Tag: statistics

Contemp Clin Trials. 2021 Mar 29:106377. doi: 10.1016/j.cct.2021.106377. Online ahead of print.

ABSTRACT

INTRODUCTION: Efficient management of study drug inventory shipments is critical to keep research sites enrolling into multisite clinical treatment trials. A standard manual drug-management process used by the Tuberculosis Trials Consortium (TBTC), did not accommodate import permit approval timelines, shipment transit-times and time-zone differences. We compared a new web-based solution with the manual process, during an international 34-site clinical trial conducted by the TBTC and the AIDS Clinical Trials Group (ACTG); TBTC Study 31/ACTG A5349.

MATERIAL AND METHODS: We developed and implemented a technological solution by integrating logistical and regulatory requirements for drug importation with statistical simulations that estimated stock-out times in an online Drug Management Module (DMM). We measured the average shipment-related drug stock-outs and time to drug availability, to assess the efficiency of the DMM compared to the manual approach.

RESULTS: An Interrupted Time-Series (ITS) analysis showed a 15% [p-value = 0.03; 95% C.I. (-28.8%, -2.0%)] reduction in average shipment-related study drug stock-out after DMM implementation. The DMM streamlined the restocking process at study sites, reducing median transit-time for sites associated with a depot by 2 days [95% C.I. (-3.0, -1.0)]. Under the DMM, study drugs were available for treatment assignment on the day received, compared to one day after receipt under the manual process.

DISCUSSION: The DMM provided TBTC’s Data and Coordinating Center and site staff with more efficient procedures to manage and consistently maintain study drug inventory at enrolling sites. This DMM framework can improve efficiency in future multicenter clinical trials.

TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (Identifier: NCT02410772) on April 8, 2015.

PMID:33794353 | DOI:10.1016/j.cct.2021.106377

Neuroimage. 2021 Mar 29:118004. doi: 10.1016/j.neuroimage.2021.118004. Online ahead of print.

ABSTRACT

This work presents a single-step deep-learning framework for longitudinal image analysis, coined Segis-Net. To optimally exploit information available in longitudinal data, this method concurrently learns a multi-class segmentation and nonlinear registration. Segmentation and registration are modeled using a convolutional neural network and optimized simultaneously for their mutual benefit. An objective function that optimizes spatial correspondence for the segmented structures across time-points is proposed. We applied Segis-Net to the analysis of white matter tracts from N=8045 longitudinal brain MRI datasets of 3249 elderly individuals. Segis-Net approach showed a significant increase in registration accuracy, spatio-temporal segmentation consistency, and reproducibility compared with two multistage pipelines. This also led to a significant reduction in the sample-size that would be required to achieve the same statistical power in analyzing tract-specific measures. Thus, we expect that Segis-Net can serve as a new reliable tool to support longitudinal imaging studies to investigate macro- and microstructural brain changes over time.

PMID:33794359 | DOI:10.1016/j.neuroimage.2021.118004

Neuroimage. 2021 Mar 29:117996. doi: 10.1016/j.neuroimage.2021.117996. Online ahead of print.

ABSTRACT

Digitized neuroanatomical atlases that can be overlaid onto functional data are crucial for localizing brain structures and analyzing functional networks identified by neuroimaging techniques. To aid in functional and structural data analysis, we have created a comprehensive parcellation of the rhesus macaque subcortex using a high-resolution ex vivo structural imaging scan. This anatomical scan and its parcellation were warped to the updated NIMH Macaque Template (NMT v2), an in vivo population template, where the parcellation was refined to produce the Subcortical Atlas of the Rhesus Macaque (SARM) with 210 primary regions-of-interest (ROIs). The subcortical parcellation and nomenclature reflect those of the 4^th edition of the Rhesus Monkey Brain in Stereotaxic Coordinates (Paxinos et al., in preparation), rather than proposing yet another novel atlas. The primary ROIs are organized across six spatial hierarchical scales from small, fine-grained ROIs to broader composites of multiple ROIs, making the SARM suitable for analysis at different resolutions and allowing broader labeling of functional signals when more accurate localization is not possible. As an example application of this atlas, we have included a functional localizer for the dorsal lateral geniculate (DLG) nucleus in three macaques using a visual flickering checkerboard stimulus, identifying and quantifying significant fMRI activation in this atlas region. The SARM has been made openly available to the neuroimaging community and can easily be used with common MRI data processing software, such as AFNI, where the atlas has been embedded into the software alongside cortical macaque atlases.

