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The Journal of Pharmacology and... Aug 2023At 125, aspirin still represents the cornerstone of anti-platelet therapy for the acute treatment and long-term prevention of atherothrombosis. The development of a... (Review)
Review
At 125, aspirin still represents the cornerstone of anti-platelet therapy for the acute treatment and long-term prevention of atherothrombosis. The development of a selective regimen of low-dose aspirin for the inhibition of platelet thromboxane production was key to maximizing its antithrombotic efficacy and minimizing its gastrointestinal toxicity. Based on about 50 observational studies, published over the past 30 years, aspirin and other cyclooxygenase inhibitors have been associated with a reduced risk of colorectal cancer, and possibly other digestive tract cancers. The apparent chemopreventive effect of aspirin has been confirmed in post-hoc analyses of randomized cardiovascular trials and their meta-analyses. Moreover, prevention of sporadic colorectal adenoma recurrence was demonstrated by randomized controlled trials of low-dose aspirin and selective cyclooxygenase-2 inhibitors. A single placebo-controlled randomized trial of aspirin has shown long-term colorectal cancer prevention in patients with the Lynch syndrome. The sequential involvement of thromboxane-dependent platelet activation and cyclooxygenase-2-driven inflammatory response in the early stages of colorectal carcinogenesis may explain these clinical benefits. The aim of this mini-review is to analyze the existing evidence for a chemopreventive effect of aspirin and other cyclooxygenase inhibitors and discuss the missing pieces of this mechanistic and clinical puzzle. SIGNIFICANCE STATEMENT: Low-dose aspirin and other cyclooxygenase inhibitors have been associated with a reduced risk of colorectal cancer, and possibly other digestive tract cancers. The sequential involvement of thromboxane-dependent platelet activation and cyclooxygenase-2-driven inflammatory response in the early stages of colorectal carcinogenesis may explain these clinical benefits. The aim of this mini-review is to analyze the evidence for a chemopreventive effect of aspirin and other cyclooxygenase inhibitors and discuss the missing pieces of this mechanistic and clinical puzzle.
Topics: Humans; Cyclooxygenase 2; Aspirin; Cyclooxygenase 2 Inhibitors; Colorectal Neoplasms; Gastrointestinal Neoplasms; Thromboxanes; Carcinogenesis; Cyclooxygenase 1; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic
PubMed: 37280092
DOI: 10.1124/jpet.122.001631 -
MMWR. Recommendations and Reports :... Sep 2023
THIS REPORT COMPILES AND SUMMARIZES ALL PUBLISHED RECOMMENDATIONS FROM CDC’S ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) FOR USE OF PNEUMOCOCCAL VACCINES IN ADULTS AGED ≥19 YEARS IN THE UNITED STATES. THIS REPORT ALSO INCLUDES UPDATED AND NEW CLINICAL GUIDANCE FOR IMPLEMENTATION FROM CDC
BEFORE 2021, ACIP RECOMMENDED 23-VALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE (PPSV23) ALONE (UP TO 2 DOSES), OR BOTH A SINGLE DOSE OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE (PCV13) IN COMBINATION WITH 1–3 DOSES OF PPSV23 IN SERIES (PCV13 FOLLOWED BY PPSV23), FOR USE IN U.S. ADULTS DEPENDING ON AGE AND UNDERLYING RISK FOR PNEUMOCOCCAL DISEASE. IN 2021, TWO NEW PNEUMOCOCCAL CONJUGATE VACCINES (PCVS), A 15-VALENT AND A 20-VALENT PCV (PCV15 AND PCV20), WERE LICENSED FOR USE IN U.S. ADULTS AGED ≥18 YEARS BY THE FOOD AND DRUG ADMINISTRATION
