of the 32 (44%, 95% CI 26-62) studied hospitals. Thirty out of 32 hospitals implemented at least one type of AMS strategy. Sixty-eight percent (22/32) of the hospitals implemented pre-authorisation and approval as their primary AMS core strategy to optimise antibacterial use. The most commonly reported challenges to the implementation of ASP across all 32 hospitals (with or without ASP) were lack of time for the ASP team (29/32, 90.6%) and lack of allocated funding for antimicrobial stewardship team (29/32, 90.6%). In this study, most hospitals in Uganda implemented at least one AMS strategy despite the low implementation of ASPs in hospitals. The ministry of health needs to sensitise and support the establishment of ASP in hospitals across the country.

PMID:35536856 | DOI:10.1371/journal.pone.0268032

Female Pelvic Med Reconstr Surg. 2022 Apr 24. doi: 10.1097/SPV.0000000000001189. Online ahead of print.

ABSTRACT

IMPORTANCE: Pelvic reconstructive surgery is often associated with transient postoperative voiding dysfunction.

OBJECTIVE: This study aimed to compare postoperative active voiding trial (AVT) outcomes before and after implementation of an enhanced recovery program (ERP) for women undergoing pelvic reconstructive surgery. In addition, risk factors for postoperative urinary retention were identified.

STUDY DESIGN: We retrospectively identified patients undergoing inpatient vaginal or robotic pelvic reconstructive surgery before and after implementation of an ERP at our institution. Demographics, operative and postoperative details, and AVT outcomes were collected. Primary outcome was AVT failure. Variables associated with increased risk of AVT failure were identified using multivariate analysis.

RESULTS: Three hundred seventeen patients were included-75 pre-ERP and 242 ERP. There was no difference in AVT failures between pre-ERP and ERP groups (21.3% vs 21.9%, P = 0.92). The AVT failures were highest among those with abnormal preoperative postvoid residual volume (PVR ≥100 mL, 25.9% vs 12.2%, P = 0.01) and those who underwent an incontinence procedure (midurethral sling or Kelly plication, 30.4% vs 16.9%, P = 0.01). Compared with a reference procedure (total vaginal hysterectomy [TVH]), the following procedures were associated with statistically significant higher odds ratios (ORs) of AVT failure: TVH with incontinence procedure (OR, 15.0; confidence interval [CI], 4.58-48.9; P < 0.001), TVH with anterior repair (OR, 4.98; CI, 1.93-12.9; P = 0.001), and robotic sacrocolpopexy (OR, 3.6; CI, 1.18-11.2; P = 0.02).

CONCLUSIONS: Postoperative AVT failure incidence did not differ pre- and post-ERP intervention. Abnormal preoperative PVR was associated with failed postoperative voiding trial. Concomitant incontinence procedures and/or anterior colporrhaphy were associated with increased incidence of voiding trial failure regardless of ERP cohort.

PMID:35536662 | DOI:10.1097/SPV.0000000000001189

J Econ Entomol. 2022 May 10:toac064. doi: 10.1093/jee/toac064. Online ahead of print.

ABSTRACT

A systems approach was developed as an alternative to a standalone quarantine disinfestation treatment for Thaumatotibia leucotreta in citrus fruit exported from South Africa. The systems approach consists of three measures: pre and postharvest controls and measurements, postpacking inspection, and postharvest exposure to low temperatures. Different cold treatment conditions with a range of efficacy levels can be used for this last measure. A series of trials reported here evaluated the efficacy of seven temperatures ranging from 0 to 5°C for durations from 14 d to 26 d. Mortality of the most cold-tolerant larval stages of T. leucotreta was determined. Temperatures of 0, 1, 2, and 3°C for 16, 19, 20, and 24 d respectively, induced 100% mortality of the tested populations. Probit 9 level treatment efficacy was achieved at 0 and 1°C for 16 and 19 d respectively. Mortalities higher than 90% were obtained with temperatures of 4, 4.5, and 5°C, after exposure for the longer durations. We demonstrated a significant difference in cold-induced insecticidal efficacy between 1, 2, 3, and 4°C. There was no significant difference in insecticidal efficacy between 4 and 4.5°C, but both of these temperatures were more efficacious than 5°C. The results of this study are valuable to support the use of cold treatment conditions with lower risk of fruit chilling injury in an effective systems approach, where the cold treatment efficacy can be augmented with other components of the systems approach.

