The Ricochet of Magic Bullets: Summary of the Institute of Medicine Report, Adverse Effects of Pertussis and Rubella Vaccines

PEDIATRICS ◽  
1992 ◽  
Vol 89 (2) ◽  
pp. 318-324
Author(s):  
Christopher P. Howson ◽  
Harvey V. Fineberg
Keyword(s):  
Adverse Effects ◽  
Adverse Events ◽  
Cost Benefit ◽  
Juvenile Diabetes ◽  
Public Law ◽  
Sudden Infant ◽  
Institute Of Medicine ◽  
National Academy Of Sciences ◽  
Reye's Syndrome ◽  
Serious Adverse Events

On July 3, 1991, the National Academy of Sciences' Institute of Medicine (IOM) released a reported entitled, Adverse Effects of Pertussis and Rubella Vaccines,1 in response to a congressional request to review evidence about a set of serious adverse events and immunization with pertussis and rubella vaccines. The request originated in the 1986 National Childhood Vaccine Injury Act (Public Law 99-660), whose primary purpose was to establish a federal compensation scheme for persons potentially injured by a vaccine; Section 312 of Public Law 99-660 called for the IOM review. Over the course of its 20-month study, the 11-member interdisciplinary committee constituted by IOM to conduct the review examined altogether 18 adverse events for pertussis vaccine—infantile spasms; hypsarhythmia; aseptic meningitis; acute encephalopathy; chronic neurologic (permanent brain) damage; deaths classified as sudden infant death syndrome (SIDS); anaphylaxis, autism; erythema multiforme or other rashes; Guillain-Barré syndrome (polyneuropathy); peripheral mononeuropathy; hemolytic anemia; juvenile diabetes; learning disabilities and hyperactivity; protracted inconsolable crying or screaming; Reye's syndrome; shock and "unusual shock-like state" with hypotonicity, hyporesponsiveness, and short-lived convulsions (usually febrile); and thrombocytopenia—and 4 adverse events for rubella vaccine—acute arthritis; chronic arthritis; radiculoneuritis and other neuropathies; and thrombocytopenic purpura. In conducting its review, the committee recognized that its charge was to focus on questions of causation and not broader topics, such as cost-benefit or risk-benefit analyses of vaccination. This summary begins with a brief history of events leading to the IOM study, then reviews the methods used by the committee to evaluate the evidence, summarizes the committee's conclusions for these adverse events, and offers directions for future investigation of adverse events in connection with widely used health interventions, such as vaccination.

Statin-induced adverse effects – facts and genes

2013 ◽  
Vol 154 (3) ◽  
pp. 83-92
Author(s):  
Mariann Harangi ◽  
Noémi Zsíros ◽  
Lilla Juhász ◽  
György Paragh
Keyword(s):  
Risk Factors ◽  
Single Nucleotide Polymorphisms ◽  
Adverse Effects ◽  
Adverse Events ◽  
Statin Therapy ◽  
Significant Proportion ◽  
Gene Mutations ◽  
Nucleotide Polymorphisms ◽  
Serious Adverse Events ◽  
Single Nucleotide

Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients. Orv. Hetil., 2013, 154, 83–92.

scholarly journals Ocular adverse events in PD-1 and PD-L1 inhibitors

2021 ◽  
Vol 9 (7) ◽  
pp. e002119
Author(s):  
LeAnne Young ◽  
Shanda Finnigan ◽  
Howard Streicher ◽  
Helen X Chen ◽  
James Murray ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Effects ◽  
Adverse Events ◽  
Anticancer Agents ◽  
Adverse Event Reporting ◽  
Lower Grade ◽  
Serious Adverse Events ◽  
Serious Adverse Event ◽  
Programmed Death ◽  
Depth Analysis

