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Endoscopic Ultrasound 2020ERCP is the current procedure of choice for patients with jaundice caused by biliary obstruction. EUS-guided biliary drainage (EUS-BD) has emerged as an alternative to... (Review)
Review
ERCP is the current procedure of choice for patients with jaundice caused by biliary obstruction. EUS-guided biliary drainage (EUS-BD) has emerged as an alternative to ERCP in patients requiring biliary drainage. The aim of the study was to conduct a systematic review and meta-analysis to report the overall efficacy and safety of EUS-BD. We conducted a comprehensive search of several databases including PubMed, EMBASE, Web of Science, Google Scholar, and LILACS databases (earliest inception to June 2018) to identify studies that reported EUS-BD in patients. The primary outcome was to look at the technical and clinical success of the procedure. The secondary analysis focused on calculating the pooled rate of re-interventions and all adverse-events, along with the commonly reported adverse-event subtypes. Twenty-three studies reporting on 1437 patients were identified undergoing 1444 procedures. Majority of the patient population were male (53.86%), with an average age of 67.22 years. The pooled technical success rates and clinical success rates were 91.5% (95% confidence interval [CI]: 87.7-94.2, I = 76.5) and 87% (95% CI: 82.3-90.6, I = 72.4), respectively. The total adverse event rates were 17.9% (95% CI: 14.3-22.2, I = 69.1). Subgroup analysis of three major individual adverse events was bile leak: 4.1% (2.7-6.2, I = 46.7), stent migration: 3.9% (2.5-6.2, I = 43.5), and infection: 3.8% (2.8-5.1, I = 0) Substantial heterogeneity was noted in the analysis. EUS-BD has high technical and clinical success rate and hence a very effective procedure. Concerns about publication bias exist. Careful consideration should be given to the adverse events and weighing the risks and benefits of the alternative nonsurgical/surgical approaches.
PubMed: 32295967
DOI: 10.4103/eus.eus_80_19 -
European Journal of Clinical... May 2024Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, though uncertainty exists regarding their immune-related safety. The objective of this study... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, though uncertainty exists regarding their immune-related safety. The objective of this study was to assess the comparative safety profile (odds ratio) of ICIs and estimate the absolute rate of immune-related serious adverse events (irSAEs) in cancer patients undergoing treatment with ICIs.
METHODS
We searched for randomized trials till February 2021, including all ICIs for all cancers. Primary outcome was overall irSAEs, and secondary outcomes were pneumonitis, colitis, hepatitis, hypophysitis, myocarditis, nephritis, and pancreatitis. We conducted Bayesian network meta-analyses, estimated absolute rates and ranked treatments according to the surface under the cumulative ranking curve (SUCRA).
RESULTS
We included 96 trials (52,811 participants, median age 62 years). Risk of bias was high in most trials. Most cancers were non-small cell lung cancer (28 trials) and melanoma (15 trials). The worst-ranked ICI was ipilimumab (SUCRA 14%; event rate 848/10,000 patients) while the best-ranked ICI was atezolizumab (SUCRA 82%; event rate 119/10,000 patients).
CONCLUSION
Each ICI showed a unique safety profile, with certain events more frequently observed with specific ICIs, which should be considered when managing cancer patients.
Topics: Humans; Middle Aged; Immune Checkpoint Inhibitors; Network Meta-Analysis; Carcinoma, Non-Small-Cell Lung; Bayes Theorem; Lung Neoplasms
PubMed: 38372756
DOI: 10.1007/s00228-024-03647-z -
The Cochrane Database of Systematic... Jun 2017Rheumatoid arthritis is a systemic auto-immune disorder that causes widespread and persistent inflammation of the synovial lining of joints and tendon sheaths.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rheumatoid arthritis is a systemic auto-immune disorder that causes widespread and persistent inflammation of the synovial lining of joints and tendon sheaths. Presently, there is no cure for rheumatoid arthritis and treatment focuses on managing symptoms such as pain, stiffness and mobility, with the aim of achieving stable remission and improving mobility. Celecoxib is a selective non-steroidal anti-inflammatory drug (NSAID) used for treatment of people with rheumatoid arthritis.
OBJECTIVES
To assess the benefits and harms of celecoxib in people with rheumatoid arthritis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and clinical trials registers (ClinicalTrials.gov and the World Health Organization trials portal) to May 18, 2017. We also searched the reference and citation lists of included studies.
