Alleviation of COVID-19 Symptoms and Reduction in Healthcare Utilization Among High-Risk Patients Treated With Nirmatrelvir/Ritonavir (NMV/R): A phase 3 randomized trial.

Background: Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral treatment for mild to moderate COVID-19.

Methods: This phase 2/3, double-blind, randomized (1:1) study assessed oral NMV/r 300 mg/100 mg versus placebo every 12 hours for 5 days in high-risk, unvaccinated, nonhospitalized, symptomatic adults with COVID-19 from 343 sites across 21 countries. In testing the primary endpoint of COVID-19‒related hospitalization and all-cause deaths and key secondary endpoints including symptom duration and COVID-19‒related medical visits, Type I error was controlled with prespecified sequential testing and the Hochberg procedure.

Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19.

Background: Nirmatrelvir in combination with ritonavir is an antiviral treatment for mild-to-moderate coronavirus disease 2019 (Covid-19). The efficacy of this treatment in patients who are at standard risk for severe Covid-19 or who are fully vaccinated and have at least one risk factor for severe Covid-19 has not been established.

Methods: In this phase 2-3 trial, we randomly assigned adults who had confirmed Covid-19 with symptom onset within the past 5 days in a 1:1 ratio to receive nirmatrelvir-ritonavir or placebo every 12 hours for 5 days.

A Randomized Placebo-Controlled Trial of the Anti-Nerve Growth Factor Antibody Tanezumab in Subjects With Cancer Pain Due to Bone Metastasis.

Background: This phase III, randomized, double-blind, placebo-controlled, parallel-group study assessed the efficacy and safety of tanezumab in subjects with cancer pain predominantly due to bone metastasis receiving background opioid therapy.

Methods: Subjects were randomized (stratified by (1) tumor aggressiveness and (2) presence/absence of concomitant anticancer treatment) to placebo or tanezumab 20 mg. Treatment was administered by subcutaneous injection every 8 weeks for 24 weeks (3 doses) followed by a 24-week safety follow-up period.

Cardiorenal risk of celecoxib compared with naproxen or ibuprofen in arthritis patients: insights from the PRECISION trial.

Aims: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs, both prescribed and over the counter. The long-term cardiovascular safety of NSAIDs in patients with arthritis has engendered controversy. Concerns remain regarding the relative incidence and severity of adverse cardiorenal effects, particularly in arthritis patients with established cardiovascular (CV) disease or risk factors for disease as illustrated by the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs.

Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.

Background: Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (M) inhibitor with potent pan-human-coronavirus activity in vitro.

Methods: We conducted a phase 2-3 double-blind, randomized, controlled trial in which symptomatic, unvaccinated, nonhospitalized adults at high risk for progression to severe coronavirus disease 2019 (Covid-19) were assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir (a pharmacokinetic enhancer) or placebo every 12 hours for 5 days. Covid-19-related hospitalization or death from any cause through day 28, viral load, and safety were evaluated.

Sertraline Pediatric Registry for the Evaluation of Safety: Design and Clinical Characteristics of Pediatric Patients Prescribed Sertraline.

To describe the study design and clinical characteristics of patients in the Sertraline Pediatric RegIstry for The Evaluation of Safety (SPRITES). SPRITES is an open-label postmarketing study of development and safety outcomes in patients aged 6 to 16 years treated with sertraline (with or without psychotherapy) compared with psychotherapy alone for up to 3 years in the United States. Baseline data included demographics and psychiatric history.

Strengthening the interpretability of clinical trial results by assessing the effect of informative censoring on the primary estimand in PRECISION.

Background: The ICH E9(R1) addendum states that the strategy to account for intercurrent events should be included when defining an estimand, the treatment effect to be estimated based on the study objective. The estimator used to assess the treatment effect needs to be aligned with the estimand that accounted for intercurrent events. Regardless of the strategy, missing data resulting from patient premature withdrawal could undermine the robustness of the study results.

Differences in Safety of Nonsteroidal Antiinflammatory Drugs in Patients With Osteoarthritis and Patients With Rheumatoid Arthritis: A Randomized Clinical Trial.

