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JAMA Network Open Oct 2023Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer.
OBJECTIVE
To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 months of first transurethral resection was required.
INTERVENTIONS
Oral selenium (200 μg/d of high-selenium yeast) and matched vitamin E placebo, vitamin E (200 IU/d of d-alfa-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo.
MAIN OUTCOME AND MEASURES
Recurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022).
RESULTS
The study randomized 270 patients (mean [SD] age, 68.9 [10.4] years; median [IQR] age, 69 [63-77] years; 202 male [75%]), with 65 receiving selenium and vitamin E placebo, 71 receiving vitamin E and selenium placebo, 69 receiving selenium and vitamin E, and 65 receiving both placebos. Median overall follow-up was 5.5 years (IQR, 5.1-6.1 years); 228 patients (84%) were followed up for more than 5 years. Median treatment duration was 1.5 years (IQR, 0.9-2.5 years). The study was halted because of slow accrual. For selenium (n = 134) vs no selenium (n = 136), there was no difference in RFI (hazard ratio, 0.92; 95% CI, 0.65-1.31; P = .65). For vitamin E (n = 140) vs no vitamin E (n = 130), there was a statistically significant detriment to RFI (hazard ratio, 1.46; 95% CI, 1.02-2.09; P = .04). No significant differences were observed for progression-free interval or overall survival time with either supplement. Results were unchanged after Cox proportional hazards regression modeling to adjust for known prognostic factors. In total, 1957 adverse events were reported; 85 were serious adverse events, and all were considered unrelated to trial treatment.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of selenium and vitamin E, selenium supplementation did not reduce the risk of recurrence in patients with NMIBC, but vitamin E supplementation was associated with an increased risk of recurrence. Neither selenium nor vitamin E influenced progression or overall survival. Vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required.
TRIAL REGISTRATION
isrctn.org Identifier: ISRCTN13889738.
Topics: Humans; Male; Aged; Vitamin E; Selenium; Non-Muscle Invasive Bladder Neoplasms; Prospective Studies; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms
PubMed: 37847504
DOI: 10.1001/jamanetworkopen.2023.37494 -
BMC Ophthalmology Jul 2023To determine the effect of ketorolac tromethamine 0.5% in preventing post-phacoemulsification macular thickening. This randomized clinical trial. patients randomized 1:1... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
To determine the effect of ketorolac tromethamine 0.5% in preventing post-phacoemulsification macular thickening. This randomized clinical trial. patients randomized 1:1 to receive either topical ketorolac three times a day or a placebo.
METHODS
A total of 101 eyes of 101 diabetic patients who were scheduled for phacoemulsification and had normal macular contour and thickness enrolled consecutively. The topical ketorolac and placebo were prescribed on the day before surgery and continued up to 4 weeks after surgery. Patients with proliferative diabetic retinopathy, a history of intravitreal injection in less than three months, a history of macular photocoagulation in less than 6 months, and any other concomitant ocular pathologies were excluded. Central macular thickness (CMT) and best corrected visual acuity (BCVA) was recorded in the follow-ups of 6, 12, and 24 weeks after the surgery and compared with the controls.
RESULTS
49 eyes in the case group and 52 eyes in the control group were analyzed. Mean BCVA was significantly improved in both groups at all follow-ups (P < 0.001 for all). There was no statistically significant difference regarding the BCVA in different time points except week 12 (P = 0.028) among the study group. In the case and control groups, CMT was increased at all follow-ups (P < 0.05). There was no statistically significant difference when comparing the two groups regarding the mean of CMT at any time point postoperatively (P > 0.05 for all).
CONCLUSION
Based on our findings, topical ketorolac tromethamine 0.5% is not effective in the prevention of post-phacoemulsification macular thickening in diabetic patients.
TRAIL REGISTRATION
The study protocol was registered into www.
CLINICALTRIAL
gov with the RCT registration number NCT03551808. (2018/06/11 ) CLINICAL TRIAL REGISTRATION NUMBER: NCT03551808.