ACIP RECOMMENDATIONS SPECIFY THE USE OF EITHER PCV20 ALONE OR PCV15 IN SERIES WITH PPSV23 FOR ALL ADULTS AGED ≥65 YEARS AND FOR ADULTS AGED 19–64 YEARS WITH CERTAIN UNDERLYING MEDICAL CONDITIONS OR OTHER RISK FACTORS WHO HAVE NOT RECEIVED A PCV OR WHOSE VACCINATION HISTORY IS UNKNOWN. IN ADDITION, ACIP RECOMMENDS USE OF EITHER A SINGLE DOSE OF PCV20 OR ≥1 DOSE OF PPSV23 FOR ADULTS WHO HAVE STARTED THEIR PNEUMOCOCCAL VACCINE SERIES WITH PCV13 BUT HAVE NOT RECEIVED ALL RECOMMENDED PPSV23 DOSES. SHARED CLINICAL DECISION-MAKING IS RECOMMENDED REGARDING USE OF A SUPPLEMENTAL PCV20 DOSE FOR ADULTS AGED ≥65 YEARS WHO HAVE COMPLETED THEIR RECOMMENDED VACCINE SERIES WITH BOTH PCV13 AND PPSV23
UPDATED AND NEW CLINICAL GUIDANCE FOR IMPLEMENTATION FROM CDC INCLUDES THE RECOMMENDATION FOR USE OF PCV15 OR PCV20 FOR ADULTS WHO HAVE RECEIVED PPSV23 BUT HAVE NOT RECEIVED ANY PCV DOSE. THE REPORT ALSO INCLUDES CLINICAL GUIDANCE FOR ADULTS WHO HAVE RECEIVED 7-VALENT PCV (PCV7) ONLY AND ADULTS WHO ARE HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS
Topics: Adult; Humans; Advisory Committees; Immunization; Pneumococcal Vaccines; United States; Vaccination; Vaccines, Conjugate
PubMed: 37669242
DOI: 10.15585/mmwr.rr7203a1 -
Therapie 2023Nonadherence to the prescribed medication can result in a poor treatment outcome. This study determined the impacts of multiple missed dose or delayed dose scenarios on...
AIM OF THE STUDY
Nonadherence to the prescribed medication can result in a poor treatment outcome. This study determined the impacts of multiple missed dose or delayed dose scenarios on quetiapine (QTP) pharmacokinetics and pharmacodynamics.
METHODS
QTP concentration-time profiles and Brief Psychiatric Rating Scale (BPRS) scores under multiple missed doses and delayed dose scenarios were simulated using Monte Carlo simulations and compared with those of the full adherence scenario using the Mann-Whitney U test. The simulations were performed using the model structure and parameter estimates obtained from Kimko et al's study.
RESULTS
Missing one, two and three consecutive QTP doses significantly decreased trough concentration (C) by 71.4, 103, and 128ng/mL. However, C rapidly increased to values close to those of the full adherence scenario when the regular dose was resumed. Further, all missed dose scenarios did not significantly impact the maximum percent reduction of BPRS score from baseline, but significant impacts on the minimum percent reduction of BPRS score from baseline were observed. However, the change in BPRS score from the full adherence scenario rapidly resumed when the regular dose was taken. Moreover, this study identified that a delayed dose as late as 6 hours did not significantly impact the maximum concentrations when the regular dose was resumed.
CONCLUSION
Based on the simulations, a missed dose can be taken as late as 6 hours before the next scheduled dose, otherwise it should be skipped. For multiple missed doses scenarios, QTP pharmacokinetics and pharmacodynamics rapidly returned to the stage close to the full adherence scenario when a single regular dose was resumed.
