European Stroke Organisation (ESO) and European Society for Minimally Invasive Neurological Therapy (ESMINT) Guideline on Acute Management of Basilar Artery Occlusion.

The aim of the present European Stroke Organisation (ESO) guideline is to provide evidence-based recommendations on the acute management of patients with basilar artery occlusion (BAO). These guidelines were prepared following the Standard Operational Procedure of the ESO and according to the GRADE methodology.Although BAO accounts for only 1-2% of all strokes, it has very poor natural outcome. We identified 10 relevant clinical situations and formulated the corresponding Population Intervention Comparator Outcomes (PICO) questions, based on which a systematic literature search and review was performed. The working group consisted of 10 voting members (five representing ESO and five ESMINT) and three non-voting junior members. The certainty of evidence was generally very low. In many PICOs, available data were scarce or lacking, hence, we provided expert consensus statements.First, we compared intravenous thrombolysis (IVT) to no IVT, but specific BAO-related data do not exist. Yet, historically, IVT was standard of care for BAO patients who were also included (albeit in small numbers) in IVT trials. Non-randomised studies of IVT-only cohorts showed high proportion of favourable outcomes. Expert Consensus suggests using IVT up to 24 hours unless otherwise contraindicated. We further suggest IVT plus endovascular treatment (EVT) over direct EVT. EVT on top of best medical treatment (BMT) was compared to BMT alone within 6 and 6-24 hours from last seen well. In both time windows, we observed a different effect of treatment depending on a) the region where the patients were treated (Europe vs. Asia), b) on the proportion of IVT in the BMT arm, and c) on the initial stroke severity. In case of high proportion of IVT in the BMT group and in patients with NIHSS below 10, EVT plus BMT was not found better than BMT alone. Based on very low certainty of evidence, we suggest EVT+BMT over BMT alone (this is based on results of patients with at least 10 NIHSS points and a low proportion of IVT in BMT). For patients with an NIHSS below 10, we found no evidence to recommend EVT over BMT. In fact, BMT was non-significantly better and safer than EVT. Furthermore, we found a stronger treatment effect of EVT+BMT over BMT alone in proximal and middle locations of BAO compared to distal location. While recommendations for patients without extensive early ischaemic changes in the posterior fossa can, in general, follow those of other PICOs, we formulated an Expert Consensus Statement suggesting against reperfusion therapy in those with extensive bilateral and/or brainstem ischaemic changes. Another Expert Consensus suggests reperfusion therapy regardless of collateral scores. Based on limited evidence, we suggest direct aspiration over stent retriever as the first-line strategy of mechanical thrombectomy. As an Expert Consensus, we suggest rescue percutaneous transluminal angioplasty and/or stenting after a failed EVT procedure. Finally, based on very low certainty of evidence, we suggest add-on antithrombotic treatment during EVT or within 24 hours after EVT in patients with no concomitant IVT and in whom EVT was complicated (defined as failed or imminent re-occlusion, or need for additional stenting or angioplasty).

European Stroke Organisation (ESO) Guidelines on the diagnosis and management of patent foramen ovale (PFO) after stroke.

