Risk-benefit Relationship Research Articles

Ketogenic Approaches for the Treatment of Alzheimer's Disease.

Dementia represents one of the largest and most urgent public health problems across the globe. Modeling projections have estimated that delaying the onset of Alzheimer's disease (AD) by 6 months would reduce the prevalence by 5%, while a delay of 12 months would reduce the prevalence by 10%. One approach to achieving a delay in the onset of AD is to investigate lifestyle interventions that could be widely implemented with a favorable risk-benefit relationship and socioeconomic profile. Amongst such interventions, there is increasing evidence to support the use of ketogenic interventions in AD. Indeed, it is well known that cerebral glucose metabolism is impaired in AD, even at a preclinical stage, and a growing body of literature suggests that these findings may represent a primary pathogenic mechanism leading to neurodegeneration. Ketones are readily taken up by the brain and can serve as an alternative energy source for neurons and glia, hypothetically bypassing the glucose uptake deficit in AD. In this invited review we discuss the preclinical as well as clinical work aiming to increase ketones as a primary intervention in AD, including variations of the ketogenic diet, medium chain triglyceride supplementation, and newer, more experimental approaches.

Requirements for regulatory acceptance of biomarkers

SummaryGenerally, biomarkers could increase the success rate of medicinal product developments and as a consequence accelerate the availability of new therapeutics with an improved benefit–risk relationship. Therefore, patient identification based on predictive biomarkers is becoming increasingly important in all therapeutic areas [1]. The increasing use of predictive biomarker-guided-personalized (precision) medicine warrants the discovery of novel biomarkers as measurable indicators of physiopathological conditions [2]. Biomarkers can be used for diagnostics and prognostics, monitoring disease progression, but also to select the most effective therapy and to predict the treatment outcome [3, 4]. The current article provides a short focus on the regulatory definition of a biomarker and the biomarker qualification process of the European Medicines Agency (EMA). With the evolving landscape, the new Regulation (EU) 2017/746 on in vitro medical devices (IVDR) [5] introduces important changes in the EU legal framework for IVDs especially by legally defining for the first time “companion diagnostic” devices (CDx). Challenges in the codevelopment of CDx and medicinal products are highlighted to provide scientific–regulatory considerations in this complex regulatory field.

Robust safety monitoring and signal detection using alternatives to the standard poisson distribution

ABSTRACT Proper and timely characterization of the safety profile of a pharmaceutical product under development is imperative for assessing the overall benefit-risk relationship of the product and for making key development decisions. For ongoing clinical development, a comprehensive and robust safety monitoring and safety signal detection program which is based upon quantitative statistical reasoning is critical. Methods presented here can be applied to safety signal detection and periodic safety monitoring. Various statistical properties, distributions, and models, all utilizing a Bayesian framework are considered and further examined in order to identify robust methods applicable to a broad set of scenarios and situations. Methods developed for incidence counts (including those with under-dispersed distributions) with variable time-at-risk and with underlying constant or non-constant hazard rates, are proposed and compared to traditional methods designed to assess adverse event incidence rates or binomial incidence proportions (which assume an underlying constant hazard rate and subsequent Poisson distribution for modeling event counts).

Pneumococcal Vaccination Rates and Associated Meningitis Events in Patients With Acute Cerebrospinal Fluid Leak.

To characterize the institutional utilization of pneumococcal vaccination during an index hospital admission for acute cerebrospinal fluid (CSF) leakage and associated infectious and clinical outcomes. This retrospective cohort study included patients hospitalized and treated for an acute CSF leak from January 2017 to June 2022. The primary outcome evaluated the incidence of pneumococcal vaccination during the index admission in patients without prior vaccination. Secondary outcomes evaluated the incidence of meningitis, time from CSF leak identification to meningitis, and mortality within 1 year of the index admission. A total of 94 patients were included. Nineteen (20.2%) patients received pneumococcal vaccination prior to admission. Of the 75 patients without prior vaccination, 4 (5.3%) patients received vaccination during the admission. Meningitis occurred in 5/94 (5.3%) patients and occurred 4-24 days from CSF leak identification. Mortality was observed in 9/94 (9.6%) patients. None of the meningitis cases were attributed to culture-positive findings of pneumococcal disease. The results of this study demonstrate an overall low institutional utilization of pneumococcal vaccination in patients with an acute CSF leak. Infectious and clinical outcomes reflected comparable to previous reported literature. Further evaluation into the risk-benefit relationship of vaccination omission is warranted in this patient population.

