Category: Statistics

Neurosciences (Riyadh). 2024 Jul;29(3):184-189. doi: 10.17712/nsj.2024.3.20240040.

ABSTRACT

OBJECTIVES: To assess clinicians’ adherence to fingolimod’s effective use according to the prescribed recommendations to reduce safety risk, identify the consequences, and highlight areas for improvement to policy makers for the benefit of both patient and care-giver.

METHODS: A retrospective observational study conducted at a tertiary hospital targeting multiple sclerosis patients on fingolimod from January 2017 to December 2021. The physicians’ adherence to the manufacturer’s instructions was assessed and categorized into good, moderate, and poor based on adherence to fingolimod instructions and monitoring measures. Four monitoring measures were assessed: bradycardia observation, ophthalmic examination, liver enzymes, and infections. In addition, the impact of adherence on patient safety was also assessed.

RESULTS: A total of 140 patients were included. Seventy-twopatients (51.4%) had physician with poor adherence (followed only one instruction or none). Sixty-five patients (46.4%) had 2-3 manufacture recommendations where physician’s adherence was moderate. Three patients (2.10%) had all manufacturer’s recommendations. In terms of fingolimod complications, 18 patients found to have bradycardia after the first does, macular oedema and infections was reported in 4 patients, and the elevation in hepatic enzymes was reported in 6 patients. Poor physician’s adherence has resulted in treatment incompleteness and highest fingolimod discontinuation or switching to other treatment options.

CONCLUSION: Adherence to fingolimod instructions was poor among physicians which resulted in highest drug switching or discontinuing rate.

PMID:38981628 | DOI:10.17712/nsj.2024.3.20240040

BMJ. 2024 Jul 9;386:e078525. doi: 10.1136/bmj-2023-078525.

NO ABSTRACT

PMID:38981624 | DOI:10.1136/bmj-2023-078525

Stat Med. 2024 Jul 9. doi: 10.1002/sim.10169. Online ahead of print.

ABSTRACT

Risky-prescribing is the excessive or inappropriate prescription of drugs that singly or in combination pose significant risks of adverse health outcomes. In the United States, prescribing of opioids and other “risky” drugs is a national public health concern. We use a novel data framework-a directed network connecting physicians who encounter the same patients in a sequence of visits-to investigate if risky-prescribing diffuses across physicians through a process of peer-influence. Using a shared-patient network of 10 661 Ohio-based physicians constructed from Medicare claims data over 2014-2015, we extract information on the order in which patients encountered physicians to derive a directed patient-sharing network. This enables the novel decomposition of peer-effects of a medical practice such as risky-prescribing into directional (outbound and inbound) and bidirectional (mutual) relationship components. Using this framework, we develop models of peer-effects for contagion in risky-prescribing behavior as well as spillover effects. The latter is measured in terms of adverse health events suspected to be related to risky-prescribing in patients of peer-physicians. Estimated peer-effects were strongest when the patient-sharing relationship was mutual as opposed to directional. Using simulations we confirmed that our modeling and estimation strategies allows simultaneous estimation of each type of peer-effect (mutual and directional) with accuracy and precision. We also show that failing to account for these distinct mechanisms (a form of model mis-specification) produces misleading results, demonstrating the importance of retaining directional information in the construction of physician shared-patient networks. These findings suggest network-based interventions for reducing risky-prescribing.

PMID:38981613 | DOI:10.1002/sim.10169

J Proteome Res. 2024 Jul 9. doi: 10.1021/acs.jproteome.4c00091. Online ahead of print.

ABSTRACT

Single-cell analysis is an active area of research in many fields of biology. Measurements at single-cell resolution allow researchers to study diverse populations without losing biologically meaningful information to sample averages. Many technologies have been used to study single cells, including mass spectrometry-based single-cell proteomics (SCP). SCP has seen a lot of growth over the past couple of years through improvements in data acquisition and analysis, leading to greater proteomic depth. Because method development has been the main focus in SCP, biological applications have been sprinkled in only as proof-of-concept. However, SCP methods now provide significant coverage of the proteome and have been implemented in many laboratories. Thus, a primary question to address in our community is whether the current state of technology is ready for widespread adoption for biological inquiry. In this Perspective, we examine the potential for SCP in three thematic areas of biological investigation: cell annotation, developmental trajectories, and spatial mapping. We identify that the primary limitation of SCP is sample throughput. As proteome depth has been the primary target for method development to date, we advocate for a change in focus to facilitate measuring tens of thousands of single-cell proteomes to enable biological applications beyond proof-of-concept.