PubMed: 36210213
DOI: 10.1016/j.therap.2022.08.001 -
Annals of Internal Medicine May 2024Many patients with rheumatologic conditions receive care from physicians other than rheumatologists. Here we note key findings from 6 studies in rheumatology published... (Review)
Review
Many patients with rheumatologic conditions receive care from physicians other than rheumatologists. Here we note key findings from 6 studies in rheumatology published in 2023 that offer valuable insights for internal medicine specialists and subspecialists outside of rheumatology. The first study investigated the effect of low-dose glucocorticoids on patients with rheumatoid arthritis (RA) over 2 years and challenged existing perceptions about the risks of glucocorticoids in this setting. The second study focused on the updated guideline for preventing and treating glucocorticoid-induced osteoporosis. With the chronic and widespread use of glucocorticoids, the American College of Rheumatology emphasized the importance of assessing fracture risk and initiating pharmacologic therapy when appropriate. The third study explored the potential use of methotrexate in treating inflammatory hand osteoarthritis, suggesting a novel approach to managing this challenging and common condition. The results of the fourth article we highlight suggest that sarilumab has promise as an adjunct treatment of polymyalgia rheumatica relapse during glucocorticoid dosage tapering. The fifth study evaluated sublingual cyclobenzaprine for fibromyalgia treatment, noting both potential benefits and risks. Finally, the sixth article is a systematic review and meta-analysis that assessed the therapeutic equivalence of biosimilars and reference biologics in the treatment of patients with RA. Knowledge of this recent literature will be useful to clinicians regardless of specialty who care for patients with these commonly encountered conditions.
Topics: Humans; Glucocorticoids; Osteoporosis; Arthritis, Rheumatoid; Antirheumatic Agents; Methotrexate; Rheumatology; Rheumatic Diseases; Biosimilar Pharmaceuticals; Polymyalgia Rheumatica; Fibromyalgia
PubMed: 38621248
DOI: 10.7326/M24-0678 -
Journal of Endocrinological... Jul 2023Dysthyroid optic neuropathy (DON) is a rare sight-threatening complication of Graves' disease. First-line treatment for DON consists of high-dose intravenous... (Review)
Review
PURPOSE
Dysthyroid optic neuropathy (DON) is a rare sight-threatening complication of Graves' disease. First-line treatment for DON consists of high-dose intravenous methylprednisolone (ivMP), followed by immediate orbital decompression (OD) if the response is poor or absent as recommended by the 2021 European Group on Graves' orbitopathy guidelines. The safety and efficacy of the proposed therapy have been proven. However, consensus regarding possible therapeutic options for patients with contraindications to ivMP/OD or resistant form of disease is missing. This paper aims to provide and summarize all available data regarding possible alternative treatment strategies for DON.
METHODS
A comprehensive literature search within an electronic database was performed including data published until December 2022.
RESULTS
Overall, 52 articles describing use of emerging therapeutic strategies for DON were identified. Collected evidence indicates that biologics, including teprotumumab and tocilizumab, may be considered as an important possible treatment option for DON patients. Rituximab should be avoided in DON due to conflicting data and risk of adverse events. Orbital radiotherapy could be beneficial for patients with restricted ocular motility classified as poor surgical candidates.
CONCLUSION
Only a limited number of studies have been dedicated to the therapy of DON, mostly retrospective with a small sample size. Clear criteria regarding diagnosis and resolution of DON do not exist, which restricts comparison of therapeutic outcomes. Randomized clinical trials and comparison studies with long-term follow-ups are necessary to verify the safety and efficacy of each therapeutic option for DON.
Topics: Humans; Graves Ophthalmopathy; Optic Nerve Diseases; Retrospective Studies; Methylprednisolone; Glucocorticoids; Graves Disease
PubMed: 36802028
DOI: 10.1007/s40618-023-02036-0 -
The Cochrane Database of Systematic... Aug 2023Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first... (Review)
Review
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first published in 2002, because several new treatments have since been tried.
OBJECTIVES
To assess the effects of treatments for bullous pemphigoid.
SEARCH METHODS
We updated searches of the following databases to November 2021: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched five trial databases to January 2022, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs of treatments for immunofluorescence-confirmed bullous pemphigoid.
DATA COLLECTION AND ANALYSIS
At least two review authors, working independently, evaluated the studies against the review's inclusion criteria and extracted data from included studies. Using GRADE methodology, we assessed the certainty of the evidence for each outcome in each comparison. Our primary outcomes were healing of skin lesions and mortality.
