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Nevin Manimala Statistics

Useful outcome measures in INPH patients evaluation

Front Neurol. 2023 Aug 7;14:1201932. doi: 10.3389/fneur.2023.1201932. eCollection 2023.

ABSTRACT

INTRODUCTION: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder that is potentially reversible and clinically characterized by a specific triad of symptoms, including gait disturbance, cognitive disorders, and urinary incontinence. In INPH assessment, the most commonly used test is the Timed Up and Go test (TUG), but a more comprehensive assessment would be necessary. The first aim of the present study is to verify the sensitivity of a protocol with both clinical and instrumental outcome measures for gait and balance in recognizing INPH patients. The second aim is to verify the most important spatio-temporal parameters in INPH assessment and their possible correlations with clinical outcome measures.

METHODS: Between January 2019 and June 2022, we evaluated 70 INPH subjects. We assessed balance performances with the Berg Balance Scale (BBS), Short Physical Performance Battery (SPPB), and TUG, both single (ST) and dual task (DT). We also performed an instrumental gait assessment with the GAITRite electronic walkway system, asking the patients to walk on the carpet for one minute at normal speed, fast speed, and while performing a dual task. We compared the results with those of 20 age-matched healthy subjects (HS).

RESULTS: INPH patients obtained statistically significant lower scores at the BBS, SPPB, and TUG DT but not at the TUG ST, likely because the DT involves cognitive factors altered in these subjects. Concerning instrumental gait evaluation, we found significant differences between HS and INPH patients in almost all spatio-temporal parameters except cadence, which is considered a relevant factor in INPH guidelines. We also found significant correlations between balance outcome measures and gait parameters.

DISCUSSION: Our results confirm the usefulness of BBS and suggest improving the assessment with SPPB. Although the TUG ST is the most commonly used test in the literature to evaluate INPH performances, it does not identify INPH; the TUG DT, instead, might be more useful. The GAITRite system is recognized as a quick and reliable tool to assess walking abilities and spatio-temporal parameters in INPH patients, and the most useful parameters are stride length, stride width, speed, and the percentage of double support. Both clinical and instrumental evaluation may be useful in recognizing subjects at risk for falls.

PMID:37609661 | PMC:PMC10441237 | DOI:10.3389/fneur.2023.1201932

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Nevin Manimala Statistics

Findings of a videofluoroscopic swallowing study in patients with dysphagia

Front Neurol. 2023 Aug 4;14:1213491. doi: 10.3389/fneur.2023.1213491. eCollection 2023.

ABSTRACT

OBJECTIVE: Swallowing examination is crucial in patients with dysphagia. We aimed to compare qualitative and quantitative videofluoroscopic swallowing study (VFSS) results to provide reference for standardizing quantitative parameters.

MATERIALS AND METHODS: In total, 117 patients with dysphagia were included, 38 with Parkinson’s disease and 39 and 40 in convalescence following cerebral hemorrhage and infarction. VFSS was both qualitatively and quantitatively analyzed.

RESULTS: A significant difference of Oral transit time was found between the oral motor function grades (p < 0.001), also was swallowing reaction times found between swallowing reaction duration grades (p < 0.001), and soft palate lift duration between the soft palate lift grades (p < 0.001). Superior hyoid bone movement (p < 0.001), anterior hyoid bone movement (p < 0.001), hyoid pause time (p < 0.001), and hyoid movement duration (p = 0.032) had significant differences between the hyoid laryngeal complex movement grades, as did the pharyngeal cavity transit time among the cricopharyngeal muscle opening duration grades (p < 0.001). The laryngeal vestibule closure duration differed among the glottic closure grades (p < 0.001). No statistically significant difference in upper esophageal sphincter opening diameter (p = 0.682) or duration (p = 0.682) among the cyclopharyngeal muscle opening duration grades. The pharyngeal area at rest did not significantly differ among the different vallecular residue (p = 0.202) and pyriform sinus residue (p = 0.116) grades.

CONCLUSION: Several quantitative parameters can reflect the swallowing assessment process well. Further optimization of quantitative parameters is recommended.

PMID:37609654 | PMC:PMC10441781 | DOI:10.3389/fneur.2023.1213491

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Nevin Manimala Statistics

Randomized Trial Comparing Prediction Accuracy of Two Swept Source Optical Coherence Tomography Biometers

Clin Ophthalmol. 2023 Aug 17;17:2423-2428. doi: 10.2147/OPTH.S407538. eCollection 2023.

ABSTRACT

PURPOSE: To compare the prediction accuracy of the Argos biometer using standard keratometry to the prediction accuracy of the IOLMaster 700 biometer using Total Keratometry.

METHODS: This was a randomized, prospective, single surgeon study of 80 right eyes of 80 patients that had preoperative biometry with both the Argos and IOLMaster 700 devices, followed by cataract surgery and intraocular lens (IOL) implantation. Prediction errors (directional and absolute) for each device were determined from the 1 month postoperative manifest refraction.