PMID:38981598 | DOI:10.1021/acs.jproteome.4c00091

Phys Med Biol. 2024 Jul 9. doi: 10.1088/1361-6560/ad611b. Online ahead of print.

ABSTRACT

Head and neck cancer patients experience systematic anatomical changes as well as random day to day anatomical changes during fractionated radiotherapy treatment. Modelling the expected systematic anatomical changes could aid in creating treatment plans which are more robust against such changes. A patient specific (SM) and population average (AM) model are presented which are able to capture the systematic anatomical changes of some head and neck cancer patients over the course of radiotherapy treatment. 
Inter- patient correspondence aligned all patients to a model space. Intra- patient correspondence between each planning CT scan and on treatment cone beam CT scans was obtained using diffeomorphic deformable image registration. The stationary velocity fields were then used to develop B-Spline based SMs and AMs. The models were evaluated geometrically and dosimetrically. A leave-one-out method was used to compare the training and testing accuracy of the models. 
Both SMs and AMs were able to capture systematic changes. The average surface distance between the registration propagated contours and the contours generated by the SM was less than 2mm, showing that the SM are able to capture the anatomical changes which a patient experiences during the course of radiotherapy. The testing accuracy was lower than the training accuracy of the SM, suggesting that the model overfits to the limited data available and therefore also captures some of the random day to day changes. For most patients the AMs were a better estimate of the anatomical changes than assuming there were no changes, but the AMs could not capture the variability in the anatomical changes seen in all patients. No difference was seen in the training and testing accuracy of the AMs. These observations were highlighted in both the geometric and dosimetric evaluations and comparisons. The large patient variability highlights the need for more complex, capable population models.

PMID:38981595 | DOI:10.1088/1361-6560/ad611b

Phys Med Biol. 2024 Jul 9. doi: 10.1088/1361-6560/ad6119. Online ahead of print.

ABSTRACT

Objective We propose a nonparametric figure of merit, the contrast equivalent
distance CED, to measure contrast directly from clinical images.
Approach A relative brightness distance δ is calculated by making use of the order
statistic of the pixel values. By multiplying δ with the grey value range R, the mean
brightness distance MBD is obtained. From the MBD, the CED and the distance-to-
noise ratio DNR can be derived. The latter is the ratio of the MBD and a previously
suggested nonparametric measure τ for the noise.
Since the order statistic is independent of the spatial arrangement of the pixel
values, the measures can be obtained directly from clinical images. We apply the new
measures to mammography images of an anthropomorphic phantom and of a phantom
with a step wedge as well as to CT images of a head phantom.
Main results For low-noise images of a step wedge, the MBD is equivalent to the
conventional grey value distance. While this measure permits the evaluation of clinical
images, it is sensitive to noise. Therefore, noise has to be quantified at the same time.
When the ratio σ/τ of the noise standard deviation σ to τ is available, validity limits
for the CED as a measure of contrast can be established. The new figures of merit
can be calculated for entire images as well as on regions of interest (ROI) with an edge
length not smaller than 32 px.
Significance The new figures of merit are suited to quantify the quality of clinical
images without relying on the assumption of a linear, shift-invariant system. They can
be used for any kind of greyscale image, provided the ratio σ/τ can be estimated. This
will hopefully help to achieve the optimisation of image quality vs dose required by
radioprotection laws.

PMID:38981591 | DOI:10.1088/1361-6560/ad6119

J Oral Maxillofac Surg. 2024 Jun 24:S0278-2391(24)00578-0. doi: 10.1016/j.joms.2024.06.166. Online ahead of print.

ABSTRACT

BACKGROUND: Virtual surgical planning (VSP) for composite microvascular free flaps has become standard of care for oncologic head and neck reconstruction. Controversy remains as to the use of three-dimensional (3D)-printed titanium patient-specific implants (PSIs) versus hand-bent stock reconstruction plates. Proponents of PSIs cite improved surgical accuracy, reduced operative times, and improved clinical outcomes. Detractors purport increased cost associated with PSIs and presumed equivalent accuracy with less expensive stock plates.