Immunosuppressive therapy in elderly patients with neuromyelitis optica spectrum disorder: a retrospective multicentre study

BackgroundThe risk–benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of...

Factors for Implementing Medical Cannabis Cultivation in Brazil

: The medicinal properties of the Cannabis genus are evident and many studies indicate its usefulness to treat many diseases. However, the production of Cannabis-based products has been hampered by its criminalization. Currently its cultivation is not allowed in Brazil, except in specific situations. It increases the price of Cannabis-based products, as it requires the importation of inputs, making it difficult for most of the population to access such medicines. In this context, this review presents an overview of Brazilian legislation on medical Cannabis and the current market for Cannabis products in Brazil. The main goal is to encourage the cultivation of medical Cannabis and the distribution of its products by the Brazilian Unified Health System. In addition, it presents recommendations to implement cultivation based on a bibliographic survey carried out in scientific databases and clinical evidence of the effectiveness of Cannabis in treating patients suffering from several diseases and conditions, although more complete studies are needed to confirm both risk-benefit relationship and dose to be administered. After searching for legislation and bills on government websites, it became evident that there was a need for changes in Brazilian legislation to enable cultivation in Brazil. However, there are several proposals for legislation in progress, and Brazil can significantly benefit from this therapeutic option.

Sports activity limitation during the COVID-19 pandemic in young Italian athletes: impact on mental health in children, adolescents, and young adults.

The closure of sports centres was implemented as a preventive measure to mitigate the transmission of SARS-CoV-2. Given the observed global decline in physical activity and concurrent rise in sedentary behaviour, even among younger age groups, a retrospective cross-sectional study was undertaken to evaluate the effects of this measure on mental health in children, adolescents, and young adults during the initial phases of the COVID-19 pandemic. A total of 1,717 non-professional athletes (age range: 6-25; 53.9% males, 44.6% females) completed an online questionnaire including widely used and validated measures for mental health assessment (SDQ and PGWB-S) and questions regarding sociodemographic characteristics (such as gender), physical activity, and screen time. The association between mental health and sociodemographic characteristics, physical activity, and screen time was evaluated by using univariate and multivariable logistic regression models. In children and adolescents, the incidence of psychological difficulties was associated with not being physically active (OR = 1.49; 95% CI: 1.09, 2.07; p = 0.015). Engaging in physical activity during the period of closures, particularly if more than twice a week, was significantly associated with less psychological difficulties for children/adolescents (OR = 0.54; 95% CI: 0.35, 0.82; p = 0.004) and psychological symptoms (i.e., psychological well-being lower than the median) for youth/young adults (OR = 0.25; 95% CI: 0.14, 0.45; p < 0.001). More psychological difficulties were also found in males for children and adolescents (OR = 1.37; 95% CI: 1.06, 1.79; p = 0.018). However, young adult males showed less psychological symptoms than females (OR = 0.35; 95% CI: 0.22, 0.55; p = 0.001). Additionally, a greater amount of screen time was associated with a higher incidence of psychological symptoms in the whole sample. Our results confirm the positive impact of physical activity on mental health during the COVID-19 pandemic among younger age groups. They also provide valuable insights into the risk-benefit relationship of interrupting sports activities as a preventive measure for infectious diseases.

Mapping the Evidence for Opioid-Mediated Changes in Malignancy and Chemotherapeutic Efficacy: Protocol for a Scoping Review.

