The Urgent Need for Breakthrough Therapies and a World Without Type 1 Diabetes.

Despite significant progress, type 1 diabetes (T1D) still results in premature death, significant complications, and a substantial daily burden for those affected. T1D remains a lifelong condition that demands constant vigilance and resilience and has a significant social and economic impact. Individuals with T1D must walk a tightrope to minimize disease-related complications that result from insufficient insulin while also avoiding adverse effects from too much insulin.

Earlier Use of Long-Acting Injectable Paliperidone Palmitate Versus Oral Antipsychotics in Patients With Schizophrenia: An Integrated Patient-Level Post Hoc Analysis.

To assess the efficacy and safety of paliperidone palmitate (PP) long-acting injectable antipsychotic (LAI) versus oral antipsychotic (OAP) treatment in adult patients diagnosed with schizophrenia (per or criteria) and varying duration of illness (0-3 years and > 3 years). Patient-level data from the PRIDE, PROSIPAL, and DREaM studies were included in a post hoc analysis. Efficacy and safety outcomes, including relapse assessments, Personal and Social Performance scale scores, Medication Satisfaction Questionnaire total scores, and treatment-emergent adverse events (TEAEs), were measured systematically.

Longitudinal Course of Adverse Events With Esketamine Nasal Spray: A Post Hoc Analysis of Pooled Data From Phase 3 Trials in Patients With Treatment-Resistant Depression.

To describe the tolerability of esketamine nasal spray based on the adverse event profile observed during treatment sessions occurring early and later over the course of treatment. In 2 long-term, phase 3 studies (NCT02493868, October 1, 2015-February 16, 2018; NCT02497287, September 30, 2015-October 28, 2017), patients with treatment-resistant major depressive disorder (per ) and nonresponse to ≥ 2 oral antidepressants received esketamine nasal spray (56 or 84 mg) twice weekly during a 4-week induction phase, weekly for weeks 5-8, and weekly or every 2 weeks thereafter as maintenance treatment, in conjunction with a new oral antidepressant. A post hoc analysis using descriptive statistics evaluated occurrence (incidence, frequency, severity) and recurrence (incidence and severity) of events of specific interest.

Impact of COVID-19 Pandemic on Prescribing of Long-Acting Injectable Antipsychotics for Schizophrenia: Results from a United States Prescriber Survey.

Purpose: To describe changes due to the COVID-19 pandemic in the prescribing of long-acting antipsychotics (LAI) for schizophrenia, patient outcomes, and patient and healthcare provider (HCP) attitudes regarding COVID-19 vaccination in the United States (US).

Methods: An anonymous online survey was administered to US-based LAI prescribers with a psychiatry specialty in May 2021. Information on prescriber and clinical practice characteristics, LAI prescribing, patient outcomes, and attitudes toward COVID-19 vaccination was collected and described.

Comparing Relapse Rates in Real-World Patients with Schizophrenia Who Were Adequately versus Not Adequately Treated with Paliperidone Palmitate Once-Monthly Injections Before Transitioning to Once-Every-3-Months Injections.

Purpose: This retrospective cohort study evaluated real-world data on relapses in adult patients with schizophrenia who transitioned to long-acting injectable paliperidone palmitate once-every-3-months (PP3M) following treatment with once-monthly paliperidone palmitate (PP1M).

Patients And Methods: Data derived from the IBM MarketScan Multi-State Medicaid Database were analyzed. Adults aged ≥18 years with ≥1 schizophrenia diagnosis claim and ≥12 months of continuous medical and prescription enrollment before and/or at index date of PP3M were eligible for inclusion.

Understanding the Health System Conditions Affecting the Use of Long-Acting Injectable Antipsychotics in the Treatment of Schizophrenia in Clinical Practice: A US Healthcare Provider Survey.

Purpose: To describe factors that enable the routine use of long-acting injectable antipsychotics (LAIs) for appropriate patients in the current clinical practice, including changes in LAI prescribing due to the COVID-19 pandemic and expectations for prescribing in 2021 in the United States (US).