PURPOSE: The study purpose was to measure and compare the 3D-volumetric accuracy of PSI versus stock reconstruction plates among subjects undergoing VSP-guided mandibular fibular free flap reconstruction.

STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study of subjects undergoing VSP-guided fibular free flap reconstructions at Mayo Clinic between 2016 and 2023 was performed. Subjects were excluded for non-VSP guidance, midfacial reconstruction, nonfibular free flaps, and lack of requisite study variables.

PREDICTOR VARIABLE: The primary predictor was the type of reconstruction plate utilized (PSI vs stock plate).

MAIN OUTCOME VARIABLE: The main outcome was volumetric surgical accuracy of the final reconstruction compared to the preoperative surgical plan by root mean square error (RMSE) calculation. Lower RMSE values indicated a higher surgical accuracy.

COVARIATES: Covariates included age, sex, race, smoking status, American Society of Anesthesiologists Physical Status Classification System, Charlson Comorbidity Index, preoperative diagnosis, and number of fibular segments.

ANALYSES: Differences in surgical accuracy were assessed between preoperative and postoperative segmented scans using volumetric overlays from which RMSE values were calculated. Univariate and multivariate modeling of plate type to RMSE calculation was performed. Statistical significance set to P < .05.

RESULTS: Total of 130 subjects were identified, 105 PSI and 25 stock plates. Calculated mean RMSE in millimeters (mm) for stock plates was 1.46 (standard deviation: 0.33) and 1.15 (standard deviation: 0.36) for PSIs. Univariate modeling demonstrated a statistically significant difference in RMSE of 0.31 (95% confidence interval: 0.16-0.47) (P < .001) equating to a 21.2% (P < .001) improved volumetric surgical accuracy for PSIs. The association of improved volumetric accuracy with PSIs has been maintained in all multivariate models controlling for confounding.

CONCLUSION AND RELEVANCE: In modern era VSP-guided head and neck fibular free flap reconstruction, patient-specific 3D-printed titanium implants confer a statistically significant improvement in volumetric surgical accuracy over stock reconstruction plates.

PMID:38981580 | DOI:10.1016/j.joms.2024.06.166

Neurosci Biobehav Rev. 2024 Jul 7:105807. doi: 10.1016/j.neubiorev.2024.105807. Online ahead of print.

ABSTRACT

The efficacy and acceptability of various non-invasive brain stimulation (NIBS) interventions for autism spectrum disorder remain unclear. We carried out a systematic review for randomized controlled trials (RCTs) regarding NIBS for reducing autistic symptoms (INPLASY202370003). Sixteen articles (N = 709) met the inclusion criteria for network meta-analysis. Effect sizes were reported as standardized mean differences (SMDs) or odds ratios with 95% confidence intervals (CIs). Fourteen active NIBS interventions, including transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation, and transcranial pulse stimulation were analyzed. Only anodal tDCS over the left dorsolateral prefrontal cortex paired with cathodal tDCS over an extracephalic location (atDCS_F3+ctDCS_E) significantly improved autistic symptoms compared to sham controls (SMD = -1.40, 95%CIs = -2.67 to -0.14). None of the NIBS interventions markedly improved social-communication symptoms or restricted/repetitive behaviors in autistic participants. Moreover, no active NIBS interventions exhibited significant dropout rate differences compared to sham controls, and no serious adverse events were reported for any intervention.

PMID:38981573 | DOI:10.1016/j.neubiorev.2024.105807

Acta Trop. 2024 Jul 7:107317. doi: 10.1016/j.actatropica.2024.107317. Online ahead of print.

ABSTRACT

BACKGROUND: Tuberculosis (TB) as a foremost infectious disease adds massive burden to morbidity and mortality rate, despite of well-structured TB control programs around the globe. Inappropriate health care management system and poor implementation on standard in relevance to TB, remain some reasons causative to TB prevalence and its rising antimicrobial resistance. Health Care Workers (HCWs) laboring as a part of TB control system, are the vital warriors in achieving the goals of TB End Strategy by 2035. Their performance is influenced by their knowledge, attitude, and practices (KAP) toward this infectious disease. This study aimed to signify the role of KAP score of health care Workers in the better control and prevention of TB in the Islamabad Capital Territory (ICT), Pakistan.