Topics: Humans; Ketorolac Tromethamine; Phacoemulsification; Ketorolac; Treatment Outcome; Macular Edema; Visual Acuity; Diabetic Retinopathy; Tomography, Optical Coherence; Diabetes Mellitus
PubMed: 37452330
DOI: 10.1186/s12886-023-03077-y -
BMJ Open Jul 2023The substitution of an in-study control population with a historical control (HC) population is considered a viable option for reducing the necessary recruitment of... (Randomized Controlled Trial)
Randomized Controlled Trial
Substituting a randomised placebo control group with a historical placebo control in an endometriosis pain trial: a case study re-evaluating trial data using historical control data from another trial.
OBJECTIVE
The substitution of an in-study control population with a historical control (HC) population is considered a viable option for reducing the necessary recruitment of control patients. However, it is necessary to evaluate whether this method is applicable to studies on indications targeting endometriosis-associated pelvic pain (EAPP). This study aims to evaluate the potential bias in the results of an EAPP study with an HC arm.
METHODS
For this case study, we re-evaluated data from a randomised, placebo-controlled trial using dienogest daily to treat EAPP with an HC arm based on data from a second randomised, placebo-controlled trial in the same indication. Propensity Score (PS) matching was used to match between the treatment and HC arm on all baseline variables. To evaluate the effect of matching on the introduced bias, we evaluated efficacy parameters with the full treatment and control group, as well as the matched group.
RESULTS
The difference between means (placebo minus treatment) in change in pain, as measured on the Visual Analogue Scale from baseline to end of treatment, deviates in the comparison treatment/pool of HC (7.15 (0.22 to 14.08)) from the overall in-study group (reference: 11.89 (6.06 to 17.73)). After PS matching on the baseline variables, the difference between means (11.79 (4.09 to 19.5)) is close to the reference.
CONCLUSIONS
Using HC with PS matching has proven to be useful in the setting of treating EAPP, while emphasis must be given to the selection mechanism and the underlying assumptions. This case study has shown that even for studies which are very similar in design, heterogeneity and between-study variations are present. With the use of an HC arm, it was possible to reproduce similar results than in the original study, while the PS matching improved the comparability considerably. For the main endpoint, PS matching could reproduce the original study results.
TRIAL REGISTRATION NUMBER
NCT00225199, NCT00185341.
Topics: Female; Humans; Endometriosis; Control Groups; Pelvic Pain; Pain Measurement; Propensity Score
PubMed: 37479520
DOI: 10.1136/bmjopen-2022-063188 -
Chembiochem : a European Journal of... Sep 2019Theranostics involves finding the biomarkers of a disease, fighting them through site specific drug delivery and following them for prognosis of the disease. Microneedle... (Review)
Review
Theranostics involves finding the biomarkers of a disease, fighting them through site specific drug delivery and following them for prognosis of the disease. Microneedle array technology has been used for drug delivery and extended for continuous monitoring of analytes present in the skin compartment. We envisage the use of microneedle arrays for future theranostic applications. The potential of combining microneedle array-based drug delivery and diagnostics as part of closed-loop control system for the management of diseases and delivery of precision drugs in individual patients is reported in this paper.
Topics: Animals; Disease Management; Drug Delivery Systems; Humans; Precision Medicine; Theranostic Nanomedicine
PubMed: 30897259
DOI: 10.1002/cbic.201900112 -
The Cochrane Database of Systematic... Dec 2020Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer's disease (AD). It has been...
BACKGROUND
Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer's disease (AD). It has been designed to support the formation and function of synapses in the brain, which are thought to be strongly correlated with cognitive function. If effective, it might improve symptoms of Alzheimer's disease and also prevent the progression from prodromal Alzheimer's disease to dementia. We sought in this review to examine the evidence for this proposition.
