Tag: nevin manimala

Neurology. 2021 May 4:10.1212/WNL.0000000000012145. doi: 10.1212/WNL.0000000000012145. Online ahead of print.

ABSTRACT

OBJECTIVE: To test the hypothesis that fundamental relationships along the amyloid, tau, and neurodegeneration (A/T/N) cascade depend on synaptic integrity in older adults in-vivo and postmortem.

METHODS: Two independent observational, cross-sectional cohorts: 1) in-vivo community-dwelling, clinically normal adults from the UCSF Memory and Aging Center completed lumbar puncture and MRI (exclusion criteria, CDR>0), and 2) postmortem decedents from the Rush Memory and Aging Project (exclusion criteria, inability to sign informed consent). In-vivo measures included cerebrospinal fluid (CSF) synaptic proteins (synaptotagmin-1, SNAP-25, neurogranin, and GAP-43), Aβ_42/40, ptau_181, and MRI gray matter volume (GMV). Postmortem measures captured brain tissue levels of presynaptic proteins (complexin-I, complexin-II, VAMP, and SNARE complex), and neuritic plaque and neurofibrillary tangle (NFT) counts. Regression models tested statistical moderation of synaptic protein levels along the A/T/N cascade (synaptic proteins*amyloid on tau, and synaptic proteins*tau on GMV).

RESULTS: 68 in-vivo older adults (age=71y, 43%F) and 633 decedents (age=90y, 68%F, 34% clinically normal) were included. Each in-vivo CSF synaptic protein moderated the relationship between Aβ_42/40 and ptau₁₈₁ (-0.23<𝛽s<-0.12, ps<0.05) and the relationship between ptau and GMV (-0.49<𝛽s<-0.32, ps<0.05). Individuals with more abnormal CSF synaptic protein demonstrated expected relationships between Aβ-ptau and ptau-brain volume, effects that were absent or reversed in those with more normal CSF synaptic protein. Postmortem analyses recapitulated CSF models. More normal brain tissue levels of complexin-I, VAMP, and SNARE moderated the adverse relationship between neuritic plaque and NFT counts (-0.10<𝛽s<-0.08, ps<0.05).

CONCLUSIONS: Pathogenic relationships of Aβ and tau may depend on synaptic state. Synaptic markers may help identify risk and/or resilience to AD proteinopathy.

PMID:33947778 | DOI:10.1212/WNL.0000000000012145

Neurology. 2021 May 4:10.1212/WNL.0000000000012153. doi: 10.1212/WNL.0000000000012153. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine whether the available operative techniques for thymectomy in myasthenia gravis (MG) confer variable chances for achieving complete stable remission (CSR), we performed a meta-analysis of comparative studies of surgical approaches to thymectomy.

METHODS: Meta-analysis of all studies providing comparative data on thymectomy approaches, with CSR reported and minimum 3 years mean follow-up.

RESULTS: 12 cohort studies and one randomized clinical trial, containing 1598 patients, met entry criteria. At 3 years, CSR from MG was similar following VATS extended vs. both basic (RR 1.00, p=1.00, 95% CI 0.39-2.58) and extended (RR 0.96, p=0.74, CI: 0.72-1.27) transsternal approaches. CSR at 3 years was also similar following extended transsternal vs. combined transcervical-subxiphoid (RR 1.08, p=0.62, CI: 0.8-1.44) approaches. VATS extended approaches remained statistically equivalent to extended transsternal approaches through 9 years of follow-up (RR 1.51, p=0.05, CI: 0.99-2.30). The only significant difference in CSR rate between a traditional open and a minimally invasive approach was seen at 10 years when comparing the now-abandoned basic (non-sternum-lifting) transcervical approach and the extended transsternal approach (RR 0.4, p=0.01, CI: 0.2-0.8).

CONCLUSIONS: A significant difference in the rate of CSR among various surgical approaches for thymectomy in MG was identified only at long-term follow-up, and only between what might be considered the most aggressive approach (extended transsternal thymectomy) and the least aggressive approach (basic transcervical thymectomy). Extended minimally invasive approaches appear to have equivalent CSR rates to extended transsternal approaches and are therefore appropriate in the hands of experienced surgeons.

PMID:33947783 | DOI:10.1212/WNL.0000000000012153

BMJ Open. 2021 May 4;11(5):e045106. doi: 10.1136/bmjopen-2020-045106.

ABSTRACT

OBJECTIVE: To assess the effects and reliability of sham procedures in manual therapy (MT) trials in the treatment of back pain (BP) in order to provide methodological guidance for clinical trial development.

DESIGN: Systematic review and meta-analysis.