RESULTS: The directional prediction error was 0.07 ± 0.32 D for the Argos and 0.08 ± 0.34 D for the IOLMaster 700. The mean of the difference in prediction error (directional) was 0.02 D, which was not statistically significant (p > 0.05). The absolute prediction error was 0.21 ± 0.25 D for the Argos and 0.25 ± 0.24 D for the IOLMaster 700. The mean of the difference in absolute prediction error was 0.04 D, which was statistically significant (p < 0.004) but not clinically significant. The percentage of eyes with absolute prediction error ≤ 0.5 D was 91% (73 eyes) for the Argos and 88% (70 eyes) for the IOLMaster 700. This difference was not statistically significant.

CONCLUSION: The prediction accuracies were similar between the Argos and IOLMaster 700 in eyes with normal axial length. There was a significant difference in mean absolute prediction error between devices; however, this was not clinically meaningful.

PMID:37609646 | PMC:PMC10441632 | DOI:10.2147/OPTH.S407538

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Nevin Manimala Statistics

DoSurvive: A webtool for investigating the prognostic power of a single or combined cancer biomarker

iScience. 2023 Jul 4;26(8):107269. doi: 10.1016/j.isci.2023.107269. eCollection 2023 Aug 18.

ABSTRACT

We present DoSurvive, a user-friendly survival analysis web tool and a cancer prognostic biomarker centered database. DoSurvive is the first database that allows users to perform multivariant survival analysis for cancers with customized gene/patient list. DoSurvive offers three survival analysis methods, Log rank test, Cox regression and accelerated failure time model (AFT), for users to analyze five types of quantitative features (mRNA, miRNA, lncRNA, protein and methylation of CpG islands) with four survival types, i.e. overall survival, disease-specific survival, disease-free interval, and progression-free interval, in 33 cancer types. Notably, the implemented AFT model provides an alternative method for genes/features which failed the proportional hazard assumption in Cox regression. With the unprecedented number of survival models implemented and high flexibility in analysis, DoSurvive is a unique platform for the identification of clinically relevant targets for cancer researcher and practitioners. DoSurvive is freely available at http://dosurvive.lab.nycu.edu.tw/.

PMID:37609633 | PMC:PMC10440714 | DOI:10.1016/j.isci.2023.107269

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Nevin Manimala Statistics

Selection of collagen IV fragments forming the outer sphere of the native protein: Assessment of biological activity for regenerative medicine

J Pept Sci. 2023 Aug 22:e3537. doi: 10.1002/psc.3537. Online ahead of print.

ABSTRACT

The aim of this research was to select the fragments that make up the outer layer of the collagen IV (COL4A6) protein and to assess their potential usefulness for regenerative medicine. It was expected that because protein-protein interactions take place via contact between external domains, the set of peptides forming the outer sphere of collagen IV will determine its interaction with other proteins. Cellulose-immobilized protein fragment libraries treated with polyclonal anti-collagen IV antibodies were used to select the peptides forming the outer sphere of collagen IV. In the first test, 33 peptides that strongly interacted with the polyclonal anti-collagen IV antibodies were selected from a library of non-overlapping fragments of collagen IV. The selected fragments of collagen IV (cleaved from the cellulose matrix) were tested for their cytotoxicity, their effects on cell viability and proliferation, and their impact on the formation of reactive oxygen species (ROS). The studies used RAW 264.7 mouse macrophage cells and Hs 680.Tr human fibroblasts. PrestoBlue, ToxiLight™, and ToxiLight 100% Lysis Control assays were conducted. The viability of fibroblasts cultured with the addition of increasing concentrations of the peptide mix did not show statistically significant differences from the control. Fragments 161-170, 221-230, 721-730, 1331-1340, 1521-1530, and 1661-1670 of COL4A6 were examined for cytotoxicity against BJ normal human foreskin fibroblasts. None of the collagen fragments were found to be cytotoxic. Further research is underway on the potential uses of collagen IV fragments in regenerative medicine.

PMID:37607826 | DOI:10.1002/psc.3537

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Decreased GABA+ ratios referenced to creatine and phosphocreatine in the left dorsolateral prefrontal cortex of females of reproductive age with major depression

J Psychiatry Neurosci. 2023 Aug 22;48(4):E285-E294. doi: 10.1503/jpn.230016. Print 2023 Jul-Aug.

ABSTRACT

BACKGROUND: It has been suggested that the dorsolateral prefrontal cortex (DLPFC), especially the left DLPFC, has an important role in the pathophysiology and the treatment of major depressive disorder (MDD); furthermore, the contributory and antidepressant role of γ-aminobutyric acid (GABA) is increasingly recognized. Given that most female patients with MDD are of reproductive age, we sought to assess in vivo baseline GABA levels in the left DLPFC among unmedicated females of reproductive age with depression.