METHODS: A cross-sectional study on Knowledge, Attitude and Practice study of Tuberculosis (TB) among health care Workers, was done in ICT, which is the capital of Pakistan. The KAP of TB was collected for the 306 Health Care Workers from all the Islamabad TB referring health facilities which refer the TB patients for testing to the National Reference Laboratory, Islamabad Pakistan. Eligible health care workers were requested to respond on KAP questionnaire after informed consent. KAP questionnaire comprised of knowledge, attitude, and practices section including demographic information. All the data was analyzed using IBM SPSS statistics 21. One Way Analysis of Variance (ANOVA) was applied to calculate KAP mean score against different variables. On the significant data sets of ANOVA output, Tukey’s Multiple Comparison Test was applied for pairwise comparison. Pearson correlation coefficient was utilized to explore the association between two qualitative variables. The non-parametric tests were applied to evaluate difference of KAP score in relation to demographic covariates individually.

RESULTS: From June to July 2023, we conducted TB KAP study among Health Care Workers of ICT, Pakistan. The average age was 33 years (range 26-30 years). Majority of the recruited subjects were not being trained for dealing with TB infection. The results demonstrated that Health Care Workers working were lacking their knowledge about mode of TB transmission, best diagnostic technique, and contraction of TB infections. The mean knowledge, attitude and practices mean scores were 15.05 (SD =3.96), 83.68 (SD =15.74) and 6.31 (SD =2.21) respectively. Mean knowledge score of Health Care Workers were significantly related to their educational level and occupation while no significant association was declared with working experience as TB staff. Pearson coefficient of attitude score with knowledge of Health Care Workers was of weak level (0.28). Practice mean score was correlated to knowledge mean score at a moderate level (r =0.40). On the other hand, practice score was r =0.29 with attitude mean score had shown weak level correlation. A number of demographic factors were strongly linked to each of the mean score of knowledge, attitude, and practices.

CONCLUSION: These findings highlighted the significant involvement of education, profession, and professional trainings in the better knowledge, attitude, and practices of the TB related health care Workers. For a better management system of infectious diseases like TB, a well-trained and professionally competent staff of Health Care Workers is important so as to achieve the goal of TB-End strategy by 2035 from Pakistan, which is the 5th highest burden country for TB.

PMID:38981566 | DOI:10.1016/j.actatropica.2024.107317

Clin Chim Acta. 2024 Jul 7:119855. doi: 10.1016/j.cca.2024.119855. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Bladder cancer (BCa) is a highly aggressive malignancy of the urinary system. Timely detection is imperative for enhancing BCa patient prognosis.

MATERIALS AND METHODS: This study introduces a novel approach for detecting long non-coding RNA (lncRNA) Mitochondrial RNA Processing Endoribonuclease (RMRP) in urine exosomes from BCa patients using the reverse transcription recombinase-aided amplification (RT-RAA) and clustered regularly interspaced short palindromic repeats and associated Cas12a proteins (CRISPR/Cas12a) technique. Various statistical methods were used to evaluate its diagnostic value for BCa.

RESULTS: The specificity of urine exosomal RMRP detection for BCa diagnosis was enhanced by using RT-RAA combined with CRISPR/Cas12a. The testing process duration was reduced to 30 min, which supports rapid detection. Moreover, this approach allows the identification of target signals in real-time using blue light, facilitating immediate detection. In clinical sample analysis, this methodology exhibited a high level of diagnostic efficacy. This was evidenced by larger area under the curve values with receiver operating characteristic curve analysis compared with using traditional RT-qPCR methods, indicating superior diagnostic accuracy and sensitivity. Furthermore, the combined analysis of RMRP expression in urine exosomes detected by RT-RAA-CRISPR/Cas12a and NMP-22 expression may further enhance diagnostic accuracy.

CONCLUSIONS: The RT-RAA-CRISPR/Cas12a technology is a swift, sensitive, and uncomplicated method for nucleic acid detection. Because of its convenient and non-invasive sampling approach, user-friendly operation, and reproducibility, this technology is very promising for automated detection and holds favorable application possibilities within clinical environments.

PMID:38981565 | DOI:10.1016/j.cca.2024.119855