Methods: Frequent LAI prescribers recruited from a nationwide panel in 2020 completed an online survey regarding practice characteristics, perspectives on healthcare system conditions enabling routine use of LAIs, and prescribing patterns and changes in patterns during the COVID-19 pandemic.

Results: Of 408 prescribers who completed the survey, 77.

Telehealth-Based Psychoeducation for Caregivers: The Family Intervention in Recent-Onset Schizophrenia Treatment Study.

Background: Schizophrenia is a lifelong illness that requires long-term treatment and caregiving. Family psychoeducation (FP) has been shown to lessen caregiver burden, improve caregiver functioning, and improve outcomes in patients. However, the impact of FP delivered specifically to caregivers on patient outcomes has not been well explored, particularly for early schizophrenia.

The effect of esketamine in patients with treatment-resistant depression with and without comorbid anxiety symptoms or disorder.

Background: Comorbid anxiety is generally associated with poorer response to antidepressant treatment. This post hoc analysis explored the efficacy of esketamine plus an antidepressant in patients with treatment-resistant depression (TRD) with or without comorbid anxiety.

Methods: TRANSFORM-2, a double-blind, flexible-dose, 4-week study (NCT02418585), randomized adults with TRD to placebo or esketamine nasal spray, each with a newly-initiated oral antidepressant.

Self-reported review of the value of esketamine in patients with treatment-resistant depression: Understanding the patient experience in the STRIVE Study.

Esketamine nasal spray (ESK) is indicated, in conjunction with an oral antidepressant (OAD), for the management of treatment-resistant depression (TRD) in adults. Select US-based patients from an open-label, long-term extension safety study of ESK (NCT02782104) participated in this study through semi-structured interviews. The study evaluated patient-reported early health changes related to emotional health, daily functioning, and social functioning in adults with TRD treated with ESK plus OAD.

Medication changes after switching from CONCERTA® brand methylphenidate HCl to a generic long-acting formulation: A retrospective database study.

Background: Observational studies of switching from branded to generic formulations of the same drug substance often lack appropriate comparators for the subjects who switched. Three generic formulations were deemed equivalent to Concerta: an authorized generic (AG) identical except for external packaging, and two other generics (EG).

Objective: Compare the incidence of a combined endpoint (switching back to Concerta, changing the use of immediate release methylphenidate (MPH), stopping all long-acting methylphenidate, or starting a new medication) among people switched from Concerta to the AG versus the EG.

Comparison of long-acting and oral antipsychotic treatment effects in patients with schizophrenia, comorbid substance abuse, and a history of recent incarceration: An exploratory analysis of the PRIDE study.

Introduction: Comorbid substance abuse is known to blunt response to treatment for underlying psychiatric disorders, but it has not been investigated in schizophrenia when comparing the effects of long-acting injectable antipsychotics with those of oral antipsychotics.

Methods: This exploratory analysis compared once-monthly paliperidone palmitate (PP1M) with daily oral antipsychotics on time to treatment failure in patients with schizophrenia and a history of incarceration. Subjects were stratified into substance abuse (reported substance or alcohol misuse in the past 30days on the baseline Addiction Severity Index-Lite Version and/or met criteria for a current MINI diagnosis of a substance abuse disorder) and nonabuse cohorts.

Once-monthly paliperidone palmitate compared with conventional and atypical daily oral antipsychotic treatment in patients with schizophrenia.

Objective: This analysis of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (NCT01157351) compared outcomes after administration of once-monthly paliperidone palmitate (PP) vs conventional oral antipsychotics (COAs) or atypical oral antipsychotics (AOAs).

Methods: PRIDE was a 15-month study of 444 individuals with schizophrenia and a history of incarceration. They were randomly assigned to PP or to 1 of 7 commonly prescribed OAs.

Randomized, 6-Week, Placebo-Controlled Study of Treatment for Adult Attention-Deficit/Hyperactivity Disorder: Individualized Dosing of Osmotic-Release Oral System (OROS) Methylphenidate With a Goal of Symptom Remission.

