Non-severe Adverse Events Research Articles

Adverse event signal mining and severe adverse event influencing factor analysis of Lumateperone based on FAERS database.

Lumateperone has been approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia in adults since 2019, however, there is still a lack of data report on adverse reactions in real-world settings. Conducting data mining on adverse events (AEs) associated with Lumateperone and investigating the risk factors for serious AEs can provide valuable insights for its clinical practice. AE reports in the FDA Adverse Event Reporting System (FAERS) from 2019 Q4 (FDA approval of Lumateperone) to 2024 Q1 were collected and analyzed. Disproportionality in Lumateperone-associated AEs was evaluated using the following parameters: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Univariate and multivariate logistic regression analyses were conducted to identify the risk factors for Lumateperone-induced severe AEs. A total of 2,644 reports defined Lumateperone as the primary suspected drug was collected, including 739 reports classified as severe AEs and 1905 reports as non-severe AEs. The analysis revealed that 130 preferred terms (PTs) with significant disproportionality were based on the four algorithms, 67 (51.53%) of which were not included in the product labeling, affecting 6 systems and organs. In addition, dizziness (81 cases) was the most reported Lumateperone-associated severe AEs, and tardive dyskinesia showed the strongest signal (ROR = 186.24). Logistic regression analysis indicated that gender, bipolar II disorder, and concomitant drug use are independent risk factors for Lumateperone-associated severe AEs. Specifically, female patients had a 1.811-fold increased risk compared with male patients (OR = 1.811 [1.302, 2.519], p = 0.000), while patients with bipolar II disorder had a 1.695-fold increased risk compared with patients diagnosed with bipolar disorder (OR = 1.695 [1.320, 2.178], p = 0.000). Conversely, concomitant use of CYP3A4 inhibitors or drugs metabolized by CYP3A4 was associated with a decreased risk of severe AEs (OR = 0.524 [0.434, 0.633], P = 0.000). Collectively, this study provides critical insights into the safety profile of Lumateperone. It highlights the need for cautious use in high-risk populations, such as females and individuals with bipolar II disorder, and emphasizes the importance of monitoring for AEs, including dizziness and tardive dyskinesia. Healthcare also should remain alert to potential AEs not listed in the prescribing information to ensure medical safety.

Monoclonal Antibody Infusions for Outpatient Management of Mild-Moderate COVID-19.

The COVID-19 pandemic has led to a rapid, exponential increase in hospitalizations and morbidity/mortality. In November 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) permitting administration of the first monoclonal antibodies (mAb) for outpatient treatment of COVID-19. Early data showed a reduction in COVID-19-related hospitalizations with few adverse events. However, since these treatments are only authorized under an EUA, real-world data are minimal. To assess efficacy and safety of mAbs in a veteran population. This retrospective study analyzed veterans at the Ralph H. Johnson Veterans Affairs Health Care System with mild-moderate COVID-19 and screened for mAb eligibility between December 1, 2020, and October 31, 2021. The primary outcome was hospitalizations and/or emergency department (ED) visits within 30 days. Secondary outcomes included 30-day mortality and post-COVID-19 conditions. Adverse events were also evaluated. Outcomes were compared between mAb-treated patients and eligible veterans who were not treated. There were 296 and 275 veterans in the mAb and control groups, respectively. No statistically significant difference was found for the primary outcome overall (25.7% vs 25.1%; P = 0.87), nor for COVID-19-related return visits or hospitalizations (13.9% v. 16%; P = 0.4). However, the mAb group had more return ED visits (P = 0.35), and the control group had significantly more hospitalizations (P = 0.02). Vaccinated veterans who received an mAb had fewer return visits and hospitalizations (P = 0.01). More mAb-treated veterans experienced post-COVID-19 conditions. No difference in mortality was found. Four nonsevere adverse events occurred after the mAb therapy. Overall, the mAbs appeared safe and effective. Sicker, higher-risk mAb-treated veterans faired similarly to less-sick, high-risk veterans not treated. Those who were vaccinated seemed to benefit the most from mAb therapy. Future prospective studies with more matched groups are needed to assess full benefits and risks of mAbs shown to neutralize the predominant variants.

A Feasibility Study Investigating an Exercise Program in Metastatic Cancer Based on the Patient-Preferred Delivery Mode.