Numerous reports contend opioids can augment or inhibit malignancy. At present, there is no consensus on the risk or benefit posed by opioids on malignancy or chemotherapeutic activity. Distinguishing the consequences of opioid use from pain and its management is challenging. Additionally, opioid concentration data is often lacking in clinical studies. A scoping review approach inclusive of preclinical and clinical data will improve our understanding of the risk-benefit relationship concerning commonly prescribed opioids and cancer and cancer treatment. The aim of the study is to map diverse studies spanning from preclinical to clinical regarding opioids with malignancy and its treatment. This scoping review will use the Arksey six stages framework to (1) identify the research question; (2) identify relevant studies; (3) select studies meeting criteria; (4) extract and chart data; (5) collate, summarize, and report results; and (6) conduct expert consultation. An initial pilot study was undertaken to (1) parameterize the extent and scale of existing data for an evidence review, (2) identify key factors to be extracted in systematic charting efforts, and (3) assess opioid concentration as a variable for its relevance to the central hypothesis. Six databases will be searched with no filters: MEDLINE, Embase, CINAHL Complete, Cochrane Library, Biological Sciences Collection, and International Pharmaceutical Abstracts. Trial registries will include ClinicalTrials.gov, Cochrane CENTRAL, International Standard Randomised Controlled Trial Number Registry, European Union Clinical Trials Register, and World Health Organization International Clinical Trials Registry. Eligibility criteria will include preclinical and clinical study data on opioids effects on tumor growth or survival, or alteration on the antineoplastic activity of chemotherapeutics. We will chart data on (1) opioid concentration from human subjects with cancer, yielding a "physiologic range" to better interpret available preclinical data; (2) patterns of opioid exposure with disease and treatment-related patient outcomes; and (3) the influence of opioids on cancer cell survival, as well as opioid-related changes to cancer cell susceptibility for chemotherapeutics. This scoping review will present results in narrative forms as well as with the use of tables and diagrams. Initiated in February 2021 at the University of Utah, this protocol is anticipated to generate a scoping review by August 2023. The results of the scoping review will be disseminated through scientific conference proceedings and presentations, stakeholder meetings, and by publication in a peer-reviewed journal. The findings of this scoping review will provide a comprehensive description of the consequences of prescription opioids on malignancy and its treatment. By incorporating preclinical and clinical data, this scoping review will invite novel comparisons across study types that could inform new basic, translational, and clinical studies regarding risks and benefits of opioid use among patients with cancer. PRR1-10.2196/38167.

Outcome measures of phase III anticancer drug trials in China.

Outcome measures of phase III anticancer drug trials in China.

A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX)

BackgroundFragile X syndrome (FXS) is associated with dysregulated endocannabinoid signaling and may therefore respond to cannabidiol therapy.DesignCONNECT-FX was a double-blind, randomized phase 3 trial assessing efficacy and safety of ZYN002, transdermal cannabidiol gel, for the treatment of behavioral symptoms in children and adolescents with FXS.MethodsPatients were randomized to 12 weeks of ZYN002 (250 mg or 500 mg daily [weight-based]) or placebo, as add-on to standard of care. The primary endpoint assessed change in social avoidance (SA) measured by the Aberrant Behavior Checklist–Community Edition FXS (ABC-CFXS) SA subscale in a full cohort of patients with a FXS full mutation, regardless of the FMR1 methylation status. Ad hoc analyses assessed efficacy in patients with ≥ 90% and 100% methylation of the promoter region of the FMR1 gene, in whom FMR1 gene silencing is most likely.ResultsA total of 212 patients, mean age 9.7 years, 75% males, were enrolled. A total of 169 (79.7%) patients presented with ≥ 90% methylation of the FMR1 promoter and full mutation of FMR1. Although statistical significance for the primary endpoint was not achieved in the full cohort, significant improvement was demonstrated in patients with ≥ 90% methylation of FMR1 (nominal P = 0.020). This group also achieved statistically significant improvements in Caregiver Global Impression‐Change in SA and isolation, irritable and disruptive behaviors, and social interactions (nominal P-values: P = 0.038, P = 0.028, and P = 0.002). Similar results were seen in patients with 100% methylation of FMR1. ZYN002 was safe and well tolerated. All treatment-emergent adverse events (TEAEs) were mild or moderate. The most common treatment-related TEAE was application site pain (ZYN002: 6.4%; placebo: 1.0%).ConclusionsIn CONNECT-FX, ZYN002 was well tolerated in patients with FXS and demonstrated evidence of efficacy with a favorable benefit risk relationship in patients with ≥ 90% methylation of the FMR1 gene, in whom gene silencing is most likely, and the impact of FXS is typically most severe.Trial registrationThe CONNECT-FX trial is registered on Clinicaltrials.gov (NCT03614663).

