Likelihood Of Serious Adverse Events Research Articles

Characterization of US Food and Drug Administration Class I Recalls from 2018 to 2022 for Moderate- and High-Risk Medical Devices: A Cross-Sectional Study.

Medical device recalls are initiated in response to safety concerns. Class I (highest severity) recalls imply a reasonable likelihood of serious adverse events or death associated with device use. Recalled devices must be identified, assessed, and corrected or removed, upon which a recall can be terminated. To characterize Class I medical device recalls and corresponding recalled devices. This was a cross-sectional study of Class I recalls posted on the Food and Drug Administration's annual log from January 1, 2018 to June 30, 2022 for moderate-risk and high-risk medical devices. Devices were categorized by therapeutic use, need for implantation, and life-sustaining designation; recalls were categorized by reason, status, and time elapsed. There were 189 unique Class I medical device recalls, including 151 (79.9%) for moderate-risk and 34 (18.0%) for high-risk devices. Sixty-five (34.4%) recalls were for cardiovascular devices, 36 (19.0%) for implanted devices, and 37 (19.6%) for life-sustaining devices. The median number of device units recalled in the US per recall notice was 4620 (interquartile range [IQR], 578-42,591), with 11 (5.8%) recalls associated with more than 1 million device units. Overall, 125 (66.1%) devices had multiple recalls, with a median of 4 (IQR, 3-11) recalls issued per recalled device. As of September 15, 2022, 50 (26.5%) recalls were terminated, with a median of 24 (IQR, 17.3-30.8) months elapsed between recall initiation and termination. Recalls were terminated more commonly among devices recalled once compared to those recalled multiple times (36.2% vs 19.2%; p=0.02) and for recalls that recommended discontinuing further use of affected devices compared to those that recommended device assessment and/or education of affected population (31.8% vs 18.2%; p=0.04). High-severity medical device recalls are common and affect millions of device units annually in the US. Recall termination takes a significant amount of time, putting patients at risk for serious safety concerns.

Effectiveness and safety profile of greater occipital nerve blockade in cluster headache: a systematic review

BackgroundGreater occipital nerve (GON) blockade is a short-term preventive therapy for cluster headache (CH). We conducted a systematic review to evaluate the effectiveness and safety of GON blockade in patients...

Endobronchial Coil System versus Standard-of-Care Medical Management in the Treatment of Subjects with Severe Emphysema

Background: Bronchoscopic lung volume reduction using endobronchial coils is a new treatment for patients with severe emphysema. To date, the benefits have been modest and have been suggested to be much larger in patients with severe hyperinflation and nonmulti-comorbidity. Objective: We aimed to evaluate the efficacy and safety of endobronchial coil treatment in a randomized multicenter clinical trial using optimized patient selection. Method: Patients with severe emphysema on HRCT scan with severe hyperinflation (residual volume [RV] ≥200% predicted and RV/total lung capacity [TLC] >55%) were randomized to coil treatment or control. Primary outcome measures were differences in the forced expiratory volume in 1 s (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total score at 6 months. Results: Due to premature study termination, a total of 120 patients (age 63 ± 7 years, FEV1 29 ± 7% predicted, RV 251 ± 41% predicted, RV/TLC 67 ± 6%, and SGRQ 58 ± 13 points), instead of 210 patients, were randomized. At study termination, 91 patients (57 coil and 34 control) had 6-month results available. Analyses showed significantly greater improvements in favor of the coil group. The increase in FEV1 was greater in the coil group than that in the control group by + 10.3 [+4.7 to +16.0] % and in SGRQ by −10.6 [−15.9 to −5.4] points. At study termination, there were 5 (6.8%) deaths in the coil cohort reported. Conclusion: Despite early study termination, coil treatment compared to control results in a significant improvement in the lung function and quality of life benefits for up to 6 months in patients with emphysema and severe hyperinflation. These improvements were of clinical importance but were associated with a higher likelihood of serious adverse events.

Systemic Management for Nonmetastatic Castration-resistant Prostate Cancer: A Systematic Review and Network Meta-Analysis.