Patent foramen ovale (PFO) is frequently identified in young patients with cryptogenic ischaemic stroke. Potential stroke mechanisms include paradoxical embolism from a venous clot which traverses the PFO, in situ clot formation within the PFO, and atrial arrhythmias due to electrical signalling disruption. The purpose of this guideline is to provide recommendations for diagnosing, treating, and long-term managing patients with ischaemic stroke and PFO. Conversely, Transient Ischaemic Attack (TIA) was not considered an index event in this context because only one RCT involved TIA patients. However, this subgroup analysis showed no significant differences between TIA and stroke outcomes. The working group identified questions and outcomes, graded evidence, and developed recommendations following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the European Stroke Organisation (ESO) standard operating procedure for guideline development. This document underwent peer-review by independent experts and members of the ESO Guideline Board and Executive Committee. The working group acknowledges the current evidentiary gap in delineating an unequivocal diagnostic algorithm for the detection of PFO. Although transoesophageal echocardiography is conventionally held as the most accurate diagnostic tool for PFO identification, its status as the 'gold standard' remains unsubstantiated by rigorously validated evidence. We found high-quality evidence to recommend PFO closure plus antiplatelet therapy in selected patients aged 18-60 years in whom no other evident cause of stroke is found but a PFO (i.e. PFO-associated stroke). The PASCAL classification system can be used to select such candidates for PFO closure. Patients with both a large right-to-left shunt and an atrial septal aneurysm benefit most from PFO closure. There is insufficient evidence to make an evidence-based recommendation on PFO closure in patients older than 60 and younger than 18 years. We found low quality evidence to suggest against PFO closure in patients with unlikely PFO-related stroke according to the PASCAL classification, except in specific scenarios (Expert Consensus). We suggest against long-term anticoagulation in patients with PFO-associated stroke unless anticoagulation is indicated for other medical reasons. Regarding the long-term AF monitoring after PFO closure, the working group concluded that there remains significant uncertainty regarding the risks and benefits associated with the use of long-term cardiac monitoring, such as implantable loop recorders. This document provides additional guidance, in the form of evidence-based recommendations or expert consensus statements, on diagnostic methods for PFO detection, and medical management after PFO closure.

European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke.

A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We addressed acute treatment (including progressive lacunar stroke) and secondary prevention in lacunar ischaemic stroke, and prioritised the interventions of thrombolysis, antiplatelet drugs, blood pressure lowering, lipid lowering, lifestyle, and other interventions and their potential effects on the clinical outcomes recurrent stroke, dependency, major adverse cardiovascular events, death, cognitive decline, mobility, gait, or mood disorders. We systematically reviewed the literature, assessed the evidence and where feasible formulated evidence-based recommendations, and expert concensus statements. We found little direct evidence, mostly of low quality. We recommend that patients with suspected acute lacunar ischaemic stroke receive intravenous alteplase, antiplatelet drugs and avoid blood pressure lowering according to current acute ischaemic stroke guidelines. For secondary prevention, we recommend single antiplatelet treatment long-term, blood pressure control, and lipid lowering according to current guidelines. We recommend smoking cessation, regular exercise, other healthy lifestyle modifications, and avoid obesity for general health benefits. We cannot make any recommendation concerning progressive stroke or other drugs. Large randomised controlled trials with clinically important endpoints, including cognitive endpoints, are a priority for lacunar ischaemic stroke.

Harmonic Scalpel Tonsillectomy Versus Coblation Tonsillectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Aim: This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to comprehensively evaluate the efficacy of coblation versus harmonic scalpel methods among patients undergoing tonsillectomy. Methods: PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and Google Scholar databases were systematically screened from inception until October 2022. The outcomes were summarized as risk ratio (RR) or mean difference/standardized mean difference (MD/SMD) with 95% confidence interval (CI) in a random-effects model. Results: Six RCTs were analyzed, encompassing a sum of 461 patients (harmonic scalpel = 233 patients and coblation = 228 patients). The overall quality assessment was low risk of bias in two RCTs, some concerns of bias in three RCTs, and high risk of bias in one RCT. There was no significant difference between harmonic scalpel and coblation groups regarding the mean operative time (n = 6 RCTs, MD=-7.45 min, 95% CI [-15.26, 0.01], p = 0.06) mean intraoperative blood loss (n = 5 RCTs, MD=-36.03 ml, 95% CI [-77.46, 5.41], p = 0.09), and rate of postoperative hemorrhage (n = 5 RCTs, RR = 0.59, 95% CI [0.25, 1.39], p = 0.23). The overall postoperative pain score was significantly reduced in favor of the coblation group compared with the harmonic scalpel group (n = 5 RCTs, MD = 0.40, 95% CI [0.10, 0.69], p = 0.009)". Conclusions: The harmonic scalpel and coblation techniques share equal efficacy among patients undergoing tonsillectomy. The reduction in postoperative pain score provided by the coblation method is not clinically meaningful in clinical practice. Additional RCTs are needed to consolidate the power and quality of the presented evidence. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04022-7.

