Impact of imatinib treatment on renal function in chronic myeloid leukaemia patients.

BACKGROUND: Recently, multiple epidemiological studies have linked imatinib with the alteration of renal function in chronic myeloid leukaemia (CML) patients. This meta-analysis aimed to summarize the impact of imatinib use on renal function in CML patients. METHODS: A systematic search was conducted on MEDLINE and Embase to identify articles assessing the impact of imatinib exposure on renal function in CML patients. The risk of bias was assessed using the Newcastle-Ottawa scale (NOS). Two authors independently performed literature-screening, risk of bias and data extraction. The risk of renal dysfunction (chronic kidney disease or acute kidney injury) among imatinib users was computed as the primary outcome of interest. The certainty of findings was assessed using the grading of recommendations assessment, development and evaluation (GRADE) criteria. RESULTS: A total of nine articles qualified for inclusion in the systematic review, of which four articles were eligible for meta-analysis. Based on the scoring on NOS, majority of the included studies were found to be of moderate risk of bias. Majority of the studies (n = 6) reported significantly (p < .05) decrease in estimated glomerular filtration rate (eGFR) after imatinib treatment. The risk of developing renal dysfunction (chronic kidney disease or acute kidney injury) was found to be significantly higher in imatinib users as compared to other tyrosine kinase inhibitor (TKI) users with a pooled relative risk of 2.70 (95% CI: 1.49-4.91). Sensitivity analysis also revealed a consistently high risk of renal dysfunction with imatinib use. GRADE criteria revealed low certainty of evidence. CONCLUSION: This meta-analysis found an increased risk of renal dysfunction in imatinib users compared to other TKI users.

Alendronate reduces the cognitive and neurological disturbances induced by combined doses of d-galactose and aluminum chloride in mice.

Neurological disturbances including cholinergic dysfunction, oxidative stress, neuroinflammation, and cognitive impairments are the well-reported consequences of old age-related disorders like Alzheimer's disease (AD) or dementia. Bisphosphonates were shown to ameliorate dementia in osteoporotic patients, neuroinflammation, and cholinesterase activity in rodents. Thus, the present study has been designed to examine the role of alendronate against cognitive and neurological disturbances in mice induced by a combined oral dose of d-galactose and aluminum chloride (AlCl3 ) for 6 weeks. d-galactose acts as a senescence agent, whereas AlCl3 is a neurotoxin and in combination generates neuropathologies and cognitive depletion resembling aging and AD. It was found that memory was markedly impaired in d-galactose + AlCl3 -treated mice as assessed in different behavioral paradigms. Additionally, d-galactose + AlCl3 led to neurotoxicity assessed on the basis of neuroinflammation, oxidative stress, glial cell activation, neuronal damage, and augmented GSK-3ß level in mice hippocampus. Consequently, alendronate administration orally for 15 days in d-galactose + AlCl3 -exposed mice prominently reversed all these behavioral and neuropathological changes. These findings show that alendronate can be a potential therapeutic molecule with multiple targets for the management of age-related neurological disorders such as AD.

Efficacy and safety of tocilizumab in treatment of Takayasu arteritis: A systematic review of randomized controlled trials.

BACKGROUND: Takayasu arteritis (TAK) is a chronic immune vasculitis in which Interleukin-6 (IL-6) receptors play a key role in pathogenesis. Tocilizumab (TCZ), an IL-6 receptor antagonist with a favorable safety and efficacy profile, has been tried as an option for patients with TAK. This systematic review analyzed the evidence from randomized control trials (RCT) assessing the safety and efficacy of TCZ in patients with TAK. METHODS: MEDLINE, Embase, the Cochrane Library, and clinical trial registries were searched from inception to July 2018. We included RCT assessing the efficacy and safety of TCZ versus placebo/other comparators for the treatment of patients with TAK. The risk of bias (RoB) was assessed using Cochrane RoB tool. RESULTS: 2799 identified articles were screened as per abstract and title; 42 selected full-texts articles were assessed for the potential inclusion. One trial, reported in two publications, comparing subcutaneous TCZ (162 mg/week) versus matching placebo in 36 patients with TAK was included. The relapse-free rate at 24 weeks was 50.6% and 22.9% in TCZ and placebo arm, respectively. The hazard ratio (HR) for time to first relapse was statistically significant in the per-protocol population (HR 0.34 [95.41% CI, 0.11-1.00]; p = .0345), while non-significant in the intention-to-treat population (HR 0.41 [95.41% CI, 0.15-1.10]; p = .0596). The serious adverse events were higher in the placebo arm. CONCLUSIONS: This systematic review finds the existing evidence from RCT on efficacy and safety profile of TCZ in TAK to be promising but limited. Additional evidence is required to draw a stronger conclusion.

