Uncontrolled Observational Studies Research Articles

Extracorporeal removal of pathogens using abiomimetic adsorber-Anew treatment strategy for the intensive care unit : Seraph® 100 Microbind® Affinity Blood Filter and its fields of application

In 2019 the World Health Organization (WHO) listed antimicrobial resistance among the top 10threats to global health. The Seraph® 100 Microbind® Affinity blood filter (Seraph® 100) has been in use since 2019 to eliminate pathogens from the bloodstream in addition to anti-infective pharmacotherapy. It is the first device used to rapidly and efficiently reduce the number of circulating bacteria and viruses. After abackground on the concept of extracorporeal pathogen removal in general, this review summarizes the preclinical and clinical data on the Seraph® 100 Affinity Blood Filter. The clinical effect of this treatment and potential therapeutic options are described. Structured PubMed review including references published up to February 2024. Case reports, uncontrolled observational studies and data from registries show widespread clinical use of the Seraph® 100 ranging from difficult to treat bacterial (super) infections to viral infections. The treatment can be done as stand-alone hemoperfusion or in combination with all forms of kidney replacement therapy as well as in extracorporeal membrane oxygenation. The use of the Seraph® 100 varies in terms of duration, concomitant therapy and clinical settings. Due to the absence of prospective controlled trials the clinical effect cannot be properly evaluated.

Efficacy and safety of leflunomide in the management of large vessel vasculitis: A systematic review and metaanalysis of cohort studies

ObjectiveThe search for new glucocorticoid-sparing disease-modifying anti-rheumatic drugs continues to be an unmet need in large vessel vasculitis (LVV). This report aims to assess the effectiveness and safety of leflunomide (LEF) in Takayasu arteritis (TA) and giant cell arteritis (GCA). MethodsWe systematically reviewed the literature, searching for studies evaluating the efficacy of LEF in LVV. A meta-analysis was conducted using the random-effects method. ResultsThe literature search identified eight studies that assessed LEF in TAK and seven in GCA. All were uncontrolled observational studies with a high risk of bias, implying a low or very-low certainty of evidence.In TAK, the pooled proportion of patients achieving at least a partial remission was 75% (95% CI: 0.64–0.84), angiographic stabilization was observed in 86% (0.77–0.94) and relapses in 12% (0.05–0.21). The mean reduction in the prednisolone dose (MRPD) after LEF treatment was 15.7 mg/d (10.28–21.16). Adverse events were observed in 8% of patients (0.02–0.16).Comparison of LEF with methotrexate (MTX) or cyclophosphamide revealed LEF to be superior in terms of remission induction, relapse prevention, and tolerance. When compared with tofacitinib, both drugs demonstrated comparable efficacy.In GCA, the pooled proportion of patients achieving at least a partial remission was 60% (0.17–0.95). The MRPD after LEF treatment was 15.63 mg/d (1.29–32.55) and 53% of the patients were able to discontinue glucocorticoids (0.25 – 0.80). Relapses were observed in 21% of cases (0.14– 0.28) and adverse events in 28% (0.12–0.46). Comparison of LEF with MTX showed similar efficacy and tolerance. ConclusionLEF is well tolerated and might be effective for patients with TAK and GCA.

ARNI Versus Perindopril for Remodeling in HFrEF. A Cohort Study.

Introduction: Ventricular remodeling is a mal-adaptive process. Both angiotensin-converting enzyme inhibitors and sacubitril/valsartan have been shown to reverse remodeling in mostly uncontrolled observational studies. There is a lack of head-to-head studies. Methods: This cohort study compares the remodeling effects of angiotensin receptor blockers combined with a neprilysin inhibitor (ARNI) and perindopril in heart failure with reduced ejection fraction (HFrEF) patients between January 2017 and December 2020. Inclusion criteria: (i) age > 18 years, (ii) recent diagnosis of de-novo HFrEF (EF < 40%), (iii) baseline echocardiography performed not more than 2 months prior to treatment onset, and (iv) follow-up echocardiography performed not earlier than 6 months and not later than 18 months posttreatment onset. No prior treatment with renin-angiotensin-aldosterone system inhibitors was permitted in the ARNI group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) were analyzed. A two-way repeated measure ANOVA (for normally distributed) and generalized estimating equation test for nonnormally distributed interval dependent variables. Mean comparison between and within groups was performed using the Bonferroni test. Results: Following an average treatment period of 9 months, LVEF improved from 24.9% to 36.4% for ARNI and from 28.7% to 40.5% for perindopril, increments of 11.5% and 11.8% resp. (Bonferroni test [P ≤ .05]). LVEDV was reduced by 8.4 mL and 3.2 mL, and LVESV by 17.9 mL and 10.8 mL for ARNI and perindopril resp. Only the reduction of LVESV for ARNI was statistically significant (P = .007). Conclusion: Both ARNI and perindopril yielded a significant improvement in the LVEF within 9 months. The remodeling effect of ARNI seems stronger because of the greater improvements in left ventricular volumes.