OBJECTIVES
To assess the effects of Souvenaid on incidence of dementia, cognition, functional performance, and safety in people with Alzheimer's disease.
SEARCH METHODS
We searched ALOIS, i.e. the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), Web of Science (ISI Web of Science), Cinahl (EBSCOhost), Lilacs (BIREME), and clinical trials registries up to 24 June 2020. We also reviewed citations of reference lists of landmark papers, reviews, and included studies for additional studies and assessed their suitability for inclusion in the review.
SELECTION CRITERIA
We included randomised, placebo-controlled trials which evaluated Souvenaid in people diagnosed with mild cognitive impairment (MCI) due to AD (also termed prodromal AD) or with dementia due to AD, and with a treatment duration of at least 16 weeks.
DATA COLLECTION AND ANALYSIS
Our primary outcome measures were incidence of dementia, global and specific cognitive function, functional performance, combined cognitive-functional outcomes and adverse events. We selected studies, extracted data, assessed the quality of trials and intended to conduct meta-analyses according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We present all outcomes grouped by stage of AD.
MAIN RESULTS
We included three randomised, placebo-controlled trials investigating Souvenaid in 1097 community-dwelling participants with Alzheimer's disease. One study each included participants with prodromal AD, mild AD dementia and mild-to-moderate AD dementia. We rated the risks of bias of all trials as low. One study (in prodromal AD) was funded by European grants. The other two studies were funded by the manufacturer of Souvenaid. One trial investigated the incidence of dementia in people with prodromal AD at baseline, and found little to no difference between the Souvenaid group and the placebo group after 24 months (RR 1.09, 95% CI 0.82 to 1.43; 1 trial, 311 participants; moderate quality of evidence). In prodromal AD, and in mild and mild-to-moderate Alzheimer's disease dementia, Souvenaid probably results in little or no difference in global or specific cognitive functions (moderate quality of evidence). Everyday function, or the ability to perform activities of daily living, were measured in mild and mild-to-moderate AD dementia. Neither study found evidence of a difference between the groups after 24 weeks of treatment (moderate quality of evidence). Two studies investigated combined cognitive-functional outcomes with the Clinical Dementia Rating Sum of Boxes and observed conflicting results. Souvenaid probably results in slight improvement, which is below estimates of meaningful change, in participants with prodromal Alzheimer's disease after 24 months (moderate quality of evidence), but probably has little to no effect in mild-to-moderate Alzheimer's disease dementia after 24 weeks (moderate quality of evidence). Adverse effects observed were low in all trials, and the available data were insufficient to determine any connection with Souvenaid.
AUTHORS' CONCLUSIONS
Two years of treatment with Souvenaid probably does not reduce the risk of progression to dementia in people with prodromal AD. There is no convincing evidence that Souvenaid affects other outcomes important to people with AD in the prodromal stage or mild-to-moderate stages of dementia. Conflicting evidence on combined cognitive-functional outcomes in prodromal AD and mild AD dementia warrants further investigation. Adverse effects of Souvenaid seem to be uncommon, but the evidence synthesised in this review does not permit us to make a definitive statement on the long-term tolerability of Souvenaid. The effects of Souvenaid in more severe AD dementia or in people with AD at risk of nutritional deficiencies remain unclear.
Topics: Alzheimer Disease; Bias; Cognition; Dementia; Dietary Supplements; Disease Progression; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Phospholipids; Placebos; Prodromal Symptoms; Randomized Controlled Trials as Topic; Time Factors
PubMed: 33320335
DOI: 10.1002/14651858.CD011679.pub2 -
The Cochrane Database of Systematic... Sep 2020Asthma is a common long-term respiratory disease affecting approximately 300 million people worldwide. Approximately half of people with asthma have an important... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Asthma is a common long-term respiratory disease affecting approximately 300 million people worldwide. Approximately half of people with asthma have an important allergic component to their disease, which may provide an opportunity for targeted treatment. Sublingual immunotherapy (SLIT) aims to reduce asthma symptoms by delivering increasing doses of an allergen (e.g. house dust mite, pollen extract) under the tongue to induce immune tolerance. Fifty-two studies were identified and synthesised in the original Cochrane Review in 2015, but questions remained about the safety and efficacy of sublingual immunotherapy for people with asthma.