METHODS AND ANALYSIS: Different databases were screened up to 20 August 2020. Randomised controlled trials involving adults affected by BP (cervical and lumbar), acute or chronic, were included.Hand contact sham treatment (ST) was compared with different MT (physiotherapy, chiropractic, osteopathy, massage, kinesiology and reflexology) and to no treatment. Primary outcomes were BP improvement, success of blinding and adverse effect (AE). Secondary outcomes were number of drop-outs. Dichotomous outcomes were analysed using risk ratio (RR), continuous using mean difference (MD), 95% CIs. The minimal clinically important difference was 30 mm changes in pain score.

RESULTS: 24 trials were included involving 2019 participants. Very low evidence quality suggests clinically insignificant pain improvement in favour of MT compared with ST (MD 3.86, 95% CI 3.29 to 4.43) and no differences between ST and no treatment (MD -5.84, 95% CI -20.46 to 8.78).ST reliability shows a high percentage of correct detection by participants (ranged from 46.7% to 83.5%), spinal manipulation being the most recognised technique.Low quality of evidence suggests that AE and drop-out rates were similar between ST and MT (RR AE=0.84, 95% CI 0.55 to 1.28, RR drop-outs=0.98, 95% CI 0.77 to 1.25). A similar drop-out rate was reported for no treatment (RR=0.82, 95% 0.43 to 1.55).

CONCLUSIONS: MT does not seem to have clinically relevant effect compared with ST. Similar effects were found with no treatment. The heterogeneousness of sham MT studies and the very low quality of evidence render uncertain these review findings.Future trials should develop reliable kinds of ST, similar to active treatment, to ensure participant blinding and to guarantee a proper sample size for the reliable detection of clinically meaningful treatment effects.

PROSPERO REGISTRATION NUMBER: CRD42020198301.

PMID:33947735 | DOI:10.1136/bmjopen-2020-045106

J Neurointerv Surg. 2021 May 4:neurintsurg-2021-017507. doi: 10.1136/neurintsurg-2021-017507. Online ahead of print.

ABSTRACT

BACKGROUND: First pass reperfusion (FPR), that is, excellent reperfusion (expanded treatment in cerebral ischemia (eTICI) 2C-3) in one pass, after endovascular treatment (EVT) of an occluded artery in the anterior circulation, is associated with favorable clinical outcome, even when compared with multiple pass excellent reperfusion (MPR). In patients with posterior circulation ischemic stroke (PCS), the same association is expected, but currently unknown. We aimed to assess characteristics associated with FPR and the influence of FPR versus MPR on outcomes in patients with PCS.

METHODS: We used data from the MR CLEAN Registry, a prospective observational study. The effect of FPR on 24-hour National Institutes of Health Stroke Scale (NIHSS) score, as percentage reduction, and on modified Rankin Scale (mRS) scores at 3 months, was tested with linear and ordinal logistic regression models.

RESULTS: Of 224 patients with PCS, 45 patients had FPR, 47 had MPR, and 90 had no excellent reperfusion (eTICI <2C). We did not find an association between any of the patient, imaging, or treatment characteristics and FPR. FPR was associated with better NIHSS (-45% (95% CI: -65% to -12%)) and better mRS scores (adjusted common odds ratio (acOR): 2.16 (95% CI: 1.23 to 3.79)) compared with no FPR. Outcomes after FPR were also more favorable compared with MPR, but the effect was smaller and not statistically significant (NIHSS: -14% (95% CI: -51% to 49%), mRS acOR: 1.50 (95% CI: 0.75 to 3.00)).

CONCLUSIONS: FPR in patients with PCS is associated with favorable clinical outcome in comparison with no FPR. In comparison with MPR, the effect of FPR was no longer statistically significant. Nevertheless, our data support the notion that FPR should be the treatment target to pursue in every patient treated with EVT.

PMID:33947768 | DOI:10.1136/neurintsurg-2021-017507

BMJ Open. 2021 May 4;11(5):e044170. doi: 10.1136/bmjopen-2020-044170.

ABSTRACT

OBJECTIVE: To systematically review and critically appraise prognostic models for falls in community-dwelling older adults.

ELIGIBILITY CRITERIA: Prospective cohort studies with any follow-up period. Studies had to develop or validate multifactorial prognostic models for falls in community-dwelling older adults (60+ years). Models had to be applicable for screening in a general population setting.

INFORMATION SOURCE: MEDLINE, EMBASE, CINAHL, The Cochrane Library, PsycINFO and Web of Science for studies published in English, Danish, Norwegian or Swedish until January 2020. Sources also included trial registries, clinical guidelines, reference lists of included papers, along with contacting clinical experts to locate published studies.