Objective: To evaluate the efficacy and safety of individualized dosing within the approved dose range for osmotic-release oral system (OROS) methylphenidate hydrochloride in adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: A double-blind, 6-week trial was conducted between July 2009 and February 2010 at 35 US sites. Adults with ADHD (DSM-IV diagnostic criteria) and a screening ADHD Investigator Symptom Rating Scale (AISRS) score > 24 were randomly assigned to OROS methylphenidate 18 mg or matching placebo.

A pragmatic analysis comparing once-monthly paliperidone palmitate versus daily oral antipsychotic treatment in patients with schizophrenia.

Background: Persons with schizophrenia often come in contact with the criminal justice system (CJS). This analysis of subjects with schizophrenia and a history of contact with the CJS estimated and compared mean cumulative function (MCF) of treatment failure events when treated with paliperidone palmitate (PP) or oral antipsychotics (OAs). All events identified during the full study period of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) trial were evaluated.

Treatment effect with paliperidone palmitate compared with oral antipsychotics in patients with recent-onset versus more chronic schizophrenia and a history of criminal justice system involvement.

Aim: Long-acting injectable antipsychotics (APs) are not well studied in recent-onset schizophrenia. This exploratory analysis of a study designed to reflect real-world schizophrenia, as defined by patients, interventions and outcomes, compared relative treatment effect between once-monthly paliperidone palmitate (PP) and daily oral APs in patients with recent-onset or chronic illness METHODS: This randomized, open-label, event monitoring board-blinded study compared treatment response in subjects with schizophrenia and a history of criminal justice system involvement following treatment with PP or oral APs for 15 months (ClinicalTrials.gov identifier, NCT01157351).

Real-world outcomes of paliperidone palmitate compared to daily oral antipsychotic therapy in schizophrenia: a randomized, open-label, review board-blinded 15-month study.

Objective: The Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study compared the effects of once-monthly paliperidone palmitate with daily oral antipsychotics on treatment failure in adults with schizophrenia.

Method: The PRIDE study is a 15-month, randomized, multicenter study (May 5, 2010, to December 9, 2013) of adult subjects with a DSM-IV diagnosis of schizophrenia and a history of incarceration. Subjects were randomly assigned to once-monthly paliperidone palmitate injections or daily oral antipsychotics (randomly assigned from 7 acceptable, prespecified oral antipsychotics) for 15 months.

Cost effectiveness of paliperidone palmitate versus oral antipsychotics in patients with schizophrenia and a history of criminal justice involvement.

Objective: Conduct a cost effectiveness analysis for the Paliperidone palmitate Research In Demonstrating Effectiveness (PRIDE) trial.

Research Design And Methods: PRIDE was a 15 month, prospective, randomized, open-label study in which once monthly paliperidone palmitate significantly delayed the time to first treatment failure (healthcare or criminal justice system [HC/CJS] events) versus oral antipsychotics in recently incarcerated adults with schizophrenia. The present analysis used a state government perspective and HC/CJS event data that were collected on a resource use questionnaire (RUQ) every 3 months.

Design and rationale of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study: a novel comparative trial of once-monthly paliperidone palmitate versus daily oral antipsychotic treatment for delaying time to treatment failure in persons with schizophrenia.

Background: Public health considerations require that clinical trials address the complex "real-world" needs of patients with chronic illnesses. This is particularly true for persons with schizophrenia, whose management is frequently complicated by factors such as comorbid substance abuse, homelessness, and contact with the criminal justice system. In addition, barriers to obtaining health care in the United States often prevent successful community reentry and optimal patient management.

Methylphenidate in children with ADHD with or without learning disability.

Objective: To explore treatment response to Osmotic Release Oral System(®) (OROS) methylphenidate in children with ADHD with and without comorbid learning disability (LD).