Feasibility of exercise in patients with metastatic cancer is still a challenge. This study aimed to determine the feasibility and preliminary efficacy of an exercise intervention based on a patient-preferred delivery mode in patients affected by metastatic cancer. Forty-four patients with a confirmed diagnosis of metastatic cancer were recruited in a 3-month exercise program. Whereas the exercise program consisted of aerobic and resistance activities performed twice a week, the participants may choose the mode of delivery: home based, personal training, or group based. The primary endpoint was the feasibility, defined by recruitment rate, attendance, adherence, dropout rate, tolerability (comparing the session RPE with the target RPE), and safety (using the Common Terminology Criteria for Adverse Events, version 5.0). Secondary endpoints included cardiorespiratory fitness (six minutes walking test), muscle strength (handgrip strength test and isometric leg press test), flexibility (the back scratch and chair sit and reach tests), anthropometric parameters (body mass index and waist-hip ratio), quality of life (EORTC QLQ C-30 questionnaire), and amount of physical exercise (Godin's Shepard Leisure Time Exercise Questionnaire). Descriptive statistics, Student t test, and Wilcoxon signed rank test were used to analyze data. The study recruitment rate was 81%. Out of 44 recruited patients, 28 chose the personal training program, 16 chose the home-based program, and none chose the group-based program. Nine dropouts occurred (20%), 6 in the personal training program, and 3 in the home-based intervention. The median attendance rate was 92%, adherence was 88%, tolerability was 100%, and 9 nonsevere adverse events were registered during the exercise sessions. An increase in cardiorespiratory fitness (P < .001) and flexibility (P = .011 for chair sit and reach; P = .040 for back scratch) was observed at the end of the intervention, while no changes in anthropometric values and muscle strength were detected. Different quality-of-life domains were improved following the intervention, including physical (P = .002), emotional (P < .001), and role functioning (P = .018), fatigue (P = .030), and appetite loss (P = .005). A 3-month exercise program based on a patient-preferred delivery mode is feasible in patients with metastatic cancer and may improve physical function and quality of life. NCT04226508.

Efficacy and Security of Tetrodotoxin in the Treatment of Cancer-Related Pain: Systematic Review and Meta-Analysis.

The pharmacological treatment of cancer-related pain is unsatisfactory. Tetrodotoxin (TTX) has shown analgesia in preclinical models and clinical trials, but its clinical efficacy and safety have not been quantified. For this reason, our aim was to perform a systematic review and meta-analysis of the clinical evidence that was available. A systematic literature search was conducted in four electronic databases (Medline, Web of Science, Scopus, and ClinicalTrials.gov) up to 1 March 2023 in order to identify published clinical studies evaluating the efficacy and security of TTX in patients with cancer-related pain, including chemotherapy-induced neuropathic pain. Five articles were selected, three of which were randomized controlled trials (RCTs). The number of responders to the primary outcome (≥30% improvement in the mean pain intensity) and those suffering adverse events in the intervention and placebo groups were used to calculate effect sizes using the log odds ratio. The meta-analysis showed that TTX significantly increased the number of responders (mean = 0.68; 95% CI: 0.19-1.16, p = 0.0065) and the number of patients suffering non-severe adverse events (mean = 1.13; 95% CI: 0.31-1.95, p = 0.0068). However, TTX did not increase the risk of suffering serious adverse events (mean = 0.75; 95% CI: -0.43-1.93, p = 0.2154). In conclusion, TTX showed robust analgesic efficacy but also increased the risk of suffering non-severe adverse events. These results should be confirmed in further clinical trials with higher numbers of patients.

Implementation of a Standardized Premedication Bundle to Improve Procedure Success for Nonemergent Neonatal Intubations.

The study workgroup developed educational material and protocol content. Process measures included premedication use, education, and audit form completion. Primary (success on first intubation attempt and adverse event rates) and secondary (trainee success) study outcomes are displayed using statistical process control charts and pre-post cohort comparisons. Forty-seven percent (97/206) of nurses completed educational intervention before protocol release, with an additional 20% (42/206) following a staff reminder. Two hundred sixteen (216) patients were intubated per protocol with 81% (174/216) audit completion. Compared with baseline (n = 158), intubation attempts decreased from 2 (IQR, 1-2) to 1 (IQR, 1-2) (P = 0.03), and success on the first attempt increased from 40% (63/158) to 57% (124/216) (P < 0.01), with a notable improvement in trainee success from less than 1% (1/40) to 43% (31/72) (P < 0.01). The rate of severe and rare adverse events remained stable; however, there was a rise in nonsevere events from 30% (48/158) to 45% (98/216). The tachycardia rate increased with atropine use. There was no change in chest wall rigidity, number of infants unable to extubate following surfactant, or decompensation awaiting medications. Standardizing procedural care delivery reduced intubation attempts and increased the attempt success rate. However, this was accompanied by an increase in the rate of nonsevere adverse events.

Leaky Gut and Severe Adverse Events in Advanced Hepatocellular Carcinoma Treated With Lenvatinib.