SELECTION CRITERIA
We included prospective randomized controlled trials (RCTs) that compared oral celecoxib (200 mg and 400 mg daily) versus no intervention, placebo or a traditional NSAID (tNSAID) in people with confirmed rheumatoid arthritis, of any age and either sex. We excluded studies with fewer than 50 participants in each arm or had durations of fewer than four weeks treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included eight RCTs with durations of 4 to 24 weeks, published between 1998 and 2014 that involved a total of 3988 adults (mean age = 54 years), most of whom were women (73%). Participants had rheumatoid arthritis for an average of 9.2 years. All studies were assessed at high or unclear risk of bias in at least one domain. Overall, evidence was assessed as moderate-to-low quality. Five studies were funded by pharmaceutical companies. Celecoxib versus placeboWe included two studies (N = 873) in which participants received 200 mg daily or 400 mg daily or placebo. Participants who received celecoxib showed significant clinical improvement compared with those receiving placebo (15% absolute improvement; 95% CI 7% to 25%; RR 1.53, 95% CI 1.25 to 1.86; number needed to treat to benefit (NNTB) = 7, 95% CI 5 to 13; 2 studies, 873 participants; moderate to low quality evidence).Participants who received celecoxib reported less pain than placebo-treated people (11% absolute improvement; 95% CI 8% to 14%; NNTB = 4, 95% CI 3 to 6; 1 study, 706 participants) but results were inconclusive for improvement in physical function (MD -0.10, 95% CI 0.29 to 0.10; 1 study, 706 participants).In the celecoxib group, 15/293 participants developed ulcers, compared with 4/99 in the placebo group (Peto OR 1.26, 95% CI 0.44 to 3.63; 1 study, 392 participants; low quality evidence). Nine (of 475) participants in the celecoxib group developed short-term serious adverse events, compared with five (of 231) in the placebo group (Peto OR 0.87 (0.28 to 2.69; 1 study, 706 participants; low quality evidence).There were fewer withdrawals among people who received celecoxib (163/475) compared with placebo (130/231) (22% absolute change; 95% CI 16% to 27%; RR 0.61, 95% CI 0.52 to 0.72; 1 study, 706 participants).Cardiovascular events (myocardial infarction, stroke) were not reported. However, regulatory agencies warn of increased cardiovascular event risk associated with celecoxib. Celecoxib versus tNSAIDsSeven studies (N = 2930) compared celecoxib and tNSAIDs (amtolmetin guacyl, diclofenac, ibuprofen, meloxicam, nabumetone, naproxen, pelubiprofen); one study included comparisons of both placebo and tNSAIDs (N = 1149).There was a small improvement, which may not be clinically significant, in numbers of participants achieving ACR20 criteria response in the celecoxib group compared to tNSAIDs (4% absolute improvement; 95% CI 0% less improvement to 8% more improvement; RR 1.10, 95% CI 0.99 to 1.23; 4 studies, 1981 participants). There was a lack of evidence of difference between participants in the celecoxib and tNSAID groups in terms of pain or physical function. Results were assessed at moderate-to-low quality evidence (downgraded due to risk of bias and inconsistency).People who received celecoxib had a lower incidence of gastroduodenal ulcers ≥ 3 mm (34/870) compared with those who received tNSAIDs (116/698). This corresponded to 12% absolute change (95% CI 11% to 13%; RR 0.22, 95% CI 0.15 to 0.32; 5 studies, 1568 participants; moderate quality evidence). There were 7% fewer withdrawals among people who received celecoxib (95% CI 4% to 9%; RR 0.73, 95% CI 0.62 to 0.86; 6 studies, 2639 participants).Results were inconclusive for short-term serious adverse events and cardiovascular events (low quality evidence). There were 17/918 serious adverse events in people taking celecoxib compared to 42/1236 among people who received placebo (Peto OR 0.71; 95% CI 0.39 to 1.28; 5 studies, 2154 participants). Cardiovascular events were reported in both celecoxib and placebo groups in one study (149 participants).