PMID:33794360 | DOI:10.1016/j.neuroimage.2021.117996

Med Educ. 2021 Apr 1. doi: 10.1111/medu.14535. Online ahead of print.

ABSTRACT

OBJECTIVE: To analyze the impact of interview date on the applicant rank for Neurology residencies in the United States.

METHODS: A multi-institutional retrospective review of interview dates and applicant rank list data for the National Resident Matching Program (NRMP) was conducted for five Neurology programs, totaling 1932 interviewed applicants over a combined total of 31 interview years. For each candidate, the interview date and applicant rank were abstracted along with the total number of interviews for that season. Statistical analyses were completed on the cumulative institution data set as well for each individual institution to assess for a possible relationship between interview date and applicant rank.

RESULTS: The cumulative institutional analysis showed that the mean applicant rank decreased as the interview season progressed. Applicants who interviewed on the first day of the interview season were ranked 11.4% higher than those who interviewed on the last interview day. Additionally, applicants interviewed on the first interview day more likely to be ranked higher when compared to all other interview dates. Independent analysis of each program’s data identified comparable, statistically significant, differences in mean applicant rank and interview position at three out of the five institutions.

CONCLUSIONS: This study evaluated the impact of interview order on the ranking of applicants by Neurology residency programs, noting a temporal relationship with applicant rank and interview date. The primacy bias appreciated in our data merits further evaluation in other medical specialties. Strategies to minimize the impact of this bias should be employed by residency programs who use medical matching services.

PMID:33794035 | DOI:10.1111/medu.14535

Horm Mol Biol Clin Investig. 2021 Apr 2. doi: 10.1515/hmbci-2020-0094. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the effects of an eight week exercise program on the lipid profile in serum, serum levels of adropin, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in male volleyball players.

METHODS: Sixteen healthy male volleyball players participated in this study. Subjects performed eight weeks of aerobic and resistance training, and body mass index (BMI), body fat ratio, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), adropin, SBP, and DBP values were measured at the start (untrained) and end (trained) of training. Non-HDL-C was calculated by subtracting HDL-C from TC.

RESULTS: Body fat percentage and BMI values decreased significantly after eight weeks of exercise training. There was a statistically significant decrease in the post-test values of LDL-C, TG, non-HDL-C, and DBP compared to pre-test measurements. There was a significant increase in the trained levels of adropin and HDL-C compared to untrained levels. Pearson’s correlation analyses revealed a negative and significant relationship between changes in DBP and adropin levels before and after exercise.

CONCLUSIONS: Eight weeks of exercise training decreased LDL-C, TG, non-HDL-C, and DBP and an increased serum levels of adropin in male volleyball players.

PMID:33794077 | DOI:10.1515/hmbci-2020-0094

Swiss Med Wkly. 2021 Mar 15;151:w20463. doi: 10.4414/smw.2021.20463. eCollection 2021 Mar 15.

ABSTRACT

BACKGROUND: During the last 20 years, treatment for chronic lymphocytic leukaemia (CLL) / small lymphocytic lymphoma (SLL) has advanced, with improved clinical outcomes in randomised controlled trials. Currently, no data have been published from Switzerland to assess effectiveness of recent healthcare advances in CLL/SLL on a population-based level. We aimed to estimate trends in incidence, mortality and survival for patients with CLL/SLL in Switzerland.

METHODS: We retrospectively studied registry data from the National Agency for Cancer Registration (NACR) database in Switzerland from 1997 to 2016. We investigated incidence, mortality and survival in consecutive 5-year periods. Age-specific rates were calculated for three age groups (<65 years, 65–74 years and ≥75 years).

