Which combined oral contraceptives to prescribe with cardiovascular safety in mind?

When prescribing combined oral contraceptives, choose one containing levonorgestrel and low-dose estrogen (20 mcg) to minimize the risks of pulmonary embolism, ischemic stroke, and myocardial infarction

Eliminating the Racial Disparity in Classroom Exclusionary Discipline

Advocates call for schools with high suspension rates to receive technical assistance in adopting “proven-effective” systematic supports. Such supports include teacher professional development. This call is justified given evidence that good teaching matters. But what types of professional development should be funded? Increasingly, research points to the promise of programs that are sustained, rigorous, and focused on teachers’ interactions with students. The current study tests whether a professional development program with these three characteristics helped change teachers’ use of exclusionary discipline practices—especially with their African American students. Exclusionary discipline is when a classroom teacher sends a student to the administrators’ office for perceived misbehavior. Administrators then typically assign a consequence, usually in the form of suspension (in-school or out-of school). The My Teaching Partner-Secondary (MTP-S) aims to improve teachers’ interactions with their students when implementing instruction and managing behavior. MTP-S helps teachers offer clear routines, implement consistent rules, and monitor behavior in a proactive way. The program also supports teachers in developing warm, respectful relationships that recognize students’ needs for autonomy and leadership. Teachers are paired with a coach for an entire school year (sustained approach), they regularly reflect on videorecordings of their classroom instruction and carefully observe how they interact with students, and they apply the validated Classroom Assessment Scoring System (CLASS-S) to improve the quality of their interactions (rigorous approach). In the current study, a randomized controlled trial found that teachers receiving MTP-S relied less on exclusionary discipline compared to the control teachers. Specifically, MTP-S teachers issued fewer exclusionary discipline referrals to their African American students. This is the first study to show that programs like MTP-S that focus on teacher-student interactions in a sustained manner using a rigorous approach can actually reduce the disproportionate use of exclusionary discipline with African American students. More broadly, the findings offer policymakers direction in identifying types of professional development programs that have promise for reducing the racial discipline gap

The Role of the Hypothalamic Paraventricular Nucleus and the Organum Vasculosum Lateral Terminalis in the Control of Sodium Appetite in Male Rats

Angiotensin II (AngII) and aldosterone cooperate centrally to produce a robust sodium appetite. The intracellular signaling and circuitry that underlie this interaction remain unspecified. Male rats pretreated with both deoxycorticosterone (DOC; a synthetic precursor of aldosterone) and central AngII exhibited a marked sodium intake, as classically described. Disruption of inositol trisphosphate signaling, but not extracellular-regulated receptor kinase 1 and 2 signaling, prevented the cooperativity of DOC and AngII on sodium intake. The pattern of expression of the immediate early gene product cFos was used to identify key brain regions that may underlie this behavior. In the paraventricular nuclei (PVN) of the hypothalamus, DOC pretreatment diminished both AngII-induced cFos induction and neurosecretion of oxytocin, a peptide expressed in the PVN. Conversely, in the organum vasculosum lateral terminalis (OVLT), DOC pretreatment augmented cFos expression. Immunohistochemistry identified a substantial presence of oxytocin fibers in the OVLT. In addition, when action potentials in the PVN were inhibited with intraparenchymal lidocaine, AngII-induced sodium ingestion was exaggerated. Intriguingly, this treatment also increased the number of neurons in the OVLT expressing AngII-induced cFos. Collectively, these results suggest that the behavioral cooperativity between DOC and AngII involves the alleviation of an inhibitory oxytocin signal, possibly relayed directly from the PVN to the OVLT

Pharmacy History exhibit (2021)

https://scholarlycommons.pacific.edu/cs-pharmacy/1000/thumbnail.jp

The effect of obsessive compulsive symptoms on psychopathology in patients with schizophrenia

