Specific Adverse Events Research Articles

120. An open-label comparative trial of SUBA-itraconazole (SUBA) versus conventional itraconazole (c-itra) for treatment of proven and probable endemic mycoses (MSG-15): a pharmacokinetic (PK) and adverse Event (AE) analysis

BackgroundC-itra is the drug of choice for treatment of most non-CNS, non-life-threatening forms of endemic mycoses (EM), including histoplasmosis, blastomycosis, coccidioidomycosis, sporotrichosis and talaromycosis. SUBA represents a new formulation of itraconazole that utilizes nanotechnology to improve bioavailability when administered orally. SUBA is formulated as nanoparticles allowing for absorption in the small bowel while not relying on gastric acidity for optimal absorption. MSG-15 is an open-label, comparative clinical trial comparing SUBA to c-itra for the treatment of EM. Herein we report the final PK and AE profiles of these two compounds.MethodsSubjects with proven and probable EM were eligible this open-label comparative study. The protocol allowed up to 14 d of prior therapy with any antifungal for this episode of EM. Subjects were randomized to receive either SUBA 130 mg po bid or c-itra 200 mg po bid for up to 6 months. Follow up occurred at 7, 14, 28, 42, 84 and 180 d post-enrollment. PK samples were obtained at 7, 14, and 42 d. Clinical assessment, including symptom assessment, AEs, overall drug tolerance, and quality of life were assessed at each visit. We used descriptive statistics for this analysis.Results89 subjects with EM entered the trial, including 43 on SUBA and 46 on c-itra. We measured PK serum levels of itra and hydroxyl-itra at days 7, 14, and 42 and these data are depicted in Figures 1-3. There were no significant differences in these levels, including combined itra/hydroxyl-itra levels, among the two study arms. AUC for itra and hydroxyl-itra were similar for both arms. AEs as assessed at each study evaluation were also quite similar among the two study arms. Overall, any AE occurred in 74% vs 85% of SUBA and c-itra recipients, respectively (NS). Drug-related AEs occurred in 35% vs 41% of SUBA and itra recipients, respectively (NS). Most common drug-related AEs included cardiovascular (edema and hypertension), nausea and loss of appetite. Combined Itraconazole and Hydroxy-itraconazole Concentration Over Time ConclusionCompared to c-itra, SUBA demonstrates almost identical serum levels despite being dosed at roughly 60% standard dosing for c-itra (130 mg po bid vs 200 mg po bid). SUBA is slightly better tolerated than c-itra, although the specific AEs are similar. Disclosures Peter G. Pappas, MD, Astellas (Research Grant or Support)Cidara (Research Grant or Support)F2G (Consultant)Matinas (Consultant, Scientific Research Study Investigator)Mayne Pharma (Research Grant or Support)Scynexis (Research Grant or Support) Andrej Spec, MD, MSCI, Mayne Pharma (Grant/Research Support) Marisa Miceli, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) George R. R. Thompson III, III, MD, Amplyx (Consultant, Grant/Research Support)Appili (Consultant)Astellas (Consultant, Grant/Research Support)Avir (Grant/Research Support)Cidara (Consultant, Grant/Research Support)F2G (Consultant, Grant/Research Support)Mayne (Consultant, Grant/Research Support)Merck (Scientific Research Study Investigator)Pfizer (Advisor or Review Panel member)

Safety and efficacy of hydroxychloroquine for treatment of non-severe COVID-19 among adults in Uganda: a randomized open label phase II clinical trial

BackgroundSeveral repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness.DesignWe conducted a randomized open label Phase II clinical trial from October–December 2020.MethodsPatients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6.ResultsOf the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3–4) vs 4(2–4): p = 0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group.ConclusionOur results show that HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution among adults with COVID-19 in Uganda.Trial registration: NCT04860284.

