Tag: statistics

Plast Reconstr Surg. 2022 Mar 1;149(3):638-649. doi: 10.1097/PRS.0000000000008830.

ABSTRACT

BACKGROUND: Mesenchymal stem cell-derived exosomes are known to produce effects similar to those of source cells and therefore represent a new approach in cell-free regenerative medicine. Their potential clinical application demands efficient isolation of stable and functional exosomes from a large volume of biological fluid.

METHODS: Exosomes from adipose-tissue conditioned medium of the same volume were isolated using either (1) ultrafiltration with size exclusion or (2) ExoQuick-TC. The isolated exosomes were characterized by protein concentration, particle size, exosomal marker expression, RNA expression profiles, and roles in dermal fibroblast proliferation and migration.

RESULTS: Both isolation methods produced exosomes within the size range defined for exosomes (50 to 200 nm) and common markers were enriched. Compared to the ExoQuick-TC precipitation method, the ultrafiltration method produced a significantly higher protein yield (p < 0.001) but a lower particle-to-protein ratio (p < 0.05); it also yielded higher RNA contents from the same fat tissue indicated by housekeeping genes, but with overall lower purity. The expression of several mRNAs and miRNAs related to tissue regeneration showed that there was no statistical difference between both methods, except miR-155 and miR-223 (p < 0.05). However, there was no difference in overall fibroblast proliferation and migration between exosomes isolated by these two methods.

CONCLUSIONS: Ultrafiltration with size exclusion demonstrated higher yields, acceptable purity, and comparable biophysical properties and biological functions to the more expensive commercial precipitation method. Therefore, it may conceivably be translated into yield-efficient and cost-effective modalities for therapeutic purposes.

CLINICAL RELEVANCE STATEMENT: Ultrafiltration with size exclusion may be amenable for exosome isolation from large-volume complex fluids such as tissue conditioned media for clinical application in future regenerative medicine.

PMID:35196679 | DOI:10.1097/PRS.0000000000008830

Psychother Psychosom. 2022 Feb 23:1-7. doi: 10.1159/000521952. Online ahead of print.

NO ABSTRACT

PMID:35196663 | DOI:10.1159/000521952

Plast Reconstr Surg. 2022 Mar 1;149(3):608-613. doi: 10.1097/PRS.0000000000008815.

ABSTRACT

BACKGROUND: Pathologic examination of young adult gynecomastia tissue is controversial given the low incidence of breast carcinoma in this population. The authors examined the pathologic findings in a large cohort of adolescents with gynecomastia to evaluate the need for routine tissue analysis in this population.

METHODS: A retrospective review of men who underwent unilateral or bilateral mastectomy for gynecomastia at a single institution between February of 2007 and November of 2019 identified demographics, medical history, surgical characteristics, and pathologic findings. Descriptive statistics were performed.

RESULTS: A total of 268 male patients were included. Mean age was 16.6 years. Mean body mass index was 27.8 kg/m2, and 42.5 percent of the sample was obese. The majority (83.2 percent) underwent bilateral subcutaneous mastectomy. There were no abnormal histopathologic findings in 95.1 percent. Among the 13 patients with abnormalities, eight (3 percent) had nonproliferative changes, two (0.8 percent) had proliferative changes without atypia, two (0.8 percent) had atypical ductal hyperplasia, and one (0.4 percent) had both bilateral atypical ductal hyperplasia and unilateral ductal carcinoma in situ. No patients had invasive carcinoma. The three patients with atypical ductal hyperplasia and/or ductal carcinoma in situ were obese but had no other breast cancer or gynecomastia risk factors.

CONCLUSIONS: Findings conferring potentially increased risk of developing breast cancer were identified in three male adolescents (1.2 percent). Incidence of these findings is similar between male adolescents and similarly aged female adolescents undergoing breast reduction surgery. Although worrisome pathology results are rare, too little is known about the natural history of atypical proliferation and ductal carcinoma in situ in young men to recommend against routine analysis.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

PMID:35196673 | DOI:10.1097/PRS.0000000000008815

Am J Nephrol. 2022 Feb 23:1-11. doi: 10.1159/000521940. Online ahead of print.