Background: There is a growing interest on the impact of comorbid obsessive-compulsive symptoms (OCS) on the course and severity of schizophrenia in recent years. Objectives: This study determined the prevalence of OCS in schizophrenia patients and the clinical outcomes of the comorbidity. Methods: A total of 220 schizophrenia patients were recruited. All the participants completed Structure Clinical Interview version, Yale Brown Obsessive Compulsive Scale, Calgary Depression Scale for Schizophrenia, Columbia Suicide Severity Rating Scale and World Health Organization Quality of Life – Brief Version (WHOQOL-BREF). Results: Significantly higher number of schizophrenia patients with OCS were taking Clozapine (p = 0.023) and antidepressants (p = 0.013). Schizophrenia patients with OCS showed more severe positive (p < 0.001) and general symptoms (p < 0.001) of schizophrenia, higher depressive symptoms (p = 0.013), higher suicidality (p < 0.001), more hospitalization (p = 0.044), poorer physical (p = 0.034) and psychological (p = 0.032) domain in WHOQOLBREF. Discussion: Schizophrenia patients with OCS are associated with more severe psychopathology and depressive symptoms which subsequently suffered poorer physical and psychological health. Hence, recognition of OCS in schizophrenia and early initiation of effective treatment may be able to reduce the burden for people with chronic mental illness

The Role of the Hypothalamic Paraventricular Nucleus and the Organum Vasculosum Lateral Terminalis in the Control of Sodium Appetite in Male Rats

Angiotensin II (AngII) and aldosterone cooperate centrally to produce a robust sodium appetite. The intracellular signaling and circuitry that underlie this interaction remain unspecified. Male rats pretreated with both deoxycorticosterone (DOC; a synthetic precursor of aldosterone) and central AngII exhibited a marked sodium intake, as classically described. Disruption of inositol trisphosphate signaling, but not extracellular-regulated receptor kinase 1 and 2 signaling, prevented the cooperativity of DOC and AngII on sodium intake. The pattern of expression of the immediate early gene product cFos was used to identify key brain regions that may underlie this behavior. In the paraventricular nuclei (PVN) of the hypothalamus, DOC pretreatment diminished both AngII-induced cFos induction and neurosecretion of oxytocin, a peptide expressed in the PVN. Conversely, in the organum vasculosum lateral terminalis (OVLT), DOC pretreatment augmented cFos expression. Immunohistochemistry identified a substantial presence of oxytocin fibers in the OVLT. In addition, when action potentials in the PVN were inhibited with intraparenchymal lidocaine, AngII-induced sodium ingestion was exaggerated. Intriguingly, this treatment also increased the number of neurons in the OVLT expressing AngII-induced cFos. Collectively, these results suggest that the behavioral cooperativity between DOC and AngII involves the alleviation of an inhibitory oxytocin signal, possibly relayed directly from the PVN to the OVLT

Inhaled methoxyflurane (Penthrox®) versus placebo for injury-associated analgesia in children - The MAGPIE trial (MEOF-002): Study protocol for a randomised controlled trial

BackgroundPain from injuries is one of the commonest symptoms in children attending emergency departments (EDs), and this is often inadequately treated in both the pre-hospital and ED settings, in part due to challenges of continual assessment and availability of easily administered analgesic options. Pain practices are therefore a key research priority, including within the field of paediatric emergency medicine. Methoxyflurane, delivered via a self-administered Penthrox® inhaler, belongs to the fluorinated hydrocarbon group of volatile anaesthetics and is unique among the group in having analgesic properties at low doses. Despite over 30 years of clinical acute analgesia use, and a large volume of evidence supporting its safety and efficacy, there is a paucity of randomised controlled trial data for Penthrox®.MethodsThis is an international multi-centre randomised, double-blind, placebo-controlled phase III trial assessing the efficacy and safety of methoxyflurane delivered via the Penthrox® inhaler for the management of moderate to severe acute traumatic pain in children and young people aged 6–17 years. Following written informed consent, eligible participants are randomised to self-administer either inhaled methoxyflurane (maximum dose of 2 × 3 ml) or normal saline placebo (maximum dose 2 × 5 ml). Patients, treating clinicians and research nurses are blinded to the treatment. The primary outcome is the change in pain intensity at 15 min after the commencement of treatment, as measured by the Visual Analogue Scale (VAS) or the Wong-Baker FACES® Pain Rating scale, with the latter converted to VAS values. Secondary outcome measures include the number and proportion of responders who achieve a 30% reduction in VAS score compared to baseline, rescue medication requested, time and number of inhalations to first pain relief, global medication performance assessment by the patient, clinician and research nurse, and evaluation of adverse events experienced during treatment and during the subsequent 14 ± 2 days. The primary analysis will be by intention to treat. The total sample size is 110 randomised and treated patients per treatment arm.DiscussionThe Methoxyflurane AnalGesia for Paediatric InjuriEs (MAGPIE) trial will provide efficacy and safety data for methoxyflurane administered via the Penthrox® inhaler, in children and adolescents who present to EDs with moderate to severe injury-related pain.Trial registrationEudraCT, 2016–004290-41. Registered on 11 April 2017.ClinicalTrials.gov, NCT03215056. Registered on 12 July 2017