Objective: To determine the relative risks of cardiovascular (CV), gastrointestinal (GI), and renal adverse events during long-term treatment with celecoxib, compared with ibuprofen and naproxen, in patients with osteoarthritis (OA) and patients with rheumatoid arthritis (RA).

Methods: A total of 24,081 patients with OA or RA who had a moderate or high risk for CV disease were enrolled internationally into a double-blind randomized controlled trial. Interventions included celecoxib at a dosage of 100-200 mg twice daily, ibuprofen at a dosage of 600-800 mg 3 times daily, or naproxen at a dosage of 375-500 mg twice daily.

Association of Osteopontin, Neopterin, and Myeloperoxidase With Stroke Risk in Patients With Prior Stroke or Transient Ischemic Attacks: Results of an Analysis of 13 Biomarkers From the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trial.

Background And Purpose: Established risk factors do not fully identify patients at risk for recurrent stroke. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) evaluated the effect of atorvastatin on stroke risk in patients with a recent stroke or transient ischemic attack and no known coronary heart disease. This analysis explored the relationships between 13 plasma biomarkers assessed at trial enrollment and the occurrence of outcome strokes.

Effect of atorvastatin, cholesterol ester transfer protein inhibition, and diabetes mellitus on circulating proprotein subtilisin kexin type 9 and lipoprotein(a) levels in patients at high cardiovascular risk.

Background: Proprotein subtilisin kexin type 9 (PCSK9) and lipoprotein (a) [Lp(a)] levels are causative risk factors for coronary heart disease.

Objectives: The objective of the study was to determine the impact of lipid-lowering treatments on circulating PCSK9 and Lp(a).

Methods: We measured PCSK9 and Lp(a) levels in plasma samples from Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events trial patients with coronary heart disease and/or type II diabetes (T2D) mellitus.

Oxidized Phospholipids on Apolipoprotein B-100 and Recurrent Ischemic Events Following Stroke or Transient Ischemic Attack.

Background: Biomarkers to predict recurrent stroke and targets of therapy to prevent stroke are lacking.

Objectives: This study evaluated whether patients with prior cerebrovascular events and elevated levels of oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB), but without prior coronary artery disease (CAD), are at risk for recurrent stroke and CAD events following high-dose statin therapy.

Methods: In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, OxPL-apoB levels were measured in 4,385 patients with stroke or transient ischemic attack at baseline and in 3,106 patients at 5 years following randomization to placebo or 80 mg atorvastatin.

Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis.

Background: The cardiovascular safety of celecoxib, as compared with nonselective nonsteroidal antiinflammatory drugs (NSAIDs), remains uncertain.

Methods: Patients who required NSAIDs for osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk were randomly assigned to receive celecoxib, ibuprofen, or naproxen. The goal of the trial was to assess the noninferiority of celecoxib with regard to the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke.

Safety of atorvastatin in Asian patients within clinical trials.

Introduction: Data on statin safety in Asian patients are limited compared with evidence from Western populations.

Aim: This study assessed atorvastatin safety among Asian patients enrolled in 58 randomized clinical trials.

Methods: Data from 52 short-term trials (median exposure 4-72 weeks) and six long-term cardiovascular outcomes trials (median exposure 3.

Fasting triglycerides predict recurrent ischemic events in patients with acute coronary syndrome treated with statins.

Background: Most patients with acute coronary syndrome (ACS) are treated with statins, which reduce atherogenic triglyceride-rich lipoproteins. It is uncertain whether triglycerides predict risk after ACS on a background of statin treatment.

Objectives: This study examined the relationship of fasting triglyceride levels to outcomes after ACS in patients treated with statins.

Efficacy and safety of nonsteroidal anti-inflammatory drugs in Asian patients with knee osteoarthritis: summary of a randomized, placebo-controlled study.

Aim: To compare the efficacy, tolerability and safety of celecoxib, naproxen and placebo in Asian patients with osteoarthritis (OA) of the knee.

Method: Patients of Asian descent with knee OA, aged ≥ 45 years, in a flare state with a functional capacity classification of I-III, received celecoxib 200 mg once daily, naproxen 500 mg twice daily or placebo, for 6 weeks. The change in Patient's Assessment of Arthritis Pain (week 6 vs.