METHODS: We compared healthy females and females with MDD. Both groups were of reproductive age. We confirmed absence of current or past psychiatric diagnosis among healthy controls or a current diagnosis of MDD via a structured interview. We measured GABA+ (including homocarnosine and macromolecules), referenced to creatine and phosphocreatine, via magnetic resonance spectroscopy using a 3 Tesla magnet.

RESULTS: We included 20 healthy controls and 13 participants with MDD. All participants were unmedicated at the time of the study. All females were scanned during the early follicular phase of the menstrual cycle. Levels of GABA+ in the left DLPFC were significantly lower among participants with MDD (median 0.08) than healthy controls (median 0.10; U = 66.0, p = 0.02, r = 0.41).

LIMITATIONS: When we adjusted for fit error as a covariate, we lost statistical significance for left DLPFC GABA+. However, when we adjusted for signal-to-noise ratio, statistical significance was maintained.

CONCLUSION: Our results suggest that GABA+ levels in the left DLPFC may vary by depression status and should be examined as a possible treatment target.

PMID:37607825 | DOI:10.1503/jpn.230016

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Predicting falls-related admissions in older adults in Alberta, Canada: a machine-learning falls prevention tool developed using population administrative health data

BMJ Open. 2023 Aug 22;13(8):e071321. doi: 10.1136/bmjopen-2022-071321.

ABSTRACT

OBJECTIVE: To construct a machine-learning (ML) model for health systems with organised falls prevention programmes to identify older adults at risk for fall-related admissions.

DESIGN: This prognostic study used population-level administrative health data to develop an ML prediction model.

SETTING: This study took place in Alberta, Canada during 2018-2019.

PARTICIPANTS: Albertans aged 65 and older with at least one prior admission. Those with palliative conditions or emigrated out of Alberta were excluded.

EXPOSURE: Unit of analysis was the individual person.

MAIN OUTCOMES/MEASURES: We identified fall-related admissions. A CatBoost model was developed on 2018 data to predict risk of fall-related emergency department visits or hospitalisations. Temporal validation was done using 2019 data to evaluate model performance. We reported discrimination, calibration and other relevant metrics measured at the end of 2019 on both ranked predictions and predicted probability thresholds. A cost-savings simulation was performed using 2019 data.

RESULTS: Final number of study participants was 224 445. The validation set had 203 584 participants with 19 389 fall-related events (9.5% pretest probability) and an ML model c-statistic of 0.70. The highest ranked predictions had post-test probabilities ranging from 40% to 50%. Net benefit analysis presented mixed results with some net benefit using the ML model in the 6%-30% range. The top 50 percentile of predicted risks represented nearly $C60 million in health system costs related to falls. Intervening on the top 25 or 50 percentiles of predicted risk could realise substantial (up to $C16 million) savings.

CONCLUSION: ML prediction models based on population-level administrative data can assist health systems with fall prevention programmes identify older adults at risk of fall-related admissions and reduce costs. ML predictions based on ranked predictions or probability thresholds could guide subsequent interventions to mitigate fall risks. Increased access to diverse forms of data could improve ML performance and further reduce costs.

PMID:37607796 | DOI:10.1136/bmjopen-2022-071321

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Comparison of high-intensity interval training versus moderate-intensity continuous training in pulmonary rehabilitation for interstitial lung disease: a randomised controlled pilot feasibility trial

BMJ Open. 2023 Aug 22;13(8):e066609. doi: 10.1136/bmjopen-2022-066609.

ABSTRACT

OBJECTIVES: This study aimed to investigate the feasibility and efficacy of high-intensity interval training (HIIT) compared with moderate-intensity continuous training (MICT) in pulmonary rehabilitation (PR) for people with interstitial lung disease (ILD).

DESIGN: Single-centre, randomised controlled feasibility, pilot trial.

SETTING: Patients were recruited from the chest clinic of a tertiary ILD centre and attended circuit-based PR in the hospital’s gym, followed by a personalised 6-month community programme.

PARTICIPANTS: 58 patients, stratified per ILD type, were randomised into two groups: 33 to HIIT (18 males:15 females) (mean age (SD): 70.2 (11.4) years) and 25 to the MICT exercise mode (14 males:11 females) (mean age (SD): 69.8 (10.8) years).

INTERVENTIONS: 8-week, twice weekly, circuit-based PR programme of exercise and education, followed by a personalised 6-month community exercise programme.

OUTCOME MEASURES: Feasibility outcomes included staff-to-patient ratio and dropout rates per group. Primary outcome was the 6 min walk distance (6MWD). Secondary outcomes included the sniff nasal pressure, mouth inspiratory and expiratory pressures, handgrip and quadriceps strength and health status. Random-effects models were used to evaluate average variation in outcomes through time across the two groups.