BackgroundProgrammed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors can cause unique immune-related adverse effects due to non-specific immunological activation. However, less is known about adverse effects of these drugs in the eye.MethodsTwo adverse event databases were retrospectively reviewed. The two databases consisted of a routine adverse event database and a serious adverse event database of expeditiously submitted reports. Patients with any malignancy who had ocular adverse events while on PD-1/PD-L1 inhibitor treatment were included. Patients received nivolumab, pembrolizumab, atezolizumab or durvalumab alone or in combination with other anticancer agents per each trial’s protocol. Databases were queried up to May 19, 2020.ResultsIn the routine adverse event database, 272 adverse events from 213 patients were reported and in the serious adverse event reporting database, 59 ocular adverse events from 47 patients were reported. A lower estimate of the prevalance from the routine adverse event database showed 259/7727 patients on study treatment arms reporting ocular adverse events (3.3% prevalence). Excluding trials that do not report lower grade adverse events to the routine adverse event database results in a higher end estimate of 242/3255 patients on study treatment arms reporting ocular adverse events (7.4% prevalence). Ocular events occurred early after drug initiation (routine database: median 6 weeks, IQR 0–16, serious adverse events database: median 11 weeks, IQR 6–21). The median Common Terminology Criteria for Adverse Events grade was grade 1 (mild) (IQR 1–2) and grade 2 (moderate) (IQR 2–3) for the routine database and the serious adverse events database, respectively. In-depth analysis of the serious adverse event reports revealed varying degrees of clinical workup, with 30/47 patients (64%) receiving ophthalmological evaluation and 16/47 (34%) of patients having to delay or discontinue treatment. However, 16/47 (34%) patients experienced resolution and 14/47 (30%) patients experienced at least some improvement.ConclusionsThis is one of the largest analyses of ocular adverse events in patients treated with PD-1/PD-L1 inhibitors in the USA. We found ocular adverse events are rare complications of PD-1/PD-L1 inhibitor therapy, can be severe enough to cause treatment discontinuation/delay, and may not always be appropriately evaluated by eye specialists. Standardized plans for ophthalmology evaluation and management of ocular toxicities are needed in studies of patients treated with PD-1/PD-L1 inhibitors.

scholarly journals Real-World Clinical Experience with SGLT2 Inhibitors: Use of Special Screening Tool for Type 2 Diabetes Patients to Avoid Serious Adverse Events: A Single-Centre Prospective Study

2020 ◽  
Vol 26 (1) ◽  
pp. 38-43
Author(s):  
Vishwa B. Unadkat ◽  
Sandeep Sharma ◽  
Ruchi Omar
Keyword(s):  
Adverse Effect ◽  
Clinical Trials ◽  
Adverse Effects ◽  
Adverse Events ◽  
Real World ◽  
Common Adverse Effect ◽  
Sglt2 Inhibitors ◽  
Serious Adverse Events ◽  
Screening Protocol ◽  
Simple Screening

<b><i>Background:</i></b> Promising results of clinical trials involving SGLT2 inhibitors urge every clinician managing diabetes to use them. However, upcoming real-world data still show increased incidence of adverse events, but efficacy is comparable to clinical trials. <b><i>Objectives:</i></b> Genitourinary infection is the most commonly reported adverse effect with SGLT2 inhibitors. We evaluated effectiveness of patient screening protocol and advice of hygiene and hydration to avoid adverse effects of SGLT2 inhibitors in real-world setting. <b><i>Method:</i></b> This was a prospective observational longitudinal study which included consecutive subjects with uncontrolled T2DM recommended with SGLT2i after a simple screening protocol from December 2017 to November 2018. The adverse effects and metabolic parameters were evaluated at 1st, 3rd, 6th, and 12th months for each patient. <b><i>Results:</i></b> Of 413 patients recommended for SGLT2 inhibitors, 335 patients started the medication. At baseline, average age, glycosylated haemoglobin (HbA1c), and weight were 53 years, 9.5%, and 82 kg, respectively. Data of 332, 299, 270, and 231 patients were available at the 1st, 3rd, 6th, and 12th months for safety follow-up, respectively. Genitourinary tract infection was the most common adverse effect (8%) followed by ketosis (4%). Two patients needed to stop the drug permanently due to recurrent transient ischaemic attack and emphysematous pyelonephritis. Significant reduction in mean weight and HbA1c was observed at 6 months (<i>n</i> = 270): 2.9 kg and 1.1%, respectively, and at 12 months (<i>n</i> = 231): 3.8 kg and 1.6%, respectively. <b><i>Conclusion:</i></b> Simple screening protocol for patients considered for SGLT2i significantly reduced incidence of genitourinary adverse events.