MAIN RESULTS
We identified 14 RCTs (1442 participants). The main treatment modalities assessed were oral steroids, topical steroids, and the oral anti-inflammatory antibiotic doxycycline. Most studies reported mortality but adverse events and quality of life were not well reported. We decided to look at the primary outcomes 'disease control' and 'mortality'. Almost all studies investigated different comparisons; two studies were placebo-controlled. The results are therefore based on a single study for each comparison except azathioprine. Most studies involved only small numbers of participants. We assessed the risk of bias for all key outcomes as having 'some concerns' or high risk, due to missing data, inappropriate analysis, or insufficient information. Clobetasol propionate cream versus oral prednisone Compared to oral prednisone, clobetasol propionate cream applied over the whole body probably increases skin healing at day 21 (risk ratio (RR 1.08, 95% confidence interval (CI) 1.03 to 1.13; 1 study, 341 participants; moderate-certainty evidence). Skin healing at 21 days was seen in 99.8% of participants assigned to clobetasol and 92.4% of participants assigned to prednisone. Clobetasol propionate cream applied over the whole body compared to oral prednisone may reduce mortality at one year (RR 0.73, 95% CI 0.53 to 1.01; 1 study, 341 participants; low-certainty evidence). Death occurred in 26.5% (45/170) of participants assigned to clobetasol and 36.3% (62/171) of participants assigned to oral prednisone. This study did not measure quality of life. Clobetasol propionate cream may reduce risk of severe complications by day 21 compared with oral prednisone (RR 0.65, 95% CI 0.50 to 0.86; 1 study, 341 participants; low-certainty evidence). Mild clobetasol propionate cream regimen (10 to 30 g/day) versus standard clobetasol propionate cream regimen (40 g/day) A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen probably does not change skin healing at day 21 (RR 1.00, 95% CI 0.97 to 1.03; 1 study, 312 participants; moderate-certainty evidence). Both groups showed complete healing of lesions at day 21 in 98% participants. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change mortality at one year (RR 1.00, 95% CI 0.75 to 1.32; 1 study, 312 participants; low-certainty evidence), which occurred in 118/312 (37.9%) participants. This study did not measure quality of life. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change adverse events at one year (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 309 participants; low-certainty evidence). Doxycycline versus prednisolone Compared to prednisolone (0.5 mg/kg/day), doxycycline (200 mg/day) induces less skin healing at six weeks (RR 0.81, 95% CI 0.72 to 0.92; 1 study, 213 participants; high-certainty evidence). Complete skin healing was reported in 73.8% of participants assigned to doxycycline and 91.1% assigned to prednisolone. Doxycycline compared to prednisolone probably decreases mortality at one year (RR 0.25, 95% CI 0.07 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) = 14; 1 study, 234 participants; moderate-certainty evidence). Mortality occurred in 2.4% (3/132) of participants with doxycycline and 9.7% (11/121) with prednisolone. Compared to prednisolone, doxycycline improved quality of life at one year (mean difference 1.8 points lower, which is more favourable on the Dermatology Life Quality Index, 95% CI 1.02 to 2.58 lower; 1 study, 234 participants; high-certainty evidence). Doxycycline compared to prednisolone probably reduces severe or life-threatening treatment-related adverse events at one year (RR 0.59, 95% CI 0.35 to 0.99; 1 study, 234 participants; moderate-certainty evidence). Prednisone plus azathioprine versus prednisone It is unclear whether azathioprine plus prednisone compared to prednisone alone affects skin healing or mortality because there was only very low-certainty evidence from two trials (98 participants). These studies did not measure quality of life. Adverse events were reported in a total of 20/48 (42%) participants assigned to azathioprine plus prednisone and 15/44 (34%) participants assigned to prednisone. Nicotinamide plus tetracycline versus prednisone It is unclear whether nicotinamide plus tetracycline compared to prednisone affects skin healing or mortality because there was only very low-certainty evidence from one trial (18 participants). This study did not measure quality of life. Fewer adverse events were reported in the nicotinamide group. Methylprednisolone plus azathioprine versus methylprednisolone plus dapsone It is unclear whether azathioprine plus methylprednisolone compared to dapsone plus methylprednisolone affects skin healing or mortality because there was only very low-certainty evidence from one trial (54 participants). This study did not measure quality of life. A total of 18 adverse events were reported in the azathioprine group and 13 in the dapsone group.