Phase 1 study of the MDM2 antagonist RO6839921 in patients with acute myeloid leukemia

In acute myeloid leukemia (AML), TP53 mutations and dysregulation of wild-type p53 is common and supports an MDM2 antagonist as a therapy. RO6839921 is an inactive pegylated prodrug of the oral MDM2 antagonist idasanutlin (active principle [AP]) that allows for IV administration. This phase 1 monotherapy study evaluated the safety, pharmacokinetics, and pharmacodynamics of RO6839921 in patients with AML. Primary objectives identified dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary objectives assessed pharmacokinetic, pharmacodynamic, and antileukemic activity. A total of 26 patients received 120-300 mg AP of idasanutlin. The MTD was 200 mg, with DLTs at 250 (2/8 patients) and 300 mg (2/5). Treatment-related adverse events in \u3e20% of patients were diarrhea, nausea, vomiting, decreased appetite, and fatigue. Six deaths (23.1%) occurred, all unrelated to treatment. Pharmacokinetics showed rapid and near-complete conversion of the prodrug to AP and dose-proportional exposure across doses. Variability ranged from 30%-47% (22%-54% for idasanutlin). TP53 was 21 (87.5%) wild-type and 3 mutant (12.5%). The composite response rate (complete remission [CR], CR with incomplete hematologic recovery/morphological leukemia-free state [CRi/MLFS], or CR without platelet recovery [CRp]) was 7.7%. Antileukemic activity (CR, CRi/MLFS, partial response, hematologic improvement/stable disease) was observed in 11 patients (disease control rate, 42%): 10/11 were TP53 wild-type; 1 had no sample. p53 activation was demonstrated by MIC-1 induction and was associated with AP exposure. There was not sufficient differentiation or improvement in the biologic or safety profile compared with oral idasanutlin to support continued development of RO6839921. NCT02098967

Bone health among patients with primary aldosteronism : a systematic review and meta-analysis

INTRODUCTION: Recent studies showed a possible association between hyperaldosteronism and secondary hyperparathyroidism leading to reduced bone health, however results are conflicting. EVIDENCE ACQUISITION: We conducted a meta-analysis to evaluate the relationship between primary aldosteronism (PA) with bone biochemical markers and to assess bone mineral density in patients with primary aldosteronism. EVIDENCE SYNTHESIS: A total of 939 subjects were examined (37.5% with PA). Patients with PA had signifi- cantly higher serum parathyroid hormone, lower serum calcium, higher urine calcium excretion and higher serum alkaline phosphatase compared to patients without PA, with no significant difference in serum vitamin D between both groups. Bone mineral density of lumbar spine, femoral neck and total neck of femur were similar between two groups. With PA treatment, there was a significant increment in serum calcium and reduction in serum parathyroid hormone. CONCLUSIONS: PA is associated with hypercalciuria with subsequent secondary hyperparathyroidism. This potentially affects bone health. We recommend this to be part of complication screening among patients with PA. (Cite this article as: Loh HH, Yee A, Loh HS. Bone health among patients with primary aldosteronism: a systematic review and meta-analysis. Minerva Endocrinol 2019;44:000–000. DOI: 10.23736/S0391-1977.18.02867-5