Aspirin and Helicobacter pylori interaction

The efficacy of aspirin in the prevention of cardiovascular disease needs to be balanced against the associated increased risk of bleeding, especially of gastrointestinal origin, which is the most common source. There is an urgent need to reduce bleeding events both in primary cardiovascular disease prevention, where the risk–benefit relationship is being questioned,1 and in secondary cardiovascular disease prevention, where the benefits exceed the bleeding risk2 but aspirin is often used in combination with other antiplatelet drugs, which increases the risk.

Ocular effects caused by viral infections and corresponding vaccines: An overview of varicella zoster virus, measles virus, influenza viruses, hepatitis B virus, and SARS-CoV-2.

Many viral infections can affect vision and the visual system. Vaccination to prevent diseases is commonplace today, acting by stimulating an immune response without developing the pathology. It involves the production of persisting antibodies against the pathogen and the activation of T cells. Certain diseases have already been eradicated by rigorous vaccination campaigns, while others are hoped to be eliminated soon. Vaccines currently available on the market are largely safe, even if they can rarely cause some adverse effects, such as ocular complications. Analyzing existing literature, we aimed to compare the pathological effects on the eye due to the most common viral infections [in particular varicella zoster virus (VZV), measles virus, influenza viruses, hepatitis B virus, and SARS-CoV-2] with the possible ocular adverse effects of their relative vaccines, in order to establish a risk-benefit relationship from an ophthalmological point of view.

Reporting of the safety from allergic rhinitis trials registered on ClinicalTrials.gov and in publications: An observational study

BackgroundIncomplete and inconsistent reporting of adverse events (AEs) through multiple sources can distort impressions of the overall safety of the medical interventions examined as well as the benefit-risk relationship. We aimed to assess completed allergic rhinitis (AR) trials registered in ClinicalTrials.gov for completeness and consistency of AEs reporting comparing ClinicalTrials.gov and corresponding publications.MethodsWe retrospectively examined completed randomised controlled trials on AR registered in ClinicalTrials.gov on or after 9/27/2009 to trials updated with results on or before 12/31/2021 along with any corresponding publications. Complete reporting of AEs in ClinicalTrials.gov were summarised in tables describing AE information, and complete reporting in publications was an explicit statement of serious AE, death or other AE. Difference in completeness, number, or description of AEs between ClinicalTrials.gov and publication was classified as inconsistent reporting of AEs.ResultsThere were 99 registered trials with 45 (45.5%) available publications. All published trials completely reported AEs in ClinicalTrials.gov, and 21 (46.7%) in publications (P < .001). In 43 (95.6%) publications, there was at least one inconsistency in the reporting of AEs (P < .001). 8 (17.8%) publications had different number of serious AEs (P = .003), 36 (80.0%) of other AEs (P < .001) while deaths reporting was inconsistent in 8 (57.1%) publications (P = .127).ConclusionThe reporting of AEs from AR trials is complete in ClinicalTrials.gov and incomplete and inconsistent in corresponding publications. There is a need to improve the reporting of AEs from AR trials in corresponding publications, and thus to improve patient safety.

ABCL-052 MINDway: A Phase Ib/II Dose Optimization Study to Assess Safety and Pharmacokinetics of Tafasitamab + Lenalidomide in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

The chemo-free immunotherapy tafasitamab + lenalidomide has been granted FDA accelerated approval and EU conditional marketing authorization for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) treatment in autologous stem cell transplant-ineligible adults. Treatment schedule optimization aims to reduce the frequency of hospital visits and decrease treatment burden and healthcare utilization. MINDway (NCT05222555) will investigate if tafasitamab administration at levels higher than the approved 12 mg/kg dose at a reduced dosing frequency maintains the benefit-risk relationship of tafasitamab + lenalidomide for patients with R/R DLBCL. To assess an optimized tafasitamab treatment schedule in patients with R/R DLBCL. Open-label, multicenter, Phase Ib/II study. Currently enrolling; the planned sample size is 51 patients. Eligible patients are aged 18-80 years with histologically confirmed R/R DLBCL and 1-3 prior systemic regimens, including CD20-targeted therapy. Patients previously treated with CD19-targeted therapy or immunomodulatory imide drugs, such as lenalidomide, are excluded. The modified dosing regimen will be investigated in a stepwise design: two sequential dose-finding cohorts (planned n=6 each) followed by an expansion cohort (planned n=39). Lenalidomide 25 mg will be administered in all cohorts on Days 1-21 of each 28-day cycle for up to 12 cycles. After Cycle 12, patients will continue tafasitamab monotherapy at the assigned dosing regimen until progression. After reviewing safety and pharmacokinetic data from Cohorts 1 and 2, patients will be enrolled in an expansion cohort to receive tafasitamab + lenalidomide (tafasitamab dose: 24 or 30 mg/kg) for further evaluation. No intra-patient dose escalation from 24 to 30 mg/kg is permitted. The primary endpoints are the incidence and severity of treatment-emergent adverse events. Key secondary endpoints are tafasitamab serum concentration after 3 and 12 cycles, best objective response rate, duration of response, and progression-free survival. Not yet available. MINDway will evaluate an optimized tafasitamab dosing regimen to reduce the frequency of hospital/clinic visits for tafasitamab-treated patients with R/R DLBCL. Reducing the frequency of visits by half is expected to reduce patient burden and support long-term treatment compliance. Fewer visits may result in less exposure to hospital infections in this already susceptible population. MorphoSys AG.