AUTHORS' CONCLUSIONS
Clobetasol propionate cream applied over the whole body is probably similarly effective as, and may cause less mortality than, oral prednisone for treating bullous pemphigoid. Lower-dose clobetasol propionate cream applied over the whole body is probably similarly effective as standard-dose clobetasol propionate cream and has similar mortality. Doxycycline is less effective but causes less mortality than prednisolone for treating bullous pemphigoid. Other treatments need further investigation.
Topics: Humans; Azathioprine; Prednisone; Clobetasol; Pemphigoid, Bullous; Doxycycline; Methylprednisolone; Dapsone; Niacinamide
PubMed: 37572360
DOI: 10.1002/14651858.CD002292.pub4 -
Annals of Internal Medicine May 2024Cardiology and all its subspecialties continue to push the envelope in developing new treatment strategies for a wide variety of diseases. After screening more than 1300... (Review)
Review
Cardiology and all its subspecialties continue to push the envelope in developing new treatment strategies for a wide variety of diseases. After screening more than 1300 articles, we highlight a selection of important cardiology articles published in 2023. Starting with prevention, we note articles that look at the effect of semaglutide in patients with obesity as well as a first-in-class drug, bempedoic acid, on cardiovascular outcomes. We have also examined new evidence comparing conservative management with invasive management of frail, older patients with non-ST-segment elevation myocardial infarction (NSTEMI). In patients with cardiac arrest secondary to NSTEMI, another article examines the rationale for expedited transfer to a cardiac arrest center. The STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) trial builds on looking at half-dose thrombolysis in older populations with STEMI. Emphasis is placed on guideline-directed medical therapy before hospital discharge in those with heart failure. In addition, in patients with stable symptomatic coronary artery disease, initial noninvasive testing using coronary computed tomography angiography may be a viable option compared with invasive strategies. More details have emerged on anticoagulation strategies in those with device-detected atrial fibrillation. Finally, transcatheter approaches to treat both mitral and tricuspid regurgitation have also been included.
Topics: Humans; Cardiology
PubMed: 38621242
DOI: 10.7326/M24-0581 -
British Journal of Nursing (Mark Allen... Aug 2023Elective surgical patients need accurate drug charts to reduce missed medication doses, decreasing the chance of peri-operative complications. The quality improvement...
Elective surgical patients need accurate drug charts to reduce missed medication doses, decreasing the chance of peri-operative complications. The quality improvement project described in this article used four interventions to improve the percentage of missed medication doses. A driver diagram was produced to interrogate the current pathway which highlighted multiple interventions, including changes to elective pro formas, the initial clerking process and nurse-based prescribing. Once implemented, a plan-do-study-act (PDSA) cycle was completed as per NHS Improvement guidelines. Overall, missed medication dose percentage decreased from 9.8% to 0% after the interventions. Two of these changes have been deemed sustainable and have been integrated into elective patient pathways, improving both patient safety and streamlining surgical elective patient services. This project highlights the importance of prescribing practice in a multidisciplinary team. Simple changes to established systems allow for better patient care, and the authors' project provides evidence that empowering nursing staff to take the lead in the medication management of patients can reduce the likelihood of negative outcomes in a patient's admission.
Topics: Humans; Elective Surgical Procedures; Hospitalization; Patient Safety; Patients; Quality Improvement
PubMed: 37596075
DOI: 10.12968/bjon.2023.32.15.730