To indirectly compare the efficacy and safety of systemic therapies used for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). The relevant randomized controlled trials were retrieved from PubMed and the Cochrane Library. Network meta-analyses were used to compare multiple drugs simultaneously for the outcomes of nmCRPC. Direct evidence in trials and indirect evidence across trials were combined by the network meta-analyses to estimate the treatment efficiency. Eight studies were included in our research. For prostate-specific antigen progression-free survival, the rate of progression was significantly decreased following apalutamide, enzalutamide, bicalutamide+dutasteride, and bicalutamide treatment compared with placebo. Compared with placebo treatment, metastases-free survival was significantly increased in patients who received apalutamide (hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.23-0.35), enzalutamide (HR: 0.29, 95% CI: 0.24-0.35), and darolutamide (HR: 0.42, 95% CI: 0.35-0.50). Direct comparison showed significant survival benefits in patients who received second-generation anti-androgen therapy (apalutamide, enzalutamide, and darolutamide: HR: 0.74, 95% CI: 0.61-0.91) compared with patients who received placebo. With respect to metastases-free survival, based on SUCRA analysis, there was 80% and 78% probability that apalutamide and enzalutamide were preferred treatment, while darolutamide was likely to be second-best choice. Compared with placebo, all agents were not associated with significantly higher likelihood of serious adverse events and grade 3 to 4 adverse events. Our outcomes support equivalent efficacy and similar risk of adverse effects between apalutamide, enzalutamide, and darolutamide, supporting the use of these antiandrogen agents in high-risk of progression nmCRPC.

General practitioners' perceptions of vaccination controversies: a French nationwide cross-sectional study

ObjectivesWe aimed to study general practitioners' (GPs') perceptions of vaccines that have been a subject of controversy in France. MethodsA cross-sectional survey in 2014 asked a representative national sample of GPs, randomly selected from the exhaustive database of health professionals in France, about their perceptions of the likelihood of serious adverse events potentially associated with six different vaccines: for two of them the association was based on some scientific evidence, whereas for the other four this is not the case. We performed a cluster analysis to construct a typology of GPs' perceptions about the likelihood of these potential six associations. Factors associated with certain clusters of interest were identified using logistic regression models. ResultsOverall, 1582 GPs participated in the questionnaire survey (1582/1712 GPs who agreed to participate, 92%). Cluster analysis identified four groups of GPs according to their susceptibility to vaccine controversies: 1) limited susceptibility to controversies (52%); 2) overall unsure, but rejected the association between hepatitis B vaccine and multiple sclerosis (32%); 3) highly susceptible to controversies (11%); and 4) unsure (5%). We found that GPs who occasionally practised alternative medicine (OR 2.71, 95% CI 1.65-4.45), and those who considered information provided by mass media as reliable (OR 2.04, 95% CI 1.65-3.99) were more susceptible to controversies. ConclusionsGPs had different profiles of susceptibility to vaccination controversies, and most of their perceptions of these controversies were not based on scientific evidence.

Daptomycin Pharmacokinetics and Pharmacodynamics in Septic and Critically Ill Patients.

Infections, including sepsis, are associated with high mortality rates in critically ill patients in the intensive care unit (ICU). Appropriate antibiotic selection and adequate dosing are important for improving patient outcomes. Daptomycin is bactericidal in bloodstream infections caused by Staphylococcus aureus and other Gram-positive pathogens cultured in ICU patients. The drug has concentration-dependent activity, and the area under the curve/minimum inhibitory concentration ratio is the pharmacokinetic/pharmacodynamic (PK/PD) index that best correlates with daptomycin activity, whereas toxicity correlates well with daptomycin plasma trough concentrations (or minimum concentration [C min]). Adequate daptomycin exposure can be difficult to achieve in ICU patients; multiple PK alterations can result in highly variable plasma concentrations, which are difficult to predict. For this reason, therapeutic drug monitoring could help clinicians optimize daptomycin dosing, thus improving efficacy while decreasing the likelihood of serious adverse events. This paper reviews the literature on daptomycin in ICU patients with sepsis, focusing on dosing and PK and PD parameters.

Stopping long-acting beta2-agonists (LABA) for adults with asthma well controlled by LABA and inhaled corticosteroids.

