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1.
PLoS One ; 19(7): e0304822, 2024.
Article in English | MEDLINE | ID: mdl-39012863

ABSTRACT

BACKGROUND: To describe outcomes of high-risk patients with coronavirus disease 2019 (COVID-19) treated with sotrovimab, other monoclonal antibodies (mAbs), or antivirals, and patients who did not receive early COVID-19 treatment. We also evaluate the comparative effectiveness of sotrovimab versus no treatment in preventing severe clinical outcomes. METHODS: This observational retrospective cohort study analyzed Mayo Clinic electronic health records. Non-hospitalized adult patients diagnosed with COVID-19 from May 26, 2021 and April 23, 2022 and at high risk of COVID-19 progression were eligible. The primary outcome was 29-day all-cause hospitalization and/or death. Outcomes were described for patients treated with sotrovimab, other mAbs, or antivirals, and eligible but untreated patients, and compared between sotrovimab-treated and propensity score (PS)-matched untreated cohorts. RESULTS: We included 35,485 patients (sotrovimab, 1369; other mAbs, 6488; antivirals, 133; high-risk untreated, 27,495). A low proportion of patients treated with sotrovimab (n = 33/1369, 2.4%), other mAbs (n = 147/6488, 2.3%), or antivirals (n = 2/133, 1.5%) experienced all-cause hospitalization or death. Among high-risk untreated patients, the percentage of all-cause hospitalization or death was 3.3% (n = 910/27,495). In the PS-matched analysis, 2.5% (n = 21/854) of sotrovimab-treated patients experienced all-cause hospitalization and/or death versus 2.8% (n = 48/1708) of untreated patients (difference, -0.4%; p = 0.66). Significantly fewer sotrovimab-treated patients required intensive care unit admission (0.5% vs 1.8%; difference, -1.3%; p = 0.002) or respiratory support (3.5% vs 8.7%; difference, -5.2%; p < 0.001). CONCLUSIONS: There was no significant difference in the proportion of sotrovimab-treated and PS-matched untreated patients experiencing 29-day all-cause hospitalization or mortality, although significantly fewer sotrovimab-treated patients required intensive care unit admission or respiratory support.


Subject(s)
Antibodies, Monoclonal, Humanized , Antiviral Agents , COVID-19 Drug Treatment , COVID-19 , Electronic Health Records , Hospitalization , Humans , Hospitalization/statistics & numerical data , Male , Female , Middle Aged , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/mortality , COVID-19/epidemiology , COVID-19/prevention & control , Retrospective Studies , Antiviral Agents/therapeutic use , United States/epidemiology , SARS-CoV-2/isolation & purification , Adult , Aged, 80 and over , Treatment Outcome , Cohort Studies , Antibodies, Neutralizing
2.
Eur J Pharmacol ; 978: 176800, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-38950835

ABSTRACT

Adiponectin plays key roles in energy metabolism and ameliorates inflammation, oxidative stress, and mitochondrial dysfunction via its primary receptors, adiponectin receptors -1 and 2 (AdipoR1 and AdipoR2). Systemic depletion of adiponectin causes various metabolic disorders, including MASLD; however adiponectin supplementation is not yet achievable owing to its large size and oligomerization-associated complexities. Small-molecule AdipoR agonists, thus, may provide viable therapeutic options against metabolic disorders. Using a novel luciferase reporter-based assay here, we have identified Apigenin-6-C-glucoside (ACG), but not apigenin, as a specific agonist for the liver-rich AdipoR isoform, AdipoR2 (EC50: 384 pM) with >10000X preference over AdipoR1. Immunoblot analysis in HEK-293 overexpressing AdipoR2 or HepG2 and PLC/PRF/5 liver cell lines revealed rapid AMPK, p38 activation and induction of typical AdipoR targets PGC-1α and PPARα by ACG at a pharmacologically relevant concentration of 100 nM (reported cMax in mouse; 297 nM). ACG-mediated AdipoR2 activation culminated in a favorable modulation of key metabolic events, including decreased inflammation, oxidative stress, mitochondrial dysfunction, de novo lipogenesis, and increased fatty acid ß-oxidation as determined by immunoblotting, QRT-PCR and extracellular flux analysis. AdipoR2 depletion or AMPK/p38 inhibition dampened these effects. The in vitro results were recapitulated in two different murine models of MASLD, where ACG at 10 mg/kg body weight robustly reduced hepatic steatosis, fibrosis, proinflammatory macrophage numbers, and increased hepatic glycogen content. Together, using in vitro experiments and rodent models, we demonstrate a proof-of-concept for AdipoR2 as a therapeutic target for MASLD and provide novel chemicobiological insights for the generation of translation-worthy pharmacological agents.