Neurocognitive effects of immune checkpoint inhibitors: A literature review

AbstractBackgroundImmune checkpoint inhibitors (ICI) are novel but rapidly growing class of cancer treatments. They have pleotropic effects on several cancer‐specific targets that underlie their therapeutic properties. These targets include programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte antigen 4 pathways. ICI have been approved in treatment guidelines of several cancers like melanoma and lung cancers and are being routinely used in clinical practice due to its proven efficacy.The mechanism of ICI primarily targets the immune system, which also serves important roles in the structure and function of the central and peripheral nervous system. The reported associated adverse effects are essentially immune mediated due to T‐cell activity upregulation that causes disrupted immune tolerance. The same mechanism leading to cancer death might be driving the neurocognitive sequalae. Several specific neurological adverse events were described due to the role of inflammatory pathways in mediating behavioral and cognitive functions.ICI have clear proven responses, leading to increase in the overall survival such that patients are now living longer with its side effects. Thus, it is essential to understand and assess the long‐term side effects and quality of life outcome among the growing population of cancer survivors previously treated with ICI.MethodThis review discusses the reported cognitive changes associated with immune checkpoint inhibitors. We employed a systematic search of literature in PubMed database, up to November 2020, mentioning neurological and cognitive side effects in patients treated with ICIs. Eligible studies included clinical trials, observational studies and case reportsResultThe clinical spectrum of neurological disorders is highly heterogeneous. Most of the reported neurological adverse events consist of non‐specific symptoms such as headache and fatigue, with the more functionally devastating ones being myasthenia gravis, demyelinating polyradiculopathy, meningitis and limbic encephalitis. Cognitive decline and memory problems were infrequently reported in the reviewed studies.ConclusionAlthough few clinical studies have targeted ICI immunotherapy for associated neurological sequelae, it appears that cognitive decline is not a common adverse effect for ICI. However, over time and with longer use of ICI, there will be a need for more rigorous studies to explore possible long‐term neurological complications.

Crystal nephropathy and amoxicillin: insights from international spontaneous reporting systems.

A substantial increase in amoxicillin-induced crystal nephropathy was recently reported in France. Our study aims to further characterize this safety issue from a worldwide perspective. We queried both the FDA Adverse Event Reporting System (FAERS) and the Eudravigilance databases, and performed disproportionality analysis, selecting only adverse events (AEs) related to crystal nephropathy where amoxicillin or amoxicillin/clavulanic acid were reported as suspect. In FAERS, the reporting odds ratios were calculated and deemed significant by the lower limit of the 95% confidence interval (LL95%CI) > 1, selecting all other drugs/events recorded in FAERS as comparator. Deduplication followed by case-by-case assessment and comparison between French and non-French cases were also performed in both databases. Overall, 57,754 and 84,764 AE reports with amoxicillin or amoxicillin/clavulanic acid were recorded in FAERS and Eudravigilance, respectively, with France accounting for 18.7% and 22.0% of cases. Specific AEs of interest were retrieved in 144 and 239 cases, respectively. Increased reporting was found in FAERS for crystalluria (N = 99; LL95%CI 53.18), crystal nephropathy (24; 27.01), medication crystal in urine present (9; 92.00), crystal urine (8; 11.90), and crystal urine present (4; 1.57). In FAERS and Eudravigilance databases, reports were classified as serious in 98.8% and 91.2% of cases, respectively. Acute kidney injury (AKI) was found in 81.2% and 71.1% of patients. Amoxicillin was mainly given intravenously, and a dose ≥ 12g/day was administered in 50.0% and 19.7% of cases in the FAERS and Eudravigilance databases, respectively. Although causal association cannot be firmly inferred, a consistent signal of crystal nephropathy with amoxicillin emerged, especially in France. Clinicians should monitor patients for possible early AKI onset, especially when dealing with intravenous administration of daily doses > 12g.

Infection prevention measures and outcomes for surgical patients during a COVID-19 outbreak in a tertiary hospital in Daegu, South Korea: a retrospective observational study.

BackgroundThe first large coronavirus disease 2019 (COVID–19) outbreak outside China occurred in Daegu. In response, we developed infection prevention measures for surgical patients during the outbreak at our hospital and retrospectively reviewed the outcomes of COVID–19–related surgical patients.MethodsWe reviewed the medical records of 118 COVID–19–related surgical patients and monitored their clinical outcomes until March 31, 2021. We also interviewed healthcare workers who participated in their perioperative care at Kyungpook National University Chilgok Hospital. The perioperative management guidelines for COVID–19–related patients were prepared through multidisciplinary discussions, including the infection control department, surgical departments, and anesthesiology department before and during the COVID–19 outbreak.ResultsOne standard operating room was temporarily converted to a negative-pressure room by increasing the exhaust air volume, creating a relative pressure of −11.3 Pa. The healthcare workers were equipped with personal protective equipment according to the patient's classification of the risk of COVID–19 transmission. The 118 COVID–19–related patients underwent emergent surgery in the negative–pressure room, including three COVID–19–confirmed patients and five COVID–19–exposed patients. ConclusionAll surgeries of the COVID–19–related patients were performed without specific adverse events or perioperative COVID–19 transmission. Our experience setting up a negative–pressure operating room and conservative perioperative protocol to prevent COVID–19 transmission will help plan and execute infection control measures in the future.

