Nevin Manimala

BDJ Open. 2020 Oct 12;6(1):19. doi: 10.1038/s41405-020-00047-0.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the fear of infection among Egyptian dentists practicing during the current coronavirus disease 2019 (COVID-19) pandemic and to explore the dentist’s knowledge about guidelines to fight the virus and to assess various modifications in dental practice.

METHODS: An online survey was submitted to dental professionals. Data were collected through a validated questionnaire consisting of 23 closed-ended questions. The gathered data were statistically analyzed.

RESULTS: An overall 216 dentists completed the survey. A total of 200 (92.6%) dental professionals were afraid of becoming infected with COVID-19 while 196 (90.7%) became anxious to treat patients showing suspicious symptoms. The majority of the participants were aware of the mode of transmission of COVID-19 and a lot of them were updated with the current Disease Control and Prevention (CDC) or World Health Organization (WHO) guidelines for cross-infection control.

CONCLUSIONS: COVID-19 pandemic has a significant impact on dental professionals.

PMID:34635638 | DOI:10.1038/s41405-020-00047-0

Gut Liver. 2021 Oct 12. doi: 10.5009/gnl210167. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: We investigated the effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on future mortality and cardiovascular disease (CVD) using a prospective community-based cohort study.

METHODS: Individuals from two community-based cohorts who were 40 to 70 years old were prospectively followed for 16 years. MAFLD was defined as a high fatty liver index (FLI ≥60) plus one of the following conditions: overweight/obesity (body mass index ≥23 kg/m²), type 2 diabetes mellitus, or ≥2 metabolic risk abnormalities. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥60 without any secondary cause of hepatic steatosis.

RESULTS: Among 8,919 subjects (age 52.2±8.9 years, 47.7% of males), 1,509 (16.9%) had MAFLD. During the median follow-up of 15.7 years, MAFLD independently predicted overall mortality after adjustment for confounders (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.05 to 1.69) but NAFLD did not (HR, 1.20; 95% CI, 0.94 to 1.53). MAFLD also predicted CVD after adjustment for age, sex, and body mass index (HR, 1.35; 95% CI, 1.13 to 1.62), which lost its statistical significance by further adjustments. Stratified analysis indicated that metabolic dysfunction contributed to mortality (HR, 1.51; 95% CI, 1.21 to 1.89) and CVD (HR, 1.27; 95% CI, 1.02 to 1.59). Among metabolic dysfunctions used for defining MAFLD, type 2 diabetes mellitus in MAFLD increased the risk of both mortality (HR, 2.07; 95% CI, 1.52 to 2.81) and CVD (HR, 1.42; 95% CI, 1.09 to 1.85).

CONCLUSIONS: MAFLD independently increased overall mortality. Heterogeneity in mortality and CVD risk of subjects with MAFLD may be determined by the accompanying metabolic dysfunctions.

PMID:34635626 | DOI:10.5009/gnl210167

Ann Lab Med. 2022 Mar 1;42(2):249-257. doi: 10.3343/alm.2022.42.2.249.

ABSTRACT

BACKGROUND: Non-invasive clinical algorithms for the detection of liver fibrosis (LF) can reduce the need for liver biopsy (LB). We explored the implementation of two serum biomarkers, enhanced liver fibrosis (ELF) and Mac-2 binding protein glycosylation isomer (M2BPGi), in clinical algorithms for LF in chronic hepatitis B (CHB) patients.

METHODS: Two clinical algorithms were applied to 152 CHB patients: (1) transient elastography (TE) followed by biomarkers (TE/ELF and TE/M2GPGi); (2) biomarker test followed by TE (ELF/TE and M2BPGi/TE). Using the cut-off value or index for the detection of advanced LF (TE≥F3; 9.8 in ELF and 3.0 in M2BPGi), LB was expected to be performed in cases with discordant TE and biomarker results.

RESULTS: In both algorithms, the expected number of LBs was lower when using M2BPGi than when using ELF (TE/ELF or ELF/TE, 13.2% [N=20]; TE/M2BPGi or M2BPGi/TE, 9.9% [N=15]), although there was no statistical difference (P=0.398). In the TE low-risk group (TE≤F2), the discordance rate was significantly lower in the TE/M2BPGi approach than in the TE/ELF approach (1.5% [2/136] vs. 11.0% [15/136], P=0.002). In the biomarker low-risk group, there was no significant difference between the ELF/TE and M2BPGi/TE approaches (3.9% [5/126] vs. 8.8% [13/147], P=0.118).