Subject(s)
Apigenin , Glucosides , Receptors, Adiponectin , Receptors, Adiponectin/agonists , Receptors, Adiponectin/metabolism , Animals , Humans , Mice , Apigenin/pharmacology , Apigenin/therapeutic use , Glucosides/pharmacology , Glucosides/therapeutic use , Male , Hep G2 Cells , HEK293 Cells , Disease Models, Animal , Mice, Inbred C57BL , Oxidative Stress/drug effects , Liver/drug effects , Liver/metabolism , Liver/pathology , AMP-Activated Protein Kinases/metabolism
3.
Drug Res (Stuttg) ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38991528

ABSTRACT

Complement cascade is a defence mechanism useful for eliminating pathogenic microorganisms and damaged cells. However, activation of alternative complement system can also cause inflammation and promote kidney and retinal disease progression. Inflammation causes tissue hypoxia, which induces hypoxia-inducible factor (HIF) and HIF helps the body to adapt to inflammation. In this study, we investigated the effect of HIF stabilizer desidustat in complement-mediated diseases. Oral administration of desidustat (15 mg/kg) was effective to reduce the kidney injury in mice that was induced by either lipopolysaccharide (LPS), doxorubicin or bovine serum albumin (BSA)-overload. Complement activation-induced membrane attack complex (MAC) formation and factor B activity were also reduced by desidustat treatment. In addition, desidustat was effective against membranous nephropathy caused by cationic BSA and retinal degeneration induced by sodium iodate in mice. C3-deposition, proteinuria, malondialdehyde, and interleukin-1ß were decreased and superoxide dismutase was increased by desidustat treatment in cBSA-induced membranous nephropathy. Desidustat specifically inhibited alternative complement system, without affecting the lectin-, or classical complement pathway. This effect appears to be mediated by inhibition of factor B. These data demonstrate the potential therapeutic value of HIF stabilization by desidustat in treatment of complement-mediated diseases.

4.
Curr Cardiol Rep ; 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39052162

ABSTRACT

PURPOSE OF REVIEW: In this review, we discuss the status of novel radiation shielding and other methods to reduce radiation exposure and its associated health risks within the CCL. RECENT FINDINGS: There are many devices on the market each with its unique advantages and inherent flaws. Several are available for widespread use with promising data, while others still in development. The field of percutaneous transcatheter interventions includes complex procedures often involving significant radiation exposure. Increased radiation exposes the proceduralist and CCL staff to potential harm from both direct effects of radiation but also from the ergonomic consequences of daily use of heavy personal protective equipment. Here we discuss several innovative efforts to reduce both radiation exposure and orthopedic injury within the CCL that are available, leading to a safer daily routine in a "lead [apron]-free" environment.

5.
Ann Fam Med ; 22(4): 329-332, 2024.
Article in English | MEDLINE | ID: mdl-39038968

ABSTRACT

Sexual and gender minority (SGM) adults experience poor health outcomes, in part due to frequent avoidance of necessary health care. Little is known, however, about factors contributing to patterns of health care utilization in this population. Using national data from the All of Us Research Program, this study evaluated the prevalence of care avoidance due to patient-clinician identity discordance (PCID) and its association with health care discrimination among SGM adults. Sexual minority (20.0% vs 9.4%; adjusted rate ratio [aRR] = 1.58; 95% CI, 1.49-1.67, P <0.001) and gender minority adults (34.4% vs 10.3%; aRR = 2.00; 95% CI, 1.79-2.21, P <0.001) were significantly more likely than their non-SGM counterparts to report care avoidance due to PCID. Exposure to health care discrimination was also more prevalent in this population and was dose-dependently associated with significantly higher rates of PCID-based care avoidance. Study findings highlight the importance of diversifying the health care workforce, expanding SGM-related clinical training, and preventing health care discrimination against SGM patients.