To identify predictors of severe adverse events (≥grade 3) in patients with advanced hepatocellular carcinoma treated with lenvatinib. Of 41 patients, 25 and 16 were stratified into the severe and non-severe adverse events groups, respectively. Of these, 19 formed a lactulose-mannitol test subgroup, which was divided into severe adverse events (n=11) and non-severe adverse events (n=8) groups. Severe adverse events were assessed by liver disease etiology and modified albumin-bilirubin grade. Intestinal permeability by lactulose-mannitol test and serum soluble CD163, soluble mannose receptor, and zonulin levels. Severe adverse event incidence rates were higher in patients with advanced hepatocellular carcinoma related to alcoholic liver disease and nonalcoholic fatty-liver disease than in those with advanced hepatocellular carcinoma of other etiologies (p=0.014). The rates were higher for modified albumin-bilirubin grades 2a and 2b compared to modified albumin-bilirubin grade 1 (p=0.0104). Zonulin levels were higher in the severe adverse event group (p=0.0331) and were independently associated with severe adverse events (odds ratio=140, 95% confidence interval=1.66-11800; p=0.029). Patients with high zonulin levels (≥0.518 ng/ml) experienced more severe adverse events than those with low levels (<0.518 ng/ml) (p=0.0137). In the lactulose-mannitol test subgroup, the urine lactulose:mannitol ratio was higher in the severe vs. non-severe adverse event group (p=0.0164). Moreover, it was higher in patients with alcoholic liver disease and nonalcoholic fatty-liver disease-related advanced hepatocellular carcinoma compared to those with other advanced hepatocellular carcinoma etiologies (p=0.0108). Serum zonulin levels predict severe adverse events in patients with advanced hepatocellular carcinoma treated with lenvatinib.

High-intensity Interval Training In Patients With Coronary Artery Disease: A Randomized Controlled Trial

PURPOSE: Coronary artery disease (CAD) is the leading cause of mortality worldwide, and the prevalence is increasing. Cardiac rehabilitation is essential after a cardiac event with exercise training having a central role. Exercise training improves quality of life and reduces cardiovascular mortality and hospital admissions in CAD patients. We aimed to investigate the feasibility and efficiency of high-intensity interval training (HIIT) in patients with stable CAD. METHODS: In this randomized controlled trial, 142 patients with stable CAD and a mean age of 66.7 years completed the study, 64 in the HIIT group and 78 in the control group (CON). Patients were randomized 1:1 to supervised HIIT or standard care. HIIT was performed by training on a rowing ergometer 3 x week for 12 weeks. Patients in CON did not change their usual behavior, and all patients continued medications as prescribed before inclusion. Prior to randomization (baseline) and after 12 weeks (post-intervention), maximal oxygen consumption (VO2max), maximal pulmonary ventilation (VEmax) and maximal power output (Wmax) were determined in all patients. During the intervention period, the training load was defined as power output during training in week 3, 6 and 9. The average intensity was quantified and normalized to the average power that patients could sustain during a 5-min-all-out rowing performance test completed at week 5. RESULTS: Adherence to training was 97% (range 86-100%). Three patients dropped out because of non-fatal adverse events, and three patients reported non-severe self-limiting adverse events. The average relative power output was 72 ± 19% during warm-up and 117 ± 11 % during the interval bouts. Weekly training duration was on average 54 min. Compared to standard care, HIIT resulted in a significant (p < 0.001) greater increase in VO2max, VEmax, and Wmax (197 mL/min [160;233], 13 L/min [11;16], and 23 W [19;27]). CONCLUSIONS: Low volume HIIT performed as rowing significantly upregulated cardiorespiratory fitness (VO2max, VEmax, and Wmax) in patients with stable CAD compared to standard care. The exercise training on rowing ergometers was convenient and feasible for this frail patient group.

Severe cutaneous adverse reactions associated with systemic ivermectin: A pharmacovigilance analysis.

Despite poor evidence, the antiparasitic ivermectin has been advocated as a potential COVID‐19 therapy. This has led to a rise in calls to poison‐control centers by people self‐medicating with ivermectin, which is sold over the counter for veterinary uses. We aimed to investigate the association between severe cutaneous adverse reactions (SCARs) and ivermectin. Postmarketing data from the FDA Adverse Event Reporting System (FAERS), gathered between 2014 and 2021, was employed to detect disproportional signals of SCARs following systemic ivermectin therapy. The reporting odds ratio (ROR) was used to quantify the strength of association, while adjusting for age, sex, and region. The search yielded 517 reports of systemic ivermectin (median age 54 years, 46.8% female), of which 25 (4.8%), 81 (15.7%), and 411 (79.5%) were classified as SCARs, nonsevere cutaneous adverse events (AEs), or noncutaneous AEs, respectively. The regional distribution differed between SCAR reports (32.0% from Africa and 12.0% from North America) compared with other AEs, which originated from North America in over half of cases. The most common SCARs were toxic epidermal necrolysis (seven cases), Stevens–Johnson syndrome (seven cases), and drug reaction with eosinophilia and systemic symptoms (four cases). Five SCAR cases (20.0%) resulted in death and 12 (48.0%) lead to hospitalization. There was a strong safety signal for any SCAR (adjusted ROR 3.34, 95% confidence interval [CI] 2.17–5.12) and toxidermias (adjusted ROR 7.08, 95% CI 4.23–11.84). This study suggests that ivermectin is associated with SCARs on rare occasions. Dermatologists should be aware of this given the increase in ivermectin misuse.