European Stroke Organisation (ESO) guidelines on Primary Angiitis of the Central Nervous System (PACNS).

The European Stroke Organisation (ESO) guideline on Primary Angiitis of the Central Nervous System (PACNS), developed according to ESO standard operating procedures (SOP) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, was elaborated to assist clinicians in the diagnostic and treatment pathway of patients with PACNS in their decision making. A working group involving vascular neurologists, neuroradiologists, rheumatologists, a neuropathologist and a methodologist identified 17 relevant clinical questions; these were addressed according to the patient/population, intervention, comparison and outcomes (PICO) framework and systematic literature reviews were performed. Notably, each PICO was addressed with respect to large vessel (LV)-PACNS and small vessel (SV)-PACNS. Data to answer many questions were scarce or lacking and the quality of evidence was very low overall, so, for some PICOs, the recommendations reflect the ongoing uncertainty. When the absence of sufficient evidence precluded recommendations, Expert Consensus Statements were formulated. In some cases, this applied to interventions in the diagnosis and treatment of PACNS which are embedded widely in clinical practice, for example patterns of cerebrospinal fluid (CSF) and Magnetic Resonance Imaging (MRI) abnormalities. CSF analysis for hyperproteinorrachia and pleocytosis does not have evidence supporting their use as diagnostic tools. The working group recommended that caution is employed in the interpretation of non-invasive vascular imaging due to lack of validation and the different sensitivities in comparison with digital subtraction angiography (DSA) and histopathological analyses. Moreover, there is not a neuroimaging pattern specific for PACNS and neurovascular issues are largely underreported in PACNS patients. The group's recommendations on induction and maintenance of treatment and for primary or secondary prevention of vascular events also reflect uncertainty due to lack of evidence. Being uncertain the role and practical usefulness of current diagnostic criteria and being not comparable the main treatment strategies, it is suggested to have a multidisciplinary team approach in an expert center during both work up and management of patients with suspected PACNS. Highlighting the limitations of the currently accepted diagnostic criteria, we hope to facilitate the design of multicenter, prospective clinical studies and trials. A standardization of neuroimaging techniques and reporting to improve the level of evidence underpinning interventions employed in the diagnosis and management of PACNS. We anticipate that this guideline, the first comprehensive European guideline on PACNS management using GRADE methodology, will assist clinicians to choose the most effective management strategy for PACNS.

Transformation of HHV-8-negative idiopathic multicentric Castleman disease into diffuse large B-cell lymphoma: A case report from Nepal.

Key Clinical Message: Idiopathic Castleman disease transforming into Diffuse Large B-cell Lymphoma has an aggressive course and can lead to mortality. Hence, early diagnosis and intervention are required. Abstract: Idiopathic Castleman disease transforming into non-Hodgkin lymphoma has an aggressive course, poor prognosis, and high mortality rate. Hence, early diagnosis and intervention are necessary. In a developing country like Nepal, where infectious diseases, particularly TB, are high, concomitant infection worsens the disease course. It also poses a diagnostic challenge as the clinical presentation may be similar.

European Stroke Organisation (ESO) Guidelines on Moyamoya angiopathy Endorsed by Vascular European Reference Network (VASCERN).