OBJECTIVES
To assess the efficacy and safety of sublingual immunotherapy compared with placebo or standard care for adults and children with asthma.
SEARCH METHODS
The original searches for trials from the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, WHO ICTRP, and reference lists of all primary studies and review articles found trials up to 25 March 2015. The most recent search for trials for the current update was conducted on 29 October 2019.
SELECTION CRITERIA
We included parallel randomised controlled trials, irrespective of blinding or duration, that evaluated sublingual immunotherapy versus placebo or as an add-on to standard asthma management. We included both adults and children with asthma of any severity and with any allergen-sensitisation pattern. We included studies that recruited participants with asthma, rhinitis, or both, providing at least 80% of trial participants had a diagnosis of asthma. We selected outcomes to reflect recommended outcomes for asthma clinical trials and those most important to people with asthma. Primary outcomes were asthma exacerbations requiring a visit to the emergency department (ED) or admission to hospital, validated measures of quality of life, and all-cause serious adverse events (SAEs). Secondary outcomes were asthma symptom scores, exacerbations requiring systemic corticosteroids, response to provocation tests, and dose of inhaled corticosteroids (ICS).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results for included trials, extracted numerical data, and assessed risk of bias, all of which were cross-checked for accuracy. Any disagreements were resolved by discussion. We analysed dichotomous data as odds ratios (ORs) or risk differences (RDs) using study participants as the unit of analysis; we analysed continuous data as mean differences (MDs) or standardised mean differences (SMDs) using random-effects models. We considered the strength of evidence for all primary and secondary outcomes using the GRADE approach.
MAIN RESULTS
Sixty-six studies met the inclusion criteria for this update, including 52 studies from the original review. Most studies were double-blind and placebo-controlled, varied in duration from one day to three years, and recruited participants with mild or intermittent asthma, often with comorbid allergic rhinitis. Twenty-three studies recruited adults and teenagers; 31 recruited only children; three recruited both; and nine did not specify. The pattern of reporting and results remained largely unchanged from the original review despite 14 further studies and a 50% increase in participants studied (5077 to 7944). Reporting of primary efficacy outcomes to measure the impact of SLIT on asthma exacerbations and quality of life was infrequent, and selective reporting may have had a serious effect on the completeness of the evidence; 16 studies did not contribute any data, and a further six studies could only be included in a post hoc analysis of all adverse events. Allocation procedures were generally not well described; about a quarter of the studies were at high risk of performance or detection bias (or both); and participant attrition was high or unknown in around half of the studies. The primary outcome in most studies did not align with those of interest to the review (mostly asthma or rhinitis symptoms), and only two small studies reported our primary outcome of exacerbations requiring an ED or hospital visit; the pooled estimate from these studies suggests SLIT may reduce exacerbations compared with placebo or usual care, but the evidence is very uncertain (OR 0.35, 95% confidence interval (CI) 0.10 to 1.20; n = 108; very low-certainty evidence). Nine studies reporting quality of life could not be combined in a meta-analysis and, whilst the direction of effect mostly favoured SLIT, the effects were often uncertain and small. SLIT likely does not increase SAEs compared with placebo or usual care, and analysis by risk difference suggests no more than 1 in 100 people taking SLIT will have a serious adverse event (RD -0.0004, 95% CI -0.0072 to 0.0064; participants = 4810; studies = 29; moderate-certainty evidence). Regarding secondary outcomes, asthma symptom and medication scores were mostly measured with non-validated scales, which precluded meaningful meta-analysis or interpretation, but there was a general trend of SLIT benefit over placebo. Changes in ICS use (MD -17.13 µg/d, 95% CI -61.19 to 26.93; low-certainty evidence), exacerbations requiring oral steroids (studies = 2; no events), and bronchial provocation (SMD 0.99, 95% CI 0.17 to 1.82; low-certainty evidence) were not often reported. Results were imprecise and included the possibility of important benefit or little effect and, in some cases, potential harm from SLIT. More people taking SLIT had adverse events of any kind compared with control (OR 1.99, 95% CI 1.49 to 2.67; high-certainty evidence; participants = 4251; studies = 27), but events were usually reported to be transient and mild. Lack of data prevented most of the planned subgroup and sensitivity analyses.