P706Treatment of hypercholesterolaemia with PCSK-9 Inhibitors in Denmark. Assessment of real-life data; safety an extent of adverse effects after the first years of clinical use

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Mulverstedt ◽  
I C Klausen ◽  
M H Martinsen ◽  
H Kanstrup ◽  
K K Thomsen ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Adverse Events ◽  
Plasma Lipids ◽  
Real Life ◽  
Outcome Studies ◽  
Control Group ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Wide Range ◽  
Significant Difference

Abstract Introduction PCSK9 Inhibitors (PCSK9 I) are a new group of drugs for treatment of hyperlipidaemia. These drugs have been available in Denmark since October 2015. From the two existing major outcome studies (FOURIER and ODYSSEY OUTCOMES) it has been shown that there was no significant difference in the risk of serious adverse events, discontinuation due to adverse events, neurocognitive events, diabetes-related events, muscle-related events, or myalgia in the treatment group, compared with the control group. In FOUIRER 12.5% came of treatment; In ODYSSEY the rate was 10.2–14.8%. Although this highlights the efficacy and safety in patients with cardiovascular disease, we have little knowledge of the use, efficacy and safety with these drugs in real-life populations Purpose We aim to describe the demography, the treatment efficacy and the extent of adverse effects among patients treated in Danish lipid clinics. Methods Data on all patients treated with PCSK9 I between October 1st, 2015 and May 1st, 2018 were obtained from lipid clinics in Denmark. A database containing information on medications before treatment, adverse effects, plasma lipids (LDL-C, Triglyceride, High density lipoprotein cholesterol (HDL-C)) and supplementary blood tests was created. Levels of plasma lipids and organ markers (Creatinine, Hba1c or Alanine aminotransferase (ALAT)) at baseline and at follow up visits were analysed. Results Nationwide, 383 patients were included, an estimated 90% of all patients undergoing treatment with PCSK9 I in Denmark. A large proportion (n=243 - 63.4%) were described as statin intolerant and only 94 patients were receiving statins at baseline. Adverse effects (AE) were reported by 71 patients (18.5%) on PCSK9 I therapy and 50 patients (13.1%) stopped treatment. Most common AE were flu like symptoms and musculoskeletal aches. In two cases an increase in serum creatinine kinase was detected. One case of angioedema and three cases of local reactions to injections had been documented. No case of anaphylaxis was reported. Of the 71 patients with AEs 55 (77.5%) were statin intolerant. Of the 50, who came off treatment, 43 (86.0%) were statin intolerant. When treatment was stopped 15 patients (30.0%) tried the alternative PCSK9 Inhibitor (cross over). Of those, nine patients were able to tolerate the alternative PCSK9 I treatment. Conclusion Many patients (18.3%) reported AEs on a wide range of symptoms, but the rate of patients terminating PCSK9 I treatment was the same as found in the outcome studies (13.1% vs. 12.2 and 10.2–14.8%). Most of the patients who stopped treatment were statin intolerant and produced the same symptoms, as they had experienced with statins. Interestingly, nine of the 15 patients that were switched to the alternate PCSK9 I seems to tolerate this treatment.

scholarly journals Evaluation of adverse effects/events of genetically modified food consumption: a systematic review of animal and human studies

2022 ◽  
Vol 34 (1) ◽  
Author(s):  
Chen Shen ◽  
Xiang-Chang Yin ◽  
Bo-Yang Jiao ◽  
Jing Li ◽  
Peng Jia ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Adverse Events ◽  
Animal Studies ◽  
Adverse Event Reporting ◽  
Human Studies ◽  
Study Quality ◽  
Industry Funding ◽  
Serious Adverse Events ◽  
Gm Food ◽  
Reporting Rates

Abstract Objective A systematic review of animal and human studies was conducted on genetically modified (GM) food consumption to assess its safety in terms of adverse effects/events to inform public concerns and future research. Methods Seven electronic databases were searched from January 1st 1983 till July 11th 2020 for in vivo, animal and human studies on the incidence of adverse effects/events of GM products consumption. Two authors independently identified eligible studies, assessed the study quality, and extracted data on the name of the periodical, author and affiliation, literature type, the theme of the study, publication year, funding, sample size, target population characteristics, type of the intervention/exposure, outcomes and outcome measures, and details of adverse effects/events. We used the Chi-square test to compare the adverse event reporting rates in articles funded by industry funding, government funding or unfunded articles. Results One crossover trial in humans and 203 animal studies from 179 articles met the inclusion criteria. The study quality was all assessed as being unclear or having a high risk of bias. Minor illnesses were reported in the human trial. Among the 204 studies, 59.46% of adverse events (22 of 37) were serious adverse events from 16 animal studies (7.84%). No significant differences were found in the adverse event reporting rates either between industry and government funding (χ2 = 2.286, P = 0.131), industry and non-industry funding (χ2 = 1.761, P = 0.185) or funded and non-funded articles (χ2 = 0.491, P = 0.483). We finally identified 21 GM food-related adverse events involving 7 GM events (NK603 × MON810 maize, GTS 40-3-2 soybean, NK603 maize, MON863 maize, MON810 maize, MON863 × MON810 × NK603 maize and GM Shanyou 63 rice), which had all been on regulatory approval in some countries/regions. Conclusion Serious adverse events of GM consumption include mortality, tumour or cancer, significant low fertility, decreased learning and reaction abilities, and some organ abnormalities. Further clinical trials and long-term cohort studies in human populations, especially on GM food-related adverse events and the corresponding GM events, are still warranted. It suggests the necessity of labelling GM food so that consumers can make their own choice.