Adverse Events Following CAR T-Cell Therapy: A Single Institution Retrospective Analysis of Toxicities Following CAR T-Cell Therapy for Children and Young Adults with Relapsed Refractory B-Cell Acute Lymphoblastic Leukemia

Introduction: CAR T-cells have demonstrated remarkable ability to induce complete remission in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r ALL). This success, however, is tempered by the toxicities associated with CAR T-cell therapy. Much has been published on cytokine release syndrome (CRS), but, to date, a comprehensive profile of specific end organ toxicities secondary to CAR T-cell therapy in the pediatric and young adult population is lacking.Methods: This retrospective, single center study, was performed to characterize the specific adverse events (AEs) experienced by pediatric and young adult patients during the first 30 days following CAR T-cell infusion. AEs graded using Common Terminology Criteria for Adverse Events (CTCAE) were collected from all patients with r/r ALL treated on one of three phase I CAR T-cell trials (CD19, CD22, and CD1922) at the Pediatric Oncology Branch of the National Cancer Institute at the National Institutes of Health from 2012-2020. The primary objective was to determine the incidence of all severe AEs, defined as > grade (Gr) 3 AEs, overall and by organ system, attributed to research or disease. Secondary objectives were to stratify severe AEs based on development of CRS and CRS grade (using ASTCT CRS grading criteria). Descriptive statistics were reported along with comparisons of continuous parameters using Mann-Whitney and binomial parameters using Fischer's exact tests.Results: We reviewed AE data from 134 patients with r/r ALL receiving one of 3 unique CAR T-cell constructs (Table). The median age was 15.2 years (Interquartile range (IQR) 9.5-21.2). The median number of prior therapies was 5 (IQR 3-6) and 57% had received a prior hematopoietic stem cell transplant (HSCT).Amongst the 134 patients, a total of 1747 individual > Gr 3 AEs were experienced by 133 patients (99%) during the first 30 days following CAR infusion (Figure 1A). The median number of > Gr 3 AEs per patient was 10 (IQR 4.8-19).Cytopenias (including neutropenia, thrombocytopenia and anemia) comprised the vast majority of total > Gr 3 AEs (n=983, 56.3%). The most common severe (> Gr 3) AEs were thrombocytopenia (n=433, 24.8%), metabolic abnormalities (i.e. electrolyte derangements) (n=333, 19.1%), neutropenia (n=332, 19%), and anemia (n=218, 12.5%).With exclusion of cytopenias, 764 > Gr 3 AEs were experienced by 111 patients (83%), with a median of 4 (IQR 1-8.3) > Gr 3 AEs per patient. One grade 5 pulmonary AE occurred in the setting of acute respiratory distress syndrome (ARDS). Focusing on non-cytopenia AEs (Figure 1B), metabolic AEs made up 43.6% of AEs; hepatic toxicities (n=115, 15%), febrile neutropenia (n=114, 14.9%), and cardiovascular toxicities (n=59, 7.7%) were the next most frequent.Of the 134 patients, 104 (77.6%) developed CRS. All 30 patients without CRS had at least 1 > Gr 3 AE (median 6, IQR 3-11.3). In contrast, the median number of > Gr 3 AEs in those with CRS was 11.5 (IQR, 6-21.5), (p=0.0021). When stratified by CRS Gr 1-2 versus CRS Gr 3-4 (Figure 2), patients with higher-grade CRS also had a higher median number of > Gr 3 AEs per patient (p= 0.0017).Conclusions: Among 134 children and young adults with r/r ALL receiving phase I CAR T-cells, we found a high incidence (99%) of severe AEs, with a per patient median of 10 (IQR 4.8-19) > Gr 3 AEs. While the majority of > Gr 3 AEs were cytopenias, 17 different categories of AEs were experienced. The development and severity of CRS associated with an increase in the median number of severe AEs per patient. As phase I trials of CAR T-cell therapy expand, it is imperative to understand the full toxicity profile of these therapies. While the definition and refined grading of CRS has helped advance the field, there is a gap in knowledge regarding patient specific end-organ toxicities beyond CRS. Our data help establish a foundation for the full toxicity profile experienced by patients enrolling on phase I CAR T-cell trials. With an emerging role for earlier intervention for CRS, we anticipate that the toxicity burden will decrease. Next steps include characterizing the specific toxicities within each AE category, evaluating duration and time to resolution, distinguishing attribution to research versus disease and studying the impact of earlier use of tocilizumab on toxicity profile. Future directions will incorporate assessment of baseline organ function pre-CAR and its impact on development of post CAR severe AEs. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Safety of mass drug coadministration with ivermectin, diethylcarbamazine, albendazole, and azithromycin for the integrated treatment of neglected tropical diseases: a cluster randomized community trial