No association between proton pump inhibitor use and risk of dementia: Evidence from a meta-analysis.

BACKGROUND AND AIM: A growing body of literature suggests the association between dementia risk and proton pump inhibitor (PPI) use. Therefore, we aimed to investigate the association between PPI use and dementia risk. METHODS: An extensive literature search was performed in PubMed, Embase, and Cochrane till March 31, 2019. All the studies (cohort and case-control) assessing the association between PPI use and dementia risk were eligible for inclusion. Articles were selected based on the screening of title and abstract, data were extracted, and risk of bias was assessed using Newcastle-Ottawa scale. The primary outcome was pooled risk of dementia among PPI user as compared with non-PPI user. Secondary outcomes include dementia risk based on subgroups. Statistical analysis was performed using review manager software. RESULTS: Twelve studies (eight cohort and four case-control) were found to be eligible for inclusion. Majority of the studies were of high quality. Dementia was diagnosed based on International Classification of Diseases 9/10 codes in majority of the included studies. PPI use was not associated with the dementia risk, with a pooled relative risk (RR) of 1.05 (95% confidence interval [CI]: 0.96-1.15), P = 0.31. Subgroup analysis based on study design (cohort: P = 0.14; case-control: P = 0.14), sex (RR 1.25 [95% CI: 0.97-1.60], P = 0.08), histamine 2 receptor antagonist blockers (P = 0.93), and Alzheimer's disease (RR 1.00 [95% CI: 0.91-1.09], P = 0.93) revealed no significant association between PPI use and dementia risk. CONCLUSION: We found no significant association between PPI use and the risk of dementia or Alzheimer's disease.

Thiazolidinedione use is associated with reduced risk of Parkinson's disease in patients with diabetes: a meta-analysis of real-world evidence.

BACKGROUND: The thiazolidinedione (TZD) class of oral antidiabetic agents are used to treat type 2 diabetes mellitus (DM). This meta-analysis aimed to understand the protective effect of TZD on Parkinson's disease (PD) in people with diabetes. METHOD: A literature search was performed in PubMed, Embase, and Cochrane central from inception to until 30 September 2019. We included all real-world evidence studies assessing the use of TZD class of drugs and the risk of PD in people with diabetes. Quality of the studies was evaluated using the Newcastle-Ottawa scale. The primary outcome was the pooled hazard ratio (HR) of PD among type 2 DM TZD users as compared with TZD non-users in people with diabetes. The secondary outcome was the HR of PD among type 2 DM TZD users as compared with non-users (include both diabetic and nondiabetic population). Meta-analysis was performed using RevMan software. RESULTS: Out of five studies selected for inclusion, four studies fulfilled the criteria for primary outcomes. The participants' mean age and follow-up duration were 66.23 ± 9.59 years and 5.25 years (2.97-7.9 years), respectively. There was a significant reduction in the risk of PD (pooled adjusted HR of 0.81 [95% CI 0.70-0.93, p = 0.004]) in TZD users compared with non-TZD users in people with diabetes. A significant protective effect of TZD was observed in Caucasian population (3 studies) (HR 0.78 (95% CI 0.66-0.92), p = 0.003). CONCLUSION: This meta-analysis demonstrates a potential neuroprotective effect of TZD for PD risk in the population with DM.

Warfarin use increases bleeding risk in hemodialysis patients with atrial fibrillation: A meta-analysis of cohort studies.

BACKGROUND AND AIM: Atrial fibrillation is one of the most common comorbid conditions in hemodialysis patients, and warfarin is widely prescribed anticoagulant to prevent thromboembolic complications in such patients. In the last decade, several epidemiological studies pointed out the risk of bleeding with the use of warfarin. So, this meta-analysis is aimed to assess the bleeding risk associated with the use of warfarin. METHODS: This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. PubMed, Embase, Scopus, and Cochrane central databases were searched from inception to June 10, 2018. The primary outcome was to quantify the bleeding risk associated with warfarin use. The secondary outcome was to assess the bleeding risk based on different subgroups. Review Manager (RevMan) version 5.3 was used for performing statistical analysis. RESULTS: A total of 15 studies, constituting a pooled sample of 53 581 patients (37.14% female), were included. Of these, 17 469 were warfarin users. We found that warfarin use had a significant association with the bleeding risk. The pooled relative risk (RR) of bleeding was estimated to be 1.35 (95% CI: 1.18-1.53, P = < 0.00001), and the pooled RR of major bleeding (five studies) was estimated to be 1.32 (95% CI: 1.07-1.63, P = 0.009). Subgroup analysis revealed a significant association of warfarin use with the intracranial hemorrhage/hemorrhagic stroke (nine studies) (pooled RR: 1.43 [95% CI: 1.20-1.71, P = < 0.0001]). CONCLUSIONS: The results indicate that warfarin use increases the risk of bleeding in hemodialysis patients with atrial fibrillation.

