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Nevin Manimala Statistics

Assessing Auditory and Cochlear Function in Alopecia Areata Patients: Exploring the Link to Cochlear Melanocyte Damage

Cureus. 2023 Sep 8;15(9):e44882. doi: 10.7759/cureus.44882. eCollection 2023 Sep.

ABSTRACT

Introduction Alopecia areata (AA) is an autoimmune disorder causing hair loss, including eyebrows, eyelashes, and body hair, primarily due to melanocyte impact. Though the precise AA melanocyte hearing loss mechanisms are not fully clear, it’s speculated that cochlear melanocyte inflammation could disrupt endolymph production, which is necessary for sound signal transmission. Cochlear melanocytes maintain crucial potassium ion levels, which are pivotal for hearing. The potential AA-melanocyte-hearing loss link underscores the need to monitor auditory and cochlear function and consider interventions for AA-related hearing challenges. The study aimed to assess auditory and cochlear function using OAE and audiometry measurements to correlate disease severity and duration with OAE outcomes. Materials and methods In this study, we included 32 patients diagnosed with AA; the control group consisted of 29 healthy volunteers. We collected data on the patient’s age, gender, onset age, family history, and disease duration. Audiological and otological evaluations were conducted, including pure tone audiometry (PTA), speech discrimination test (SD), and otoacoustic emission (DPOAE) measurements at frequencies of 500, 1000, 2000, 4000, 6000, 8000, and 10000 Hz. The patients were divided into two groups based on age: 18-25 and over 25 years old, and all parameters were compared. To examine differences between the right and left ears, gender, and age groups, we initially tested the variables for normal distribution using the Kolmogorov-Smirnov and Shapiro-Wilk tests. An independent sample t-test was conducted to compare the means for normally distributed variables. Results There were statistical differences at the 5% significance level in the mean DPOAE values of the 1 KHz SNR and 6 KHz SNR variables. According to the Mann-Whitney U test results, a significant difference was found in the gender-based DPOAE value at 2 kHz SNR (p=0.041), which was lower in men than women. Although there were no significant differences in the audiological parameters based on age, significant differences were found in the otoacoustic emission values. Variables, including 4 kHz DP1 (p=0.049), 500 Hz SNR (p=0.045), and 1 kHz SNR (p=0.023), differed significantly between age groups, with these values being lower in patients over 25 years old. Conclusion Overall, our study contributes to the growing body of evidence supporting an association between AA and auditory dysfunction, emphasizing the need for comprehensive assessment and management of hearing-related issues in individuals with AA.

PMID:37814747 | PMC:PMC10560379 | DOI:10.7759/cureus.44882

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Nevin Manimala Statistics

Unraveling the Complexity of Atypical Serological Profiles in Chronic Hepatitis B: Insights Into Disease Dynamics and Clinical Implications

Cureus. 2023 Sep 8;15(9):e44899. doi: 10.7759/cureus.44899. eCollection 2023 Sep.