DATA EXTRACTION AND RISK OF BIAS: Two authors performed all review stages independently. Data extraction followed the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist. Risk of bias assessments on participants, predictors, outcomes and analysis methods followed Prediction study Risk Of Bias Assessment Tool.

RESULTS: After screening 11 789 studies, 30 were eligible for inclusion (n=86 369 participants). Median age of participants ranged from 67.5 to 83.0 years. Falls incidences varied from 5.9% to 59%. Included studies reported 69 developed and three validated prediction models. Most frequent falls predictors were prior falls, age, sex, measures of gait, balance and strength, along with vision and disability. The area under the curve was available for 40 (55.6%) models, ranging from 0.49 to 0.87. Validated models’ The area under the curve ranged from 0.62 to 0.69. All models had a high risk of bias, mostly due to limitations in statistical methods, outcome assessments and restrictive eligibility criteria.

CONCLUSIONS: An abundance of prognostic models on falls risk have been developed, but with a wide range in discriminatory performance. All models exhibited a high risk of bias rendering them unreliable for prediction in clinical practice. Future prognostic prediction models should comply with recent recommendations such as Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis.

PROSPERO REGISTRATION NUMBER: CRD42019124021.

PMID:33947733 | DOI:10.1136/bmjopen-2020-044170

BMJ Open. 2021 May 4;11(5):e044902. doi: 10.1136/bmjopen-2020-044902.

ABSTRACT

INTRODUCTION: Some empirical studies have identified an association between informal caregiving for adults and loneliness or social isolation. However, there is a lack of a review systematically synthesising empirical studies that have examined these associations. Hence, the aim of this systematic review is to provide an overview of evidence from observational studies.

METHODS AND ANALYSIS: Three electronic databases (Medline, PsycINFO, CINAHL) will be searched (presumably in May 2021), and reference lists of included studies will be searched manually. Cross-sectional and longitudinal observational studies examining the association between informal caregiving for adults and loneliness or social isolation will be included. Studies focusing on grandchildren care or private care for chronically ill children will be excluded. Data extraction will include information related to study design, definition and measurement of informal caregiving, loneliness and social isolation, sample characteristics, statistical analysis and main results. The quality of the studies will be evaluated using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Two reviewers will perform the selection of studies, data extraction and assessment of study quality. Figures and tables will be used to summarise and report results. A narrative summary of the findings will be provided. If data permit, a meta-analysis will be conducted.

ETHICS AND DISSEMINATION: No primary data will be collected. Therefore, approval by an ethics committee is not required. We plan to publish our findings in a peer-reviewed journal.

PROSPERO REGISTRATION NUMBER: CRD42020193099.

PMID:33947734 | DOI:10.1136/bmjopen-2020-044902

Immun Inflamm Dis. 2021 May 4. doi: 10.1002/iid3.444. Online ahead of print.

ABSTRACT

INTRODUCTION: CD4 count is an important predictor of disease progression, opportunities infection, deaths, and to understand the time interval between initial HIV infection to the first diagnosis. However, baseline CD4 count and the time period between initial infection and the diagnosis amongst PLHIV in Bhutan never been evaluated.

METHODS: This is a retrospective study of the diagnosed PLHIV from the existing data system from January 10 to 30, 2021. Out of 512 reported HIV cases, 488 of those who were more than or equal to 18 years old and had their CD4 count testing within 6 months before initiating ART were considered for analysis. Descriptive statistical analysis was used to analyze the characteristics of the study population and relationship were established using the χ² Test. We have sought ethics approval and waiver for informed consent as it is the retrospective study of the client’s record. The client’s confidentiality was ensured by removing all the identifiers.

RESULTS: The mean CD4 was 345 cells/ml for males and females. Twenty-five percent of the clients had CD4 counts below 200, 30%, between 200 and 349, 25% between 350 and 499, and 20% above 500 cells/ml. A larger number of males showed a CD4 count below 200 cells/ml while more females showed a CD4 count more than 500 cells/ml. The mean time interval between initial infection to the first diagnosis was 4 years in males and females. However, about one-fourth were found to have been infected between 5 and 8 years before diagnosis and less than 10% were diagnosed within less than 1 year of infection.

CONCLUSIONS: The study revealed a late diagnosis of HIV infection in Bhutan thereby risking the transmission to the community and risk of severe disease and mortality. The upscaling of voluntary counseling and testing, medical screening, and alternative methods like community-based testing including HIV Self Testing for early detection needs to be implemented in the country.

PMID:33945664 | DOI:10.1002/iid3.444

Acta Ophthalmol. 2021 May;99(3):260-268. doi: 10.1111/aos.14553. Epub 2020 Aug 9.