AUTHORS' CONCLUSIONS
Celecoxib may improve clinical symptoms, alleviate pain and contribute to little or no difference in physical function compared with placebo. Celecoxib was associated with fewer numbers of participant withdrawals. Results for incidence of gastroduodenal ulcers (≥ 3 mm) and short-term serious adverse events were uncertain; however, there were few reported events for either.Celecoxib may slightly improve clinical symptoms compared with tNSAIDs. Results for reduced pain and improved physical function were uncertain. Particpants taking celecoxib had lower incidence of gastroduodenal ulcers (≥ 3 mm) and there were fewer withdrawals from trials. Results for cardiovascular events and short-term serious adverse events were also uncertain.Uncertainty about the rate of cardiovascular events between celecoxib and tNSAIDs could be due to risk of bias; another factor is that these were small, short-term trials. It has been reported previously that both celecoxib and tNSAIDs increase cardiovascular event rates. Our confidence in results about harms is therefore low. Larger head-to-head clinical trials comparing celecoxib to other tNSAIDs is needed to better inform clinical practice.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Celecoxib; Humans; Myocardial Infarction; Pain Measurement; Randomized Controlled Trials as Topic; Stomach Ulcer; Stroke; Treatment Outcome
PubMed: 28597983
DOI: 10.1002/14651858.CD012095.pub2 -
Evidence-based Complementary and... 2015As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events... (Review)
Review
As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events in acupuncture treatment reported from 1980 to 2013 in China. All first-hand case reports of acupuncture-related complications and adverse events that could be identified in the scientific literature were reviewed and classified according to the type of complication and adverse event, circumstance of the event, and long-term patient outcome. The selected case reports were published between 1980 and 2013 in 3 databases. Relevant papers were collected and analyzed by 2 reviewers. Over the 33 years, 182 incidents were identified in 133 relevant papers. Internal organ, tissue, or nerve injury is the main complications of acupuncture especially for pneumothorax and central nervous system injury. Adverse effects also included syncope, infections, hemorrhage, allergy, burn, aphonia, hysteria, cough, thirst, fever, somnolence, and broken needles. Qualifying training of acupuncturists should be systemized and the clinical acupuncture operations should be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world.
PubMed: 26339265
DOI: 10.1155/2015/432467 -
Pain Research & Management 2022The dose of intrathecal morphine is important because of its narrow therapeutic range. Due to a compounding error, pharmacy-compounded, ready-to-use syringes contained... (Review)
Review
BACKGROUND
The dose of intrathecal morphine is important because of its narrow therapeutic range. Due to a compounding error, pharmacy-compounded, ready-to-use syringes contained 1 mg ml morphine instead of the intended 50 mcg ml. Six patients consequently received this twenty-fold dose. This study aims to describe the serious adverse events in these six patients and a systematic review is added to describe the characteristics of serious adverse events after intrathecal morphine.
METHODS
A retrospective case series described all six patients that received the erroneous morphine intrathecally for analgesia after laparoscopic segmental colonic resections. The patients' charts were reviewed for the occurrence, timing, duration and management of adverse events, the vital signs at the night after surgery, and length of hospital stay. A systematic review investigated characteristics of serious adverse events after intrathecal morphine in a perioperative setting.
RESULTS
Four patients had a serious adverse event, which was respiratory depression combined with somnolence ( = 3) and hypotension ( = 1). The review yielded 63 cases with serious adverse events, predominantly somnolence and/or respiratory depression. The onset occurred between 2 and 24 hours after injection. The severity of symptoms varied and life-threatening respiratory depression only occurred after a dose >900 mcg or when potentiating medication was used. Naloxone did not affect analgesia. No prolonged sequalae occurred.
CONCLUSION
This study reveals that respiratory depression and somnolence are the predominant serious adverse events after intrathecal morphine in a perioperative setting and demonstrated a large variation in the presentation of symptoms.
Topics: Analgesia; Humans; Injections, Spinal; Morphine; Naloxone; Retrospective Studies
PubMed: 35311036
DOI: 10.1155/2022/4567192 -
PloS One 2021Bisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients, attempts at comprehensive quantification of potential adverse effects have been limited. We undertook a meta-analysis with novel methodology to identify and quantify these adverse effects.