Subject(s)
Sexual and Gender Minorities , Humans , Sexual and Gender Minorities/statistics & numerical data , Sexual and Gender Minorities/psychology , Male , Female , Adult , Middle Aged , United States , Physician-Patient Relations , Young Adult , Patient Acceptance of Health Care/statistics & numerical data , Patient Acceptance of Health Care/psychology , Adolescent , Aged
6.
BMC Infect Dis ; 24(1): 670, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965495

ABSTRACT

BACKGROUND: The clinical benefit of coronavirus disease 2019 (COVID-19) treatments against new circulating variants remains unclear. We sought to describe characteristics and clinical outcomes of highest risk patients with COVID-19 receiving early COVID-19 treatments in Scotland. METHODS: Retrospective cohort study of non-hospitalized patients diagnosed with COVID-19 from December 1, 2021-October 25, 2022, using Scottish administrative health data. We included adult patients who met ≥ 1 of the National Health Service highest risk criteria for early COVID-19 treatment and received outpatient treatment with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or no early COVID-19 treatment. Index date was defined as the earliest of COVID-19 diagnosis or early COVID-19 treatment. Baseline characteristics and acute clinical outcomes in the 28 days following index were reported. Values of ≤ 5 were suppressed. RESULTS: In total, 2548 patients were included (492: sotrovimab, 276: nirmatrelvir/ritonavir, 71: molnupiravir, and 1709: eligible highest risk untreated). Patients aged ≥ 75 years accounted for 6.9% (n = 34/492), 21.0% (n = 58/276), 16.9% (n = 12/71) and 13.2% (n = 225/1709) of the cohorts, respectively. Advanced renal disease was reported in 6.7% (n = 33/492) of sotrovimab-treated and 4.7% (n = 81/1709) of untreated patients, and ≤ 5 nirmatrelvir/ritonavir-treated and molnupiravir-treated patients. All-cause hospitalizations were experienced by 5.3% (n = 25/476) of sotrovimab-treated patients, 6.9% (n = 12/175) of nirmatrelvir/ritonavir-treated patients, ≤ 5 (suppressed number) molnupiravir-treated patients and 13.3% (n = 216/1622) of untreated patients. There were no deaths in the treated cohorts; mortality was 4.3% (n = 70/1622) among untreated patients. CONCLUSIONS: Sotrovimab was often used by patients who were aged < 75 years. Among patients receiving early COVID-19 treatment, proportions of 28-day all-cause hospitalization and death were low.


Subject(s)
Antiviral Agents , COVID-19 Drug Treatment , COVID-19 , Disease Progression , SARS-CoV-2 , Humans , Antiviral Agents/therapeutic use , Retrospective Studies , Male , Female , Middle Aged , Aged , SARS-CoV-2/drug effects , COVID-19/mortality , Adult , Treatment Outcome , Scotland/epidemiology , Antibodies, Monoclonal, Humanized/therapeutic use , Ritonavir/therapeutic use , Aged, 80 and over , Cytidine/analogs & derivatives , Hydroxylamines
7.
Curr Med Res Opin ; : 1-12, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38975862

ABSTRACT

OBJECTIVE: To describe characteristics and acute clinical outcomes for patients with COVID-19 treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or untreated patients at highest risk per National Health Service (NHS) criteria. METHODS: Retrospective study of non-hospitalized patients between 1 December 2021 and 31 May 2022, using data from the Discover-NOW dataset (North-West London). Included patients were aged ≥12 years and treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or untreated but expected to be eligible for early treatment per NHS highest-risk criteria. COVID-19-related and all-cause hospitalizations were reported for 28 days from COVID-19 diagnosis (index). Subgroup analyses were conducted in patients with advanced renal disease, those aged 18-64 and ≥65 years, and by period of Omicron BA.1, BA.2 and BA.5 (post-hoc exploratory) predominance. RESULTS: Overall, 1503 treated and 4044 eligible high-risk untreated patients were included. A high proportion of patients on sotrovimab had advanced renal disease (29.3%), ≥3 high-risk comorbidities (47.6%) and were aged ≥65 years (36.9%). Five of 696 (0.7%) patients on sotrovimab, <5/337 (0.3-1.2%) on nirmatrelvir/ritonavir, 10/470 (2.1%) on molnupiravir and 114/4044 (2.8%) untreated patients were hospitalized with COVID-19. Similar results were observed across all subgroups. The proportion of patients dying within 28 days of the index period was similarly low across all cohorts (<2%). CONCLUSION: Patients receiving sotrovimab appeared to show evidence of multiple high-risk comorbidities. Low hospitalization rates were observed for all treated cohorts across subgroups and periods of predominant variants of concern. These results require confirmation with comparative effectiveness analyses adjusting for differences in underlying patient characteristics.