Method: Data were analyzed from two 6-week, double-blind, randomized, placebo-controlled, crossover studies evaluating individually determined doses of OROS methylphenidate versus placebo in 135 children (ages 9 to 12 years) with ADHD with or without an LD in reading, math, or both. The sample was demographically diverse, with 31% females and more than 40% minority, predominantly African American and Hispanic.

Population pharmacodynamic modeling of various extended-release formulations of methylphenidate in children with attention deficit hyperactivity disorder via meta-analysis.

Placebo and pharmacodynamic (PD) models were developed which link temporal measures of efficacy in children with attention deficit hyperactivity disorder (ADHD) and methylphenidate (MPH) plasma concentrations from adults. These models can be used to predict daily pediatric clinical measure profiles following administration of different MPH formulations in children without conducting pediatric pharmacokinetic (PK) or PD studies by using more easily obtained adult PK data. Mean PK data from various extended-release MPH formulations studied in adults and mean PD data from nine pediatric efficacy studies were obtained from the literature.

Time course of treatment effect of OROS® methylphenidate in children with ADHD.

Objective: The authors evaluated the time course of the treatment effect of Osmotic-Release Oral System methylphenidate (OROS(®) MPH) HCl (Concerta(®), Raritan, NJ) CII in children with ADHD.

Method: Data were combined from two double-blind, randomized, placebo-controlled, cross-over, analog classroom studies in children (9-12 years) with ADHD. Participants received an individualized dose of placebo or OROS(®) MPH on two laboratory school days.

Pharmacokinetics and therapeutic effect of OROS methylphenidate under different breakfast conditions in children with attention-deficit/hyperactivity disorder.

Objective: To examine the pharmacokinetics (PKs) and pharmacodynamics (PDs) of OROS methylphenidate (OROS MPH) dosed once daily (QD) versus an early standard regimen (immediate-release [IR] MPH dosed three times daily [TID]) under various breakfast conditions.

Methods: This single-center, double-blind, double-dummy, randomized, crossover study of OROS MPH (NCT00269815) in children aged 6 to 12 years with attention-deficit/hyperactivity disorder evaluated the PKs and PDs of MPH given with different breakfast conditions: OROS MPH administered after a high-fat breakfast, after a normal breakfast, or after fasting and IR MPH administered after a normal breakfast or after fasting in the morning and at two subsequent time points during the day. To maximize information, patients were divided into two groups, each receiving three of the five treatments for 1 day in a three-period, randomized, crossover design.

Academic, behavioral, and cognitive effects of OROS® methylphenidate on older children with attention-deficit/hyperactivity disorder.

Objective: To assess the effect of Osmotic-Release Oral System (OROS) methylphenidate (MPH) on a variety of measures evaluating academic performance, cognition, and social behavior in children with attention-deficit/hyperactivity disorder (ADHD).

Methods: This double-blind, randomized, placebo-controlled, crossover laboratory school study enrolled 78 children aged 9-12 years with ADHD who responded to OROS MPH. After determining individualized OROS MPH dosing (18-54 mg/day), 71 subjects received blinded treatment (OROS MPH or placebo then vice versa) on each of 2 laboratory school days, separated by 1 week.

Effects of OROS methylphenidate on academic, behavioral, and cognitive tasks in children 9 to 12 years of age with attention-deficit/hyperactivity disorder.

Objective: To assess effects of OROS methylphenidate on cognitive and academic tasks in 9 to 12 year olds with attention-deficit/hyperactivity disorder (ADHD).

Methods: A double-blind, within-subject, crossover design was used to compare OROS methylphenidate with placebo in a laboratory classroom setting on several cognitive and academic tasks for 68 children who met randomization criteria.

Results: Performance on the following measures was significantly better when children received individually optimized OROS methylphenidate than placebo: math fluency and accuracy measured by the Permanent Product Math Test, ADHD symptoms observed in the laboratory setting, computerized indices of attention and impulsivity as measured by the Test of Variables of Attention (TOVA), and visual-spatial working memory (Finger Windows Backwards).