Poorly controlled asthma often leads to preventable exacerbations that require additional medications, as well as unscheduled hospital and clinic visits.Long-acting beta2-agonists (LABA) are commonly given to adults with asthma whose symptoms are not well controlled by inhaled corticosteroids (ICS). US and UK regulators have issued warnings for LABA in asthma, and now recommend they be used "for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved". To compare cessation of long-acting beta2-agonists (LABA) versus continued use of LABA/inhaled corticosteroids (LABA/ICS) for adults whose asthma is well controlled, and to determine whether stopping LABA:1. results in loss of asthma control or deterioration in quality of life;2. increases the likelihood of asthma attacks or 'exacerbations'; or3. increases or decreases the likelihood of serious adverse events of any cause. We searched the Cochrane Airways Group Specialised Register (CAGR), www.ClinicalTrials.gov, www.who.int/ictrp/en/, reference lists of primary studies and existing reviews and manufacturers' trial registries (GlaxoSmithKline (GSK) and AstraZeneca). We searched all databases from their inception to April 2015, and we imposed no restriction on language of publication. We looked for parallel randomised controlled trials (RCTs) of at least eight weeks' duration, in which adults whose asthma was well controlled by any dose of ICS+LABA combination therapy were randomly assigned to (1) step-down therapy to ICS alone versus (2) continuation of ICS and LABA. Two review authors independently screened all records identified by the search strategy. We used an Excel extraction tool to manage searches, document reasons for inclusion and exclusion and extract descriptive and numerical data from trials meeting inclusion criteria.Prespecified primary outcomes were (1) exacerbations requiring oral steroids, (2) asthma control and (3) all-cause serious adverse events. Six randomised, double-blind studies between 12 and 24 weeks' long met the inclusion criteria. Five studies contributed data to the meta-analysis, assigning 2781 people with stable asthma to the comparison of interest. The definition of stable asthma and inclusion criteria varied across studies, and Global Initiative for Asthma (GINA) criteria were not used. Risk of bias across studies was generally low, and most evidence was rated as moderate quality.Stopping LABA might increase the number of people having exacerbations and requiring oral corticosteroids (odds ratio (OR) 1.74, 95% confidence interval (CI) 0.83 to 3.65; participants = 1257; studies = 4), although the confidence intervals did not exclude the possibility that stopping LABA was beneficial; over 17 weeks, 19 people per 1000 who continued their LABA had an exacerbation, compared with 32 per 1000 when LABA were stopped (13 more per 1000, 95% CI 3 fewer to 46 more).People who stopped LABA had worse scores on the Asthma Control Questionnaire (mean difference (MD) 0.24, 95% CI 0.13 to 0.35; participants = 645; studies = 3) and on measures of asthma-related quality of life (standardised mean difference (SMD) 0.36, 95% CI 0.15 to 0.57; participants = 359; studies = 2) than those who continued LABA, but the effects were not clinically relevant.Too few events occurred for investigators to tell whether stopping LABA has a greater effect on serious adverse events compared with continuing LABA+ICS (OR 0.82, 95% CI 0.28 to 2.42; participants = 1342; studies = 5), and no study reported exacerbations requiring an emergency department visit or hospitalisation as a separate outcome. Stopping LABA may result in fewer adverse events of any kind compared with continuing, although the effect was not statistically significant (OR 0.83, 95% CI 0.66 to 1.05; participants = 1339; studies = 5), and stopping LABA made people more likely to withdraw from participation in research studies (OR 1.95, 95% CI 1.47 to 2.58; participants = 1352; studies = 5). This review suggests that stopping LABA in adults who have stable asthma while they are taking a combination of LABA and ICS inhalers may increase the likelihood of asthma exacerbations that require treatment with oral corticosteroids, but this is not certain. Stopping LABA may slightly reduce asthma control and quality of life, but evidence was insufficient to show whether this had an effect on important outcomes such as serious adverse events and exacerbations requiring hospital admission, and longer trials are warranted. Trialists should include patient-important outcomes such as asthma control and quality of life and should use validated measurement tools. Definitions of exacerbations should be provided.

Post-polypectomy complications: high risk in the cecum

Colorectal cancer (CRC) is the third most frequently occurring cancer in the world [1]. Several randomized trials have shown that screening significantly reduces CRC incidence and mortality [2] [3] [4] The benefit of screening strategies is largely dependent on the effectiveness of colonoscopy, the procedure onto which all screening strategies converge. Colonoscopy allows the detection and removal of advanced adenomas, the precancerous lesions responsible for most CRCs. Endoscopic polypectomy is generally considered a safe procedure, and complications are frequently mild. However, the risk of life-threatening complications does exist, and the likelihood of serious adverse events associated with colonoscopy with polypectomy is almost nine times that of colonoscopy without polypectomy [5]. The most severe post-polypectomy complications are bleeding and perforation. Research on predictive factors for major post-polypectomy complications is of the utmost importance for the development of specific management strategies