Neglected tropical diseases control programmes run separately. For settings with more than one endemic disease, combined mass drug administration (MDA) has potential practical advantages compared with separate programmes but needs confirmation of safety. We assessed the safety of combined MDA for multiple neglected tropical diseases using ivermectin, diethylcarbamazine, albendazole (IDA) and azithromycin (AZI). We conducted an open-label, cluster-randomized trial involving individuals living in 34 wards (smaller administrative division) in two study sites, Namatanai District and Lihir Island, Papua New Guinea. We randomly assigned wards to the combined treatment arm (which received a single dose of the triple combination IDA and a single dose of AZI at the same visit) or the control arm (which received IDA separately followed by AZI separately one week after). All participants underwent safety assessments one day after drug administration. Methodology for collecting the adverse events (AEs) was a general question (in Namatanai) and individual questions about specific AEs (in Lihir). The primary endpoint was the prevalence of AEs. Safety of combined treatment was taken to be non-inferior to that of IDA if the upper limit of the two-sided CI for the difference in rates was equal or lower than 5%. The study enrolled 15,656 participants. Of those enrolled, 7,281 (46.3%) received the combined regimen and 8,375 (53.3%) received standard treatment with IDA for lymphatic filariasis between Nov 1, 2018, and Apr 15, 2019. Of the individuals in the control group, 4,228 (50.5%) attended a second visit one week apart to receive AZI for yaws. In Namatanai, the proportion of AEs was similar in the combined group (0.8%) compared to the IDA group (1.3%, difference 0.5% [95CI -2.5% to 1.4%]) or the AZI group (3.6%, d -2.8% [95CI -8.6% to 2.8%]). In Lihir, the proportion of AEs was higher in the combined group (23.0%) compared to the IDA group (12.2%, d 10.8% [95% CI 1.5% to 20.2%]) or the AZI group (11.1%, d 11.9% [95% CI 2.7% to 21.1%]).We observed 21 (0.3%) grade-2 AEs in the combined treatment group, 33 (0.4%) in the IDA separately group, and 18 (0.2%) in the AZI separately group. No participants required treatment for any AE. We observed no deaths, serious AEs, or AEs of special interest. In the largest trial so far involving coadministration of regimens based on IDA and AZI, the combination was safe and feasible in a population of more than 15,000 people. Combined MDA based on these two regimens opens up new potential for the control of neglected tropical diseases in the Western Pacific region.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Perioperative Spine: Preoperative Nutritional Assessment.

Preoperative malnutrition has been implicated in adverse events after elective surgery, potentially impacting patient outcomes. As a potentially modifiable risk factor, we sought to determine which assessments of nutritional status were associated with specific adverse events after spine surgery. In addition, we explored if a preoperative nutritional improvement intervention may be beneficial in lowering the rates of these adverse events. The literature search yielded 115 abstracts relevant to the PICO (patient/population, intervention, comparison, and outcomes) questions included in this chapter. The task force selected 105 articles for full text review, and 13 met criteria for inclusion in this systematic review. Malnutrition, assessed preoperatively by a serum albumin <3.5g/dL or a serum prealbumin <20mg/dL, is associated with a higher rate of surgical site infections (SSIs), other wound complications, nonunions, hospital readmissions, and other medical complications after spine surgery. A multimodal nutrition management protocol decreases albumin and electrolyte deficiencies in patients with normal preoperative nutritional status. It also improves overall complication rates but does not specifically impact SSIs. It is recommended to assess nutritional status using either serum albumin or prealbumin preoperatively in patients undergoing spine surgery.The full guidelines can be accessed at https://www.cns.org/guidelines/browse-guidelines-detail/4-preoperative-nutritional-assessment.

Adjuvant trials suggest changes to non-small cell lung cancer treatment paradigm: Results from clinical trials presented at the 2021 annual meeting of the American Society of Clinical Oncology may point to new ways to improve individualized therapy.