P-149: Immunogenicity of SARS-CoV-2 vaccine in patients with multiple myeloma

We evaluated the safety and immunogenicity of the BNT162b2 vaccine in 52 patients with multiple myeloma (MM). Median age was 71.3 (range, 39.6-90.8) years. 26 (50%) patients had received active treatment including an immunomodulatory drug (IMiD) (n=21), an anti-CD38 monoclonal antibody (n=11) and/or a proteasome inhibitor (n=4). 21 had received previous treatment interrupted at a median of 27.5 (range, 3.5-169.3) months before first vaccine inoculum. 5 patients had indolent untreated MM. 35 patients had a history of autologous hematopoietic cell transplantation (HSCT) performed at a median of 44.4 (range, 3.5-169.3) months before first vaccine inoculum. The vaccination was well tolerated with few non-severe adverse events. Immune efficacy evaluated by antibody seroconversion showed a significant increase of anti-Spike (S) IgG antibodies between day (d)28 and d42 (p<0.0001). However, anti-S IgG at d42 was significantly lower in patients compared to healthy controls (p=0.0035). Neutralizing antibodies (NAb) correlated with anti-S IgG d42 titers (Spearman r=0.832, p<0.0001). An anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥30%, the positivity cut-off for NAb (p<0.0001). Only 44% (n=23) of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. We then performed a multivariable logistic regression to identify parameters parameters associated with achievement of protective anti-S IgG d42 level (>= 3100 UA/mL). We found that patients’ age (>=71 years versus 25 versus = 120/L) had no impact on achievement of a protective anti-S IgG level after two BNT162b2 inocula. In contrast, male gender, and ongoing chemotherapy were associated with a significantly decreased probability of achieving the defined protective anti-S IgG level after two BNT162b2 inocula [odds ratio (OR) 0.126, 95% confidence interval (95% CI) 0.022-0.709, p=0.02; OR 0.146, 95%CI 0.025-0.866, p=0.03, respectively]. Finally, using the IFN-g ELISPOT assay in 12 patients, we found a significant increase in T cell response in 12 MM patients against the S protein, with 7 patients (58%) having an anti-S IgG positive ELISPOT after the second BNT162b2 inoculum.ConclusionThese findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with MM, but only around half of the patients are likely to achieve effective immune protection against COVID-19.

A Prospective Phase II of Daratumumab in Previously-Treated Systemic Light-Chain (AL) Amyloidosis

Background: Daratumumab (DARA) is a novel, high-affinity, therapeutic, IgG1ĸ human mAb that specifically recognizes CD38. It has emerged as a breakthrough targeted therapy for patients with multiple myeloma. Plasma cells in AL amyloidosis are similar to plasma cells in myeloma and always express CD38 (Matsuda, M. et al., Amyloid, 2003. 10(2): p. 110-6.). We report here the preliminary results of a prospective multi-center, phase II study of DARA in AL amyloidosis (NCT02816476).Methods:Forty patients will be recruited in this trial. Patients aged ≥18 years with evaluable AL amyloidosis, who have received ≥1 prior therapy and are not in very good partial response (VGPR) or better with a measurable plasma cell dyscrasia with dFLC > 50 mg/L (difference between involved and uninvolved free light chain levels), with at least one major vital organ involvement, with ECOG performance status 0,1 or 2, no chronic atrial fibrillation, a supine blood pressure > 100 mmHg and NT-proBNP < 8500 ng/L are eligible. They receive DARA intravenously in a standard schedule and dose: 16 mg/kg weekly during the first two 28-day cycles and every other week during cycles 3 through 6 for a total of six 28-day cycles. Hematologic responses are measured after 1 injection of DARA and at each cycle. The objectives are to assess hematologic responses, organ responses and safety.Results:At data cut-off (July 31, 2017), 30 of the 40 planned patients have been enrolled in 9 French centers. The median age is 69 years (range, 45-81), and median number of prior therapies is 2.5 (range, 1-5): 13 patients (43%) have received Melphalan and Dexamethasone, 28 patients (93%) bortezomib, and 14 patients (46%) lenalidomide. The median time from diagnosis to enrollment is 23 months (range, 3.5-116). The median number of organ system involvement is 2 (range, 1-5), 8 patients (27%) have >2 organ system involvement, 18 patients (60%) have cardiac and 16 patients (53%) renal involvement, 14 patients (47%) have cardiac biomarker stage II and 4 patients (13%) stage III disease. There was one on-study death due to cardiac progression. Four patients have discontinued study treatment before 6 cycles due to disease progression (n=2), death (n=1) or lung cancer (n=1). Nine patients have received 6 cycles and 17 patients are on therapy. Six patients (20 %) experienced at least one grade ≥3 AE (any cause) and only one was considered as drug related (lymphopenia). The most common drug-related AEs were infusion reaction in 10 patients (33%), all grade I or II. Hematologic complete response (CR) was observed in 4 of 24 evaluable (completing at least 1 cycle) patients (17%), VGPR in 7 patients (29%) and partial response in 4 patients (17%). The overall response rate is 63%. The responses were usually very rapid (Figure 1). After a single DARA injection all 15 responding patients had a decrease in dFLC of more than 30 % with a median dFLC decrease after 1 injection in these 15 responding patients of 57% (range 31-96).Conclusion: Daratumumab demonstrates encouraging efficacy in previously-treated patients with AL amyloidosis with deep and rapid responses. The administration of DARA in these patients is associated with a good safety profile and non-severe adverse events mostly after the first infusion. Further studies on DARA-based associations in AL amyloidosis patients are warranted. The data will be updated at the meeting. [Display omitted] DisclosuresRoussel:JANSSEN: Honoraria, Research Funding. Perrot:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Sanofi: Honoraria; Amgen: Honoraria. Karlin:Janssen: Honoraria, Other: Travel expenses. Macro:JANSSEN: Honoraria. Frenzel:Shire: Research Funding. Palladini:Jannsen-Cilag: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Travel grants; Prothena: Honoraria, Other: Travel grant. Jaccard:Celgene: Honoraria, Other: Travel expenses, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Amgen: Honoraria.

Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis

Numerous iron preparations are available for the treatment of iron deficiency anaemia in pregnancy. We aimed to provide a summary of the effectiveness and safety of iron preparations used in this setting. We did a systematic review and network meta-analysis of randomised trials. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature for trials published in any language from Jan 1, 2011, to Feb 28, 2021. We included trials including pregnant women with iron deficiency anaemia and evaluating iron preparations, irrespective of administration route, with at least 60 mg of elemental iron, in comparison with another iron or non-iron preparation. Three authors independently selected studies, extracted data, and did a risk of bias assessment using the Cochrane tool (version 1.0). The primary outcome was the effectiveness of iron preparations, evaluated by changes in haemoglobin concentration at 4 weeks from baseline. The secondary outcomes were change in serum ferritin concentration at 4 weeks from baseline and treatment-related severe and non-severe adverse events. We did random-effects pairwise and network meta-analyses. Side-effects were reported descriptively for each trial. This study is registered with PROSPERO, CRD42018100822. Among 3037 records screened, 128 full-text articles were further assessed for eligibility. Of the 53 eligible trials (reporting on 9145 women), 30 (15 interventions; 3243 women) contributed data to the network meta-analysis for haemoglobin and 15 (nine interventions; 1396 women) for serum ferritin. The risk of bias varied across the trials contributing to network meta-analysis, with 22 of 30 trials in the network meta-analysis for haemoglobin judged to have a high or medium global risk of bias. Compared with oral ferrous sulfate, intravenous iron sucrose improved both haemoglobin (mean difference 7·17 g/L, 95% CI 2·62-11·73; seven trials) and serum ferritin (mean difference 49·66 μg/L, 13·63-85·69; four trials), and intravenous ferric carboxymaltose improved haemoglobin (mean difference 8·52 g/L, 0·51-16·53; one trial). The evidence for other interventions compared with ferrous sulfate was insufficient. The most common side-effects with oral iron preparations were gastrointestinal effects (nausea, vomiting, and altered bowel movements). Side-effects were less common with parenteral iron preparations, although these included local pain, skin irratation, and, on rare occasions, allergic reactions. Iron preparations for treatment of iron deficiency anaemia in pregnancy vary in effectiveness, with good evidence of benefit for intravenous iron sucrose and some evidence for intravenous ferric carboxymaltose. Clinicians and policy makers should consider the effectiveness of individual preparations before administration, to ensure effective treatment. None.

Palliation of malignant esophageal obstruction using an anti-migration self-expandable metal stent: Results of a prospective multicenter study

BackgroundSelf-expanding metal stents (SEMS) placement is primarily indicated to palliate dysphagia for patients with expected short-term survival. We aimed to assess the migration rate and other stent-related adverse events (AEs) of a fully covered SEMS with an anti-migration system (FCSEMS-AMS) for palliation of malignant dysphagia. MethodsThis is a prospective study including patients with inoperable esophageal cancer that received a FCSEMS-AMS (Taewoong, Niti-S Beta™), in five tertiary-care endoscopic centers from January 2014 to February 2016. ResultsFifty-three consecutive patients were enrolled. Tumor location was proximal, mid and distal esophagus±esophago-gastric junction (EGJ) in 6, 14, and 33 cases, respectively. Overall, non-severe AEs were reported in 18 patients (34.0%), 13 of them required an additional endoscopic procedure. Migration occurred in 7 patients (13.2%): 3 from the upper and 4 from the lower esophagus and EGJ. Stent retrieval was necessary in one patient due to intolerable pain. Food bolus impaction and tumor overgrowth occurred in 2 patients (3.8%) and 4 (7.5%) patients respectively. Four patients complained of gastroesophageal reflux as late AEs. Median follow-up was 19.3 months. Dysphagia significantly improved until 3 and 6 months from stent insertion (median score before FCSEMS-AMS: 3, vs median score: 1). Median dysphagia-free time was 10 months. ConclusionsPlacement of the Taewoong, Niti-S Beta™ stent appeared to be a safe and effective treatment of malignant dysphagia. The anti-migration system reduced the overall migration rate, although it remained high in strictures located in the upper esophagus and when the stent was placed across the EGJ.

Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19

ObjectivesTo assess the efficacy of hydroxychloroquine in combination with azithromycin in terms of clinical and biochemical outcomes in adult patients with COVID-19 hospitalized for acute respiratory distress syndrome (ARDS), and to describe the occurrence of adverse events. MethodRetrospective comparative study, based in a quaternary private hospital in Rio de Janeiro, Brazil, involving 193 adult patients hospitalized for mild and moderate COVID-19 related ARSD, analyzing treatment efficacy based on clinical and biochemical outcomes. ResultsThe active group comprised 101 (52.3%) patients using hydroxychloroquine associated with azithromycin and the control group 92 (47.7%) patients who did not take these medications. Median age was 59 (47–70) in the active group and 65 (47−77) in the control group (p < 0.05). Patients in the control group had greater extent of pulmonary involvement on baseline chest CT scans (p < 0.05). All other baseline variables (BMI, comorbidities, previous use of medications and biochemical assessments) were similar between groups. In the medication group, 25% (25 out of 101) were admitted to the ICU, compared to 21% (19 out of 92) in the control group (p > 0.05). No difference in mortality, duration of non-invasive oxygen use or duration of hospitalization was seen between groups. The therapeutic regimen was well tolerated, with only eight (7.9%) patients presenting gastrointestinal symptoms and eight (7.9%) patients withdrawn treatment due to QTc prolongation. ConclusionsPatients treated with hydroxychloroquine combined with azithromycin and the control group had similar clinical outcomes. This therapeutic regimen was considered ineffective in hospitalized patients with mild to moderate COVID-19 related ARDS and was associated with few non-severe adverse events.

Impact of SAfinamide on Depressive Symptoms in Parkinson's Disease Patients (SADness-PD Study): A Multicenter Retrospective Study.

Background: We aimed to assess the effects of safinamide on depression, motor symptoms, and the serotonin syndrome related to its co-administration with antidepressants in patients with Parkinson’s disease (PD). Methods: We retrospectively analyzed the data of patients at 1 and 3 months of follow-up compared to baseline. Results: n = 82 (safinamide 50 mg = 22, 100 mg = 60, with antidepressants = 44). First, we found improvement in depression (Hamilton Depression Rating Scale: −6 ± 5.10 at 1 month and −7.27 ± 5.10 at 3 months, p < 0.0001; Patient Global Impression of Improvement Scale: 60.3% and 69.5% of patients at 1 and 3 months reported some improvement). Second, safinamide improved the daily life activities and motor symptoms/motor complications (Unified Parkinson’s Disease Rating Scale (UPDRS-II): −2.51 ± 6.30 and −2.47 ± 6.11 at 1 and 3 months, p < 0.0001; III: −3.58 ± 8.68 and −4.03 ± 8.95 at 1 and 3 months, p < 0.0001; IV: −0.61 ± 2.61 and −0.8 ± 2.53 at 1 and 3 months, p < 0.0001). Third, 7.31% and 8.53% of patients developed non-severe adverse events related to safinamide at 1 and 3 months. Serotonin syndrome was not observed in the patients treated with antidepressants; some isolated serotonin syndrome symptoms were reported. Conclusions: Safinamide could be useful for treating depression in PD; it was effective for motor symptoms and motor complications and safe even when co-administered with antidepressants.

Effects of Muscle Strength Training on Muscle Mass Gain and Hypertrophy in Older Adults With Osteoarthritis: A Systematic Review and Meta-Analysis.

To investigate the effect of muscle strength exercise training (MSET) on lean mass (LM) gain and muscle hypertrophy in older patients with lower extremity osteoarthritis (OA). A comprehensive search of online databases was performed on April 20, 2019. Randomized controlled trials (RCTs) that reported the effects of MSET on LM, muscle thickness, and cross-sectional area (CSA) in older patients with OA were identified. A risk of bias assessment and meta-analysis were performed for the included RCTs. We included 19 RCTs with a median Physiotherapy Evidence Database score of 6 of 10 (range 3-7). In total, data from 1,195 patients (65% women, 85% with knee OA) with a mean age of 62.1 years (range 40-86 years) were analyzed. MSET resulted in significantly higher LM gain (standardized mean difference [SMD] 0.49 [95% confidence interval (95% CI) 0.28, 0.71], P < 0.00001) than did the nonexercise controls. Meta-analysis results revealed significantly positive effects of MSET on muscle thickness (SMD 0.82 [95% CI 0.20, 1.43], P = 0.009) and CSA (SMD 0.80 [95% CI 0.25, 1.35], P = 0.004) compared with nonexercise controls. No significant effects in favor of MSET were observed for any muscle outcome compared with exercise controls. Five RCTs reported nonsevere adverse events in response to MSET, whereas no RCTs reported severe events. MSET is effective in increasing LM and muscle size in older adults with OA. Clinicians should incorporate MSET into their management of patients at risk of low muscle mass to maximize health status, particularly for older individuals with OA.

Oral Treatment With Bisphosphonates of Osteoporosis Does Not Increase the Risk of Severe Gastrointestinal Side Effects: A Meta-Analysis of Randomized Controlled Trials.