Meta-Analysis of Randomized Trials on First Line and Adjunctive Levetiracetam

New evidence suggests that levetiracetam may be as effective as traditional agents, with better safety profile. To synthesize evidence regarding efficacy and tolerability of levetiracetam as first line, adjunctive or prophylactic antiepileptic agent. Study Selection & Data Extraction: Eligible studies were randomized controlled trials (RCTs) of levetiracetam used in adults with epilepsy. MEDLINE, EMBASE, CENTRAL, CINHAL, PAPERSFIRST, PROCEEDINGSFIRST, PROQUEST and conference proceedings identified studies (to September 30, 2010). Two investigators independently selected, appraised studies, collected and analyzed data. Of ten eligible randomized trials, eight investigated adjunctive levetiracetam for refractory seizures, one as monotherapy for newly diagnosed seizures, one as monotherapy for prophylaxis. Eight RCTs of adjunctive levetiracetam were of moderate quality (GRADE criteria), with two showing lack of allocation concealment. Meta-analyses showed adjunctive levetiracetam was more effective than placebo in achieving at least 50% reduction of seizure frequency, when added to baseline antiepileptic regimen (pooled RR 2.15 [1.65,2.82], I2 = 45%, p value (heterogeneity) = 0.08, p value (overall effect) < 0.01). Likelihood of serious adverse events necessitating withdrawal from study was not significantly different between levetiracetam and control (pooled RR 1.37 [0.88,2.13], I2 = 0%, p value (heterogeneity) = 0.84, p value (overall effect) = 0.17). Subgroup analyses suggested similar effects across different dosages. Sensitivity analysis of studies with adequate concealment showed similar effects. Levetiracetam is an effective adjunctive agent for refractory epilepsy. More studies are needed to establish whether it is effective as monotherapy for newly diagnosed seizures, and for prophylaxis in traumatic brain injury.

The management of glaucoma and intraocular hypertension: current approaches and recent advances

In the last decade, numerous novel ocular hypotensive agents have been introduced for the control of intraocular pressure (IOP). Clinicians now have more options than ever in the selection of medical therapy for the treatment of glaucoma and ocular hypertension. When selecting an ocular hypotensive medication for their patients, clinicians should consider not only the IOP-lowering efficacy of an agent, but also the ability of the drug to allow patients to achieve target levels of IOP that are low enough to stop the progression of glaucomatous damage. Other considerations should include how well the drug controls diurnal IOP, the likelihood of serious adverse events, the versatility of the medication for use as an adjunctive agent, as well as other potential attributes (ie, neuroprotection).

Evolving Paradigms in the Medical Treatment of Glaucoma

In the last 5 years, numerous novel ocular hypotensive agents have been introduced for the control of intraocular pressure (IOP). Clinicians now have more options than ever in medical therapy for the treatment of glaucoma and ocular hypertension. When selecting an ocular hypotensive medication for their patients, clinicians should consider not only the IOP-lowering efficacy of an agent but also the ability of the drug to achieve target levels of IOP that are low enough to stop the progression of glaucomatous damage. Other considerations should include how well the drug controls diurnal IOP, the likelihood of serious adverse events, the versatility of the medication for use as an adjunctive agent, as well as other potential attributes (e.g., neuroprotection).

Characterizing variability in cardiovascular drug responses

Characterizing variability in cardiovascular drug responses

Antiepileptic drug pharmacokinetics and interactions: impact on treatment of epilepsy.

An understanding of epilepsy therapy's pharmacokinetic and drug interaction principles-combined with knowledge of antiepileptic drug (AED) clinical pharmacology-allows more effective use of these drugs. The most desirable pharmacokinetic characteristic is a linear relationship between dose and steady-state concentration, as this determines the ease or difficulty in determining the appropriate dose. Drug-drug interactions affecting AED metabolism are common, clinically important, and, until recently, often unpredictable. Advances in molecular biology have identified specific enzymes responsible for AED metabolism and interactions. Clinicians now can identify potential interactions and avoid or manage them by adjusting drug dosage. Most newer AEDs follow or approximate linear pharmacokinetics, are absorbed extensively and consistently, are not significantly bound to plasma proteins, do not form active metabolites, and have few, if any, drug interactions. In cases where interactions occur between newer AEDs and other drugs, knowledge of these interactions reduces the likelihood of serious adverse events. The pharmacokinetics of the newer AEDs simplify drug dosing and monitoring and should lead to improved patient care.