RESULTS: The 6MWD peaked earlier with HIIT compared with MICT (at 4 months vs 5 months) but values were lower at peak (mean (95% CI): 26.3 m (3.5 to 49.1) vs 51.6 m (29.2 to 73.9)) and declined faster at 6 months post-PR. Secondary outcomes showed similar faster but smaller improvements with HIIT over MICT and more consistent maintenance 6 months post-PR with MICT than HIIT.

CONCLUSIONS: HIIT is feasible in circuit-based ILD PR programmes and provides quick improvements but requires closer supervision of training and resources than MICT and benefits may be less well sustained. This would make it a less attractive option for clinical PR programmes. A definitive, multicentre randomised controlled trial is required to address the role of HIIT in ILD.

TRIAL REGISTRATION NUMBER: ISRCTN55846300.

PMID:37607782 | DOI:10.1136/bmjopen-2022-066609

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Association of body indices and risk of mortality in patients with type 2 diabetes

BMJ Open Diabetes Res Care. 2023 Aug;11(4):e003474. doi: 10.1136/bmjdrc-2023-003474.

ABSTRACT

INTRODUCTION: A body shape index (ABSI) is independently associated with mortality in general population, but studies on the predictability of ABSI in the risk of mortality in patients with type 2 diabetes (T2D) are limited. We aimed to examine the independent and joint association of ABSI, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body roundness index (BRI) with mortality in patients with T2D.

RESEARCH DESIGN AND METHODS: The study included 11 872 patients (46.5% women) aged 30 years and older and who took part in diabetes care management program of a medical center in Taiwan. Body indices were evaluated by anthropometric measurements at baseline between 2001 and 2016, and their death status was followed up through 2021. Multivariate Cox regression models were used to assess the effect of body indices on mortality.

RESULTS: During a mean follow-up of 10.2 years, 560 cardiovascular disease (CVD) deaths and 3043 deaths were recorded. For ABSI, WC, WHR, WHtR and BRI, all-cause mortality rates were statistically significantly greater in Q4 versus Q2. For BMI and WHtR, all-cause mortality rates were also statistically significantly greater in Q1 versus Q2. The combination of BMI and ABSI exhibited a superiority in identifying risks of all-cause mortality and CVD mortality (HRs: 1.45 and 1.37, both p<0.01).

CONCLUSIONS: Combined use of ABSI and BMI can contribute to the significant explanation of the variation in death risk in comparison with the independent use of BMI or other indices.

PMID:37607771 | DOI:10.1136/bmjdrc-2023-003474

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Is the number of ideal cardiovascular health metrics in midlife associated with lower risk of cancer? Evidence from 3 European prospective cohorts

CMAJ Open. 2023 Aug 22;11(4):E774-E781. doi: 10.9778/cmajo.20220175. Print 2023 Jul-Aug.

ABSTRACT

BACKGROUND: Primordial prevention may be a relevant strategy for the prevention of cancer. Given the commonality of risk factors and mechanisms between cancer and cardiovascular disease, we examined the associations between the number of ideal cardiovascular health metrics in midlife and incident cancer.

METHODS: In 3 European cohorts (NutriNet-Santé and GAZEL, France; Whitehall II, United Kingdom), the number of ideal cardiovascular health metrics was determined at baseline (range 0-7). Follow-up for cancer events was until October 2020 (NutriNet-Santé), March 2017 (Whitehall II) and December 2015 (GAZEL). Cox regression was conducted in each cohort, and results were thereafter pooled using a random-effects model.

RESULTS: Data were available on 39 718 participants. A total of 16 237 were from NutriNet-Santé (mean age 51.3 yr; 28% men), 9418 were from Whitehall II (mean age 44.8 yr; 68% men) and 14 063 were from GAZEL (mean age 45.2 yr; 75% men). The median follow-up was 8.1 years in NutriNet-Santé, 29.6 years in Whitehall II and 24.8 years in GAZEL, and yielded a total of 4889 cancer events. A greater number of ideal cardiovascular health metrics was associated with a lower overall cancer risk in each cohort, with an aggregate hazard ratio (HR) per 1 increment in number of ideal metrics of 0.91 (95% confidence interval [CI] 0.88-0.93). This association remained after removal of the smoking metric (aggregate HR per unit increment in number of ideal metrics: 0.94, 95% CI 0.90-0.97), and site-specific analysis demonstrated a significant association with lung cancer.

INTERPRETATION: A greater number of ideal cardiovascular health metrics in midlife was associated with lower cancer risk, notably lung cancer. Primordial prevention of cardiovascular risk factors in midlife may be a complementary strategy to prevent the onset of cancer.

PMID:37607746 | DOI:10.9778/cmajo.20220175