A Phase 2, Randomized, Multicenter, Placebo-Controlled, Proof-of-Concept Trial of Oral Fexinidazole in Adults With Chronic Indeterminate Chagas Disease.

Chagas disease (CD) has significant global health impact, but safe, effective treatments remain elusive. The nitroimidazole fexinidazole is a potential treatment. This double-blind, randomized, placebo-controlled, dose-finding, proof-of-concept study was conducted in Bolivia. Adults with serologically confirmed chronic indeterminate CD and positive PCR were randomly assigned to 1 of 6 fexinidazole regimens (1200 or 1800 mg/day for 2, 4, or 8 weeks) or placebo. Target recruitment was 20 patients/arm. The primary endpoint was sustained parasitological clearance by serial negative qPCR from end of treatment (EOT) until 6 months follow-up in the intention-to-treat (ITT) population. Follow-up was extended to 12 months. Enrollment was interrupted after 4/47 patients presented with transient asymptomatic grade 3 and 4 neutropenia. Treatment of ongoing patients was stopped in all patients administered >2 weeks. A total of 40 patients received treatment with fexinidazole from 3 days to 8 weeks. Delayed-onset neutropenia (n = 8) and increased liver enzymes (n = 8) were found in fexinidazole patients vs none in the placebo arm. In the ITT analysis, sustained parasitological clearance from EOT to 12 months follow-up varied between 66.7% (1200 mg-2 week) and 100.0% (1800 mg-2 week). Rapid, sustained clearance of parasitemia was observed in all treated patients with available data, but not in any patients in the placebo group, at 12 months (P = .0056). Further exploratory exposure-response analysis suggested low dosages of fexinidazole may be safe and effective. Further evaluation is needed to establish fexinidazole's minimum effective dosage and risk-benefit relationship. Results suggest potential for effective treatment regimens <10 days. NCT02498782.

PB2112: MINDWAY: A PHASE IB/II DOSE OPTIMIZATION STUDY TO ASSESS SAFETY AND PHARMACOKINETICS OF TAFASITAMAB + LENALIDOMIDE IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA

Background: Tafasitamab is an Fc-enhanced, humanized, anti-CD19 monoclonal antibody which, in combination with the immunomodulatory drug lenalidomide, has been granted accelerated FDA approval and EU conditional marketing authorization based on results from L-MIND (NCT02399085) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in adult patients ineligible for autologous stem cell transplant. Treatment schedule optimization aims to reduce the frequency of hospital visits and decrease treatment burden and healthcare utilization while maintaining clinical benefits. Aims: MINDway (NCT05222555) will investigate if administration of tafasitamab at levels higher than the approved 12 mg/kg dose at a reduced dosing frequency can maintain the benefit-risk relationship of tafasitamab + lenalidomide treatment for patients with R/R DLBCL. Methods: MINDway is an open-label, multicenter, Phase Ib/II study in patients aged 18‒80 years with histologically confirmed DLBCL and R/R status after at least one, but no more than three, prior systemic regimens, including CD20-targeted therapy. Patients previously treated with CD19-targeted therapy or with immunomodulatory imide drugs such as lenalidomide are excluded. The modified tafasitamab dosing regimen will be investigated in a stepwise design with two sequential dose-finding cohorts (planned n=6 each) followed by an expansion cohort (planned n=39; Figure). Lenalidomide 25 mg will be administered in all cohorts on Day (D) 1‒21 of each 28-D cycle for up to 12 cycles. After Cycle 12, patients will continue tafasitamab monotherapy at the assigned dosing regimen until progression. Following a review of the safety and pharmacokinetic data from Cohorts 1 and 2, patients will be enrolled in an expansion cohort to receive tafasitamab + lenalidomide at the tafasitamab dose of 24 mg/kg or 30 mg/kg for further evaluation. No intra-patient dose escalation from 24 mg/kg to 30 mg/kg is permitted. The primary endpoint is the incidence and severity of treatment-emergent adverse events; key secondary endpoints include tafasitamab serum concentrations after 3 and 12 treatment cycles and best objective response rate, duration of response, and progression-free survival by investigator assessment. All endpoints will be analyzed using descriptive statistics; no formal statistical tests will be performed. MINDway is currently enrolling, with a planned sample size of 51 patients. Results: Results for this study are not yet available: outcome data as described above will be presented in due course. Image:Summary/Conclusion: MINDway will optimize the tafasitamab dosing regimen to reduce the frequency of hospital/clinic visits for tafasitamab treated R/R DLBCL patients. Reducing the overall frequency of clinic visits by half is expected to reduce the patient burden and support long-term treatment compliance. Furthermore, given the severity of the disease, reduced hospital visits may result in less exposure to hospital infections in this already susceptible population.

Treatment clinical trial - three types - for children with fluency disorders and stuttering.

To present a treatment clinical trial, involving three types of treatment for chronic developmental stuttering (CDS), to verify whether they present indicators and sufficient information to establish an effective and safe benefit-risk relationship. The study included 252 children between 2 and 12 years old, who underwent assessment and treatment for CDS. Among the selected children, 93 met the established inclusion criteria. After obtaining the scores for the risk of CDS (Protocol for the Risk of Developmental Stuttering), all children were assessed according to their fluency profile and the severity level of stuttering. The children underwent treatment for CDS Green, Yellow and Red Programs. The treatment chosen for each child was based on the analysis of the risk for CDS. All therapeutic programs presented positive results in the post-treatment assessment considering the analyzed parameters, with the exception of word repetition, sound prolongation at the end of words, and intrusion of sounds/word segments. The tested therapeutic programs - green, yellow, and red - were efficient for most of the participants. The direct intervention used in the Red Program was highly efficient in promoting fluent speech. This result suggests that for most of the patients with a higher risk of developing the chronic form of stuttering, the use of specific fluency promotion techniques is indicated.