CONCLUSIONS: Both ELF and M2BPGi can be implemented in non-invasive clinical algorithms for assessing LF in CHB patients. Given the lowest possibility of losing advanced LF cases in the low-risk group when using the TE/M2BPGi approach, this combination seems useful in clinical practice.

PMID:34635616 | DOI:10.3343/alm.2022.42.2.249

Aging (Albany NY). 2021 Oct 11;13(undefined). doi: 10.18632/aging.203622. Online ahead of print.

ABSTRACT

Metabolic syndrome (MetS) is a significant factor for cardiometabolic comorbidities in people living with HIV (PLWH) and a barrier to healthy aging. The long-term consequences of HIV-infection and combination antiretroviral therapy (cART) in metabolic reprogramming are unknown. In this study, we investigated metabolic alterations in well-treated PLWH with MetS to identify potential mechanisms behind the MetS phenotype using advanced statistical and machine learning algorithms. We included 200 PLWH from the Copenhagen Comorbidity in HIV-infection (COCOMO) study. PLWH were grouped into PLWH with MetS (n = 100) defined according to the International Diabetes Federation (IDF) consensus worldwide definition of the MetS or without MetS (n = 100). The untargeted plasma metabolomics was performed using ultra-high-performance liquid chromatography/mass spectrometry (UHPLC/MS/MS) and immune-phenotyping of Glut1 (glucose transporter), xCT (glutamate/cysteine transporter) and MCT1 (pyruvate/lactate transporter) by flow cytometry. We applied several conventional approaches, machine learning algorithms, and linear classification models to identify the biologically relevant metabolites associated with MetS in PLWH. Of the 877 identified biochemicals, 9% (76/877) differed significantly between PLWH with and without MetS (false discovery rate < 0.05). The majority belonged to amino acid metabolism (43%). A consensus identification by combining supervised and unsupervised methods indicated 11 biomarkers of MetS phenotype in PLWH. A weighted co-expression network identified seven communities of positively intercorrelated metabolites. A single community contained six of the potential biomarkers mainly related to glutamate metabolism. Transporter expression identified altered xCT and MCT in both lymphocytic and monocytic cells. Combining metabolomics and immune-phenotyping indicated altered glutamate metabolism associated with MetS in PLWH, which has clinical significance.

PMID:34635603 | DOI:10.18632/aging.203622

Proc Natl Acad Sci U S A. 2021 Oct 19;118(42):e2105570118. doi: 10.1073/pnas.2105570118.

ABSTRACT

The reintegration of former members of violent extremist groups is a pressing policy challenge. Governments and policymakers often have to change minds among reticent populations and shift perceived community norms in order to pave the way for peaceful reintegration. How can they do so on a mass scale? Previous research shows that messages from trusted authorities can be effective in creating attitude change and shifting perceptions of social norms. In this study, we test whether messages from religious leaders-trusted authorities in many communities worldwide-can change minds and shift norms around an issue related to conflict resolution: the reintegration of former members of violent extremist groups. Our study takes place in Maiduguri, Nigeria, the birthplace of the violent extremist group Boko Haram. Participants were randomly assigned to listen to either a placebo radio message or to a treatment message from a religious leader emphasizing the importance of forgiveness, announcing the leader’s forgiveness of repentant fighters, and calling on followers to forgive. Participants were then asked about their attitudes, intended behaviors, and perceptions of social norms surrounding the reintegration of an ex-Boko Haram fighter. The religious leader message significantly increased support for reintegration and willingness to interact with the ex-fighter in social, political, and economic life (8 to 10 percentage points). It also shifted people’s beliefs that others in their community were more supportive of reintegration (6 to 10 percentage points). Our findings suggest that trusted authorities such as religious leaders can be effective messengers for promoting peace.

PMID:34635594 | DOI:10.1073/pnas.2105570118

Open Heart. 2021 Oct;8(2):e001835. doi: 10.1136/openhrt-2021-001835.