The European Stroke Organisation (ESO) guidelines on Moyamoya Angiopathy (MMA), developed according to ESO standard operating procedure and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, were compiled to assist clinicians in managing patients with MMA in their decision making. A working group involving neurologists, neurosurgeons, a geneticist and methodologists identified nine relevant clinical questions, performed systematic literature reviews and, whenever possible, meta-analyses. Quality assessment of the available evidence was made with specific recommendations. In the absence of sufficient evidence to provide recommendations, Expert Consensus Statements were formulated. Based on low quality evidence from one RCT, we recommend direct bypass surgery in adult patients with haemorrhagic presentation. For ischaemic adult patients and children, we suggest revascularization surgery using direct or combined technique rather than indirect, in the presence of haemodynamic impairment and with an interval of 6-12 weeks between the last cerebrovascular event and surgery. In the absence of robust trial, an Expert Consensus was reached recommending long-term antiplatelet therapy in non-haemorrhagic MMA, as it may reduce risk of embolic stroke. We also agreed on the utility of performing pre- and post- operative haemodynamic and posterior cerebral artery assessment. There were insufficient data to recommend systematic variant screening of RNF213 p.R4810K. Additionally, we suggest that long-term MMA neuroimaging follow up may guide therapeutic decision making by assessing the disease progression. We believe that this guideline, which is the first comprehensive European guideline on MMA management using GRADE methods will assist clinicians to choose the most effective management strategy for MMA.

A multi-site randomized trial of a clinical decision support intervention to improve problem list completeness.

OBJECTIVE: To improve problem list documentation and care quality. MATERIALS AND METHODS: We developed algorithms to infer clinical problems a patient has that are not recorded on the coded problem list using structured data in the electronic health record (EHR) for 12 clinically significant heart, lung, and blood diseases. We also developed a clinical decision support (CDS) intervention which suggests adding missing problems to the problem list. We evaluated the intervention at 4 diverse healthcare systems using 3 different EHRs in a randomized trial using 3 predetermined outcome measures: alert acceptance, problem addition, and National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set (NCQA HEDIS) clinical quality measures. RESULTS: There were 288 832 opportunities to add a problem in the intervention arm and the problem was added 63 777 times (acceptance rate 22.1%). The intervention arm had 4.6 times as many problems added as the control arm. There were no significant differences in any of the clinical quality measures. DISCUSSION: The CDS intervention was highly effective at improving problem list completeness. However, the improvement in problem list utilization was not associated with improvement in the quality measures. The lack of effect on quality measures suggests that problem list documentation is not directly associated with improvements in quality measured by National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set (NCQA HEDIS) quality measures. However, improved problem list accuracy has other benefits, including clinical care, patient comprehension of health conditions, accurate CDS and population health, and for research. CONCLUSION: An EHR-embedded CDS intervention was effective at improving problem list completeness but was not associated with improvement in quality measures.

Efficacy and safety of colchicine for the treatment of osteoarthritis: a systematic review and meta-analysis of intervention trials.

OBJECTIVE: Colchicine, an approved treatment for gout, has been trialed in many diseases including osteoarthritis (OA) due to its anti-inflammatory effects. However, its efficacy and safety remain unclear in OA. This systematic review and meta-analysis evaluated the efficacy and safety of colchicine for the treatment of OA. METHODS: PubMed, Web of Science, Scopus, and Cochrane Central were searched from inception through September 2022. Two reviewers independently screened for randomized controlled trials (RCTs) comparing colchicine with placebo or other active comparators for the treatment of OA (knee, hand, or hip OA), extracted data, and performed Cochrane risk of bias assessments. RESULT: Nine RCTs for the knee OA and one for the hand OA were identified, consisting of 847 patients (429 in colchicine arms, 409 in control arms). The studies were conducted between 2002 and 2021 with follow-up periods ranging from 2 to 12 months, in India, Iran, Turkey, Australia, Singapore, and Iraq. Moderate-quality evidence showed no clinically important pain reduction with colchicine compared to control (standardized mean difference [SMD], 0.17; 95% confidence interval [CI], - 0.55, 0.22). Moderate-quality evidence showed no improvement in function with colchicine compared to control in knee OA patients (SMD, - 0.37; 95% CI, - 0.87, 0.13). Colchicine showed an acceptable safety profile with AEs/SAEs comparable to control. CONCLUSION: Current evidence does not suggest a benefit of colchicine in reducing pain and improving physical function in the overall cohort of hand/knee OA patients. Future trials should focus on the subgroups of OA patients with local or systemic inflammation and/or mineralization who might benefit from colchicine.