At the 2021 annual meeting of the American Society of Clinical Oncology, positive data from several phase 3 clinical trials indicated an earlier role for novel therapeutic treatments for patients with metastatic disease. The studies suggest that adjuvant therapy with newer agents may increase disease-free survival in a range of tumor types and benefit select subsets of patients with a higher risk of recurrence after primary treatment. The results of 4 clinical trials in total were presented; they investigated adjuvant treatment versus placebo or best supportive care in resected renal cell carcinoma, locally advanced cervical cancer, early-stage non–small cell lung cancer (NSCLC), and BRCA1/2-mutant, HER2-negative early breast cancer.1 Among the trials that were presented, data from the OlympiA trial (ClinicalTrials.gov identifier NCT02032823) regarding the use of olaparib (Lynparza), a poly(adenosine diphosphate ribose) polymerase inhibitor, revealed that the invasive (3-year) diseasefree survival rate improved to 85.9% (in contrast to 77.1% with a placebo) for patients with HER2-negative breast cancer and a BRCA1/2 mutation present (hazard ratio [HR] 0.58; 99.5% CI, 0.41-0.82; P < 0.0001). These patients were considered to have a high risk of recurrence after initial local treatment and neoadjuvant/adjuvant therapy.1, 2 The KEYNOTE-564 trial (ClinicalTrials.gov identifier NCT03142334) showed an estimated disease-free survival rate of 77.3% with the use of pembrolizumab (Keytruda), a PD-1 inhibitor (in contrast to 68.1% with a placebo), in patients with clear cell renal cell carcinoma. The patients studied were categorized as intermediate high risk or high risk for recurrence after nephrectomy. A trend suggesting a 96.6% overall survival benefit with pembrolizumab versus a placebo (93.5%) was also noted by investigators.1, 3 Negative trial data from patients with advanced cervical cancer and a high rate of potential relapse were also discussed during the plenary session. Data from the OUTBACK trial (ACTRN12610000732088) illustrated similar progressionfree survival rates (63% vs 61%; 95% CI, -5 to +9; P = 0.61) without improved overall survival (72% vs 71%; 95% CI, -6 to +7; P = 0.91) at 5 years for patients with advanced cervical cancer who were given adjuvant chemotherapy after the administration of cisplatin-based chemoradiation.1, 4 IMpower010 (ClinicalTrials.gov identifier NCT02486718), a randomized, global, open-label trial of atezolizumab (Tecentriq), an anti–PD-L1, versus best supportive care after adjuvant treatment, studied patients with resected stage IB to IIIA NSCLC. A total of 1280 patients were enrolled; they received 4 cycles of cisplatin with vinorelbine, docetaxel, pemetrexed, or gemcitabine. Patients were randomized to receive 16 cycles of atezolizumab every 3 weeks or best supportive care. Those enrolled in the atezolizumab arm were given a median of 16 doses with periodic radiologic imaging; cycles in both phases lasted for 21 days.5 The primary results of the IMpower010 study illustrated a disease-free survival benefit with adjuvant atezolizumab after adjuvant chemotherapy in the PD-L1 TC ≥1% stage II-IIIA (stratified HR 0.66; P = 0.0039) and all randomized stage II-IIIA populations (stratified HR 0.79; P = 0.0205). Although adverse events of any grade occurred in 92.7% of the patients in the atezolizumab arm, the discontinuation rate in this population was 18.2%, and the safety profile was similar to that of prior use of atezolizumab as a monotherapy. Specific adverse events were not detailed in the published abstract results.5 Suresh S. Ramalingam, MD, of the Winship Cancer Institute at Emory University in Atlanta, Georgia, gave a virtual interview to CancerNetwork (https://www.cancernetwork.com/) related to the American Society of Clinical Oncology plenary session. “The notion that we could use immune checkpoint inhibitors in early-stage disease to improve overall outcomes is very exciting and an important step forward in the management of early-stage lung cancer.” —Suresh S. Ramalingam, MD Conversely, tailoring treatment interventions in the adjuvant setting may also dictate that some patients will do best by avoiding more toxic treatments. Placing an emphasis on improved outcomes for patients who face a possibly increased residual risk after their initial treatment highlights the importance of the comprehensive selection and strategy of therapy in the adjuvant care setting.

