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Journal of Clinical Hypertension... Sep 2023Hypertension is the leading cause of death worldwide, affecting 1.4 billion people. Treatment options include the widely used calcium channel blockers, among which... (Review)
Review
Hypertension is the leading cause of death worldwide, affecting 1.4 billion people. Treatment options include the widely used calcium channel blockers, among which amlodipine, a dihydropyridine, has unique characteristics that distinguish it from other drugs within this class. This review aims to provide an updated overview of the evidence supporting the use of amlodipine over the past 30 years and highlights its cardiovascular benefits in current hypertension management. Amlodipine has low renal clearance (7 mL/min/mg) and long half-life (35-50 h) and duration of action, which allows it to sustain its anti-hypertensive effect for more than 24 h following a single dose. Additionally, blood pressure (BP) control is maintained even when a dose has been missed, providing continuous protection in case of incidental noncompliance. It has proven to reduce BP variability and successfully lower BP. Amlodipine also controls BP in patients with a systolic/diastolic BP of 130/80 mm Hg or higher, diabetes, or chronic kidney disease without worsening glycemic or kidney function. Additionally, amlodipine is a wise choice for older adults due to its ability to control BP and protect against stroke and myocardial infarction. Side effects of amlodipine include edema, palpitations, dizziness, and flushing, which are more common with the higher dose of 10 mg. Amlodipine is cost effective and predicted to be cost saving when compared with usual care.
Topics: Humans; Aged; Amlodipine; Hypertension; Antihypertensive Agents; Calcium Channel Blockers; Blood Pressure
PubMed: 37551050
DOI: 10.1111/jch.14709 -
JAMA Nov 2023Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute...
IMPORTANCE
Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage.
OBJECTIVE
To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol.
DESIGN, SETTING, AND PARTICIPANTS
CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US major trauma centers from August 2017 to November 2021. Eligible patients were injured adults requiring activation of the hospital's major hemorrhage protocol with evidence of active hemorrhage, systolic blood pressure less than 90 mm Hg at any time, and receiving at least 1 U of a blood component transfusion.
INTERVENTION
Patients were randomly assigned (in a 1:1 ratio) to receive standard care, which was the local major hemorrhage protocol (reviewed for guideline adherence), or cryoprecipitate, in which 3 pools of cryoprecipitate (6-g fibrinogen equivalent) were to be administered in addition to standard care within 90 minutes of randomization and 3 hours of injury.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause mortality at 28 days in the intention-to-treat population.
RESULTS
Among 1604 eligible patients, 799 were randomized to the cryoprecipitate group and 805 to the standard care group. Missing primary outcome data occurred in 73 patients (principally due to withdrawal of consent) and 1531 (95%) were included in the primary analysis population. The median (IQR) age of participants was 39 (26-55) years, 1251 (79%) were men, median (IQR) Injury Severity Score was 29 (18-43), 36% had penetrating injury, and 33% had systolic blood pressure less than 90 mm Hg at hospital arrival. All-cause 28-day mortality in the intention-to-treat population was 26.1% in the standard care group vs 25.3% in the cryoprecipitate group (odds ratio, 0.96 [95% CI, 0.75-1.23]; P = .74). There was no difference in safety outcomes or incidence of thrombotic events in the standard care vs cryoprecipitate group (12.9% vs 12.7%).
CONCLUSIONS AND RELEVANCE
Among patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empirical high-dose cryoprecipitate to standard care did not improve all cause 28-day mortality.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04704869; ISRCTN Identifier: ISRCTN14998314.
Topics: Adult; Male; Humans; Middle Aged; Female; Hemorrhage; Fibrinogen; Blood Transfusion; Blood Component Transfusion; Wounds, Penetrating
PubMed: 37824155
DOI: 10.1001/jama.2023.21019 -
AIDS (London, England) Jan 2024The objective of this study was to assess the pharmacokinetics, safety, and efficacy and confirm the dose of once-daily bictegravir/emtricitabine/tenofovir alafenamide...
OBJECTIVE
The objective of this study was to assess the pharmacokinetics, safety, and efficacy and confirm the dose of once-daily bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; B/F/TAF) during pregnancy.
DESIGN
An open-label, multicenter, single-arm, phase 1b study (NCT03960645) was conducted in 33 virologically suppressed pregnant women with HIV-1.
METHODS
Participants received B/F/TAF (50/200/25 mg) from the second or third trimester through ∼16 weeks postpartum. Steady-state maternal plasma pharmacokinetic samples were collected at the second and third trimesters and 6 and 12 weeks postpartum for BIC, FTC, and TAF. Neonates ( n = 29) were followed from birth to 4-8 weeks with sparse washout pharmacokinetic sampling for BIC and TAF. The proportion of participants with HIV-1 RNA less than 50 copies/ml at delivery (missing = excluded) was evaluated.
RESULTS
Mean areas under the concentration-time curve over the dosing interval (AUC tau ) for BIC, FTC, and TAF were lower during pregnancy versus postpartum but were closer to AUC tau values for nonpregnant adults with HIV reported in other studies. Geometric least-squares mean ratios for BIC, FTC, and TAF AUC tau during pregnancy versus postpartum ranged from 41 to 45%, 64 to 69% and 57 to 78%, respectively. Mean BIC trough concentrations during pregnancy were more than 6.5-fold greater than the protein-adjusted 95% effective concentration. In neonates, the median BIC half-life was 43 h. Virologic suppression was maintained in all adult participants throughout the study, with no virologic failure or treatment-emergent resistance to HIV-1, no discontinuations because of adverse events, and no perinatal transmission.