How Effective Are Non-Operative Intra-Articular Treatments for Bone Marrow Lesions in Knee Osteoarthritis in Adults? A Systematic Review of Controlled Clinical Trials.

Knee osteoarthritis (KOA) is a progressive joint disease and a leading source of chronic pain and disability. OA-bone marrow lesions (BMLs) are a recognised aetiopathological feature of KOA. Several intra-articular injectable therapies are recommended and used for management of KOA. This systematic review assessed the efficacy and safety of intra-articular therapies for improving OA-BMLs and reducing pain in adults with KOA. The study was conducted following registered review protocol (PROSPERO CRD42020189461) and six bibliographic databases, and two clinical trial registries were searched. We included eight randomised clinical trials involving 1294 participants, reported in 12 publications from 2016 to 2021. Two studies of sprifermin, one of autologous protein solution (APS) and one of high-dose TissueGene-C, reported a positive effect on OA-BMLs under 1-year follow-up. Two studies with corticosteroids reported mixed findings with no beneficial effect beyond 14 weeks of follow-up. One study assessing platelet-rich plasma found no significant improvement in OA-BMLs at 12 months follow-up. Knee pain was improved in two studies evaluating TissueGene-C and one study assessing APS; the remaining studies found no improvement in knee pain. Overall, we found mixed evidence on the efficacy of intra-articular therapy for improving OA-BMLs in KOA. Additional studies with long-term follow-up are needed to confirm the effect of various intra-articular therapies on OA-BMLs in KOA.

COVID-19 vaccine booster hesitancy (VBH) of healthcare professionals and students in Poland: Cross-sectional survey-based study.

Since healthcare professionals (HCPs) play a critical role in shaping their local communities' attitudes toward vaccines, HCPs' beliefs and attitudes toward vaccination are of vital importance for primary prevention strategies. The present study was designed as a cross-sectional survey-based study utilizing a self-administered questionnaire to collect data about COVID-19 vaccine booster hesitancy (VBH) among Polish HCPs and students of medical universities (MUSs). Out of the 443 included participants, 76.3% were females, 52.6% were HCPs, 31.8% were previously infected by SARS-CoV-2, and 69.3% had already received COVID-19 vaccine booster doses (VBD). Overall, 74.5% of the participants were willing to receive COVID-19 VBD, while 7.9 and 17.6% exhibited their hesitance and rejection, respectively. The most commonly found promoter for acceptance was protection of one's health (95.2%), followed by protection of family's health (81.8%) and protection of community's health (63.3%). Inferential statistics did not show a significant association between COVID-19 VBH and demographic variables, e.g., age and gender; however, the participants who had been previously infected by SARS-CoV-2 were significantly more inclined to reject the VBD. Protection from severe infection, community transmission, good safety profile, and favorable risk-benefit ratio were the significant determinants of the COVID-19 VBD acceptance and uptake. Fear of post-vaccination side effects was one of the key barriers for accepting COVID-19 VBD, which is consistent with the pre-existing literature. Public health campaigns need to highlight the postulated benefits of vaccines and the expected harms of skipping VBD.

Does the journal impact factor predict individual article citation rate in otolaryngology journals?

OBJECTIVE: Citation skew is a phenomenon that refers to the unequal citation distribution of articles in a journal. The objective of this study was to establish whether citation skew exists in Otolaryngology-Head and Neck Surgery (OHNS) journals and to elucidate whether journal impact factor (JIF) was an accurate indicator of citation rate of individual articles. METHODS: Journals in the field of OHNS were identified using Journal Citation Reports. After extraction of the number of citations in 2020 for all primary research articles and review articles published in 2018 and 2019, a detailed citation analysis was performed to determine citation distribution. The main outcome of this study was to establish whether citation skew exists within OHNS literature and whether JIF was an accurate prediction of individual article citation rate. RESULTS: Thirty-one OHNS journals were identified. Citation skew was prevalent across OHNS literature with 65% of publications achieving citation rates below the JIF. Furthermore, 48% of publications gathered either zero or one citation. The mean and median citations for review articles, 3.66 and 2, respectively, were higher than the mean and median number of citations for primary research articles, 1 and 2.35, respectively (P < .001). A statistically significant correlation was found between citation rate and JIF (r = 0.394, P = 0.028). CONCLUSIONS: The current results demonstrate a citation skew among OHNS journals, which is in keeping with findings from other surgical subspecialties. The majority of publications did not achieve citation rates equal to the JIF. Thus, the JIF should not be used to measure the quality of individual articles. Otolaryngologists should assess the quality of research through the use of other metrics, such as the evaluation of sound scientific methodology, and the relevance of the articles.