High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.

BackgroundVitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).Methods and findingsThis multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study.ConclusionsIn this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days.Trial registrationClinicalTrials.gov NCT04344041.

P 32 Stereotactically guided brain modulation of the frontostriatal circuits for Huntington's disease: current state

Introduction: Huntingtońs disease (HD) is a genetically determined, rare neurodegenerative disorder with pathological motor, behavioral and cognitive neurological characteristics. In light of the lack of disease-modifying therapies, stereotactically assisted intracranial therapies targeting the pallidal area (globus pallidus) and the frontostriatal circuits, such as deep-brain stimulation (DBS), stereotactic lesioning (pallidotomy), and brain-grafting approaches have gained increased recognition for the treatment of Huntington’s disease-associated motor symptoms. Material and Methods: We conducted a narrative review of in-human studies targeting the globus pallidus and adjunct structures (nucleus caudatus and putamen) using stereotactically guided intracranial approaches, such as ablative procedures (pallidotomy) and deep-brain stimulation of the internal/external globus pallidus, as well as intracranial brain-graft injection. We assessed the terms Huntingtońs disease, chorea, parkinsonism, dystonia, globus pallidus externus/internus, deep brain stimulation, lesioning, ablation, pallidotomy, brain grafts, fetal neural grafts, unified Huntingtońs disease rating scale (UHDRS), safety, efficacy and quality of life in data sources derived through searches of PubMed, Ovid MEDLINE, and Scopus, and through manual searches of the bibliographies of known primary and review articles covering the period 1990-2021. Results: Stereotactic lesioning (pallidotomy) was performed on a few HD patients (70 subjects). The outcome of this approach is similar to brain-grafting strategies, with inconsistent findings and mild-to-moderate clinical responsiveness. We also identified a total of 19 in-human DBS trials targeting the globus pallidus internus/externus for HD-associated motor symptoms (chorea, dystonia, and parkinsonism). The majority comprised case reports, along with a few prospective observational cohort studies. At the end of the average observation period, we did not detect any significant changes in the UHDRS total score after pallidotomy and restorative injections, while in contrast, the use of deep-brain stimulation resulted in a significant reduction in chorea symptoms, with the global UHDRS remaining unchanged. Conclusions: Currently, stereotactically guided treatment strategies (DBS, pallidotomy, and brain grafts) should be considered in cases where selective HD-related treatment resistance (chorea, dystonia, and parkinsonism/hyperkinesia) is present. In contrast to the case for PD, the experience of using DBS for HD is currently very limited, as the majority of published trials consist of uncontrolled observational cohort studies. The comparison of UHDRS scores pre- and post-pallidal DBS in a large proportion of HD patients demonstrated the meaningful impact of DBS on chorea symptoms without any worsening of the overall UHDRS score, due, for example, to an increase in bradykinesia.