IntroductionBisphosphonates (BPs) are first-line therapy for osteoporosis. Adherence is usually low in chronic, asymptomatic diseases, but gastrointestinal (GI) side-effects can also contribute to low adherence in BP therapy and may necessitate a review by a gastroenterologist with or without gastroscopy.AimsOur meta-analysis aims to determine the risk of severe GI adverse events due to oral BP therapy in osteoporotic patients.MethodsA systematic search was conducted in three databases up to September 2020 for randomized controlled trials (RCTs) detailing GI adverse events in adults with osteoporosis on BP compared to placebo. Risk ratios (RRs) with 95% confidence intervals (CI) were calculated for non-severe and severe adverse events indicating endoscopic procedure with the random-effects model. Statistical heterogeneity was assessed using chi2 and I2 statistics.ResultsForty-two RCTs with 39,047 patients with 9,999 non-severe and 1,503 severe GI adverse events were included. The incidence of non-severe and severe adverse events ranged between 0.3–54.9 and 0–10.3%, respectively. There was no difference between BP and control groups in terms of the risk of non-severe or severe side effects: RR=1.05 (CI: 0.98–1.12), I2 = 48.1%, and RR=1.01 (CI: 0.92–1.12), I2 = 0.0%, respectively. Subgroup analysis of the most commonly used BP, once-weekly alendronate 70 mg, revealed an association between bisphosphonates and the risk of non-severe GI adverse events, RR=1.16 (CI: 1.00–1.36), I2 = 40.7%, while the risk of severe GI side effects was not increased in this subgroup, RR=1.20 (CI: 0.83–1.74), I2 = 0.0%.ConclusionOur results show that bisphosphonates do not increase the risk of severe GI adverse events. However, the marked variability of the screening for side effects in the included studies, and the fact that in most of the studies GI diseases were exclusion criteria limits the strenght of evidence of our results. The conclusions drawn from the meta-analysis are therefore restricted to selected populations, and the results must be interpreted with caution.

One-year effectiveness, retention rate, and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a real-life multicenter study

ABSTRACT Background Secukinumab (SEC) is effective for ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in randomized trials, but real-life data are lacking. Research design and methods Real-life, prospective observational study on 169 consecutive outpatients at baseline (T0) and at 6 (T6) and 12 months (T12) after starting SEC (39 AS, 23%; 130 PsA, 77%). Results Significant improvement was seen at T6 and T12 for all clinical variables, including TJC, SJC, ESR, CRP, DAPSA, ASDAS-CRP, and BASDAI, as well as in patient-reported outcomes like VAS-pain. By multivariable regression analysis, in AS patients high BASDAI at T0 correlated with diagnostic delay (R2 = 0.4; p = 0.009) and peripheral joint involvement (R2 = 0.4; p = 0.04). During follow-up, reduction of BASDAI positively correlated with high ESR (R2 = 0.65; p = 0.04). ASDAS-CRP at T0 positively correlated with high ESR (R2 = 0.34; p = 0.004). Reduction of ASDAS-CRP from T0 to T6 correlated with current smoking status (R2 = 0.42; p = 0.003). In PsA patients, reduction of DAPSA score from T0 to T12 is negatively correlated with the presence of metabolic syndrome (R2 = 0.41; p = 0.0025). SEC was well tolerated; 10 patients discontinued treatment for non-severe adverse events. Conclusions Secukinumab is effective and safe in patients with AS and PsA in a real-life setting.

Long-term real world clinical outcomes of macitentan therapy in chronic thromboembolic pulmonary hypertension.

Macitentan treatment for chronic thromboembolic pulmonary hypertension (CTEPH) in the routine clinical setting is increasing. However, 'real world' macitentan experience is scarce and is needed to differentiate from controlled clinical trial settings. We describe our outcomes and clinical 'real world' experience of macitentan mono- and combination therapy with riociguat or sildenafil in CTEPH. We included all consecutive CTEPH patients, either non-operated or with residual PH after pulmonary endarterectomy (PEA), treated with macitentan in the St. Antonius hospital in Nieuwegein, the Netherlands, between 01-2014 and 11-2019. We describe clinical outcomes and adverse events (AEs) until 2 years after macitentan initiation. In total 73 CTEPH patients on macitentan were included, of which 18 patients were clinically inoperable (n=7 declined PEA, n=11 nonacceptable risk-benefit) and 55 had technically inoperable CTEPH (n=48)/residual PH (n=7). Clinically inoperable patients (mean age 72.4±10.2 years, 61% female, 28% macitentan monotherapy, observation period 2.0 (1.9-2.0) years) had a survival of 100% and clinical worsening (CW)-free survival of 88% at 2-year follow-up respectively, with a significant increased 6-min walking distance (6MWD). Technically inoperable/residual PH patients (mean age 62.1±14.1 years, 60% female, 27% macitentan monotherapy, observation period 2.0 (1.0-2.0) years) had a 2-year survival and CW-free survival of 86% and 68% respectively, with significant improved 6MWD and NT-proBNP. Nonsevere AEs were reported in 30% of all patients. Macitentan mono- and combination therapy in non-operated CTEPH and residual PH is safe and improves clinical outcomes till 2-year follow-up.

Risks and contraindications of medical compression treatment - A critical reappraisal. An international consensus statement.