Proton pump inhibitors' use and risk of hip fracture: a systematic review and meta-analysis.

In the last decade, epidemiological studies presented inconsistent findings concerning the proton pump inhibitors (PPI) use and the risk of hip fracture. So, this systematic review and meta-analysis were performed with the aim to quantify the risk of hip fracture associated with PPI use. PubMed® and Cochrane Central databases were searched from inception to January 2018. The quality of included studies in meta-analysis was assessed using Newcastle-Ottawa scale. Primary outcome of this study was to assess the risk of hip fracture among PPI user. Secondary outcomes include subgroup analysis based on study design, study quality, duration of PPI use, calcium intake, and geographical region. Sensitivity analysis was also performed. Review Manager (RevMan) was used to perform statistical analysis. This meta-analysis was based on seventeen studies. Pooled risk ratio showed a statistically significant association between PPI use and hip fracture risk (RR 1.26 [95% CI 1.17-1.35], p < 0.00001). Subgroup analysis, based on the study design, showed a highly significant association between PPI use and risk of hip fracture (p < 0.0001). The risk of hip fracture persisted even when stratified by calcium adjustment and the duration of PPI use (p < 0.0001). This meta-analysis suggests that PPI user have a 26% increased risk of hip fracture as compared to non-PPI user. Physicians should take caution in prescribing PPI to patients who are at increased risk of hip fracture.

Vitamin D supplementation for the management of knee osteoarthritis: a systematic review of randomized controlled trials.

Conflicting evidence exists concerning the supplementation of vitamin D in knee osteoarthritis condition. This systematic literature review was done to explore the effects of vitamin D supplementation in the management of knee osteoarthritis. Electronic literature search was done in databases like PubMed®, Embase®, and Cochrane CENTRAL from inception to 6th July 2016. The quality of included Randomized Controlled Trials (RCTs) was assessed using Cochrane risk of bias tool. We considered change in Western Ontario and McMaster Universities (WOMAC) index, Visual Analog Scale (VAS) and Functional Pain Score (FPS) as the primary outcome measure. Change in tibial cartilage thickness, joint space width and safety profile was considered as secondary outcomes. Participants were randomized either to treatment or placebo group. Participants received cholecalciferol as an intervention through oral route in the dose range of 800-60,000 IU except in the one study where participants received ergocalciferol. All included RCTs showed a significant increase in serum vitamin D level in the treatment group compared to the placebo group at the end point. No significant reduction in pain and function was reported on WOMAC scale except in one study. No significant difference was reported for WOMAC stiffness in any study. VAS was assessed in three studies in which two showed statistically significant improvement in knee pain. Three of the RCTs reported safety data with one incidence of calculus ureteric and hip fracture found to be related to the drug. The study found evidence from RCTs to be insufficient to support the use of vitamin D supplementation for patients with knee osteoarthritis.

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.

Pharmacological interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units: a network meta-analysis.

OBJECTIVES: To assess the efficacy and safety of pharmacological interventions for preventing upper gastrointestinal (GI) bleeding in people admitted to intensive care units (ICUs). DESIGN AND SETTING: Systematic review and frequentist network meta-analysis using standard methodological procedures as recommended by Cochrane for screening of records, data extraction and analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. PARTICIPANTS: Randomised controlled trials involving patients admitted to ICUs for longer than 24 hours were included. SEARCH METHODS: The Cochrane Gut Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Latin American and Caribbean Health Science Information database (LILACS) databases were searched from August 2017 to March 2022. The search in MEDLINE was updated in April 2023. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). MAIN OUTCOME MEASURES: The primary outcome was the prevention of clinically important upper GI bleeding. RESULTS: We included 123 studies with 46 996 participants. Cimetidine (relative risk (RR) 0.56, 95% CI 0.40 to 0.77, moderate certainty), ranitidine (RR 0.54, 95% CI 0.38 to 0.76, moderate certainty), antacids (RR 0.48, 95% CI 0.33 to 0.68, moderate certainty), sucralfate (RR 0.54, 95% CI 0.39 to 0.75, moderate certainty) and a combination of ranitidine and antacids (RR 0.13, 95% CI 0.03 to 0.62, moderate certainty) are likely effective in preventing upper GI bleeding.The effect of any intervention on the prevention of nosocomial pneumonia, all-cause mortality in the ICU or the hospital, duration of the stay in the ICU, duration of intubation and (serious) adverse events remains unclear. CONCLUSIONS: Several interventions seem effective in preventing clinically important upper GI bleeding while there is limited evidence for other outcomes. Patient-relevant benefits and harms need to be assessed under consideration of the patients' underlying conditions.

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.

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.

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 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.

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.

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.