Nevin Manimala

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 <25^th percentile, study >75^th 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

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

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

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

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

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

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

BMJ Open. 2023 Oct 9;13(10):e071100. doi: 10.1136/bmjopen-2022-071100.

ABSTRACT

BACKGROUND: Prevalent physical inactivity and poor nutrition contribute to high non-communicable disease (NCD) morbidity and mortality in Kosovo. To improve health services for patients with NCD the Accessible Quality Healthcare project developed behaviour change interventions following the principles of the WHO Package of Essential NCD (PEN) protocol. They were implemented into the public primary healthcare (PHC) system of five early-stage implementation municipalities (ESIM, 2018) and seven late-stage implementation municipalities (2020).

OBJECTIVE: To assess the effect of the behaviour change interventions; motivational stages of behaviour change for physical activity and nutrition; and body mass index (BMI).

DESIGN: Prospective cohort study.

DATA COLLECTION AND ANALYSIS: We included 891 public PHC users aged 40 years and above, who were enrolled in the KOSCO (Kosovo Non-Communicable Disease Cohort) cohort in 2019 and followed-up biannually until February 2021. The PHC users who consulted for themselves any health service were approached and recruited for cohort participation. Each participant contributed up to four self-reports of nutrition and physical activity, and up to three reports of motivation to change for a better lifestyle. These outcomes were modelled prospectively with robust mixed-effects Poisson regressions. The association between behaviour change interventions and BMI was quantified using linear regression.

RESULTS: There was a high rate of smokers 20.5% and obesity 53.1%, and high rates of self-reported diagnoses of diabetes: 57.1%; hypertension 62.6%. We found no effect of residing in an ESIM, but adherence to both guidelines was higher in ESIM at the latest follow-up time point. ESIM residence was also associated with a twofold increase in the probability of reporting a high motivation for a better lifestyle and with a statistically non-significant decrease in BMI of -0.14 kg/m² (95% CI: -0.46 to 0.19) at the latest follow-up.

CONCLUSION: The longitudinal results extend evidence on the effect of WHO PEN protocol in promoting physical activity and nutritional behaviour in the Kosovo context.

PMID:37813529 | DOI:10.1136/bmjopen-2022-071100

Reg Anesth Pain Med. 2023 Oct 9:rapm-2023-104840. doi: 10.1136/rapm-2023-104840. Online ahead of print.

ABSTRACT

INTRODUCTION: Low back pain is a significant burden to society and the lack of reliable outcome measures, combined with a prevailing inability to quantify the biopsychosocial elements implicated in the disease, impedes clinical decision-making and distorts treatment efficacy. This paper aims to validate the utility of a biopsychosocial spine platform to provide standardized wearable sensor-derived functional motion assessments to assess spine function and differentiate between healthy controls and patients. Secondarily, we explored the correlation between these motion features and subjective biopsychosocial measures.

METHODS: An observational study was conducted on healthy controls (n=50) and patients with low back pain (n=50) to validate platform utility. The platform was used to conduct functional assessments along with patient-reported outcome assessments to holistically document cohort differences. Our primary outcomes were motion features; and our secondary outcomes were biopsychosocial measures (pain, function, etc).

RESULTS: Our results demonstrated statistically significant differences in motion features between healthy and patient cohorts across anatomical planes. Importantly, we found velocity and acceleration in the axial plane showed the largest difference, with healthy controls having 49.7% and 55.7% higher values, respectively, than patients. In addition, we found significant correlations between motion features and biopsychosocial measures for pain, physical function and social role only.

CONCLUSIONS: Our study validated the use of wearable sensor-derived functional motion metrics in differentiating healthy controls and patients. Collectively, this technology has the potential to facilitate holistic biopsychosocial evaluations to enhance spine care and improve patient outcomes.

TRIAL REGISTRATION NUMBER: NCT05776771.

PMID:37813527 | DOI:10.1136/rapm-2023-104840

Kidney Res Clin Pract. 2023 Sep;42(5):606-616. doi: 10.23876/j.krcp.22.148. Epub 2023 Sep 27.

ABSTRACT

BACKGROUND: Prevention and diagnosis of postcontrast acute kidney injury (AKI) after contrast-enhanced computed tomography is burdensome in outpatient department. We investigated whether an electronic alert system could improve prevention and diagnosis of postcontrast AKI.

METHODS: In March 2018, we launched an electronic alert system that automatically identifies patients with a baseline estimated glomerular filtration rate of &lt;45 mL/min/1.73 m2, provides a prescription of fluid regimen, and recommends a follow-up for serum creatinine measurement. Participants prescribed contrast-enhanced computed tomography at outpatient department before and after the launch of the system were categorized as historical and alert group, respectively. Propensity for the surveillance of postcontrast AKI was compared using logistic regression. Risks of AKI, admission, mortality, and renal replacement therapy were analyzed.

RESULTS: The historical and alert groups included 289 and 309 participants, respectively. The alert group was more likely to be men and take diuretics. The most frequent volume of prophylactic fluid in historical and alert group was 1,000 and 750 mL, respectively. Follow-up for AKI was more common in the alert group (adjusted odds ratio, 6.00; p &lt; 0.001). Among them, incidence of postcontrast AKI was not statistically different. The two groups did not differ in risks of admission, mortality, or renal replacement therapy.

CONCLUSION: The electronic alert system could assist in the detection of high-risk patients, prevention with reduced fluid volume, and proper diagnosis of postcontrast AKI, while limiting the prescribing clinicians’ burden. Whether the system can improve long-term outcomes remains unclear.

PMID:37813523 | DOI:10.23876/j.krcp.22.148