Zolpidem use and risk of suicide: A systematic review and meta-analysis.

INTRODUCTION: Zolpidem is one of the most commonly prescribed nonbenzodiazepine hypnotic drugs for insomnia. Published epidemiological studies linked zolpidem with the risk of suicide. However, to date, no meta-analysis investigated this association. Hence, we systematically reviewed and meta-analysed the current evidence from real-world studies reporting the risk of suicide with the use of zolpidem. METHODS: Medline (Ovid), Embase (Ovid), and PsycINFO databases were searched from inception till June 2021 for real-world evidence studies reporting the risk of suicide with the use of zolpidem. The quality assessment of included studies was assessed using the New-Castle Ottawa Scale (NOS). Random-effect meta-analysis was performed using a generic inverse variance method. RESULTS: This meta-analysis was based on four studies with 344,753 participants, of which 42,279 were zolpidem users. The methodological quality of all the included studies was of high quality. A significantly increased risk of suicide or suicide attempt was found in zolpidem users compared to non-users, with a pooled relative risk of 1.88 (95% CI: 1.54 - 2.30). Furthermore, an increased risk of suicidal death was observed in zolpidem users compared to non-users, with a pooled relative risk of 1.82 (95% CI: 1.43 - 2.30). Dose-response analysis also revealed a significantly increased risk of suicide in patients receiving ≥ 180cDDD (cumulative defined daily doses) of zolpidem (124 times), followed by 90-179cDDD (113 times) and <90cDDD (93 times) of zolpidem compared to non-users. CONCLUSION: In conclusion, zolpidem use was associated with an increased risk of suicide or suicide attempt and suicidal death. Therefore, careful prescribing practices must be followed by considering the risk-benefit profile.

Proton Pump Inhibitors Use and Risk of Preeclampsia: A Meta-Analysis.

Evidence from preclinical studies suggests a preventive effect of proton pump inhibitors (PPIs) in preeclampsia. Recently, several epidemiological studies have described a conflicting association between the use of PPIs during pregnancy and preeclampsia risk. This study aimed to evaluate the association between PPI use and the risk of preeclampsia. We searched databases, including MEDLINE, Embase, Scopus, Web of Science Core Collection, Emcare, CINAHL, and the relevant grey literature from inception until 13 September 2021. Studies reporting the preeclampsia risk with the use of PPIs were eligible for inclusion. Literature screening, data extraction, and the risk of bias assessment were performed independently by two investigators. Random-effect meta-analysis was performed to generate relative risks (RR) and 95% confidence intervals (CI). The risk of preeclampsia and preterm preeclampsia among women receiving PPIs during pregnancy were the primary outcomes of interest. This meta-analysis comprised three studies involving 4,877,565 pregnant women, of whom 119,017 were PPI users. The included studies were judged to have a low risk of bias. The risk of preeclampsia among pregnant women who received PPIs anytime during pregnancy was significantly increased (RR 1.27 (95% CI: 1.23-1.31)), although the increase was trivial in absolute terms (2 per 1000). The subgroup analysis revealed that the risk was increased in each of the three trimesters. The risk of preterm preeclampsia among pregnant women receiving PPIs anytime during pregnancy was not significantly increased (RR 1.04 (95% CI: 0.70-1.55)). The certainty evaluated by GRADE in these estimates was low. PPI use may be associated with a trivial increase in the risk of preeclampsia in pregnant women. There is no evidence supporting that PPI use decreases the risk of preeclampsia or preterm preeclampsia.