Phosphene perceptions and safety of chronic visual cortex stimulation in a blind subject

2020 ◽  
Vol 132 (6) ◽  
pp. 2000-2007 ◽  
Author(s):  
Soroush Niketeghad ◽  
Abirami Muralidharan ◽  
Uday Patel ◽  
Jessy D. Dorn ◽  
Laura Bonelli ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Adverse Events ◽  
Clinical Intervention ◽  
Occipital Cortex ◽  
Neuronal Population ◽  
Serious Adverse Events ◽  
Stimulation Parameters ◽  
The Right ◽  
Visual Cortical ◽  
Stimulation Of

Stimulation of primary visual cortices has the potential to restore some degree of vision to blind individuals. Developing safe and reliable visual cortical prostheses requires assessment of the long-term stability, feasibility, and safety of generating stimulation-evoked perceptions.A NeuroPace responsive neurostimulation system was implanted in a blind individual with an 8-year history of bare light perception, and stimulation-evoked phosphenes were evaluated over 19 months (41 test sessions). Electrical stimulation was delivered via two four-contact subdural electrode strips implanted over the right medial occipital cortex. Current and charge thresholds for eliciting visual perception (phosphenes) were measured, as were the shape, size, location, and intensity of the phosphenes. Adverse events were also assessed.Stimulation of all contacts resulted in phosphene perception. Phosphenes appeared completely or partially in the left hemifield. Stimulation of the electrodes below the calcarine sulcus elicited phosphenes in the superior hemifield and vice versa. Changing the stimulation parameters of frequency, pulse width, and burst duration affected current thresholds for eliciting phosphenes, and increasing the amplitude or frequency of stimulation resulted in brighter perceptions. While stimulation thresholds decreased between an average of 5% and 12% after 19 months, spatial mapping of phosphenes remained consistent over time. Although no serious adverse events were observed, the subject experienced mild headaches and dizziness in three instances, symptoms that did not persist for more than a few hours and for which no clinical intervention was required.Using an off-the-shelf neurostimulator, the authors were able to reliably generate phosphenes in different areas of the visual field over 19 months with no serious adverse events, providing preliminary proof of feasibility and safety to proceed with visual epicortical prosthetic clinical trials. Moreover, they systematically explored the relationship between stimulation parameters and phosphene thresholds and discovered the direct relation of perception thresholds based on primary visual cortex (V1) neuronal population excitation thresholds.

Naldemedine: Peripherally Acting Opioid Receptor Antagonist for Treating Opioid-induced Adverse Effects

2020 ◽  
Vol 20 (31) ◽  
pp. 2830-2842
Author(s):  
Masanao Inagaki ◽  
Toshiyuki Kanemasa ◽  
Takaaki Yokota
Keyword(s):  
Adverse Effects ◽  
Adverse Events ◽  
Severe Pain ◽  
Lead Compound ◽  
Inhibitory Effects ◽  
Pharmacokinetic Profiles ◽  
Structure Activity ◽  
The Usa ◽  
Relationship Study ◽  
The Eu

Opioids are widely used for pain management in moderate-to-severe pain. However, opioids are associated with adverse events, such as constipation and emesis/vomiting. To reduce these undesired effects, a structure–activity relationship study of morphinan derivatives was conducted, and a promising lead compound with inhibitory effects on opioid receptors was obtained. Further improvement in the potency and pharmacokinetic profiles of the lead compound led to the discovery of naldemedine, which showed anti-constipation and anti-emetic effects against these adverse events that were induced by morphine without influencing morphine’s analgesic effect. Naldemedine was launched in Japan and the USA in 2017 and in the EU in 2019, for treating opioid-induced constipation.

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

2019 ◽  
Vol 14 (1) ◽  
pp. 31-36
Author(s):  
Raafat Abdel-Malek ◽  
Kyrillus S. Shohdy ◽  
Noha Abbas ◽  
Mohamed Ismail ◽  
Emad Hamada ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Transitional Cell ◽  
Chemotherapeutic Agents ◽  
Serious Adverse Events ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

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