607 Use of Autologous Skin Cell Suspension (ASCS) for Full-thickness Burn Injuries Reduces Autograft Procedures

IntroductionPediatric burn patients and patients with large TBSA injuries are vulnerable to morbidity and mortality, requiring multiple autograft (AG) procedures to obtain definitive closure due to limited donor site availability. The primary objective of this study was to understand the impact of ASCS, as an AG-sparing technology, on the number of AG procedures required to achieve definitive closure of full-thickness (FT) acute thermal burns.MethodsRetrospective analyses of real-world data were conducted, evaluating clinical outcomes of ASCS-treated patients in prospective, uncontrolled observational studies compared to control data from patients in the National Burn Repository version 8.0 (NBR) who had conventional AG (SOC). The pediatric population consisted of patients < 18 years of age, inclusive of any size TBSA, and the adult cohort included patients ≥ 18 years of age with >50% TBSA injury. Propensity score stratification was used to reduce bias attributable to potential differences in age, sex, %TBSA, and Baux scores between nonrandomized cohorts. Clinical outcomes evaluated included number of AG treatments, length of stay (LOS), healing, and mortality. Additional adverse events were evaluated and compared to historical SOC data sets.ResultsThe median number of AG procedures for pediatric patients treated with ASCS and control NBR cohorts was 1.0 (1.0-5.0) and 2.0 (1.0-20.0), respectively. For adult patients, the ASCS-treated and NBR cohorts had medians of 2.0 (1.0-6.0) and 5.0 (1.0-32.0) treatments, respectively. Overall, ASCS lead to approximately 60% fewer mean AG procedures for both populations. By week 8, re-epithelialization was observed in 91.8% and 90.6% of wounds in the pediatric and adult ASCS-treated cohorts. Median LOS for both cohorts were not different between the treatment groups. No significant differences were observed for mortality between cohorts and no adverse events attributed to ASCS were reported.ConclusionsASCS treatment reduced the number of AG procedures needed to achieve closure, benefiting patients and offering burn centers reduced complexity and cost in the patient care pathway. While LOS was not significantly reduced in this study as seen in other reports, this finding may be confounded due to potential differences in the patient cohorts relative comorbidities and polytrauma, as well as variability in clinical site inpatient/outpatient management strategies for OT/PT.

'Real-world' clinical trials in diabetes care: meaningful or meaningless?

So-called 'real-world' studies seem increasingly popular in diabetes care, as are the economic evaluations in secondary literature based upon them. The term is usually used for pharmacoepidemiological uncontrolled observational studies of different designs. Interpretation of the study findings is, however, badly undermined by the very reasons that the randomised controlled blinded study was invented – namely, non-medication study effects and biases in investigator selection and behaviour. In diabetes studies, glucose control seems particularly susceptible to such effects, perhaps through changes in patient motivation and education. Further, insulin studies are heavily influenced by baseline factors such as the site of starting insulin, the health circumstances of the patient at the time and the clinician involved. It is rare to see these issues adequately addressed or attempts made to understand their influence. In this article an attempt is made to discuss some of the issues further.

The effect of exchange transfusion on mortality in neonatal sepsis: a meta-analysis.

Although antimicrobials are the cornerstone of neonatal sepsis management, adjunctive therapies are required to improve outcomes. The aim of our study was to evaluate the effect of exchange transfusion (ET) on mortality (primary outcome) in neonatal sepsis, as well as on immunoglobulin, complement and neutrophil levels and assess its complications (secondary outcomes). Databases searched include PubMed, NCBI, Google Scholar, CINHAL, Ovid and Scopus. Randomized controlled trials (RCTs), controlled observational studies (COSs) and uncontrolled observational studies (UOSs) reporting mortality data from using ET in neonatal sepsis were included. Studies with additional interventions, non-septic ET indications and populations aged > 28days were excluded. Data extracted include demographics, features of study, sepsis and ET, as well as mortality rates, immunological and laboratory changes and complications. Data was meta-analysed and displayed using forest plots. The meta-analysis of 14 studies (3 RCTs, 11 COSs) revealed a mortality benefit in septic neonates who underwent ET-RR 0.72 (CI 0.61-0.86, p = 0.01) and a significant increase in pooled immunological parameters (immunoglobulin, complement levels) (SMD 1.13, [0.25, 2.02], p = 0.02) and neutrophil levels (SMD 1.07 [0.04, 2.11], p = 0.03) compared to controls. The descriptive analysis of 9 UOSs revealed thrombocytopenia as the most frequently reported complication (n = 48). Moderate-high risk of bias was largely due to inadequate sample sizes and follow-up durations.Conclusion: Currently, the use of ET in neonatal sepsis is not directly recommended due to low certainty of evidence, inadequate power and moderate-high risk of bias and heterogeneity.Trial registration: PROSPERO (CRD42020176629) ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176629 ) What is Known: • Exchange transfusion is one of the adjunctive methods for treatment of neonatal sepsis. What is New: • The pooled analysis of all studies shows that exchange transfusion has a low certainty of evidence in the context of neonatal mortality. However, at this point, this intervention cannot be refuted or recommended due to heterogeneity of studies and inadequate power.