AUTHORS' CONCLUSIONS
Despite continued study in the field, the evidence for important outcomes such as exacerbations and quality of life remains too limited to draw clinically useful conclusions about the efficacy of SLIT for people with asthma. Trials mostly recruited mixed populations with mild and intermittent asthma and/or rhinitis and focused on non-validated symptom and medication scores. The review findings suggest that SLIT may be a safe option for people with well-controlled mild-to-moderate asthma and rhinitis who are likely to be at low risk of serious harm, but the role of SLIT for people with uncontrolled asthma requires further evaluation.
Topics: Adolescent; Adult; Animals; Asthma; Child; Disease Progression; Hospitalization; Humans; Placebos; Pollen; Pyroglyphidae; Quality of Life; Randomized Controlled Trials as Topic; Rhinitis, Allergic; Sublingual Immunotherapy
PubMed: 32926419
DOI: 10.1002/14651858.CD011293.pub3 -
Wiley Interdisciplinary Reviews.... May 2022The emergence of SARS-COV-2, the causative agent of new coronavirus disease (COVID-19) has become a pandemic threat. Early and precise detection of the virus is vital... (Review)
Review
The emergence of SARS-COV-2, the causative agent of new coronavirus disease (COVID-19) has become a pandemic threat. Early and precise detection of the virus is vital for effective diagnosis and treatment. Various testing kits and assays, including nucleic acid detection methods, antigen tests, serological tests, and enzyme-linked immunosorbent assay (ELISA), have been implemented or are being explored to detect the virus and/or characterize cellular and antibody responses to the infection. However, these approaches have inherent drawbacks such as nonspecificity, high cost, are characterized by long turnaround times for test results, and can be labor-intensive. Also, the circulating SARS-COV-2 variant of concerns, reduced antibody sensitivity and/or neutralization, and possible antibody-dependent enhancement (ADE) have warranted the search for alternative potent therapeutics. Aptamers, which are single-stranded oligonucleotides, generated artificially by SELEX (Evolution of Ligands by Exponential Enrichment) may offer the capacity to generate high-affinity neutralizers and/or bioprobes for monitoring relevant SARS-COV-2 and COVID-19 biomarkers. This article reviews and discusses the prospects of implementing aptamers for rapid point-of-care detection and treatment of SARS-COV-2. We highlight other SARS-COV-2 targets (N protein, spike protein stem-helix), SELEX augmented with competition assays and in silico technologies for rapid discovery and isolation of theranostic aptamers against COVID-19 and future pandemics. It further provides an overview on site-specific bioconjugation approaches, customizable molecular scaffolding strategies, and nanotechnology platforms to engineer these aptamers into ultrapotent blockers, multivalent therapeutics, and vaccines to boost both humoral and cellular immunity against the virus. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > Biosensing Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease.
Topics: COVID-19; Humans; Oligonucleotides; Pandemics; SARS-CoV-2; Theranostic Nanomedicine
PubMed: 35238490
DOI: 10.1002/wnan.1785 -
JSLS : Journal of the Society of... 2022To evaluate the efficacy of intracervical injection of liposomal bupivacaine for postoperative pain control among women undergoing minimally invasive supracervical... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the efficacy of intracervical injection of liposomal bupivacaine for postoperative pain control among women undergoing minimally invasive supracervical hysterectomy.