8.
JAAD Int ; 16: 192-198, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39040844

ABSTRACT

Background: Current assessments on topical treatment attributes in actinic keratosis (AK) do not evaluate safety, effectiveness, and satisfaction from both clinician and patient perspectives, creating an unmet need for more comprehensive AK-specific measures that fully capture the patient experience. Objective: To develop an actinic keratosis-specific expert panel questionnaire (AK-EPQ) of patient-reported outcomes and clinician-reported outcomes for use in research studies. Methods: Using interviews of patients with AK and targeted literature reviews, a 9-person consensus panel of dermatologists with expertise in AK treatment was convened to develop the AK-EPQ to assess AK-specific patient-reported outcomes and clinician-reported outcomes. Results: Nine expert advisers achieved consensus on 11 AK-EPQ items that encompass patient and clinician perspectives of treatment-related local skin reactions, clinical and cosmetic outcomes associated with AK, and satisfaction with treatment; the AK-EPQ will be first implemented in the Patient-Reported Outcomes for Actinic Keratosis study (NCT05260073). Limitations: The AK-EPQ does not directly measure quality of life, although it can be used with validated quality of life instruments. Conclusion: The newly developed AK-EPQ elicits insights into the patient and clinician experience with AK treatments. Comparative probing of these perspectives may help optimize precision medicine in AK treatment.

9.
JAMA Dermatol ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39046711

ABSTRACT

Importance: Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant disease in the US. Although it typically carries a good prognosis, a subset of CSCCs are highly aggressive, carrying regional and distant metastatic potential. Due to its high incidence, this aggressive subset is responsible for considerable mortality, with an overall annual mortality estimated to equal or even surpass melanoma. Despite this morbidity, CSCC is excluded from national cancer registries, making it difficult to study its epidemiology and outcomes. Therefore, the bulk of the CSCC literature is composed of single-center and multi-institutional retrospective cohort analyses. Given variations in reporting measures and analyses in these studies, interpretability between studies and the ability to pool results are limited. Objective: To define standardized reporting measures for retrospective CSCC studies. Findings: An expert panel was convened to determine standardized guidelines for recording and analyzing retrospective CSCC data. A total of 13 dermatologists and dermatologic surgeons with more than 5 years of posttraining experience and considerable experience with performing CSCC outcomes research were recruited to the panel. Consensus recommendations were achieved for CSCC retrospective study reporting measures, definitions, and analyses. Conclusions and Relevance: The recommendations in this report present the potential to standardize future CSCC retrospective studies. With such standardization, future work may have greater interstudy interpretability and allow for pooled analyses.

11.
JAMA Intern Med ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38913367

ABSTRACT

This cross-sectional study examines self-reported poor or fair health status, frequent mental distress, and depression among transgender and gender-diverse respondents compared with cisgender respondents to the 2014 to 2022 Behavioral Risk Factor Surveillance System.

12.
Cureus ; 16(4): e59424, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38826606

ABSTRACT

Introduction Sepsis poses a significant threat in Indian hospitals, with high mortality rates and complications. This study explores the correlation between serum albumin levels and sepsis outcomes in an intensive care unit (ICU) setting. The challenges of diagnosing tropical infections further complicate sepsis management in India. Methodology A longitudinal study was conducted at Vinayaka Mission's Kirupananda Variyar Medical College and Hospital, Salem, India. Adult patients admitted between July 2020 and March 2021 with sepsis were included. Serum albumin levels, demographic data, and clinical outcomes were analyzed. The study used a convenient sampling technique with a sample size of 102 patients. Results Among the 102 patients in the ICU, 22 have expired and the mortality rate in the study was 21.6%. Hypoalbuminemia was present in 56.9% (n = 58) of the patients. The mortality rate is higher among the sepsis patients with the occurrence of hypoalbuminemia (29.3%) compared to patients without hypoalbuminemia (11.4%) and the difference in proportion between the two groups was statistically significant (p-value = 0.029). The requirement of vasopressor support is higher among sepsis patients with the occurrence of hypoalbuminemia (56.9%) compared to patients without hypoalbuminemia (27.3%). The chi-square test reveals that the difference in proportion between the two groups was statistically significant (p-value = 0.005). No substantial impact on systemic inflammatory response scores, readmission to ICU, or progression to chronic illness was observed based on albumin levels. Conclusion This study underscores the predictive value of hypoalbuminemia in sepsis outcomes. Patients with decreased albumin levels showed higher mortality rates and increased vasopressor usage. While albumin levels did not significantly influence certain parameters, hypoalbuminemia may serve as an indicator of severity and adverse prognosis in sepsis, emphasizing the need for further research and tailored interventions.