ABSTRACT

INTRODUCTION: Metabolomics could offer novel prognostic biomarkers and elucidate mechanisms of diabetic kidney disease (DKD) progression. Via metabolomic analysis of urine samples from 995 CRIC participants with diabetes and state-of-the-art statistical modeling, we aimed to identify metabolites prognostic to DKD progression.

METHODS: Urine samples (N = 995) were assayed for relative metabolite abundance by untargeted flow-injection mass spectrometry, and stringent statistical criteria were used to eliminate noisy compounds, resulting in 698 annotated metabolite ions. Utilizing the 698 metabolites’ ion abundance along with clinical data (demographics, blood pressure, HbA1c, eGFR, and albuminuria), we developed univariate and multivariate models for the eGFR slope using penalized (lasso) and random forest models. Final models were tested on time-to-ESKD (end-stage kidney disease) via cross-validated C-statistics. We also conducted pathway enrichment analysis and a targeted analysis of a subset of metabolites.

RESULTS: Six eGFR slope models selected 9-30 variables. In the adjusted ESKD model with highest C-statistic, valine (or betaine) and 3-(4-methyl-3-pentenyl)thiophene were associated (p < 0.05) with 44% and 65% higher hazard of ESKD per doubling of metabolite abundance, respectively. Also, 13 (of 15) prognostic amino acids, including valine and betaine, were confirmed in the targeted analysis. Enrichment analysis revealed pathways implicated in kidney and cardiometabolic disease.

CONCLUSIONS: Using the diverse CRIC sample, a high-throughput untargeted assay, followed by targeted analysis, and rigorous statistical analysis to reduce false discovery, we identified several novel metabolites implicated in DKD progression. If replicated in independent cohorts, our findings could inform risk stratification and treatment strategies for patients with DKD.

PMID:35196658 | DOI:10.1159/000521940

Cardiology. 2022 Feb 23. doi: 10.1159/000523718. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) assigned to the ‘observe’ zone of the ESC 0/1-hour algorithm form a heterogeneous group known to have an unfavourable prognosis. We aim to elucidate the clinical characteristics and management of these patients and generate a model that is predictive of a coronary diagnosis at index visit to the emergency department (ED).

METHODS: A retrospective observational cohort study including adult patients presenting to the ED with suspected NSTE-ACS assigned to the ‘observe’ zone of the ESC 0/1-hour algorithm. Multivariable logistic regression analysis was performed for the prediction of a coronary diagnosis. Internal validation was performed using bootstrap resampling.

RESULTS: 750 patients were included; mean age 66±13 years, 35% women, 50% with prior history of coronary artery disease. In 372 (50%) patients a diagnosis was established within 30-days of index presentation, of whom 169 (45%) patients had a coronary-related event. Multivariable logistic regression analysis generated a 12-point risk score incorporating 5 variables for the prediction of such event, including type of angina, chest pain occurring during inspiration, prior history of CAD, ST-segment deviation on electrocardiogram and estimated glomerular filtration rate<60. The final model had an optimism-corrected c-statistic of 0.78 (95% confidence interval [CI] 0.74-0.82). A score <6 ruled out a coronary event in 276 (37%) patients, with a sensitivity and NPV of 90% (95% CI 84-94) and 94% (91-96), respectively.

CONCLUSION: A score <6 identifies patients at low-risk of a coronary diagnosis and can guide clinical decision making in choosing the appropriate diagnostic test.

PMID:35196652 | DOI:10.1159/000523718

Aust J Rural Health. 2022 Feb 23. doi: 10.1111/ajr.12850. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate whether practice rurality and rural training pathway are associated with general practitioner registrars’ participation in their practice’s after-hours care roster.

DESIGN: A cross-sectional analysis of data (2017-2019) from the Registrar Clinical Encounters in Training study, an ongoing inception cohort study of Australian general practitioner registrars. The principal analyses used logistic regression.

SETTING: Three national general practitioner regional training organisations across 3 Australian states.

PARTICIPANTS: General practitioner registrars in training within regional training organisations.

MAIN OUTCOME MEASURE: Involvement in practice after-hours care was indicated by a dichotomous response on a 6-monthly Registrar Clinical Encounters in Training study questionnaire item.