Safety of topical corticosteroids in atopic eczema: an umbrella review

ObjectiveAn umbrella review summarising all safety data from systematic reviews of topical corticosteroids (TCS) in adults and children with atopic eczema.MethodsEmbase, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and the...

Optimal designs of clinical studies in the context of their inclusion in systematic reviews.

In this article I focus on the designs of clinical studies that have a high likelihood of producing reliable findings and those that do not, but that are still being published in large numbers in scientific journals. The former category includes randomized trials, controlled before-after studies and interrupted time series, while the latter category comprises non-randomized trials, uncontrolled before-after studies, case-control/cohort studies and other observational studies. This distinction is important, particularly when studies of inferior design are used in systematic reviews that inform clinical practice guidelines, thereby potentially exerting adverse effects on clinical practice. I also highlight the implications of failing to enrol adequate numbers of patients in clinical trials.

Potential therapeutic uses of cannabinoids to treat behavioural problems in children and adolescents with developmental disorders.

There is a great deal of interest in thepotential symptomatic benefits ofmedicinal cannabis among parents ofchildren and adolescents with developmental disorders. This article provides an overview of what is known about medicinal cannabis as a treatment for paediatric developmental disorders. While there is emerging evidence in support of medicinal cannabis for some adult mental health disorders, to date the evidence in children and adolescents is scant. Reports from uncontrolled observational studies suggest that cannabidiol-rich products may be helpful in reducing behavioural problems in autistic youth. Cannabidiol appears to have a relatively benign adverse effect profile and therefore may be worth considering as a treatment option in some cases. Several controlled clinical trials are underway that will provide more definitive information on the therapeutic value of medicinal cannabis in paediatric developmental and behavioural disorders.

Disease-modifying anti-rheumatic drugs for the management of Takayasu arteritis-a systematic review and meta-analysis.

The pharmacotherapy of Takayasu arteritis (TAK) with disease-modifying anti-rheumatic drugs (DMARDs) is an evolving area. A systematic review of Scopus, Web of Science, Pubmed Central, clinical trial databases and recent international rheumatology conferences for interventional and observational studies reporting the effectiveness of DMARDs in TAK identified four randomized controlled trials (RCTs, with another longer-term follow-up of one RCT) and 63 observational studies. The identified trials had some concern or high risk of bias. Most observational studies were downgraded on the Newcastle-Ottawa scale due to lack of appropriate comparator groups. Studies used heterogenous outcomes of clinical responses, angiographic stabilization, normalization of inflammatory markers, reduction in vascular uptake on positron emission tomography, reduction in prednisolone doses and relapses. Tocilizumab showed benefit in a RCT compared to placebo in a secondary per-protocol analysis but not the primary intention-to-treat analysis. Abatacept failed to demonstrate benefit compared to placebo for preventing relapses in another RCT. Pooled data from uncontrolled observational studies demonstrated beneficial clinical responses and angiographic stabilization in nearly 80% patients treated with tumour necrosis factor alpha inhibitors, tocilizumab or leflunomide. Certainty of evidence for outcomes from RCTs ranged from moderate to very low and was low to very low for all observational studies. There is a paucity of high-quality evidence to guide the pharmacotherapy of TAK. Future observational studies should attempt to include appropriate comparator arms. Multicentric, adequately powered RCTs assessing both clinical and angiographic responses are necessary in TAK.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10067-021-05743-2.

Effect of yoga on glycemia and lipid parameters in type-2 diabetes: a meta-analysis.