Effect of atorvastatin on C-reactive protein and benefits for cardiovascular disease in patients with type 2 diabetes: analyses from the Collaborative Atorvastatin Diabetes Trial.

Aims/hypothesis: We investigated whether atorvastatin 10 mg daily lowered C-reactive protein (CRP) and whether the effects of atorvastatin on cardiovascular disease (CVD) varied by achieved levels of CRP and LDL-cholesterol.

Methods: CRP levels were measured at baseline and 1 year after randomisation to atorvastatin in 2,322 patients with type 2 diabetes (40-75 years, 69% males) in a secondary analysis of the Collaborative Atorvastatin Diabetes Study, a randomised placebo-controlled trial. We used Cox regression models to test the effects on subsequent CVD events (n = 147) of CRP and LDL-cholesterol lowering at 1 year.

A pooled analysis of the efficacy of desvenlafaxine for the treatment of major depressive disorder in perimenopausal and postmenopausal women.

Background: Few studies in the literature have examined the efficacy of antidepressant drugs in perimenopausal and postmenopausal women. The objective of the current study was to assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) separately in perimenopausal and postmenopausal women with major depressive disorder (MDD).

Methods: Data were pooled from two double-blind, placebo-controlled clinical trials enrolling perimenopausal and postmenopausal women (40-70 years old) diagnosed with MDD.

Relationship of oxidized phospholipids on apolipoprotein B-100 to cardiovascular outcomes in patients treated with intensive versus moderate atorvastatin therapy: the TNT trial.

Background: Oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) is a biomarker of increased risk for major adverse cardiovascular events (MACE) in community cohorts, but its role in patients with stable coronary heart disease (CHD) is unknown.

Objectives: This study sought to examine the relationship between these oxidative biomarkers and cardiovascular outcomes in patients with established CHD.

Methods: In a random sample from the TNT (Treating to New Targets) trial, OxPL-apoB levels were measured in 1,503 patients at randomization (after an 8-week run-in period taking atorvastatin 10 mg) and 1 year after being randomized to atorvastatin 10 or 80 mg.

Prediction of cardiovascular events in statin-treated stable coronary patients of the treating to new targets randomized controlled trial by lipid and non-lipid biomarkers.

Unlabelled: Several plasma non-lipid biomarkers have been shown to predict major cardiovascular events (MCVEs) in population studies. Our objective was to investigate the relationship between lipid and non-lipid biomarkers levels achieved during statin therapy and the incidence of MCVEs in patients with stable coronary heart disease (CHD). We conducted a substudy of the TNT (Treating to New Targets) study, which was a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of CHD.

LADA and CARDS: a prospective study of clinical outcome in established adult-onset autoimmune diabetes.

Objective: Diabetes-associated autoantibodies can be detected in adult-onset diabetes, even when initially non-insulin requiring, i.e., with latent autoimmune diabetes.

Impact of high-dose atorvastatin therapy and clinical risk factors on incident aortic valve stenosis in patients with cardiovascular disease (from TNT, IDEAL, and SPARCL).

Clinical trials have not provided evidence for a role of statin therapy in reducing aortic valve stenosis (AVS) severity in patients with documented AVS. However, whether statin therapy could prevent the onset of AVS is unknown. Our objectives were (1) to compare the incidence rates of AVS among patients treated with high-dose versus usual-dose statin or placebo and (2) to identify clinical risk factors associated with the development of AVS.

Post hoc analysis of the efficacy and safety of desvenlafaxine 50 mg/day in a randomized, placebo-controlled study of perimenopausal and postmenopausal women with major depressive disorder.

Objective: This post hoc analysis assessed the efficacy of desvenlafaxine 50 mg/day for treating major depressive disorder in perimenopausal versus postmenopausal women enrolled in a 10-week, double-blind, placebo-controlled study.

Methods: Perimenopausal and postmenopausal women (40-70 y) diagnosed with major depressive disorder were randomly assigned to receive desvenlafaxine 50 mg/day or placebo. Changes from baseline in the primary efficacy variable (17-item Hamilton Rating Scale for Depression [HAM-D17] score, week 8) and in other secondary efficacy variables (Sheehan Disability Scale and Menopause Rating Scale) were analyzed using analysis of covariance with treatment, region, and baseline in the model.