IgG4-related autoimmune manifestations in Alemtuzumab-treated multiple sclerosis patients

We aimed to determine whether Alemtuzumab-induced immune reconstitution affects immunoglobulin and complement levels in the serum of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. IgG4-levels were increased 24-months after treatment initiation compared to baseline levels in twenty-nine patients. Alemtuzumab-treated patients with the highest IgG4-levels were more prone to thyroid-related autoimmune manifestations and specific autoimmune adverse events such as Crohn's disease, Graves' disease, and hemolytic anemia. Compared to baseline, total IgG-levels showed a trend towards reduced levels following two-courses of Alemtuzumab, but no significant change of C3 and/or C4-levels was observed. In conclusion, monitoring of IgG4-levels can serve as a marker for secondary autoimmunity risk in multiple sclerosis patients treated with Alemtuzumab.

Health-related benefits and adverse events associated with yoga classes among participants that are healthy, in poor health, or with chronic diseases

BackgroundOur previous study demonstrated that 42% of yoga class participants in Japan had chronic diseases requiring medication. This raises the question as to whether those with chronic diseases would benefit from practicing yoga or if they are at higher risk for specific adverse events compared to healthy individuals receiving the same instruction.MethodsTo address these questions, 328 adults who started practicing yoga for the first time were asked to complete the Profile of Mood States (POMS), Perceived Stress Scale (PSS), and Medical Outcomes Study Short Form 8, standard version (SF-8™) and to record any adverse events on the first day of the yoga class and again three months later. The participants consisted of three groups: a healthy (H) group (n = 70), a poor health (PH) group (n = 117), and a chronic disease (CD) group (n = 141). The degree of subjective symptoms was also compared between the pre- and post-intervention period in the PH and CD groups.ResultsTypically, yoga classes were held once a week for 60–90 min. The programs included asanas, pranayamas, meditation, isometric yoga, and sukshma vyayama. In the PH and CD groups, the POMS tension-anxiety and fatigue scores decreased and the vigor score increased significantly after the first class. Furthermore, PSS scores decreased and the SF-8™ scores increased significantly three months later. The degree of subjective symptoms such as easy fatigability, shoulder stiffness, and insomnia also decreased over three months. Individuals in these groups experienced more frequent adverse events than those in the H group. The PH and CD groups also experienced a greater variety of symptoms, including psychological ones, not reported by the H group. Adverse events were not so serious that participants stopped practicing yoga during the class. About 60% of all participants were highly satisfied with participating in yoga classes.ConclusionsIf yoga classes are conducted with attention to possible adverse events, yoga practice in a yoga studio may have beneficial effects for people with functional somatic symptoms and chronic diseases, as well as healthy participants. These benefits include reductions in perceived stress and uncomfortable symptoms as well as improved mood and quality of life.

Allergen-specific immunotherapy for local allergic rhinitis: a systematic review and meta-analysis.

Local allergic rhinitis (LAR) is a phenotype of chronic rhinitis exhibiting a local Th2-driven inflammation without positive clinical markers of atopy. Immunomodulatory effects of allergen-specific immunotherapy (AIT) induce allergen-specific tolerance. However, AIT is not well-recognized as a treatment for LAR. Systematic search on six electronic databases and registries was performed. Experimental and observational studies of AIT for LAR patients were retrieved. The primary outcomes were symptom score, medication score, combined symptom medication score, and disease-specific quality of life. Secondary outcomes were serum specific(s) IgG4, sIgE, and adverse events. Four double-blind randomized controlled trials (156 patients) from two research units assessed the effects of subcutaneous immunotherapy (SCIT). Compared with placebo, SCIT showed significant reductions in symptom score, medication score, combined symptom medication score, disease-specific quality of life, and an increase in serum sIgG4. There was no significant change in serum sIgE. Likewise, two observational studies (one using SCIT and one using sublingual immunotherapy) improved post-therapeutic symptom score. No studies assessed the effects after discontinuation of treatment. AIT was safe without serious adverse events. AIT has beneficial effects and safe for LAR. Its effects are restricted to studies with short-term follow-up. AIT may be considered in LAR patients.

Efficacy and safety of bevacizumab-containing therapy for refractory advanced breast cancer: a retrospective study.