ObjectivesMedical compression therapy is used for non-invasive treatment of venous and lymphatic diseases. Medical compression therapy-associated adverse events and contraindications have been reported, although some contraindications are theoretically based. This consensus statement provides recommendations on medical compression therapy risks and contraindications.MethodsA systematic literature search of medical compression therapy publications reporting adverse events up until November 2017 was performed. A consensus panel comprising 15 international experts critically reviewed the publications and formulated the recommendations.ResultsSixty-two publications reporting medical compression therapy adverse events were identified. The consensus panel issued 21 recommendations on medical compression therapy contraindications and adverse event risk mitigation, in addition to reviewing medical compression therapy use in borderline indications. The most frequently reported non-severe medical compression therapy-associated adverse events included skin irritation, discomfort and pain. Very rare but severe adverse events, including soft tissue and nerve injury, were also identified.ConclusionThis consensus statement summarises published medical compression therapy-associated adverse events and contraindications, and provides guidance on medical compression therapy. Severe medical compression therapy-associated adverse events are very rarely encountered if compression is used correctly and contraindications are considered.

Homeopathic medicinal products for preventing and treating acute respiratory tract infections in children.

Acute respiratory tract infections (ARTIs) are common and may lead to complications. Most children experience between three and six ARTIs annually. Although these infections are self-limiting, symptoms can be distressing. Many treatments are used to control symptoms and shorten illness duration. Most have minimal benefit and may lead to adverse effects. Oral homeopathic medicinal products could play a role in childhood ARTI management if evidence for effectiveness is established. To assess the effectiveness and safety of oral homeopathic medicinal products compared with placebo or conventional therapy to prevent and treat acute respiratory tract infections in children. We searched CENTRAL (2017, Issue 11) including the Cochrane Acute Respiratory Infections Specialised Register, MEDLINE (1946 to 27 November 2017), Embase (2010 to 27 November 2017), CINAHL (1981 to 27 November 2017), AMED (1985 to December 2014), CAMbase (searched 29 March 2018), British Homeopathic Library (searched 26 June 2013 - no longer operating). We also searched the WHO ICTRP and ClinicalTrials.gov trials registers (29 March 2018), checked references, and contacted study authors to identify additional studies. Double-blind, randomised controlled trials (RCTs) or double-blind cluster-RCTs comparing oral homeopathy medicinal products with identical placebo or self-selected conventional treatments to prevent or treat ARTIs in children aged 0 to 16 years. We used standard methodological procedures expected by Cochrane. We included eight RCTs of 1562 children receiving oral homeopathic medicinal products or a control treatment (placebo or conventional treatment) for upper respiratory tract infections (URTIs). Four treatment studies examined the effect on URTI recovery, and four studies investigated the effect on preventing URTIs after one to three months of treatment, followed up for the remainder of the year. Two treatment and two prevention studies involved homeopaths individualising treatment. The other studies used predetermined, non-individualised treatments. All studies involved highly diluted homeopathic medicinal products.We found several limitations to the included studies, in particular methodological inconsistencies and high attrition rates, failure to conduct intention-to-treat analysis, selective reporting, and apparent protocol deviations. We assessed three studies as at high risk of bias in at least one domain, and many had additional domains with unclear risk of bias. Three studies received funding from homeopathy manufacturers; one support from a non-government organisation; two government support; one was cosponsored by a university; and one did not report funding support.Methodological inconsistencies and significant clinical and statistical heterogeneity precluded robust quantitative meta-analysis. Only four outcomes were common to more than one study and could be combined for analysis. Odds ratios (OR) were generally small with wide confidence intervals (CI), and the contributing studies found conflicting effects, so there was little certainty that the efficacy of the intervention could be ascertained. All studies assessed as at low risk of bias showed no benefit from oral homeopathic medicinal products; trials at uncertain and high risk of bias reported beneficial effects.We found low-quality evidence that non-individualised homeopathic medicinal products confer little preventive effect on ARTIs (OR 1.14, 95% CI 0.83 to 1.57). We found low-quality evidence from two individualised prevention studies that homeopathy has little impact on the need for antibiotic usage (N = 369) (OR 0.79, 95% CI 0.35 to 1.76). We also assessed adverse events, hospitalisation rates and length of stay, days off school (or work for parents), and quality of life, but were not able to pool data from any of these secondary outcomes.There is insufficient evidence from two pooled individualised treatment studies (N = 155) to determine the effect of homeopathy on short-term cure (OR 1.31 favouring placebo, 95% CI 0.09 to 19.54; very low-quality evidence) and long-term cure rates (OR 0.99, 95% CI 0.10 to 9.67; very low-quality evidence). Adverse events were reported inconsistently; however, serious events were not reported. One study found an increase in the occurrence of non-severe adverse events in the treatment group. Pooling of two prevention and two treatment studies did not show any benefit of homeopathic medicinal products compared to placebo on ARTI recurrence or cure rates in children. We found no evidence to support the efficacy of homeopathic medicinal products for ARTIs in children. Adverse events were poorly reported, so conclusions about safety could not be drawn.