13.
Cureus ; 16(5): e59883, 2024 May.
Article in English | MEDLINE | ID: mdl-38854233

ABSTRACT

Acute liver failure (ALF) exemplifies a rapid decline in liver function among individuals with previously healthy livers, often manifesting through symptoms such as jaundice, confusion, and potentially life-threatening complications. Timely medical intervention, and, in severe instances, liver transplantation, are essential for enhancing outcomes and averting further deterioration. While the causes of ALF are multifaceted, in developed nations, it predominantly arises from drug-induced liver injury. Treatment primarily revolves around supportive measures, with severe cases necessitating liver transplantation. In instances where acute overdose with acetaminophen serves as the instigating factor, N-acetylcysteine (NAC) emerges as a pivotal component of management, as indicated by the Rumack-Matthew nomogram. The Rumack-Matthew nomogram guides treatment for acetaminophen overdose by correlating serum levels with the risk of liver damage. If levels exceed a set threshold, NAC is administered to prevent toxicity by replenishing glutathione. The decision to administer NAC is typically guided by this clinical tool, which aids healthcare providers in determining the appropriate course of action. NAC assumes a critical role in ameliorating the detrimental effects of acetaminophen overdose, particularly in averting liver damage, thus holding significant importance in patient care and recovery. While chronic acetaminophen overdose cases leading to ALF may also benefit from NAC, the supporting evidence remains weak. In this context, we present a case of ALF stemming from chronic acetaminophen ingestion, managed with NAC when liver transplantation was not a viable option.

14.
JPGN Rep ; 5(2): 175-177, 2024 May.
Article in English | MEDLINE | ID: mdl-38756110

ABSTRACT

Pancreatitis is a condition much more commonly found in adults, but when diagnosed in the pediatric population, is often due to medications, congenital pathology, and critical illness. This patient had previously undergone treatment with 6-mercaptopurine and presented with pancreatitis that eventually worsened to a walled-off necrotic collection with paracolic extensions reaching the pelvis. Given clinical worsening with development of shock, procedural options for source control were weighed with gastroenterology, pediatric surgery, and interventional radiology, before pancreatic necrosectomy was determined to be the treatment of choice, given the adjacency of the collection to the stomach. A total of three separate endoscopic pancreatic necrosectomy procedures were performed and the patient s clinical status improved greatly, with vast improvement later seen on outpatient imaging. This successful treatment course argues for the efficacy of pancreatic necrosectomy even in very large walled off collections, and most importantly, lead to a positive outcome in this young patient.

15.
Article in English | MEDLINE | ID: mdl-38754996

ABSTRACT

The International League Against Epilepsy (ILAE) is an organization of 120 national chapters providing the most widely accepted and updated guidelines on epilepsy. In 2022, the ILAE Task Force revised the prior (2011) classification of focal cortical dysplasias to incorporate and update clinicopathologic and genetic information, with the aim to provide an objective classification scheme. New molecular-genetic information has led to the concept of "integrated diagnosis" on the same lines as brain tumors, with a multilayered diagnostic model providing a phenotype-genotype integration. Major changes in the new update were made to type II focal cortical dysplasias, apart from identification of new entities, such as mild malformations of cortical development and cortical malformation with oligodendroglial hyperplasia. No major changes were made to type I and III focal cortical dysplasias, given the lack of significant new genetic information. This review provides the latest update on changes to the classification of focal cortical dysplasias with discussion about the new entities. The ILAE in 2017 updated the classification of seizure and epilepsy with 3 levels of diagnosis, including seizure type, epilepsy type, and epilepsy syndrome, which are also briefly discussed here.

16.
J Drugs Dermatol ; 23(5): 338-346, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38709702

ABSTRACT

BACKGROUND: The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States.  Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24. RESULTS: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P<0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%). CONCLUSIONS: Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.


Subject(s)
Keratosis, Actinic , Patient Reported Outcome Measures , Patient Satisfaction , Quality of Life , Humans , Keratosis, Actinic/drug therapy , Keratosis, Actinic/diagnosis , Male , Female , United States , Aged , Middle Aged , Treatment Outcome , Aged, 80 and over , Administration, Cutaneous , Ointments , Follow-Up Studies , Adult , Surveys and Questionnaires/statistics & numerical data
18.
BMC Infect Dis ; 24(1): 428, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649824