ABSTRACT

Introduction Chronic hepatitis B (CHB) continues to be a significant global public health problem. Conventional serological markers play a pivotal role in diagnosing and prognosticating CHB, but atypical serological profiles deviating from established norms pose challenges. Methods A cohort of 35 CHB patients who did not receive an antiviral treatment with atypical serological markers was followed for five years (2017-2022). Demographics, serological parameters, and changes were documented. Serological parameters and serum viral loads (hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) levels) were assayed at the central laboratory during their routine follow-ups. Three groups of atypical serological markers are defined: hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) positivity; hepatitis B e antigen (HBeAg) and anti-hepatitis B e-antigen (anti-HBe) positivity; and isolated core (anti-hepatitis B core (anti-HBc) immunoglobulin G (IgG)) positivity. Patients with concomitant HBsAg and anti-HBs were also stratified into seroreversion groups. Changes in serological markers and HBV-DNA levels across the study period were documented and evaluated at the end of the study period. Statistical analysis was conducted using the Kruskal-Wallis test and IBM SPSS Statistics software for Windows, Version 23.0 (IBM Corp., Armonk, NY, USA). Results In a cohort of 35 patients with atypical hepatitis B serology, demographic analysis revealed that 51.4% (n=18) were female and 48.6% (n=17) were male, with a mean age of 45.7 years. Educational distribution showed that 45.7% (n=16) completed primary education, 22.8% (n=8) had a high school education, and 31.5% (n=11) held university degrees. Among these patients, 10 displayed the concurrent presence of HBsAg and anti-HBs, with 60% (n=6) being female. Serum HBV-DNA was detectable in all cases. After five years, 60% (n=6) exhibited seroconversion from HBsAg to anti-HBs, particularly notable in females (66.7%). These patients showed lower HBsAg titers and serum HBV-DNA levels (p = 0.048, p = 0.036). A subset of 15 patients demonstrated simultaneous HBeAg and anti-HBe positivity. The HBeAg seropositivity waned over time, with 40% (n=6) and 26.7% (n=4) females and males, respectively, retaining positivity by the fifth year. During this period, serum HBV-DNA levels decreased. The remaining five patients sustained HBeAg and anti-HBe positivity. Among 10 patients solely positive for anti-HBc IgG, three had concurrent HBV-DNA positivity. Strikingly, three patients with negative HBV-DNA developed anti-HBs positivity after five years. Conclusion The complexity of CHB infection demands a comprehensive understanding. Atypical serological profiles suggest distinct disease stages, immune response variations, and viral mutations. This study enhances comprehension of viral replication, immune responses, and disease progression, potentially guiding tailored therapeutic strategies.

PMID:37814733 | PMC:PMC10560487 | DOI:10.7759/cureus.44899

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Nevin Manimala Statistics

Factors associated with postoperative muscle reconnection in children’s congenital muscular torticollis

Transl Pediatr. 2023 Sep 18;12(9):1707-1714. doi: 10.21037/tp-23-144. Epub 2023 Sep 4.

ABSTRACT

BACKGROUND: In prior studies, there has been no report of clinical observation of postoperative reconnection of the sternocleidomastoid muscle (SCM) in children with congenital muscular torticollis (CMT). Therefore, the objective of this study is to investigate the factors associated with postoperative reconnection of the SCM in children with CMT, and to provide clinical evidence.

METHODS: A retrospective study was conducted, wherein 83 CMT children without any missing data were followed up from November 2019 to June 2021. The age at the time of surgery, sex, preoperative and postoperative follow-up duration, laterality, neck mass history, preoperative physical therapy history, and severity type were recorded. The severity classification of CMT was based on clinical features and ultrasound images of SCM. The postoperative reconnection of SCM was measured.

RESULTS: Out of 83 patients, ten had postoperative reconnection. The rate of postoperative reconnection of SCM in children with CMT who had undergone unipolar SCM release surgery was 18.994 times higher than in patients who had not undergone such surgery. This difference was statistically significant [odds ratio (OR) =18.994, 95% confidence interval (CI): 1.583 to 227.897, P=0.020].

CONCLUSIONS: The history of SCM release surgery in CMT children can predict the postoperative reconnection of SCM, which will aid in determining the optimal surgical approach for recurrent CMT patients.

PMID:37814721 | PMC:PMC10560359 | DOI:10.21037/tp-23-144

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Plasma proteoglycan 4: a novel biomarker for acute lung injury after pediatric cardiac surgery

Transl Pediatr. 2023 Sep 18;12(9):1668-1675. doi: 10.21037/tp-23-194. Epub 2023 Sep 11.

ABSTRACT

BACKGROUND: Identification of biological molecules related to post cardiopulmonary bypass (CPB) lung injury could help diagnose, predict and potentially impact patient’s clinical course after cardiac surgery. Proteoglycan 4 (PRG4) initially identified as potential biomarker for patients with prolonged mechanical ventilation following CPB in a prior study. To further validate these findings, we sought to understand the association of lower plasma PRG4 with prolonged mechanical ventilation and worse lung compliance in a larger cohort of pediatric patients post CPB.

METHODS: Retrospective chart review study. Pediatric Cardiac Intensive Care Unit, Tertiary Hospital. Infants <1 year old with tetralogy of Fallot, ventricular septal defect, or atrioventricular septal defect who underwent surgical repair 2012-2020 and had stored plasma samples in our biorepository were screened for inclusion. Patients with mechanical ventilation before surgery were excluded. Patients were divided into quartiles based on postoperative duration of mechanical ventilation (control <25th percentile, study >75th percentile). Preoperative and 48-hour postoperative samples for each cohort (20 patients each) were tested for PRG4 level using enzyme-linked immunosorbent assay (ELISA) technique.