ABSTRACT

PURPOSE: To compare the effects of ageing and glaucoma progression on the thickness of the circumpapillary retinal nerve fibre layer (cpRNFL) and to evaluate the performance of a set of optical coherence tomography (OCT) progression analyses.

METHODS: The cpRNFL was measured twice by OCT at each of two visits made 10 years apart in 69 healthy individuals and 49 glaucoma patients. Both visits also included Humphrey 24-2 SITA standard testing. The change in cpRNFL thickness was analysed by linear regression, and a sub-analysis was performed on glaucoma patients with a perimetric mean deviation better than -10 dB at the first visit. The proportion of individuals whose OCT progression analyses indicated progression was also evaluated for the same groups.

RESULTS: The average cpRNFL thickness deteriorated by a mean of -0.16 μm/year in the healthy cohort, increased by 0.03 μm/year in the glaucoma cohort, and deteriorated by -0.24 μm/year in eyes with less severe glaucoma; there were no statistically significant differences between the groups. For 17 (30%) of 56 healthy individuals, at least one of the three different OCT progression analyses incorrectly indicated progression.

CONCLUSIONS: No significant differences in change of cpRNFL thickness between visits were found when comparing healthy subjects with glaucoma patients. Also, further cpRNFL thinning was not observed in glaucomatous eyes in which at least one-third of the visual field had been lost. The OCT progression analyses generated a relatively high proportion of false positives. Using OCT for glaucoma follow-up may not be entirely straightforward.

PMID:33945669 | DOI:10.1111/aos.14553

Proteomics. 2021 May 4:e2000278. doi: 10.1002/pmic.202000278. Online ahead of print.

ABSTRACT

In managing patients with coronavirus disease 2019 (COVID-19), early identification of those at high risk and real-time monitoring of disease progression to severe COVID-19 is a major challenge. We aimed to identify potential early prognostic protein markers and to expand understanding of proteome dynamics during clinical progression of the disease. We performed in-depth proteome profiling on 137 sera, longitudinally collected from 25 patients with COVID-19 (non-severe patients, n = 13; patients who progressed to severe COVID-19, n = 12). We identified 11 potential biomarkers, including the novel markers IGLV3-19 and BNC2, as early potential prognostic indicators of severe COVID-19. These potential biomarkers are mainly involved in biological processes associated with humoral immune response, interferon signalling, acute phase response, lipid metabolism, and platelet degranulation. We further revealed that the longitudinal changes of 40 proteins persistently increased or decreased as the disease progressed to severe COVID-19. These 40 potential biomarkers could effectively reflect the clinical progression of the disease. Our findings provide some new insights into host response to SARS-CoV-2 infection, which are valuable for understanding of COVID-19 disease progression. This study also identified potential biomarkers that could be further validated, which may support better predicting and monitoring progression to severe COVID-19. This article is protected by copyright. All rights reserved.

PMID:33945677 | DOI:10.1002/pmic.202000278

PLoS One. 2021 May 4;16(5):e0251152. doi: 10.1371/journal.pone.0251152. eCollection 2021.

ABSTRACT

PURPOSE: To compare the biometry and prediction of postoperative refractive outcomes of four different formulae (Haigis, SRK/T, Holladay1, Barrett Universal II) obtained by swept-source optical coherence tomography (SS-OCT) biometers and partial coherence interferometry (PCI; IOLMaster ver 5.4).

METHODS: We compared the biometric values of SS-OCT (ANTERION, Heidelberg Engineering Inc., Heidelberg, Germany) and PCI (IOLMaster, Carl Zeiss Meditec, Jena, Germany). Predictive errors calculated using four different formulae (Haigis, SRKT, Holladay1, Barrett Universal II) were compared at 1 month after cataract surgery.

RESULTS: The mean preoperative axial length (AL) showed no statistically significant difference between SS-OCT and PCI (SS-OCT: 23.78 ± 0.12 mm and PCI: 23.77 ± 0.12 mm). The mean anterior chamber depth (ACD) was 3.30 ± 0.04 mm for SS-OCT and 3.23 ± 0.04 mm for PCI, which was significantly different between the two techniques. The mean corneal curvature also differed significantly between the two techniques. The difference in mean arithmetic prediction error was significant in the Haigis, SRKT, and Holladay1 formulae. The difference in mean absolute prediction error was significant in all four formulae.

CONCLUSIONS: SS-OCT and PCI demonstrated good agreement on biometric measurements; however, there were significant differences in some biometric values. These differences in some ocular biometrics can cause a difference in refractive error after cataract surgery. New type SS-OCT was not superior to the IOL power prediction calculated by PCI.

PMID:33945581 | DOI:10.1371/journal.pone.0251152