ABSTRACT

INTRODUCTION: Incomplete cardiac revascularisation (ICR) assessed by residual SYNTAX score (rSs) is associated with increased 5-year mortality. Furthermore, in the general population, our group has demonstrated that impaired autonomic function determined by heart rate recovery time between 10 and 20 s (HRR_10-20) following an active stand is associated with increased all-cause mortality.

PURPOSE: We hypothesised that ICR would be associated with impaired autonomic function determined by HRR_10-20.

METHODS: After ethical approval and informed consent, consecutive patients attending cardiac rehabilitation in a tertiary referral centre were enrolled. All patients had percutaneous coronary revascularisation. During an active stand, real-time heart rate, blood pressure and ECG recordings were taken using non-invasive digital photoplethysmography and HRR_10-20 determined. Assessment of autonomic function was performed by determining speed of HRR_10-20 post-orthostatic challenge.Patients with an rSs >0 were considered incompletely revascularised and those with an rSs of 0 fully revascularised. Demographic data were recorded and statistical analysis performed.

RESULTS: Patients (n=53) comprised those with complete revascularisation (CR) (n=37) and ICR (n=16). In the ICR group, mean rSs was 9.4.HRR_10-20 was impaired in the ICR group (-3±0.60) compared with the CR cohort (-6.56±0.52) (p<0.0001). Completeness of revascularisation was strongly associated with HRR_10-20 (Pearson’s correlation coefficient 0.529; p<0.0001). Baseline demographics did not differ significantly. Use of rate-limiting medication was similar between cohorts (beta blockers, calcium channel blockers, ivabradine).

CONCLUSIONS: Our data confirm significant correlation between ICR and impaired autonomic function determined by speed of heart rate recovery. Thus, determining autonomic dysfunction post-ICR may identify those at increased mortality risk.

PMID:34635578 | DOI:10.1136/openhrt-2021-001835

Cancer Discov. 2021 Oct 11:candisc.0538.2021. doi: 10.1158/2159-8290.CD-21-0538. Online ahead of print.

ABSTRACT

Personalized medicine aims to match the right drug with the right patient by utilizing specific features of the individual patients’ tumor. However, current strategies of personalized therapy matching only provide treatment opportunities for less than 10% of cancer patients. A promising method may be drug profiling of patient biopsies with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival (PFS) compared to their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude, that therapy matching by scFPM is clinically feasible, and effective in advanced aggressive hematologic cancers.

PMID:34635570 | DOI:10.1158/2159-8290.CD-21-0538

J Neurol Neurosurg Psychiatry. 2021 Oct 11:jnnp-2021-327236. doi: 10.1136/jnnp-2021-327236. Online ahead of print.

ABSTRACT

OBJECTIVE: The optimal timing to start direct oral anticoagulants (DOACs) after an acute ischaemic stroke (AIS) related to atrial fibrillation (AF) remains unclear. We aimed to compare early (≤5 days of AIS) versus late (>5 days of AIS) DOAC-start.

METHODS: This is an individual patient data pooled analysis of eight prospective European and Japanese cohort studies. We included patients with AIS related to non-valvular AF where a DOAC was started within 30 days. Primary endpoints were 30-day rates of recurrent AIS and ICH.

RESULTS: A total of 2550 patients were included. DOACs were started early in 1362 (53%) patients, late in 1188 (47%). During 212 patient-years, 37 patients had a recurrent AIS (1.5%), 16 (43%) before a DOAC was started; 6 patients (0.2%) had an ICH, all after DOAC-start. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent AIS, while 2 patients (0.1%) had an ICH. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent AIS; 4 patients (0.3%) suffered from ICH. In the propensity score-adjusted comparison of late versus early DOAC-start groups, there was no statistically significant difference in the hazard of recurrent AIS (aHR=1.2, 95% CI 0.5 to 2.9, p=0.69), ICH (aHR=6.0, 95% CI 0.6 to 56.3, p=0.12) or any stroke.

CONCLUSIONS: Our results do not corroborate concerns that an early DOAC-start might excessively increase the risk of ICH. The sevenfold higher risk of recurrent AIS than ICH suggests that an early DOAC-start might be reasonable, supporting enrolment into randomised trials comparing an early versus late DOAC-start.