METHODS
We systematically reviewed randomised controlled trials in breast cancer where at least one of the treatments was a bisphosphonate (zoledronic acid, ibandronate, pamidronate, alendronate or clodronate). Neoadjuvant, adjuvant and metastatic settings were examined. Primary outcomes were adverse events of any type or severity (excluding death). We carried out pairwise and network meta-analyses to estimate the size of any adverse effects potentially related to bisphosphonates. In order to ascertain whether adverse effects differed by individual factors such as age, or interacted with other common adjuvant breast cancer treatments, we examined individual-level patient data for one large trial, AZURE.
FINDINGS
We identified 56 trials that reported adverse data, which included a total of 29,248 patients (18,301 receiving bisphosphonate drugs versus 10,947 not). 24 out of the 103 different adverse outcomes analysed showed a statistically and practically significant increase in patients receiving a bisphosphonate drug compared with those not (2 additional outcomes that appeared statistically significant came only from small studies with low event counts and no clinical suspicion so are likely artifacts). Most of these 24 are already clinically recognised: 'flu-like symptoms, fever, headache and chills; increased bone pain, arthralgia, myalgia, back pain; cardiac events, thromboembolic events; hypocalcaemia and osteonecrosis of the jaw; as well as possibly stiffness and nausea. Oral clodronate appeared to increase the risk of vomiting and diarrhoea (which may also be increased by other bisphosphonates), and there may be some hepatotoxicity. Four additional potential adverse effects emerged for bisphosphonate drugs in this analysis which have not classically be recognised: fatigue, neurosensory problems, hypertonia/muscle spasms and possibly dysgeusia. Several symptoms previously reported as potential side effects in the literature were not significantly increased in this analysis: constipation, insomnia, respiratory problems, oedema or thirst/dry mouth. Individual patient-level data and subgroup analysis revealed little variation in side effects between women of different ages or menopausal status, those with metastatic versus non-metastatic cancer, or between women receiving different concurrent breast cancer therapies.
CONCLUSIONS
This meta-analysis has produced estimates for the absolute frequencies of a range of side effects significantly associated with bisphosphonate drugs when used by breast cancer patients. These results show good agreement with previous literature on the subject but are the first systematic quantification of side effects and their severities. However, the analysis is limited by the availability and quality of data on adverse events, and the potential for bias introduced by a lack of standards for reporting of such events. We therefore present a table of adverse effects for bisphosphonates, identified and quantified to the best of our ability from a large number of trials, which we hope can be used to improve the communication of the potential harms of these drugs to patients and their healthcare providers.
Topics: Adult; Aged; Aged, 80 and over; Bone Density Conservation Agents; Breast Neoplasms; Diphosphonates; Female; Humans; Middle Aged; Network Meta-Analysis; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33544765
DOI: 10.1371/journal.pone.0246441 -
The Journal of Bone and Joint Surgery.... Feb 2013In the United States, hip fracture rates have declined by 30% coincident with bisphosphonate use. However, bisphosphonates are associated with sporadic cases of atypical... (Review)
Review
Bisphosphonates and nonhealing femoral fractures: analysis of the FDA Adverse Event Reporting System (FAERS) and international safety efforts: a systematic review from the Research on Adverse Drug Events And Reports (RADAR) project.
BACKGROUND
In the United States, hip fracture rates have declined by 30% coincident with bisphosphonate use. However, bisphosphonates are associated with sporadic cases of atypical femoral fracture. Atypical femoral fractures are usually atraumatic, may be bilateral, are occasionally preceded by prodromal thigh pain, and may have delayed fracture-healing. This study assessed the occurrence of bisphosphonate-associated nonhealing femoral fractures through a review of data from the U.S. FDA (Food and Drug Administration) Adverse Event Reporting System (FAERS) (1996 to 2011), published case reports, and international safety efforts.
METHODS
We analyzed the FAERS database with use of the proportional reporting ratio (PRR) and empiric Bayesian geometric mean (EBGM) techniques to assess whether a safety signal existed. Additionally, we conducted a systematic literature review (1990 to February 2012).
RESULTS
The analysis of the FAERS database indicated a PRR of 4.51 (95% confidence interval [CI], 3.44 to 5.92) for bisphosphonate use and nonhealing femoral fractures. Most cases (n = 317) were attributed to use of alendronate (PRR = 3.32; 95% CI, 2.71 to 4.17). In 2008, international safety agencies issued warnings and required label changes. In 2010, the FDA issued a safety notification, and the American Society for Bone and Mineral Research (ASBMR) issued recommendations about bisphosphonate-associated atypical femoral fractures.