Advanced breast cancer (ABC) is difficult to treat due to the primary and acquired resistance, which is the main cause of rescue treatment failure. Thus, developing a new rescue treatment strategy for clinicians is a challenge. This study retrospectively collected the medical information of patients with refractory ABC who were treated with bevacizumab at our department to analyze the efficacy and safety of bevacizumab-containing therapy as a new treatment method for refractory ABC. The complete medical information of patients receiving bevacizumab treatment from November 2017 to November 2020 was collected, and patients' general medical history and disease characteristics were analyzed. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), time to failure (TTF), overall survival (OS), and safety were also analyzed using SPSS 20.0 statistical software. The data of 68 women with refractory ABC who received bevacizumab-containing therapy were collected. The last follow-up examinations were performed on March 31, 2021. The ORR was 41.2% and the DCR was 88.2%. The median PFS, TTF, and OS were 6.0 months [95% confidence interval (CI): 3.4-8.6 months], 4.0 months (95% CI: 3.2-4.8 months), and 26.6 months (95% CI: 10.2-43.0 months), respectively. Treatment was discontinued in 2 patients due to chemo-related adverse reactions. The main adverse events related to bevacizumab were hypertension (7.4%) and bleeding (2 cases, 2.9%), both of which were grade 1. No specific adverse events causing the discontinuation of bevacizumab treatment were observed in the other patients. Among patients with refractory ABC, bevacizumab-containing therapy is feasible and safe, and can be used as a new treatment strategy. However, the question of who can benefit the most from bevacizumab-containing therapy requires further exploration.

Administration of Autologous Mesenchymal Cells for the Treatment of Arthritis.

Injection of autologous mesenchymal stem cells (AMSCs) as stromal vascular fraction, culture expanded adipose derived stem cells, minimally manipulated fat graft, bone marrow aspirate or cultured bone marrow MSCs, for osteo- and inflammatory arthritis have shown good clinical efficacy in many studies. Questions have been raised as to their safety despite no evidence known to us that they are unsafe when used this way. We hypothesized that AMSC injections are completely safe for the treatment of arthritis. A PubMed literature search was performed to identify adverse events specifically related to the injection of autologous mesenchymal or hematopoietic stem cells into arthritic joints or intravenously. 2,011 reported injections were found. No stem cell specific adverse events were identified. Specifically no infections, tumorigenesis, or chondrolysis from collagenase were found. Intra-articular injection of autologous mesenchymal stem cells for the treatment of arthritis is completely safe with no stem cell specific adverse events yet documented, and no increased risk compared with other traditional treatments for arthritis.

Association of Infliximab and Vedolizumab Trough Levels with Reported Rates of Adverse Events: A Cross-Sectional Study.

Infliximab and vedolizumab are effective treatments for inflammatory bowel disease (IBD), although associated with adverse events (AE). While low or non-existent drug levels and positive antidrug antibodies have been associated with therapeutic failure, there is no clear association between higher drug levels and AE. A cross-sectional study consisting of Crohn’s disease (CD) and ulcerative colitis (UC) patients receiving infliximab or vedolizumab at the Sheba Medical Center was performed. Patients completed a questionnaire regarding AEs related to biological therapy. Serum trough levels obtained on the same day were analyzed. Objective measures of outcomes were retrieved from medical records. Questionnaires were completed by infliximab (n = 169) and vedolizumab (n = 88)-treated therapy patients. Higher infliximab levels were only numerically associated with the occurrence of at least one AE (p = 0.08). When excluding fatigue and abdominal pain, higher infliximab levels were statistically associated with the occurrence of at least one AE (p = 0.03). Vedolizumab drug levels > 18 μg/mL were also linked with the occurrence of more AEs. No specific association was observed between the increased levels of either infliximab or vedolizumab and specific AEs (neurological symptoms, upper GI symptoms, infectious complications, and musculoskeletal symptoms). As significant AEs are very rare, additional multi-center studies are required.

Ramucirumab in Indian Patients with Advanced Gastric Cancer-Does Borderline Performance Status and Heavy Burden of Disease in Real World Practice Impact Clinical Benefit?

Vikas OstwalBackground Ramucirumab is considered a standard of care as second-line therapy (CT2) in advanced gastric cancers (AGCs). The aim of this study was to assess practice patterns and outcomes with ramucirumab among Indian patients with AGCs. Materials and Methods A computerized clinical data entry form was formulated by the coordinating center's (Tata Memorial Hospital) medical oncologists and disseminated through personal contacts at academic conferences as well as via email for anonymized patient data entry. The data was analyzed for clinical characteristics, response rates, and survival outcomes. Results A total of 26 physicians contributed data, resulting in 55 patients receiving ramucirumab and being available for analysis. Median age was 53 years (range: 26–78), 69.1% of patients had greater than two sites of disease, and baseline Eastern Cooperative Oncology Group's performance score (ECOG PS) ≥ 2 was seen in 61.8% of patients. Ramucirumab was used as monotherapy in 10.9% of patients, while the remaining 89.1% received ramucirumab combined with chemotherapy. Median event-free survival (EFS) and median overall survival (OS) with ramucirumab were3.53 months (95% CI: 2.5–4.57) and 5.7 months (95% CI: 2.39–9.0), respectively. Common class specific grade adverse events seen with ramucirumab included gastrointestinal (GI) hemorrhage (9.1% - all grades) and uncontrolled hypertension (Grade 3/4 - 3.6%). Conclusions Ramucirumab appears to have similar efficacy in Indian AGC patients when compared with real-world data from other countries in terms of median EFS, but OS appears inferior due to more patients having borderline ECOG PS and high metastatic disease burden. GI hemorrhages appear more common than published data, although not unequivocally related to ramucirumab.