RESULTS: We obtained 6301 cases with CLL/SLL. Median age at diagnosis was 72 years. From 7.0 per 100,000 person-years in 1997–2002, age-adjusted incidence rates peaked at 7.8 per 100,000 person-years in the second time period, 2002–2006, and declined afterwards to 6.4 per 100,000 person-years in 2012–2016. Mortality declined from 2.4 per 100,000 person-years in 1997–2002 to 2.0 per 100,000 in 2012–2016. Five- and 10-year age-standardised relative survival increased from 77.9% and 55.6%, respectively, in 1997–2001 to 83.6% (p = 0.009) and 64.2% (p = 0.005), respectively, in 2012–2016. Improvement in age-specific relative survival was only significant in the middle age group (65–74 years). Incidence and mortality were significantly higher in males. Females had better relative survival.

CONCLUSION: We found no clear down- or upward trend in age-adjusted incidence rates. Age-standardised survival improved over time, mainly in the two younger age-groups, but this improvement was statistically significant in those aged 65–74 years only. Males have higher incidence rates, higher mortality and shorter survival than females. Reporting delay and underreporting are major limitations in the interpretation of registry data from patients diagnosed with CLL/SLL.

PMID:33793959 | DOI:10.4414/smw.2021.20463

Swiss Med Wkly. 2021 Apr 1;151:w20462. doi: 10.4414/smw.2021.20462. eCollection 2021 Mar 15.

ABSTRACT

AIMS OF THE STUDY: Although many studies have investigated the influence of personal characteristics on recidivism, knowledge about the impact of correctional policies remains limited. The present study adds to this debate by investigating the effect of the dualistic system of custodial sanctions in Switzerland over time. Specifically, we: (1) tested the influence that different types of custodial sanctions – sentences (offering regular prison treatment) and measures (offering crime-related rehabilitation programmes) – have on reconviction rates; and (2) forecasted future reconviction rates to estimate their value in the year 2020.

METHODS: National level data from the Swiss Federal Statistical Office were collected, including 3-year reconviction rates after release from custody and the number of persons serving custodial sentences and measures. A time series framework was used for the analyses, which included data available from 1988 to 2013 (n = 26 years).

RESULTS: The number of persons serving custodial sentences had no effect on recidivism (p = 0.582); however, a higher number of persons serving custodial measures was significantly associated with a decrease in recidivism (p = 0.003). For the year 2020, a reconviction rate of 28% (range 23–33%) was predicted.

CONCLUSIONS: Custodial measures seem to be associated with a reduction in recidivism. However, owing to the indeterminate time associated with some custodial measures, often at the cost of the prisoners’ rights and the criminal justice system, future studies are needed to determine the optimal serving time for custodial measures.

PMID:33793962 | DOI:10.4414/smw.2021.20462

Cancer. 2021 Apr 1. doi: 10.1002/cncr.33516. Online ahead of print.

ABSTRACT

BACKGROUND: Endometrial cancers (ECs) with somatic mutations in DNA polymerase epsilon (POLE) are characterized by unfavorable pathological features, which prompt adjuvant treatment. Paradoxically, women with POLE-mutated EC have outstanding clinical outcomes, and this raises concerns of overtreatment. The authors investigated whether favorable outcomes were independent of treatment.

METHODS: A PubMed search for POLE and endometrial was restricted to articles published between March 1, 2012, and March 1, 2018, that provided individual patient data (IPD), adjuvant treatment, and survival. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting guidelines for IPD, the authors used univariate and multivariate one-stage meta-analyses with mixed effects Cox models (random effects for study cohorts) to infer the associations of treatment, traditional prognostic factors, and outcome, which was defined as the time from first diagnosis to any adverse event (progression/recurrence or death from EC).

RESULTS: Three hundred fifty-nine women with POLE-mutated EC were identified; 294 (82%) had pathogenic mutations. Worse outcomes were demonstrated in patients with nonpathogenic POLE mutations (hazard ratio, 3.42; 95% confidence interval, 1.47-7.58; log-rank P < .01). Except for stage (P < .01), traditional prognosticators were not associated with progression/recurrence or death from disease. Adverse events were rare (11 progressions/recurrences and 3 disease-specific deaths). Salvage rates in patients who experienced recurrence were high and sustained, with 8 of 11 alive without evidence of disease (range, 5.5-14.2 years). Adjuvant treatment was not associated with outcome.