METHODS
A randomized double-blinded placebo-controlled trial of intracervical injection of combination liposomal bupivacaine and bupivacaine for postoperative pain among patients undergoing laparoscopic and robotic supracervical hysterectomy. Patients were enrolled between October 1, 2018 and April 30, 2019. The primary outcome was pain at 12 hours postoperatively using a numeric rating scale from zero to 10. Pain scores were also recorded pre-operatively, immediately postoperatively, at 12, 24, and 48 hours postoperatively. The secondary outcome was the number of patients who required opioid analgesic medications up to 48 hours postoperatively.
RESULTS
Sixty participants were randomized into the control (n = 30) and intervention (n = 30) groups. Pain scores were 1 and 1.75 (p = 0.89) immediately postoperatively, 3 and 3.5 (p = 0.85) at 12 hours, 3.5 and 5 (p = 0.22) at 24 hours, and 2.75 and 4 (p = 0.18) at 48 hours for the control and intervention groups, respectively. Within the first 24 hours, 10 patients in the control and 14 patients in the intervention group used narcotics (p = 0.37). From the 24 to 48 hours window, 6 and 8 patients in the control and intervention groups used narcotics (p = 0.74), respectively.
CONCLUSION
There was no statistically significant difference in pain scores between patients receiving combination liposomal bupivacaine and bupivacaine intracervical block and those receiving placebo in the first 48 hours after surgery. There was no difference in analgesic use between the two study groups.
Topics: Analgesia; Analgesics, Opioid; Anesthetics, Local; Bupivacaine; Female; Humans; Hysterectomy; Liposomes; Pain Measurement; Pain, Postoperative
PubMed: 35815323
DOI: 10.4293/JSLS.2022.00008 -
Anesthesiology Feb 2023There are no effective pharmacologic interventions for preventing postoperative cognitive dysfunction in daily practice. Since the antibiotic minocycline is known to... (Randomized Controlled Trial)
Randomized Controlled Trial
Prevention of Postoperative Cognitive Dysfunction by Minocycline in Elderly Patients after Total Knee Arthroplasty: A Randomized, Double-blind, Placebo-controlled Clinical Trial.
BACKGROUND
There are no effective pharmacologic interventions for preventing postoperative cognitive dysfunction in daily practice. Since the antibiotic minocycline is known to suppress postoperative neuroinflammation, this study hypothesized and investigated whether minocycline might have a preventive effect on postoperative cognitive dysfunction after noncardiac surgery.
METHODS
This study included patients aged more than 60 yr undergoing total knee arthroplasty under general anesthesia. They were randomly assigned to minocycline and placebo groups, to orally receive 100 mg of minocycline or placebo twice daily from the day before surgery until the seventh day after surgery. Cognitive function was evaluated before surgery, and 1 week and 3 months after surgery, using a battery of four cognitive function tests, including Visual Verbal Learning Test, Trail Making Test, Stroop Color and Word Test, and Letter-Digit Coding Task. Additionally, 30 healthy volunteers were subjected to the same tests as the patients to examine the learning effect of repeated tests. The occurrence of postoperative cognitive dysfunction was judged from the results of the neurocognitive test battery, with consideration of the learning effect. The secondary endpoints were the effects of minocycline on postoperative delirium and postoperative pain.
RESULTS
A total of 100 patients were randomized to the minocycline group, and 102 were randomized to the placebo group. The average age of patients was 75 yr. Evaluation showed no significant difference in the incidence of postoperative cognitive dysfunction between the minocycline and placebo groups at both 1 week (8 of 90 [8.9%] vs. 4 of 95 [4.2%]; odds ratio, 2.22 [95% CI, 0.64 to 7.65]; P = 0.240) and 3 months (15.3 of 90 [17.0%] vs. 15.3 of 95 [16.1%]; odds ratio, 1.07 [95% CI, 0.49 to 2.32]; P = 0.889) postoperatively. Missing data 3 months after surgery were corrected by the multiple imputation method. There were no differences between the two groups in postoperative delirium and postoperative pain.