CONCLUSION
Exposures to BIC, FTC, and TAF were lower during pregnancy than postpartum. However, mean BIC trough concentrations were maintained at levels indicative of efficacious exposure, and FTC/TAF data were concordant with published literature in this population. Pharmacokinetic and safety data, combined with maintenance of robust virologic suppression, suggest that once-daily B/F/TAF without dose adjustment is appropriate during pregnancy.
Topics: Adult; Female; Humans; Infant, Newborn; Pregnancy; Anti-HIV Agents; Drug Combinations; Emtricitabine; Heterocyclic Compounds, 3-Ring; HIV Infections; HIV Seropositivity; Pregnant Women
PubMed: 37939141
DOI: 10.1097/QAD.0000000000003783 -
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 -
Annals of the Rheumatic Diseases Mar 2024This phase 2b, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of telitacicept, a novel fusion protein that neutralises signals of B... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
This phase 2b, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of telitacicept, a novel fusion protein that neutralises signals of B lymphocyte stimulator and a proliferation-inducing ligand, in active systemic lupus erythematosus (SLE).
METHODS
Adult patients with active SLE (n=249) were recruited from 29 hospitals in China and randomised 1:1:1:1 to receive subcutaneous telitacicept at 80 mg (n=62), 160 mg (n=63), 240 mg (n=62) or placebo (n=62) once weekly in addition to standard therapy. The primary endpoint was the proportion of patients achieving an SLE Responder Index 4 (SRI-4) response at week 48. Missing data were imputed using the last observation carried forward method.
RESULTS
At week 48, the proportion of patients achieving an SRI-4 response was 75.8% in the 240 mg telitacicept group, 68.3% in the 160 mg group, 71.0% in the 80 mg group and 33.9% in the placebo group (all p<0.001). Significant treatment responses were observed in secondary endpoints, including a ≥4-point reduction on the Systemic Lupus Erythematosus Disease Activity Index, a lack of Physician's Global Assessment score worsening and a glucocorticoid dose reduction in the 240 mg group. Telitacicept was well tolerated, and the incidence of adverse events and serious adverse events was similar between the telitacicept and placebo groups.
CONCLUSIONS
This phase 2b clinical trial met the primary endpoint. All telitacicept groups showed a significantly higher proportion of patients achieving an SRI-4 response than the placebo group at week 48, and all doses were well tolerated. These results support further investigations of telitacicept in clinical trials involving more diverse populations and larger sample sizes.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov Registry (NCT02885610).
Topics: Adult; Humans; Double-Blind Method; Glucocorticoids; Lupus Erythematosus, Systemic; Recombinant Fusion Proteins; Severity of Illness Index; Treatment Outcome
PubMed: 38129117
DOI: 10.1136/ard-2023-224854 -
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 -
CNS Drugs Sep 2023Real-world evidence studies of brivaracetam (BRV) have been restricted in scope, location, and patient numbers. The objective of this pooled analysis was to assess... (Review)
Review
BACKGROUND AND OBJECTIVE
Real-world evidence studies of brivaracetam (BRV) have been restricted in scope, location, and patient numbers. The objective of this pooled analysis was to assess effectiveness and tolerability of brivaracetam (BRV) in routine practice in a large international population.
METHODS
EXPERIENCE/EPD332 was a pooled analysis of individual patient records from multiple independent non-interventional studies of patients with epilepsy initiating BRV in Australia, Europe, and the United States. Eligible study cohorts were identified via a literature review and engagement with country lead investigators, clinical experts, and local UCB Pharma scientific/medical teams. Included patients initiated BRV no earlier than January 2016 and no later than December 2019, and had ≥ 6 months of follow-up data. The databases for each cohort were reformatted and standardised to ensure information collected was consistent. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within 3 months before timepoint), continuous seizure freedom (no seizures from baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Patients with missing data after BRV discontinuation were considered non-responders/not seizure free. Analyses were performed for all adult patients (≥ 16 years), and for subgroups by seizure type recorded at baseline; by number of prior antiseizure medications (ASMs) at index; by use of BRV as monotherapy versus polytherapy at index; for patients who switched from levetiracetam to BRV versus patients who switched from other ASMs to BRV; and for patients with focal-onset seizures and a BRV dose of ≤ 200 mg/day used as add-on at index. Analysis populations included the full analysis set (FAS; all patients who received at least one BRV dose and had seizure type and age documented at baseline) and the modified FAS (all FAS patients who had at least one seizure recorded during baseline). The FAS was used for all outcomes other than ≥ 50% seizure reduction. All outcomes were summarised using descriptive statistics.
RESULTS
Analyses included 1644 adults. At baseline, 72.0% were 16-49 years of age and 92.2% had focal-onset seizures. Patients had a median (Q1, Q3) of 5.0 (2.0, 8.0) prior antiseizure medications at index. At 3, 6, and 12 months, respectively, ≥ 50% seizure reduction was achieved by 32.1% (n = 619), 36.7% (n = 867), and 36.9% (n = 822) of patients; seizure freedom rates were 22.4% (n = 923), 17.9% (n = 1165), and 14.9% (n = 1111); and continuous seizure freedom rates were 22.4% (n = 923), 15.7% (n = 1165), and 11.7% (n = 1111). During the whole study follow-up, 551/1639 (33.6%) patients discontinued BRV. TEAEs since prior visit were reported in 25.6% (n = 1542), 14.2% (n = 1376), and 9.3% (n = 1232) of patients at 3, 6, and 12 months, respectively.
CONCLUSIONS
This pooled analysis using data from a variety of real-world settings suggests BRV is effective and well tolerated in routine clinical practice in a highly drug-resistant patient population.
Topics: Adult; Humans; Aged, 80 and over; Pyrrolidinones; Levetiracetam; Australia; Databases, Factual
PubMed: 37684497
DOI: 10.1007/s40263-023-01033-4