Prior systematic reviews on yoga and diabetes have given conflicting results. They have been limited by inclusion of uncontrolled unblinded single group observational studies. No reviews are available which have used the Cochrane methodology and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. This meta-analysis evaluated the efficacy of yoga on glycaemia and lipids in T2DM using the Cochrane methodology and GRADE approach. Major repositories were searched to pick randomized controlled trials involving T2DM patients receiving yoga. Primary outcome was to evaluate changes in fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c). Secondary outcomes were to evaluate changes in post-prandial plasma glucose (PPG), total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Sub-group analysis involving people undergoing structured exercise regimen (SER) versus those undergoing standard diabetes care in controls was done. Data from 13 studies involving 1440 patients were analysed. Compared to controls, individuals doing yoga had significantly lower FPG [mean difference (MD) -17.22mg/dl (95% CI: -26.19 - -8.26mg/dl); p < 0.01; considerable heterogeneity (CH); low certainty of evidence (LCE)], PPG [MD -27.77mg/dl (95% CI: -35.73 - -19.81mg/dl); p < 0.01; low heterogeneity; moderate certainty of evidence (MCE)], TC [MD -19.48mg/dl (95% CI: -31.97 - -6.99mg/dl); p < 0.01; CH; LCE], triglycerides [MD -12.99mg/dl (95% CI: -23.74 - -2.25mg/dl); p < 0.01; CH; LCE], LDL-C [MD -11.71mg/dl (95% CI: -17.49 - -5.93mg/dl); p < 0.01; I2= 69% CH; LCE] and significantly higher HDL-C [MD 4.58mg/dl (95% CI: 3.98-5.18mg/dl); p < 0.01; low heterogeneity; MCE]. On sub-group analysis, where yoga was compared to SER, FPG was significantly lower in yoga group. Yoga improves glycaemia and lipid parameters in T2DM with additional benefits seen both in people doing/not doing structured exercise. The online version contains supplementary material available at 10.1007/s40200-021-00751-0.

Disease-modifying antirheumatic drugs for the management of takayasu arteritis – Protocol for a systematic review

Takayasu arteritis (TAK) is a rare systemic large-vessel vasculitis. The evidence base to guide the medical management of TAK is sparse. This systematic review aims to synthesize the published literature on the use of disease-modifying antirheumatic drugs (DMARDs) in TAK. Scopus (which includes data from MEDLINE), Web of Science, PubMed central, the Cochrane Central Register of Controlled Trials (CENTRAL), and the World Health Organization International clinical trials registry platform shall be searched for relevant studies, both observational and interventional, on the use of DMARDs in TAK. Outcomes assessed shall be remission based on clinical, composite measures, inflammatory markers, angiographic assessment, and relapses. Screening of references and data extraction on predesigned pro formas shall be done in duplicate. Quality assessment of studies shall be done at the study level, using the Cochrane Risk of Bias 2 tool for interventional studies and the Newcastle–Ottawa scale for interventional studies. Publication bias shall be assessed wherever appropriate. Proportions of outcomes with DMARDs shall be pooled for uncontrolled observational studies. For controlled observational studies and interventional studies, pooled risk of outcomes versus comparator treatment or placebo shall be presented. Preplanned subgroup analyses are based on whether participants are adults or children with TAK. Certainty of evidence for DMARDs across studies shall be assessed by the GRADE profiler tool. The findings of the present systematic review shall help to understand better the current landscape of evidence for the use of DMARDs in TAK. This might help to guide future recommendations for the management of TAK. Future clinical trials on TAK might also be designed to avoid lacunae identified in the existing evidence for DMARD use on TAK.

Burst Motor Cortex Stimulation Evokes Sustained Suppression of Thalamic Stroke Pain: A Narrative Review and Single-Case Overview.