RESULTS: Study group had lower lung compliance, higher mean airway pressure and higher oxygen need postoperative when compared to control group. Plasma PRG4 levels before surgery and 48 hours postoperative were lower in study group compared to control group (P=0.0232 preoperative; P=0.0016 postoperative). Plasma PRG4 levels were compared preoperative to PRG4 levels postoperative in both group, there was no statistically significant difference (study group: P=0.0869; control group: P=0.6500).

CONCLUSIONS: Lower levels of plasma PRG4 is associated with longer duration of mechanical ventilation, worse ventilator compliance and higher oxygen requirement after cardiac surgery in our patient population. Further validation of this finding in a larger and more diverse patient population is necessary prior to its application at the bedside.

PMID:37814710 | PMC:PMC10560364 | DOI:10.21037/tp-23-194

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Benefits of accurate and guided endoureterotomy versus ureteral balloon dilatation in the management of ureteral strictures-comparative animal study

Transl Androl Urol. 2023 Sep 30;12(9):1375-1382. doi: 10.21037/tau-23-222. Epub 2023 Sep 11.

ABSTRACT

BACKGROUND: Endoscopic treatment of ureteral strictures provides a minimally invasive approach with a shorter hospital stay and less postoperative pain. There are different therapeutic options, the dilatation balloon and endoureterotomy with holmium yttrium-aluminum-garnet (Ho:YAG) laser are the most used. To assess histological changes after endoureterotomy in the ureteral stricture treatment comparing Ho:YAG laser endoureterotomy versus balloon dilatation endoureterotomy.

METHODS: The subjects used were a total of 48 female pigs. The initial assessment consisted of an endoscopic, nephrosonographic, and contrast fluoroscopic evaluation of the urinary tract. Subsequently, a model of ureteral stricture was performed. Three weeks later, the ureteral stricture was diagnosed and treated. Then animals were randomly assigned to two groups (group A, Balloon dilatation endoureterotomy and group B, Holmium laser retrograde endoureterotomy) in which a double-pigtail ureteral stent was placed for 3 weeks. Follow-up assessments were performed at 3-6 weeks. The final follow-up was completed at 5 months and included the pathological study.

RESULTS: In terms of therapeutic effectiveness, the overall success was 81.2%. The success rate was 91.7% in group B and 70.8%in group A without statistical significance. No evidence of vesicoureteral reflux nor urinary tract anomalies were observed. Histological assessment showed statistical significance in overall score, lamina propria fibrosis and serosal alterations in group A with higher histological changes.

CONCLUSIONS: The overall histopathological score after ureteral stricture treatment in an animal model showed better remodeling of incised ureteral wall healing after Ho:YAG laser endoureterotomy. Laser endoureterotomy tends to have higher success rate compared to balloon dilatation.

PMID:37814702 | PMC:PMC10560343 | DOI:10.21037/tau-23-222

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Nevin Manimala Statistics

Implant abutment using hand drivers versus torque wrench

Bioinformation. 2023 Feb 28;19(2):221-225. doi: 10.6026/97320630019221. eCollection 2023.