RESULTS: 1576 registrars provided 3158 observations (response rate 90.3%). Of these, 1574 (48.6% [95% confidence interval: 46.8-50.3]) involved registrars contributing to their practice’s after-hours roster. In major cities, 40% of registrar terms involved contribution to their practice’s after-hours roster; in regional and remote practices, 62% contributed to the after-hours roster. On multivariable analysis, both level of rurality of practice (odds ratio(OR) 1.75, P = .007; and OR 1.74, P = .026 for inner regional and outer regional/remote locations, respectively, versus major city) and rural training pathway of registrar (OR 1.65, P = .008) were significantly associated with more after-hours roster contribution. Other associations were registrars’ later training stage, larger practices and practices not routinely bulk billing. Significant regional variability in after-hours care was identified (after adjusting for rurality).

CONCLUSION: These findings suggest that registrars working rurally and those training on the rural pathway are more often participating in practice after-hours rosters. This has workforce implications, and implications for the educational richness of registrars’ training environment.

PMID:35196416 | DOI:10.1111/ajr.12850

Transbound Emerg Dis. 2022 Feb 23. doi: 10.1111/tbed.14495. Online ahead of print.

ABSTRACT

Brucellosis is a zoonotic disease of considerable economic and public health significance globally. Despite the limited bacteriological evidence, a large number of serological works revealed that it is prevalent both in livestock and humans in Ethiopia. The current comprehensive review was carried out to provide apparent pooled seroprevalence (APS) estimates at individual animal and herd levels in livestock, and identify factors causing variability between studies conducted over the last two decades, show the spatial distribution, as well as summarizes Brucella species reported from livestock. It also provides APS of brucellosis in humans and evaluates the public health awareness of zoonotic brucellosis. In this review, systematic and synthetic review approaches were followed to summarize the available information. For the systematic review and meta-analysis, articles were selected based on predefined criteria. Data extracted from these articles were analyzed using meta-analytical approaches to provide APS estimates and in-between study variations for humans and all livestock species considered. Sensitivity analyses and bias assessments were conducted using influence plot analysis and, Egger’s and Begg’s statistics along with funnel plots, respectively. Synthetic review approaches were used to summarize data on isolates and public health awareness. Pooled seroprevalence estimate of brucellosis at national level was 2.6% (95% CI, 2.2-3.0) in cattle, 4% (95% CI, 3.1-5.1) in goats, 3% (95% CI, 2.3-3.9) in sheep and 3% (95% CI, 2.4-3.7) in camels. At a herd level, 16.3% (95% CI, 12.9, 20.5) of cattle, 12.1% (7.1, 19.9) of goat, 13.3% (7.6, 22.1) of sheep and 19.7% (13.8, 27.4) of camel herds in the country had at least one seropositive animal. Cattle in the pastoral/agropastoral production systems had significantly higher (p < 0.05) APS compared to mixed crop-livestock and urban/peri-urban dairy production systems. Pooled seroprevalence of brucellosis in small ruminants (8.3%, 95% CI, 6.3, 10.8) and camels (4.4%, 95% CI, 3.5, 5.6) in Afar were significantly higher (p<0.05) than in other regions. Reports conducted using ELISA and serial Rose Bengal plate test (RBPT)-ELISA had higher (p<0.05) APS estimates than serial RBPT and complement fixation test. Brucella melitensis and B. abortus were reported from goats and cattle, respectively, from three available reports. The APS of brucellosis in humans was 5% (95% CI: 3.3, 7.3). Public awareness of brucellosis was low (18.4%), while, practices that expose humans to Brucella infection were high. Scenario-based control interventions on regions and production systems using one health approach are suggested. This article is protected by copyright. All rights reserved.

PMID:35196417 | DOI:10.1111/tbed.14495

Epilepsia. 2022 Feb 23. doi: 10.1111/epi.17187. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the pharmacokinetics, safety, and tolerability of brivaracetam (BRV) as 15-min intravenous (IV) infusion and bolus (≤2-min injection).

METHODS: EP0065 (ClinicalTrials.gov: NCT03405714) was a Phase 2, multicenter, open-label trial in patients ≥1 month to <16 years of age with epilepsy. Patients received up to 5 mg/kg/day BRV (not exceeding 200 mg/day). Enrollment was sequential by descending age, depending on safety review. Outcomes included BRV plasma concentrations before and after IV administration, treatment-emergent adverse events (TEAEs), and discontinuations due to TEAEs.