CONCLUSIONS
Nonhealing femoral fractures are unusual adverse drug reactions associated with bisphosphonate use, as up to 26% of published cases of atypical femoral fractures exhibited delayed healing or nonhealing.
Topics: Adverse Drug Reaction Reporting Systems; Bayes Theorem; Bone Density Conservation Agents; Diphosphonates; Femoral Fractures; Fracture Healing; Humans; Risk Factors; United States; United States Food and Drug Administration
PubMed: 23426763
DOI: 10.2106/JBJS.K.01181 -
International Ophthalmology Jun 2024This meta-analysis reviews the evidence for the risks and benefits associated with orthokeratology (OK) treatment compared with other methods of myopia control in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This meta-analysis reviews the evidence for the risks and benefits associated with orthokeratology (OK) treatment compared with other methods of myopia control in children and adults.
METHODS
A systematic search of Cochrane Central Register of Controlled Trials, Pubmed, Embase and Ovid was conducted from database inception to 22nd August 2021. Studies that reported on risks, visual and ocular biometric effects of OK in patients > 5 years of age with myopia (- 0.75 to - 6.00D) were included. Main outcomes are change in axial length and any adverse event.
RESULTS
Fourty-five papers were included in this systematic review and meta-analysis. The quality of data was variable and of moderate certainty, and selection bias likely skewed the results towards a relative benefit for OK. The rate of axial elongation in children was lower for OK treatment compared to other treatment modalities at one year (MD - 0.16 mm, 95% CI - 0.25 to - 0.07). Rate of change in axial length in children rebounded after OK discontinuation compared to participants who continued treatment (MD 0.10 mm, 95% CI 0.06 to 0.14). Adults and children wearing OK were up to 3.79 times more likely to experience an adverse event when compared with conventional contact lenses (OR 3.79, 95% CI 1.24 to ll.), though this evidence base is underdeveloped and requires additional well-designed studies for substantial conclusions to be drawn.
CONCLUSIONS
OK arrests myopia progression while in use, however, there remain unanswered questions about the optimal duration of treatment, discontinuation effects and long-term risk for adverse events.
Topics: Humans; Orthokeratologic Procedures; Myopia; Refraction, Ocular; Visual Acuity; Axial Length, Eye; Contact Lenses; Child; Risk Assessment
PubMed: 38904856
DOI: 10.1007/s10792-024-03175-w -
Journal of the American Medical... 2012Adverse drug events (ADEs), defined as adverse patient outcomes caused by medications, are common and difficult to detect. Electronic detection of ADEs is a promising... (Review)
Review
OBJECTIVE
Adverse drug events (ADEs), defined as adverse patient outcomes caused by medications, are common and difficult to detect. Electronic detection of ADEs is a promising method to identify ADEs. We performed this systematic review to characterize established electronic detection systems and their accuracy.
METHODS
We identified studies evaluating electronic ADE detection from the MEDLINE and EMBASE databases. We included studies if they contained original data and involved detection of electronic triggers using information systems. We abstracted data regarding rule characteristics including type, accuracy, and rationale.
RESULTS
Forty-eight studies met our inclusion criteria. Twenty-four (50%) studies reported rule accuracy but only 9 (18.8%) utilized a proper gold standard (chart review in all patients). Rule accuracy was variable and often poor (range of sensitivity: 40%-94%; specificity: 1.4%-89.8%; positive predictive value: 0.9%-64%). 5 (10.4%) studies derived or used detection rules that were defined by clinical need or the underlying ADE prevalence. Detection rules in 8 (16.7%) studies detected specific types of ADEs.
CONCLUSION
Several factors led to inaccurate ADE detection algorithms, including immature underlying information systems, non-standard event definitions, and variable methods for detection rule validation. Few ADE detection algorithms considered clinical priorities. To enhance the utility of electronic detection systems, there is a need to systematically address these factors.
Topics: Algorithms; Clinical Laboratory Information Systems; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Evaluation Studies as Topic; Humans; Information Systems; Medication Systems; Pharmacovigilance
PubMed: 22155974
DOI: 10.1136/amiajnl-2011-000454