Myocarditis After SARS-CoV-2 Vaccination: True, True, and… Related?

Myocarditis After SARS-CoV-2 Vaccination: True, True, and… Related?

Conjoined tendon preserving posterior approach in hemiarthroplasty for femoral neck fractures: A prospective multicenter clinical study of 322 patients.

The posterior approach is widely used in femoral hemiarthroplasty. The major problem with this approach is the high risk of postoperative dislocation. A modified posterior approach, the conjoined tendon preserving posterior approach (CPP), was developed to reduce postoperative dislocations. The objective of this multicenter study was to evaluate the efficacy and safety of hemiarthroplasty performed using the CPP approach for femoral neck fractures. A total of 322 patients with femoral neck fracture, from 10 facilities, were prospectively studied. Bipolar hemiarthroplasty using the CPP approach was performed, using the same type of implants. Hip joint movement was not restricted following surgery, regardless of a patient's cognitive status. Final follow-up was performed 9.1 ± 1.5months after surgery. Hemiarthroplasty was undertaken in 320 patients using the CPP approach. The mean age, operative time, and intraoperative blood loss were 83.3 ± 7.4years, 70.0 ± 22.7min, and 134.8 ± 107.9mL, respectively. No postoperative dislocations were observed during the study period. Intraoperative adverse events related to the hip joint included femoral fractures in five patients (1.6%) and trochanteric fractures in four patients (1.3%). Postoperative hip joint adverse events included a periprosthetic fracture in one patient (0.3%), deep infection in two patients (0.6%), and stem subsidence in one patient (0.3%). Postoperative deaths occurred in 23 patients (7.2%). One patient (0.3%) had a severe non-hip adverse event unrelated to surgery that prevented independent living, while five patients (1.6%) had a moderate non-hip adverse event that required treatment. The CPP approach prevented postoperative dislocation following femoral hemiarthroplasty in elderly patients, with no CPP-associated specific adverse events.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Con Side of the Argument.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Con Side of the Argument.

Evolving Factors in Hospital Safety: A Systematic Review and Meta-Analysis of Hospital Adverse Events.

This study aimed to estimate the frequency of hospital adverse events (AEs) and explore the rate of AEs over time, and across and within hospital populations. Validated search terms were run in MEDLINE and EMBASE; gray literature and references of included studies were also searched. Studies of any design or language providing an estimate of AEs within the hospital were eligible. Studies were excluded if they only provided an estimate for a specific AE, a subgroup of hospital patients or children. Data were abstracted in duplicate using a standardized data abstraction form. Study quality was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis estimated the occurrence of hospital AEs, and meta-regression explored the association between hospital AEs, and patient and hospital characteristics. A total of 45,426 unique references were identified; 1,265 full-texts were reviewed and 94 studies representing 590 million admissions from 25 countries from 1961 to 2014 were included. The incidence of hospital AEs was 8.6 per 100 patient admissions (95% confidence interval [CI], 8.3 to 8.9; I2 = 100%, P < 0.001). Half of the AEs were preventable (52.6%), and a third resulted in moderate/significant harm (39.7%). The most evaluated AEs were surgical AEs, drug-related AEs, and nosocomial infections. The occurrence of AEs increased by year (95% CI, -0.05 to -0.04; P < 0.001) and patient age (95% CI = -0.15 to -0.14; P < 0.001), and varied by country income level and study characteristics. Patient sex, hospital type, hospital service, and geographical location were not associated with AEs. Hospital AEs are common, and reported rates are increasing in the literature. Given the increase in AEs over time, hospitals should reinvest in improving hospital safety with a focus on interventions targeted toward the more than half of AEs that are preventable.