Analysis of Particle Size and Concentration in Die Sinking Electric Discharge Machining.

Electric discharge machining with a powder mix dielectric is a promising technique to harden a work piece's surface using electricity with a high energy density. The quality of the electrical discharge-machined surface is related to its surface integrity in which the surface's roughness, residual stresses, micro hardness and surface micro cracks are some of the major factors. In this research, graphite powder was mixed in a dielectric with a particle size of 20 µm, 30 µm, and 40 µm, with the concentration of the graphite powder ranging from 2 g/L to 4 g/L. Moreover, the peak current and pulse time on were also coupled with an additive of graphite powder to investigate the effect on the surface quality, i.e., the recast layer thickness, micro hardness and crater depth as well as the material removal rate (MRR) and tool wear rate (TWR). A Box-Behnken design was employed to design the experiments and the experimental results revealed that the graphite powder size and concentration coupled with the electrical parameters (peak current and pulse time on) significantly influenced the recast layer thickness, micro hardness, crater size, MRR and TWR. The crater depth and micro hardness were maximized at a higher concentration and particle size, while the recast layer thickness was reduced with a higher gain size.

Beta-adrenergic drugs and risk of Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Parkinson's Disease (PD) is a neurodegenerative disorder manifested by rest tremor, rigidity, bradykinesia, and postural instability. Recent pharmaco-epidemiological studies evaluating beta-adrenergic drug use and risk of PD have reported conflicting findings. OBJECTIVES: This systematic review and meta-analyses evaluate the association between beta-adrenergic (agonists and antagonists) drugs' use and PD. METHODS: An electronic literature search of eight databases was performed from inception to July 2021 to identify pharmaco-epidemiological studies (case-control and cohort) reporting the risk of PD in beta-adrenergic users compared to non-users. We used the generic inverse variance method and RevMan (5.3.5) to estimate pooled adjusted risk ratios (aRRs) of PD using a random-effects model. RESULTS: Of 3168 records, 15 studies (10 case-control; five cohort) with 6508,877 participants, including 87,011 PD cases, were included. In the pooled analysis (n = 10) including any beta-antagonist users, compared with non-users, the aRR for PD was 1.19 (CI: 1.05,1.35); for any beta-agonist users (n = 8) aRR for PD was 0.87 (CI: 0.78,0.97). Propranolol users had a significantly increased risk of PD (aRR:1.91; CI:1.20,3.06), whereas salbutamol use was associated with reduced risk of PD (aRR:0.95; CI:0.92,0.99). Significant heterogeneity (I2 >87%) was observed, but the majority (n = 13) of the studies were of high quality, based on the JBI tool. CONCLUSIONS: Beta-antagonist use was associated with a modestly increased risk of PD, whereas beta-agonist use was associated with a modest decreased risk of PD. Future epidemiological studies should address the issues of protopathic bias and indirect association using appropriate epidemiological methods.