CONCLUSIONS
Minocycline is likely to have no preventive effect on postoperative cognitive dysfunction.
Topics: Aged; Humans; Minocycline; Postoperative Cognitive Complications; Emergence Delirium; Arthroplasty, Replacement, Knee; Pain, Postoperative; Double-Blind Method; Cognitive Dysfunction
PubMed: 36538374
DOI: 10.1097/ALN.0000000000004439 -
Lancet (London, England) Sep 2020Angina might persist or reoccur despite successful revascularisation with percutaneous coronary intervention (PCI) and antianginal therapy. Additionally, PCI in stable... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Angina might persist or reoccur despite successful revascularisation with percutaneous coronary intervention (PCI) and antianginal therapy. Additionally, PCI in stable patients has not been shown to improve survival compared with optimal medical therapy. Trimetazidine is an antianginal agent that improves energy metabolism of the ischaemic myocardium and might improve outcomes and symptoms of patients who recently had a PCI. In this study, we aimed to assess the long-term potential benefits and safety of trimetazidine added to standard evidence-based medical treatment in patients who had a recent successful PCI.
METHODS
We did a randomised, double-blind, placebo-controlled, event-driven trial of trimetazidine added to standard background therapy in patients who had undergone successful PCI at 365 centres in 27 countries across Europe, South America, Asia, and north Africa. Eligible patients were aged 21-85 years and had had either elective PCI for stable angina or urgent PCI for unstable angina or non-ST segment elevation myocardial infarction less than 30 days before randomisation. Patients were randomly assigned by an interactive web response system to oral trimetazidine 35 mg modified-release twice daily or matching placebo. Participants, study investigators, and all study staff were masked to treatment allocation. The primary efficacy endpoint was a composite of cardiac death; hospital admission for a cardiac event; recurrence or persistence of angina requiring an addition, switch, or increase of the dose of at least one antianginal drug; or recurrence or persistence of angina requiring a coronary angiography. Efficacy analyses were done according to the intention-to-treat principle. Safety was assessed in all patients who had at least one dose of study drug. This study is registered with the EU Clinical Trials Register (EudraCT 2010-022134-89).
FINDINGS
From Sept 17, 2014, to June 15, 2016, 6007 patients were enrolled and randomly assigned to receive either trimetazidine (n=2998) or placebo (n=3009). After a median follow-up of 47·5 months (IQR 42·3-53·3), incidence of primary endpoint events was not significantly different between the trimetazidine group (700 [23·3%] patients) and the placebo group (714 [23·7%]; hazard ratio 0·98 [95% CI 0·88-1·09], p=0·73). When analysed individually, there were no significant differences in the incidence of the components of the primary endpoint between the treatment groups. Similar results were obtained when patients were categorised according to whether they had an elective or urgent PCI. 1219 (40·9%) of 2983 patients in the trimetazidine group and 1230 (41·1%) of 2990 patients in the placebo group had serious treatment-emergent adverse events. Frequencies of adverse events of interest were similar between the groups.
INTERPRETATION
Our results show that the routine use of oral trimetazidine 35 mg twice daily over several years in patients receiving optimal medical therapy, after successful PCI, does not influence the recurrence of angina or the outcome; these findings should be taken into account when considering the place of trimetazidine in clinical practice. However, the long-term prescription of this treatment does not appear to be associated with any statistically significant safety concerns in the population studied.
FUNDING
Servier.
Topics: Administration, Oral; Africa, Northern; Aged; Angina, Stable; Angina, Unstable; Asia; Case-Control Studies; Coronary Angiography; Death; Europe; Female; Hospitalization; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Placebos; Recurrence; Safety; South America; Treatment Outcome; Trimetazidine; Vasodilator Agents
PubMed: 32877651
DOI: 10.1016/S0140-6736(20)31790-6