CONCLUSIONS: Clinical outcomes for ECs with pathogenic POLE mutations are not associated with most traditional risk parameters, and patients do not appear to benefit from adjuvant therapy. The observed low rates of recurrence/progression and the high and sustained salvage rates raise the possibility of safely de-escalating treatment for these patients.

LAY SUMMARY: Ten percent of all endometrial cancers have mutations in the DNA repair gene DNA polymerase epsilon (POLE). Women who have endometrial cancers with true POLE mutations experience almost no recurrences or deaths from their cancer even when their tumors appear to have very unfavorable characteristics. Additional therapy (radiation and chemotherapy) does not appear to improve outcomes for women with POLE-mutated endometrial cancer, and this supports the move to less therapy and less associated toxicity. Diligent classification of endometrial cancers by molecular features provides valuable information to inform prognosis and to direct treatment/no treatment.

PMID:33793971 | DOI:10.1002/cncr.33516

Med Ultrason. 2021 Mar 14. doi: 10.11152/mu-2692. Online ahead of print.

ABSTRACT

AIMS: The aim of this study was to compare technical success and tolerability between hysterosalpingography (HSG) and hysterosalpingo-contrast ultrasonography (HyCoUs) as a first-line evaluation method in a single fertility center.

MATERIAL AND METHODS: The study included 56 infertile women: 27 patients underwent HSG and 29 patients underwent HyCoUs. Pain perception was measured by means of an 11-point visual analog scale (VAS) and the Stacy score. Side-effects, technical aspects, complications and variable correlations were documented.

RESULTS: The median VAS scale was 5 (4;6) for HSG and 1 (1;2) for HyCoUs. The median Stacy score was 2 (1;3) for HSG and 1 (0;1) for HyCoUs. The difference in pain perception was statistically significant for both pain scores (p<0.001). All patients undergoing HyCoUs reported a visual analog (VAS) pain score of <5 and 59.3% of patients undergoing an HSG reported a score of >5. Increased pain scores showed a statistically significant association with duration and total volume of substance infused. The type of procedure and volume infused were independently associated with the VAS scale. In the HSG group, 14.8% (4) of patients reported a vagal effect (p<0.001), one patient requiring hospitalization. No vagal effects were reported following HyCoUs and the method was technically successful in 100% (29) of cases. HSG was successful in 88.9% (24) of cases.

CONCLUSIONS: HyCoUs is a well-tolerated procedure with reduced frequency of adverse effects. Low pain perception is strongly correlated with a low volume infused. It is non-invasive and efficient in rendering good quality images.

PMID:33793700 | DOI:10.11152/mu-2692

J Pharm Pharmacol. 2021 Mar 4;73(2):247-262. doi: 10.1093/jpp/rgaa022.

ABSTRACT

OBJECTIVES: To explore the intervention mechanism of combining Polygala tenuifolia (PT) with Magnolia officinalis (MO) on gastrointestinal motility disorders caused by PT.

METHODS: Urine and faeces of rats were collected; the effects of PT and MO on the gastric emptying and small intestine advancing rates in mice were analysed via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) to determine the potential metabolites. Changes in the metabolic profiles of the urine and faeces were revealed by untargeted metabolomics, followed by multivariate statistical analysis. The integration of urine and faeces was applied to reveal the intervention mechanism of PT-MO on PT-induced disorders.

KEY FINDINGS: PT + MO (1:2) improved the gastrointestinal function in mice suffering from PT-induced gastrointestinal motility disorder. Metabolomics indicated that the PT-MO mechanism was mainly associated with the regulations of 17 and 12 metabolites and 11 and 10 pathways in urine and faeces, respectively. The common metabolic pathways were those of tyrosine, purine, tricarboxylic acid cycle, pyruvate and gluconeogenesis, which were responsible for the PT-MO intervention mechanism.

CONCLUSIONS: The PT-MO (1:2) couple mechanism mitigated the PT-induced disorders, which were related to the energy, amino acid and fatty metabolisms.

PMID:33793803 | DOI:10.1093/jpp/rgaa022