Latanoprostene Bunod 0.024% in Patients with Open-Angle Glaucoma Switched from Prior Pharmacotherapy: A Retrospective Chart Review.

Introduction: Latanoprostene bunod 0.024% (LBN, Vyzulta®) is a nitric oxide-donating prostaglandin analog (PGA). We investigated the real-world efficacy and safety of LBN in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) who switched their existing intraocular pressure (IOP)-lowering treatment(s) to LBN. Methods: This non-interventional, multicenter (United States), retrospective chart review included patients aged ≥18 years with OHT and/or mild-to-moderate OAG diagnoses taking 1-2 IOP-lowering treatments at the time of switch to LBN (index visit). Chart-extracted data included demographics, diagnoses, IOP and ocular assessments, other IOP-lowering treatments, adverse events (AEs), and reasons for discontinuation. The main study outcome was IOP change from the index visit to each of the next 2 chart-recorded follow-up visits. Analysis groups included the overall dataset and 2 subgroups of patients switched from PGA therapy to LBN: "PGA-all" subgroup [all patients previously on a PGA with/without another IOP-lowering product] and "PGA-monotherapy" subgroup [patients previously on a PGA alone]). Additional ocular outcomes (eg, visual acuity) were examined, if available. Results: The overall dataset included 49 patients (46 had OAD alone, 2 had OHT alone, and 1 had both). The PGA-all subgroup and PGA-monotherapy subgroups had 41 and 32 patients, respectively. Switching to LBN led to a ~25% IOP reduction from the index visit to Visit 1 that was sustained at Visit 2. IOP findings in the PGA-all and PGA-monotherapy subgroups were consistent with the overall dataset. No meaningful changes in other ocular outcomes were found. Of 14 ocular AEs, 3 were recorded as such (mild in severity, considered unrelated to treatment), and 11 were identified through review of interval ocular histories (no severity/relatedness information); none led to discontinuation. Conclusion: In this short-term retrospective chart review of mild-to-moderate OAG/OHT, switching prior IOP-lowering therapy to LBN produced an additional ~25% IOP reduction and appeared to be well tolerated.

Long-term follow-up of patients with congenital thrombotic thrombocytopenia purpura receiving a plasma-derived factor VIII (Koate) that contains ADAMTS13.

BACKGROUND: Hereditary thrombotic thrombocytopenia purpura (hTTP) is an ultra-rare disorder resulting from an inherited deficiency of ADAMTS13, a von Willebrand factor (VWF)-cleaving metalloprotease. The plasma-derived factor VIII/VWF Koate (FVIII/VWFKoate ) has been shown to contain ADAMTS13, allowing for its use to treat hTTP at home by the patient/caregiver. AIM: Based on prior demonstration of safe and effective use of FVIII/VWFKoate in eight patients with hTTP, we conducted a retrospective study to gather additional data regarding the use of FVIII/VWFKoate for hTTP. METHODS: This was a multicentre, retrospective, noninterventional chart review of patients who had received FVIII/VWFKoate for the management of hTTP. Data collected included demographics, medical history, relevant family history, past use and tolerability of fresh frozen plasma, and details regarding FVIII/VWFKoate therapy. RESULTS: The cohort included 11 patients (seven males, four females) with hTTP, ranging in age at study entry from 2 to 28 years. The average duration of FVIII/VWFKoate therapy was 4.8 years (range, 0.5-6.5 years). Among nine patients using FVIII/VWFKoate as prophylaxis, the normalized annual rate of breakthrough TTP episodes ranged from 0.2 to 1.1 episodes/year. All nine patients who received FVIII/VWFKoate prophylaxis had thrombocytopenia recorded at baseline, while eight (88.9%) did not have thrombocytopenia after using FVIII/VWFKoate . There was one AE (unspecified) attributed to FVIII/VWFKoate . CONCLUSION: These data suggest that FVIII/VWFKoate is a safe and well-tolerated source of the missing ADAMTS13 enzyme in patients with hTTP, producing a marked reduction in thrombocytopenia prevalence, low frequency of TTP episodes, and with the added benefit of self- or caregiver-administration.

Corporate Integrity Agreements: What They Say About Publications, Publication Planning, Transparency, and ICMJE.

Corporate integrity agreements (CIAs) have become a significant means of compliance enforcement for the Office of the Inspector General (OIG) of the US Department of Health and Human Services. The objective of this review is to present in a factual manner common clauses from recent CIAs that affect publications, publication planning, and transparency. Fourteen CIAs issued to biopharmaceutical companies from January 1, 2009, through July 31, 2012, were reviewed. All documents were publicly accessible on the OIG website. Eight CIAs included similar verbiage relating to industry-sponsored publication activities and transparency. Each included specific recommendations for author agreements, publication plans, needs assessments, publication monitoring, posting of study results, and disclosure of relationships with authors. The publishing behaviors OIG seeks to effect are consistent with currently accepted guidelines described in the Uniform Requirements for Manuscripts Submitted to Biomedical Journals, as prepared by the International Committee of Medical Journal Editors (ICMJE) and Good Publication Practices for Communicating Company-sponsored Medical Research (GPP2), as well as added training, monitoring, and reporting requirements. By making clear the importance of publication planning, needs assessments, adherence to ICMJE, and reporting of physician payments, and by becoming readily accessible to everyone, CIAs provide the industry not only with clear direction for, but also an expectation of, responsible behavior when it comes to sponsored medical publications.

Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia.

STUDY OBJECTIVES: To evaluate clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia (VAP), including the implementation of and outcomes associated with deescalation therapy. DESIGN: Prospective, observational, cohort study. SETTING: Twenty ICUs throughout the United States. PATIENTS: A total of 398 ICU patients meeting predefined criteria for suspected VAP. INTERVENTIONS: Prospective, handheld, computer-based data collection regarding routine VAP management according to local institutional practices, including clinical and microbiological characteristics, treatment patterns, and outcomes. MEASUREMENTS AND RESULTS: The most frequent ICU admission diagnoses in patients with VAP were postoperative care (15.6%), neurologic conditions (13.3%), sepsis (13.1%), and cardiac complications (10.8%). The mean (+/- SD) duration of mechanical ventilation prior to VAP diagnosis was 7.3 +/- 6.9 days. Major pathogens were identified in 197 patients (49.5%) through either tracheal aspirate or BAL fluid and included primarily methicillin-resistant Staphylococcus aureus (14.8%), Pseudomonas aeruginosa (14.3%), and other Staphylococcus species (8.8%). More than 100 different antibiotic regimens were prescribed as initial VAP treatment, the majority of which included cefepime (30.4%) or a ureidopenicillin/monobactam combination (27.9%). The mean duration of therapy was 11.8 +/- 5.9 days. In the majority of cases (61.6%), therapy was neither escalated nor deescalated. Escalation of therapy occurred in 15.3% of cases, and deescalation occurred in 22.1%. The overall mortality rate was 25.1%, with a mean time to death of 16.2 days (range, 0 to 49 days). The mortality rate was significantly lower among patients in whom therapy was deescalated (17.0%), compared with those experiencing therapy escalation (42.6%) and those in whom therapy was neither escalated nor deescalated (23.7%; chi2= 13.25; p = 0.001). CONCLUSIONS: Treatment patterns for VAP vary widely from institution to institution, and the overall mortality rate remains unacceptably high. The deescalation of therapy in VAP patients appears to be associated with a reduction in mortality, which is an association that warrants further clinical study.