PMID:34635567 | DOI:10.1136/jnnp-2021-327236

Neurology. 2021 Oct 11:10.1212/WNL.0000000000012929. doi: 10.1212/WNL.0000000000012929. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Aerobic exercise has become a useful method to assist with post-concussion management. Exercise can exacerbate concussion symptoms even when symptoms are not apparent at rest. Few studies have examined the reasons for symptom exacerbation during exercise following a concussion. We had two primary objectives. 1) To delineate cardiopulmonary and cerebrovascular responses to exercise in adolescents and young adults with a concussion and healthy controls. 2) To determine the association between cerebrovascular responses and symptom burden.

METHODS: We recruited participants with a recent concussion from a sport concussion clinic between 9/1/2018-2/22/2020. They were included if their concussion occurred <3 weeks before initial testing and if they were symptomatic at rest. Participants were excluded if they sustained a concussion in the past year (excluding index injury), reported history of neurological disorders, or were using medications/devices that may alter neurological function. Participants completed a progressive, symptom-limited, sub-maximal exercise protocol on a stationary bike. We assessed heart rate, blood pressure, fraction of end tidal CO2 (FETCO₂) and middle cerebral artery blood flow velocity (CBF) and cerebrovascular function (vasoreactivity and autoregulation) at seated rest and during exercise.

RESULTS: We conducted 107 exercise tests (40 concussed, 37 healthy participants initially; 30 concussed at follow-up). Concussed participants were tested initially (mean=17.6±2.2 [SD] years old; 55% female; mean=12.5±4.7 days post-concussion) and again 8 weeks later (mean=73.3±9.5 days post-concussion). Control participants (mean=18.3±2.4 years; 62% female) were tested once. FETCO₂ increased throughout the exercise protocol as heart rate increased, reached a plateau, and declined at higher exercise intensities. CO₂ explained >25% of the variation in resting CBF (R²>0.25; p<0.01) in most (73% individuals). Within the concussion group, resting symptom severity and the heart rate at which FETCO₂ reached a plateau explained ∼two-thirds of variation in exercise-induced symptom exacerbation (R ² =0.65; FETCO₂ β=-1.210±0.517[S.E.], p<0.05). There was a moderate, statistically significant relationship between cerebrovascular responses to CO₂ at rest (cerebral vasoreactivity) and cerebrovascular responses to exercise-induced changes in FETCO₂ (R²=0.13, p=0.01).

DISCUSSION: The arterial CO₂ response and symptom exacerbation relationship during post-concussion aerobic exercise may be mediated by increased sensitivity of cerebral vasculature to exercise-related increase in CO₂.

PMID:34635563 | DOI:10.1212/WNL.0000000000012929

Neurology. 2021 Oct 11:10.1212/WNL.0000000000012930. doi: 10.1212/WNL.0000000000012930. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: One year since the onset of the COVID-19 pandemic, we aimed to summarize the frequency of neurological manifestations reported in COVID-19 patients and investigate the association of these manifestations with disease severity and mortality.

METHODS: We searched PubMed, Medline, Cochrane library, clinicaltrials.gov and EMBASE from 31^st December 2019 to 15^th December 2020 for studies enrolling consecutive COVID-19 patients presenting with neurological manifestations. Risk of bias was examined using Joanna Briggs Institute (JBI) scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% Confidence Intervals (CI) were calculated for neurological manifestations. Odds ratio (OR) and 95%CI were calculated to determine the association of neurological manifestations with disease severity and mortality. Presence of heterogeneity was assessed using I-square, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2.

RESULTS: Of 2,455 citations, 350 studies were included in this review, providing data on 145,721 COVID-19 patients, 89% of whom were hospitalized. Forty-one neurological manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurological symptoms included: fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%) and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurological diagnosis (pooled prevalence- 2%). In COVID-19 patients aged ≥60, the pooled prevalence of acute confusion/delirium was 34% and the presence of any neurological manifestations in this age group was associated with mortality (OR 1.80; 95%CI 1.11 to 2.91).

DISCUSSION: Up to one-third of COVID-19 patients analysed in this review experienced at least one neurological manifestation. One in 50 patients experienced stroke. In those over 60, more than one-third had acute confusion/delirium; the presence of neurological manifestations in this group was associated with near doubling of mortality. Results must be interpreted keeping in view the limitations of observational studies and associated bias.

PMID:34635561 | DOI:10.1212/WNL.0000000000012930