Chronic refractory central post-stroke pain (CPSP), one of the most disabling consequences of cerebral stroke, occurs in up to 10% of patients with CPSP. Because a considerable proportion of these patients with chronic pain remain resistant to pharmacological and behavioral therapies, adjunctive invasive and non-invasive brain stimulation therapies are needed. We performed a review of human studies applying burst and conventional motor cortex stimulation (burstMCS and cMCS, respectively) for chronic pain states, on the basis of data sources identified through searches of PubMed, MEDLINE/OVID, and SCOPUS, as well as manual searches of the bibliographies of known primary and review articles. Our aim was to review and discuss clinical data on the indications of burstMCS for various chronic pain states originating from central stroke (excluding trigeminal facial pain). In addition, we assessed the efficacy and safety of burst versus cMCS for central post-stroke pain with an extended follow-up of 5 years in a 60-year-old man. According to our review, uncontrolled observational human cohort studies and one RCT using cMCS waveforms have revealed a meaningful clinical response; however, these studies lacked placebo groups and extended observation periods. In our case report, we found that 3 months of adjunctive cMCS reduced pain levels [visual analog scale (VAS) pre: 9/10 versus VAS post 7/10], whereas the pain decreased further under burstMCS (VAS pre: 7/10 versus VAS post: 2/10); the study involved a follow-up of 5 years and the following parameters: burst rate 40 Hz (500 Hz), 1–1.75 mA, 1 ms, bipolar configuration. To date, only limited evidence exists for the efficacy and safety of burst motor cortex stimulation for the treatment of refractory chronic pain. BurstMCS resulted in significantly decreased post-stroke pain observed after 5 years of cMCS. The available literature suggests similar efficacy as that of conventional (tonic) motor cortex stimulation, although the results are preliminary. Mechanistically, the precise mechanism of action is not fully understood. However, burstMCS may interact with the nociceptive thalamic-cingulate and descending spinal pain networks. To determine the potential utility of this treatment, large-scale sham-controlled trials comparing cMCS and burstMCS are highly recommended.Supplementary InformationThe online version of this article (10.1007/s40122-020-00221-0) contains supplementary material, which is available to authorized users.

The effect of botulinum toxin A on patients with persistent idiopathic dentoalveolar pain-A systematic review.

It has been suggested that botulinum toxin A (BONT-A) is a safe and effective treatment in relieving pain in patients with persistent idiopathic dentoalveolar pain (PIDP). This study aimed to systematically evaluate all the available studies investigating the pain-relieving effects of BONT-A in patients with PIDP. A systematic search with specific search terms was made in PubMed, Web of Science and Scopus. Two authors screened titles and abstracts and selected eligible studies for inclusion in the systematic review. The quality of the studies was evaluated by the 12 items Quality Assessment Tool for Observational studies (Pre-Post) Studies with No Control Group, and the level of evidence was assessed according to GRADE. Three observational studies of 3695 identified were included (445 overlapping studies; 3247 excluded studies). All studies were uncontrolled observational studies investigating the pain-relieving effect of BONT-A in patients with PIDP. The included studies had a fair quality (moderate risk of bias) and insufficient level of evidence. The pain reducing effect by BONT-A injections was in average 50% or more in two studies, in one study 3 out of 4 patients became almost pain free. This systematic review shows that presently the level of scientific evidence is insufficient to evaluate the pain-relieving effect of BONT-A injections in patients with PIDP. There are indications that BONT-A injections could be a possible management option for patients with PIDP that seems to be safe and with few adverse events. There is a need for well-designed placebo-controlled, double-blind RCTs.

Current State of Research About Chinese Herbal Medicines (CHM) for the Treatment of Coronavirus Disease 2019 (COVID-19): A Scoping Review.

Background: There is currently no effective treatment against coronavirus disease 2019 (COVID-19). The optimal selection of interventions targeting the virus is unknown. Therefore, evidence from randomized controlled trials (RCTs) to support specific treatment against COVID-19 is urgently needed. The use of Chinese herbal medicines (CHMs) might have a role in the treatment and symptomatic management of patients with COVID-19. It was aimed at providing an overview of the available evidence and ongoing trials concerning the effects of CHMs for the treatment of COVID-19. Methods: This is a narrative review of relevant studies. Searches were conducted to identify documents published till April 22, 2020. Electronic databases, evidence-based collections, websites of relevant organizations, and trial registries were consulted. Results: A total of 25 guidelines on the treatment of patients with COVID-19 were identified. Four guidelines provided recommendations on the use of CHMs; these guidelines were developed in China and South Korea and were based on the consensus of experts exclusively. The remaining 21 guidelines provided no guidance on CHMs. No finished RCTs of CHMs for the treatment of patients with COVID-19 was found. According to the evidence evaluated in this review, a Cochrane review of CHMs for severe acute respiratory syndrome and five uncontrolled observational studies of the effects of CHMs in patients with COVID-19, the effects of CHMs for COVID-19 are unknown. A total of 52 ongoing clinical trials of CHM interventions for the treatment of COVID-19 were found. These trials will be carried out mostly in China (n = 51). Forty (77%) of the ongoing trials will be randomized, whereas 12 (23%) have an unclear sequence generation procedure. Forty-seven trials (90%) will have a sample size <400 participants. Conclusions: To the authors' knowledge, only the Chinese and the South Korean guidelines recommend CHMs as a treatment option for patients with COVID-19. These guidelines base their recommendations on the consensus of experts. Clinical guidelines or health authorities from other countries do not provide advice on CHMs. Due to the absence of RCT, there is currently no reliable evidence on the effects of any specific CHM intervention for the treatment of patients with COVID-19. A high number of clinical trials of different herbal products are being currently conducted in China.

Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The “Gabrin sign”

Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The “Gabrin sign”

A246 POPULATION WIDE STUDY OF THE EPIDEMIOLOGY AND OUTCOMES OF ANTI-TNF DOSE AUGMENTATION IN INFLAMMATORY BOWEL DISEASE

Abstract Background Inflammatory bowel disease (IBD) patients who experience loss of response to anti-tumor necrosis factor (anti-TNF) therapy are often treated with augmented doses of anti-TNF to recapture response. Despite this, factors associated with dose augmentation and treatment outcomes following dose augmentation remain largely undefined. Aims To examine the epidemiology of anti-TNF dose augmentation and determine the associated treatment outcomes among a province-wide cohort of anti-TNF treated IBD subjects. Methods The University of Manitoba Inflammatory Bowel Disease Epidemiological Database was used to identify patients receiving infliximab or adalimumab maintenance therapy for IBD in the Canadian province of Manitoba. Anti-TNF dose augmentation was defined as a ≥50% increase in anti-TNF dose or a shortening of dosing interval to ≤42 days for infliximab or ≤10 days for adalimumab. Anti-TNF failure was defined as corticosteroid use, IBD-related hospitalization, resective IBD surgery, or change in anti-TNF agent. Competing risks regression using a proportional subhazards model was used to determine the associations between dose augmentation, anti-TNF failure, anti-TNF discontinuation and a number of patient, disease, and treatment factors. Results 871 persons (624 Crohn’s disease (CD), 247 ulcerative colitis (UC)) using anti-TNF maintenance therapy were identified. Cumulative incidence of dose augmentation among continued users was 25.7% at 90 days, 52.3% at 1 year, and 72.8% at 5 years. Anti-TNF failure occurred in 261 of 575 dose augmented subjects, with corticosteroid use the most common failure-defining event. Failure of standard dose anti-TNF in the 90 days preceding dose augmentation was strongly associated with failure of dose augmentation (HR 2.98 (2.27–3.93); p&amp;lt;0.0001). Persons with CD were less likely to receive corticosteroids but more likely to switch anti-TNF agents than persons with UC. Conclusions Rates of adverse IBD outcomes remain high after dose augmentation, particularly when dose augmentation is undertaken shortly after (or in response to) one of these adverse events. Our data suggest that dose augmentation may not be as effective as uncontrolled observational studies have indicated. Funding Agencies None

The effectiveness of omalizumab in the control of severe uncontrolled asthma in Latin America. An exploratory systematic review and meta-analysis

Omalizumab is effective in the treatment of severe persistent allergic asthma that is not controlled with long-acting beta-agonists/ high-dose inhaled corticosteroids. To conduct a systematic exploratory review and meta-analysis of studies with omalizumab in Latin America. A search of real-life studies on the effectiveness of omalizumab in asthma control conducted in Latin America was carried out. The average of the aggregate effectiveness of omalizumab in asthma control (Pooled Analysis) was estimated by using a random effects model. Nine open uncontrolled observational studies were identified; these studies included a total of 1 118 patients with severe uncontrolled asthma. The average of the estimated aggregate effectiveness of omalizumab in the good control of severe asthma was of 80.6 % in children and 78.9 % in adults. The average of the estimated aggregate effectiveness of omalizumab in the control of severe asthma in both children and adults in Latin America was over 78 %. Randomized controlled studies are required in order to establish the efficacy and effectiveness of omalizumab in the control of severe asthma and in the different subgroups by level of eosinophils.