Cost-effectiveness analyses of durvalumab consolidation therapy versus no consolidation therapy after chemoradiotherapy in stage-III NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Recently, Durvalumab was approved as a potential immunotherapy for the management of unresectable stage III NSCLC. Economic studies from different parts of the world presented varying findings. Therefore, the objective of this study was to assess the cost-effectiveness of durvalumab consolidation therapy versus no consolidation therapy in patients with unresectable stage III NSCLC. METHODS: PubMed, Embase, and Cochrane databases were searched till March 2022 to identify all the studies assessing the economic evaluation of durvalumab in patients with unresectable stage III NSCLC who had not progressed after chemoradiotherapy. Eligible studies were screened by two reviewers independently and the quality of included studies was evaluated using the updated version of Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022) checklists. All costs were converted to 2022 US dollars ($) by adjusting for the gross domestic product (GDP) deflator index and purchasing power parities for GDP. RESULTS: A total of seven studies were found to be eligible for inclusion. The majority of studies were conducted in the US (n = 3), while one study each was conducted in China, Italy, Switzerland, and the UK. The healthcare payers' perspective was most commonly observed among the included studies and the time horizon varied from 5 years to a lifetime. Three studies received funding from Industry. Four included studies used the Markov model, while two employed the semi-Markov model and, one study used decision-analytic model. The ICER of durvalumab consolidation therapy in the US was found to be in the range of $59,850 to $145,543 per Quality-Adjusted Life Years (QALY). Likewise, the ICER of durvalumab in European countries ranged from $62,021 to $76,068 per QALY. The ICER was below the implemented country-specific willingness-to-pay thresholds in all the included studies. CONCLUSION: Durvalumab consolidation therapy was found to be cost-effective compared to no consolidation therapy after chemoradiotherapy in stage-III NSCLC patients.

The Importance of Scar Cosmesis across the Surgical Specialties: Factors, Perceptions, and Predispositions.

Existing disparities in the perception of scars between patients and practitioners can translate into undesirable physical and psychological outcomes. An understanding of the determinants of surgeons' perceptions on the importance of scar cosmesis is a first step toward bridging this gap. Methods: In an online survey, surgeons were asked about the extent to which various patient and technical factors affect the importance of scar cosmesis. Additional data were obtained on surgeon characteristics, including their specialty, gender, years of experience, and work sector to investigate potential relationships. Results: A total of 303 responses were obtained from surgeons across six specialties. Based on the survey, the importance of scar cosmesis was rated highest among plastic surgeons and obstetricians and gynecologists, and lowest among orthopedic and vascular surgeons. Compared with surgeons in private practice, publicly employed surgeons' rating of the importance of cosmesis was lower. The patient's request for a cosmetic outcome was the most highly rated factor. Regarding the influence of patient demographics on surgeons' attitudes, scar cosmesis in young and female patients was favored in comparison with older and male patients. Factors that reduced the importance of cosmesis were emergency and late-night surgeries followed by lengthy procedures, large incisions, and busy operative lists. Conclusions: These initial findings highlight a need to investigate means of fostering a more holistic, impartial approach toward scar cosmesis, as well as addressing potential workplace barriers that may prevent surgeons from seeking a more cosmetic result. Greater alignment between the priorities of surgeons and patients may manifest in objective and subjective improvements in patient's scars and well-being.

A systematic review of cost-effectiveness analyses of continuous versus intermittent renal replacement therapy in acute kidney injury.

INTRODUCTION: Though cost-effectiveness analyses (CEAs) have evaluated continuous renal replacement therapy (RRTs) and intermittent RRTs in acute kidney injury (AKI) patients; it is yet to establish which RRT technique is most cost-effective. We systematically reviewed the current evidence from CEAs of CRRT versus IRRT in patients with AKI. AREAS COVERED: PubMed, EMBASE, and Cochrane databases searched for CEAs comparing two RRTs. Overall, seven CEAs, two from Brazil and one from US, Canada, Colombia, Belgium, and Argentina were included. Five CEAs used Markov model, three reported following CHEERS, none accounted indirect costs. Time horizon varied from 1-year-lifetime. Marginal QALY gain with CRRT compared to IRRT was reported across CEAs. Older CEAs found CRRT to be costlier and not cost-effective than IRRT (ICER 2019 US$: 152,671$/QALY); latest CEAs (industry-sponsored) reported CRRT to be cost-saving versus IRRT (-117,614$/QALY). Risk of mortality, dialysis dependence, and incidence of renal recovery were the key drivers of cost-effectiveness. EXPERT OPINION: CEAs of RRTs for AKI show conflicting findings with secular trends. Latest CEAs suggested CRRT to be cost-effective versus IRRT with dialysis dependence rate as major driver of cost-effectiveness. Future CEAs, preferably non-industry sponsored, may account for indirect costs to improve the generalizability of CEAs.