PMID:35536661 | DOI:10.1093/jee/toac064

J Proteome Res. 2022 May 10. doi: 10.1021/acs.jproteome.2c00030. Online ahead of print.

ABSTRACT

Liquid chromatography coupled to mass spectrometry is a key metabolomics/metabonomics technology. Reversed-phase liquid chromatography (RPLC) is very widely used as a separation step, but typically has poor retention of highly polar metabolites. Here, we evaluated the combination of two alternative methods for improving retention of polar metabolites based on 6-aminoquinoloyl-N-hydroxysuccinidimyl carbamate derivatization for amine groups, and ion-pairing chromatography (IPC) using tributylamine as an ion-pairing agent to retain acids. We compared both of these methods to RPLC and also to each other, for targeted analysis using a triple-quadrupole mass spectrometer, applied to a library of ca. 500 polar metabolites. IPC and derivatization were complementary in terms of their coverage: combined, they improved the proportion of metabolites with good retention to 91%, compared to just 39% for RPLC alone. The combined method was assessed by analyzing a set of liver extracts from aged male and female mice that had been treated with the polyphenol compound ampelopsin. Not only were a number of significantly changed metabolites detected, but also it could be shown that there was a clear interaction between ampelopsin treatment and sex, in that the direction of metabolite change was opposite for males and females.

PMID:35536659 | DOI:10.1021/acs.jproteome.2c00030

JMIR Serious Games. 2022 May 10;10(2):e34402. doi: 10.2196/34402.

ABSTRACT

BACKGROUND: Virtual reality (VR) is a computer technology that immerses a user in a completely different reality. The application of VR in acute pain settings is well established. However, in chronic pain, the applications and outcome parameters influenced by VR are less clear.

OBJECTIVE: This review aimed to systematically identify all outcome parameters that are reported in relation to VR in patients with chronic pain.

METHODS: A total of 4 electronic databases (PubMed, Scopus, Web of Science, and Embase) were searched for relevant studies. Multilevel random-effect meta-analyses were performed, whereby the standardized mean difference was chosen as the effect size to denote the difference between measurements before and after a VR intervention.

RESULTS: The initial database search identified 1430 studies, of which 41 (2.87%) were eventually included in the systematic review. Evidence has been found for the effects of VR on pain, functioning, mobility, functional capacity, psychological outcomes, quality of life, neuropsychological outcomes, and physical sensations. The overall effect size (a total of 194 effect sizes from 25 studies) based on a three level meta-analysis was estimated at 1.22 (95% CI 0.55-1.89; z=3.56; P<.001), in favor of improvements after a VR intervention. When categorizing effect sizes, the overall effect sizes were reported as follows: 1.60 (95% CI 0.83-2.36; z=4.09; P<.001) for the effect of VR on pain (n=31), 1.40 (95% CI 0.13-2.67; z=2.17; P=.03) for functioning (n=60), 0.49 (95% CI -0.71 to 1.68; z=0.80; P=.42) for mobility (n=24), and 0.34 (95% CI -1.52 to 2.20; z=0.36; P=.72) for functional capacity (n=21).

CONCLUSIONS: This systematic review revealed a broad range of outcome variables influenced by an intervention of VR technology, with statistically significant pain relief and improvements in functioning. These findings indicate that VR not only has applications in acute pain management but also in chronic pain settings, whereby VR might be able to become a promising first-line intervention as complementary therapy for patients with chronic pain.

TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42021227016; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=227016.

PMID:35536641 | DOI:10.2196/34402