ABSTRACT

The most frequent instrument used to begin tightening screws is a manually regulated screwdriver. Regarding manually regulated screwdrivers, predicted margins of error vary between fifteen percent to forty eight percent. Mechanical Torque restricting devices can consistently produce the requisite torques. As a result, devices like wrenches are needed to achieve the desirable values of torque. Hence, the present study was designed to evaluate the torque difference between handheld drivers and torque wrench and thereby its effect on the internal threads of implant surface.120 blocks was prepared from an autopolymerizing type of acrylic material each with a dimension of 1 inch. The centre of each block was affixed with analogue of dental impalnts with dimensions of 3.5 mm width and 13 mm length. With 60 specimens each, these models were split into two categories: hand torque specimens category and torque wrench specimens category. A stereomicroscope was used to look at the implant analog’s internal threading architecture at a magnification of 100. At the bottom and top, four threads were spaced apart by a certain amount. Biowizard software was used for the assessment, and the results were recorded. Threads on the internal surface of dental implants were produced once more following torquing the implant’s impression, and the stereomicroscope was used to quantify the separation between the 4 threads. Statistics were used to correlate the readings. All study participants’ hand torque as well as torque wrench measurements were documented and statistical analysis was performed on them. When there was statistical analysis of the measurements then it was observed that mean values of torque in specimens included category of manual torque application was found out to be 33.6 ± 6.510 Ncm. On the other hand the mean values of torque in specimens included in category of torque application by torque wrench were found out to be 33.57 ± 3.472 Ncm. The outcome showed operator heterogeneity for both categories and operator variance when using a manual driver to generate torque. One independent – sample t test was used to contrast the mean data between the two categories, and P< 0.05 was chosen to determine whether the intergroup difference was meaningful. Because the torque values obtained with hand tightening were uneven, it may be concluded that different levels of hand torquing skill caused the torque to fluctuate. The torque wrench device displayed the desired torque data in the range that the manufacturer had advised. However, utilising manual drivers and a mechanical torque instrument did not cause any modifications to thread on the internal surface, and it rarely underwent significant deformation during the preliminary tightening torque readings. Thus, given that manually hand regulated drivers create a range of torques, it may be inferred that the employment of mechanical torque restricting instruments should be required.

PMID:37814682 | PMC:PMC10560308 | DOI:10.6026/97320630019221

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Nevin Manimala Statistics

Single Nucleotide Polymorphisms Associated With Motor Recovery in Patients With Nondisabling Stroke: GWAS Study

Neurology. 2023 Oct 9:10.1212/WNL.0000000000207716. doi: 10.1212/WNL.0000000000207716. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Despite notable advances in genetic understanding of stroke recovery, most studies focus only on candidate genes. To date, only two genome-wide association studies (GWAS) have focused on stroke outcomes but they were limited to the modified Rankin Scale (mRS). The mRS maps poorly to biological processes. Therefore, we performed a GWAS to discover single nucleotide polymorphisms (SNPs) associated with motor recovery post-stroke.

METHODS: We used the Vitamin Intervention for Stroke Prevention (VISP) dataset of 2,100 genotyped participants with non-disabling stroke. We included only participants that had motor impairment at randomization. Participants with a recurrent stroke during the trial were excluded. Genotyped data underwent strict quality control and imputation. The GWAS utilized logistic regression models with generalized estimating equations (GEE) to leverage the repeated NIH Stroke Scale (NIHSS) motor score measurements spanning six time points over 24 months. The primary outcome was a decrease in the motor drift score of 1 vs <1 at each time point. Our model estimated the odds ratio of motor improvement for each SNP after adjusting for age, sex, race, days from stroke to visit, initial motor score, VISP treatment arm, and principal components.

RESULTS: A total of 488 (64%) participants with a mean (SD) age of 66 +/- 11 years were included in the GWAS. Although no associations reached genome-wide significance (p<5×10-8), our analysis detected 115 suggestive associations (p<5×10-6). Notably, we found multiple SNP clusters near genes with plausible neuronal repair biology mechanisms. The CLDN23 gene had the most convincing association with rs1268196-T as its most significant SNP (odds ratio 0.32; 95% CI 0.21, 0.48; pvalue 6.19×10-7). CLDN23 affects blood-brain barrier integrity, neurodevelopment, and immune cell transmigration.

CONCLUSION: We identified novel suggestive genetic associations with the first-ever motor-specific post-stroke recovery GWAS. The results seem to describe a distinct stroke recovery phenotype compared to prior genetic stroke outcome studies that use outcome measures, like the mRS. Replication and further mechanistic investigation are warranted. Additionally, this study demonstrated a proof-of-principle approach to optimize statistical efficiency with longitudinal datasets for genetic discovery.

PMID:37813584 | DOI:10.1212/WNL.0000000000207716

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Nevin Manimala Statistics

Left atrial appendage closure in very elderly patients in the French National Registry

Heart. 2023 Oct 9:heartjnl-2023-322871. doi: 10.1136/heartjnl-2023-322871. Online ahead of print.