RESULTS: Fifty patients were enrolled, received BRV, and completed the trial. Twenty-six patients (52.0%) received 15-min infusions and 24 (48.0%) received bolus injections. Most patients (80.0%) received one IV dose. In the 15-min infusion group, geometric mean (GeoMean) BRV concentrations 15 (±2) min (n = 21) and 3 h (±15 min) (n = 21) post dose were 1903.0 ng/mL (geometric coefficient of variation [GeoCV]: 60.7%) and 1130.3 ng/mL (58.8%), respectively. In the bolus group, GeoMean BRV concentrations 15 (±2) min (n = 19) and 3 h (±15 min) (n = 21) post dose were 1704.8 ng/mL (GeoCV: 74.5%) and 1383.9 ng/mL (85.0%), respectively. Overall, 14 patients (28.0%) had TEAEs (15-min infusion: 8 [30.8%]; bolus: 6 [25.0%]), most commonly (≥5% of patients) somnolence (3 [6.0%]). Ten patients (20.0%) had drug-related TEAEs (15-min infusion: 6 [23.1%]; bolus: 4 [16.7%]). No patients discontinued due to TEAEs, and no deaths occurred.

SIGNIFICANCE: IV BRV (up to 200 mg/day) was well tolerated in patients ≥1 month to <16 years of age, regardless of whether BRV was administered as 15-min infusion or bolus. No unexpected safety or pharmacokinetic differences were observed between patients receiving 15-min infusions or bolus, and plasma concentrations were in the expected range. Safety results were consistent with the known safety profile of oral BRV, with no new safety concerns identified.

PMID:35196395 | DOI:10.1111/epi.17187

PLoS One. 2022 Feb 23;17(2):e0264389. doi: 10.1371/journal.pone.0264389. eCollection 2022.

ABSTRACT

In 2019, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is transmitted via the airborne route, caused a new pandemic namely, “coronavirus disease 2019” (COVID-19). Although the effectiveness of face masks to prevent the transmission of SARS-CoV-2 is debated, no study has evaluated the virus-blocking efficacy of masks used by patients. We aimed to evaluate this efficacy of masks used by SARS-CoV-2-infected individuals. Data, masks used, and nasopharyngeal swab samples were obtained from these patients. Forty-five paired samples of nasopharyngeal swabs and masks were obtained and processed; the majority of masks were woven. Viral RNAs were amplified using quantitative reverse-transcription polymerase chain reaction and detected only on the inner parts of masks. Median viral load (VL) values of swabs and masks were 1.954×106 and 2,51×103, respectively. Statistically, there was a difference of approximately 1000 RNA copies/mL between swabs and masks and no significant difference in VL values among different types of masks. There were statistically significant differences in VL values between men and women and between symptomatic and asymptomatic patients. Our findings suggest the blocking of virus transmission by different types of masks and reinforce the use of masks by both infected and non-infected individuals.

PMID:35196363 | DOI:10.1371/journal.pone.0264389

J Am Med Inform Assoc. 2022 Feb 21:ocac025. doi: 10.1093/jamia/ocac025. Online ahead of print.

ABSTRACT

In response to the coronavirus disease-19 (COVID-19) pandemic, numerous institutions published COVID-19 dashboards for reporting epidemiological statistics at the county, state, or national level. However, statistics for smaller cities were often not reported, requiring these areas to develop their own data processing pipelines. For under-resourced departments of health, the development of these pipelines was challenging, leading them to rely on nonspecific and often delayed infection statistics during the pandemic. To avoid this issue, the Stamford, Connecticut Department of Health (SDH) contracted with the Columbia Mailman School of Public Health to develop an online dashboard that displays real-time case, death, test, vaccination, hospitalization, and forecast data for their city, allowing SDH to monitor trends for specific demographic and geographic groups. Insights from the dashboard allowed SDH to initiate timely and targeted testing/vaccination campaigns. The dashboard is widely used and highlights the benefit of public-academic partnerships in public health, especially during the COVID-19 pandemic.

PMID:35196368 | DOI:10.1093/jamia/ocac025