ABSTRACT

BACKGROUND: The impact of the constantly evolving severe acute respiratory syndrome coronavirus 2 on the effectiveness of early coronavirus disease 2019 (COVID-19) treatments is unclear. Here, we report characteristics and acute clinical outcomes of patients with COVID-19 treated with a monoclonal antibody (mAb; presumed to be sotrovimab) across six distinct periods covering the emergence and predominance of Omicron subvariants (BA.1, BA.2, and BA.5) in England. METHODS: Retrospective cohort study using data from the Hospital Episode Statistics database from January 1-July 31, 2022. Included patients received a mAb delivered by a National Health Service (NHS) hospital as a day-case, for which the primary diagnosis was COVID-19. Patients were presumed to have received sotrovimab based on NHS data showing that 99.98% of COVID-19-mAb-treated individuals received sotrovimab during the study period. COVID-19-attributable hospitalizations were reported overall and across six distinct periods of Omicron subvariant prevalence. Subgroup analyses were conducted in patients with severe renal disease and active cancer. RESULTS: Among a total of 10,096 patients, 1.0% (n = 96) had a COVID-19-attributable hospitalization, 4.6% (n = 465) had a hospital visit due to any cause, and 0.3% (n = 27) died due to any cause during the acute period. COVID-19-attributable hospitalization rates were consistent among subgroups, and no significant differences were observed across periods of Omicron subvariant predominance. CONCLUSIONS: Levels of COVID-19-attributable hospitalizations and deaths were low in mAb-treated patients and among subgroups. Similar hospitalization rates were observed whilst Omicron BA.1, BA.2, and BA.5 were predominant, despite reported reductions in in vitro neutralization activity of sotrovimab against BA.2 and BA.5.


Subject(s)
Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , COVID-19 Drug Treatment , COVID-19 , Hospitalization , SARS-CoV-2 , Humans , Male , Female , Retrospective Studies , Middle Aged , England/epidemiology , Antibodies, Monoclonal, Humanized/therapeutic use , Aged , COVID-19/mortality , COVID-19/epidemiology , Adult , Hospitalization/statistics & numerical data , Aged, 80 and over , Treatment Outcome , Young Adult , Antibodies, Monoclonal/therapeutic use , Hospitals/statistics & numerical data , State Medicine , Antiviral Agents/therapeutic use , Adolescent
19.
Cureus ; 16(3): e56786, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38650782

ABSTRACT

The journey of clinical research in India spans centuries, marked by significant milestones and advancements in scientific, ethical, and regulatory domains. From early trials conducted by pioneers like James Lind to modern standards shaped by landmark events such as the Nuremberg Code and the adoption of Good Clinical Practice guidelines, India's progression reflects a commitment to ethical conduct and patient welfare. The Indian Council of Medical Research (ICMR) has played a pivotal role in this evolution, establishing national research centers and ethical committees to oversee biomedical research. Regulatory frameworks, exemplified by Schedule Y of the Drugs and Cosmetics Act, have adapted over time to align with global standards, facilitating India's integration into the international clinical development landscape. Despite challenges and setbacks, including misconceptions surrounding regulatory reforms, India's clinical trial ecosystem continues to evolve, driven by a dedication to ethical research practices and excellence in healthcare.

20.
Cureus ; 16(2): e55242, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38558747

ABSTRACT

Regorafenib is a multikinase inhibitor with anti-vascular endothelial growth factor receptor (VEGF) activity used as an antiangiogenic agent for metastatic colorectal cancer treatment and has been studied as a potential therapeutic agent for several other cancer treatments. Adverse reactions commonly reported with the use of regorafenib and similar oral multikinase inhibitors include hemorrhage, gastrointestinal fistulas, hypertension, and incomplete wound healing. We report a case of a 59-year-old man with metastatic colorectal adenocarcinoma post-colostomy on regorafenib treatment presenting to the emergency department with altered mental status. MRI showed a left frontoparietal mass, which was resected with a left frontal craniotomy. Postoperative MRI showed a resection cavity without significant hemorrhage. He had been prescribed regorafenib preceding his hospitalization, which was continued after admission before surgery and on postoperative day 1. Thirty-two hours after surgery, the patient exhibited sudden right-sided facial droop and right arm weakness. Imaging revealed an acute intraparenchymal hemorrhage within and adjacent to the tumor resection bed, which was managed conservatively. The patient was subsequently discharged to an inpatient rehabilitation facility. The unusual timing of the hemorrhage suggests that the hemorrhage was due to adverse effects of regorafenib. Patients undergoing neurosurgery should have regorafenib discontinued in preparation for surgery. Similar management should be considered for other anti-VEGF medications to avoid serious complications.

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