ABSTRACT

OBJECTIVE: Left atrial appendage closure (LAAC) is recommended to decrease the stroke risk in patients with atrial fibrillation and contraindications to anticoagulation. However, age-stratified data are scarce. The aim of this study was to provide information on the safety and efficacy of LAAC, with emphasis on the oldest patients.

METHODS: A nationwide, prospective, multicentre, observational registry was established by 53 French cardiology centres in 2018-2021. The composite primary endpoint included ischaemic stroke, systemic embolism, and unexplained or cardiovascular death. Separate analyses were done in the groups <80 years and ≥80 years.

RESULTS: Among the 1053 patients included, median age was 79.7 (73.6-84.3) years; 512 patients (48.6%) were aged ≥80 years. Procedure-related serious adverse events were non-significantly more common in octogenarians (7.0% vs 4.4% in patients aged <80 years, respectively; p=0.07). Despite a higher mean CHA2DS2-VASc score in octogenarians, the rate of thromboembolic events during the study was similar in both groups (3.0 vs 3.1/100 patient-years; p=0.85). By contrast, all-cause mortality was significantly higher in octogenarians (15.3 vs 10.1/100 patient-years, p<0.015), due to a higher rate of non-cardiovascular deaths (8.2 vs 4.9/100 patient-years, p=0.034). The rate of the primary endpoint was 8.1/100 patient-years overall with no statistically significant difference between age groups (9.4 and 7.0/100 patient-years; p=0.19).

CONCLUSION: Despite a higher mean CHA2DS2-VASc score in octogenarians, the rate of thromboembolic events after LAAC in this age group was similar to that in patients aged <80 years.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03434015).

PMID:37813560 | DOI:10.1136/heartjnl-2023-322871

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Secondary analysis of child hospital admission data for dental caries in London, UK: what the data tells us about oral health inequalities

BMJ Open. 2023 Oct 9;13(10):e072171. doi: 10.1136/bmjopen-2023-072171.

ABSTRACT

OBJECTIVES: Dental caries is the most common reason for hospital admissions for children aged 6-10 years in England. The prevalence in the experience of hospital admission is not uniform across all populations. This paper reports on the analysis of secondary data on dental hospital episodes for children residing in London, and its association with oral health inequalities.

DESIGN, SETTING AND PARTICIPANTS: Retrospective, non-identifiable patient data sourced from the Hospital Episode Statistics dataset was analysed. Finished consultant episodes (FCEs) were extracted for children aged 1-19 years, residing in London and admitted with a primary diagnosis of caries between 2015/2016 and 2020/2021.

OUTCOME MEASURES: The number and rates of FCEs with a primary diagnosis of dental caries for children aged 1-19 years old was analysed for six consecutive financial years (2015/2016 to 2020/2021). To assess oral health inequalities in children experiencing hospital admission due to dental caries, several demographic variables were analysed: deprivation, age, and sex.

RESULTS: Between the financial years of 2015-2016 and 2020-2021, there were a total of 57 055 hospital admissions for dental caries for children aged 1-19 years (average rate of admission was 465.1 per 100 000 of children). A year-on-year decline was noted between 2015-2016 and 2020-2021. Regression analysis demonstrated clear social gradients with significant oral health inequalities; those from the most deprived areas experienced over two times the number of hospital admissions (58%). Children aged 4-9 years accounted for 68.9% (39 325) for the total dental hospital episodes from 2015-2016 to 2020-2021.

CONCLUSION: London’s year-on-year reduction in hospital admission for dental caries is due to various factors including effective prevention interventions and an effective paediatric clinical care pathway. Sociodemographic factors remain to act as key predictors for hospital admission for child with dental caries. While health service level changes may reduce the number of hospital admissions, persistent child oral health inequalities continue to exist.

PMID:37813534 | DOI:10.1136/bmjopen-2023-072171

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Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol

BMJ Open. 2023 Oct 9;13(10):e073162. doi: 10.1136/bmjopen-2023-073162.

ABSTRACT

INTRODUCTION: Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.

METHODS AND ANALYSIS: Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.

ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.

PMID:37813531 | DOI:10.1136/bmjopen-2023-073162