POST-ACUTE COVID-19 SYNDROME AND DIGITAL NECROSIS: A VIRAL SEQUELAE

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coronavirus disease 2019 (COVID-19) undoubtedly produces a hypercoagulable state. Even though the pathogenesis of this phenomenon is incompletely understood, the extensive endothelial injury and elevated prothrombotic microparticles can produce clinical manifestations ranging from asymptomatic microthrombosis to death [1]. Moreover, the chronic stasis a demented and institutionalized patient has, exponentially increases the risk of embolization. CASE PRESENTATION: An 88-year-old woman with past medical history of Alzheimer's dementia, schizophrenia, paroxysmal atrial fibrillation and COVID-19 pneumonia one month prior, presented from a nursing home complaining of right hand pain. Physical examination revealed a right hand with necrosis on the tip of all five fingers and nail avulsion in the fifth digit (Figure 1, 2). The patient's apixaban had been recently discontinued due to a gastrointestinal bleed. Upon further review, no recent trauma, radiation or procedures on the right arm were noted. Initial work-up was remarkable for elevated fibrinogen activity and a D-dimer of 3350 ng/ml (reference range: less than 500). Antinuclear antibody (ANA) was positive but prothrombin time, activated partial thromboplastin time, international normalized ratio, rheumatoid factor, antineutrophil cytoplasmic antibody (ANCA), p-ANCA, C3 and C4 were within normal limits. An electrocardiogram and continuous telemetry monitoring showed normal sinus rhythm. Right hand x-ray revealed digital soft tissue swelling of the first, second and fifth digits on the right hand with no evidence of fracture (Figure 3). Ultrasound of the right upper extremity showed a non-compressible occlusive thrombus in the right cephalic vein. She was started on antibiotics while Orthopedic surgery performed partial amputation of the first and second right hand digits with debridement of the remaining fingers. Apixaban was restarted and she made a full recovery thereafter. DISCUSSION: COVID-19's dysregulated immune response inevitably leads to microvascular inflammation and cell injury. These phenomenons, in conjunction with chronic immobilization, produce a critical risk for a hypercoagulable state [1]. Furthermore, emergent research has elucidated an extensive array of manifestations in the mediate course of this viral infection. Multivariate analyses have demonstrated how the rate of venous thromboembolism in the post-acute COVID-19 patients can be up to 5% with a median of 23 days post discharge [2]. Moreover, a positive ANA without an underlying immunological disease has been described in patients with COVID-19 [3]. CONCLUSIONS: Digital necrosis should be included in potential post-COVID-19 complications and patients with high thrombosis risk must be considered for prophylactic anticoagulation. Further research is warranted to establish the potential risk-benefit relationship of treatment and the most appropriate time of prophylaxis. REFERENCE #1: Bilaloglu S, Aphinyanaphongs Y, Jones S, Iturrate E, Hochman J, Berger JS. Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System. JAMA. 2020;324(8):799. doi:10.1001/jama.2020.13372 REFERENCE #2: Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nature Medicine. 2021;27(4):601-615. doi:10.1038/s41591-021-01283-z REFERENCE #3: Lerma LA, Chaudhary A, Bryan A, Morishima C, Wener MH, Fink SL. Prevalence of autoantibody responses in acute coronavirus disease 2019 (COVID-19). Journal of Translational Autoimmunity. 2020;3:100073. doi:10.1016/j.jtauto.2020.100073 DISCLOSURES: No relevant relationships by Abdul Rahman Al Armashi, source=Web Response No relevant relationships by Faris Hammad, source=Web Response No relevant relationships by Keyvan Ravakhah, source=Web Response No relevant relationships by Francisco Somoza-Cano, source=Web Response

Necesidad de una estrategia integral en el tratamiento de la osteoartrosis

Osteoarthritis is a major health care issue. It is estimated that more than 579 million people have osteoarthritis worldwide. Despite guidelines and recommendations, including pharmacological and non-pharmacological treatments to manage it, patients’ satisfaction is low. That responds to the lack of patients’ participation when making decisions, adverse events caused by the prescribed drugs, and the different therapeutic interventions made in isolation; thus, effectiveness is lost. Likewise, it is necessary to prescribe pharmacological therapies with the best benefit-risk relationship and consider the herbal medicines with proven efficacy and safety in the first line. It is crucial to implement a comprehensive treatment with a strategy that adequately coordinates all the therapeutic approaches and favors the patient’s participation. This article aims to provide the reader a perspective of the importance of the comprehensive management of the patients with osteoarthritis.

Primary Prevention of CVD with Aspirin: Benefits vs Risks.

Low-dose aspirin (acetylsalicylic acid [ASA]; 75 to 100 mg/d) is widely used in the prevention of cardiovascular (CV) events based on the results of large-scale studies supporting a benefit. However, questions remain regarding the benefit-risk relationship in certain settings since long-term use of ASA is not devoid of risk. Incontrovertible evidence supports the benefits of ASA treatment, which exceed the risks, in patients who have had a previous CV event (myocardial infarction, stroke, unstable angina, or transient ischemic attack). Nonetheless, the question remains for those patients who have not had a previous event (primary prevention), where the risk of CV events is lower and, consequently, the absolute benefit is also lower than in patients who have a history of a CV event or its equivalent (secondary prevention). Recent evidence from large-scale clinical trials shows that administration of low-dose ASA is associated with a reduced risk of CV events with a corresponding small absolute increase in the risk of major bleeding (eg, gastrointestinal bleeding and hemorrhagic stroke). Although the benefit and the risk of low-dose ASA in primary prevention are numerically similar, the clinical consequences of an increased risk of bleeding and a decreased risk of a CV event may not be equivalent. If these data are applied to patients with higher levels of CV outcome risk, more patients may potentially benefit from aspirin use in primary prevention.