Implementation of a Level III neonatal intensive care unit was associated with reduced NICU mortality in a resource limited public tertiary care hospital in Guyana, South America.

Neonatal mortality is a significant contributor to child mortality, and there is increasing interest in low resource settings to implement neonatal intensive care practices to lower neonatal mortality. In Guyana, South America neonatal mortality remains relatively high. At Georgetown Public Hospital Corporation (GPHC), the only tertiary referral hospital in Guyana, a Level III NICU was developed starting in January, 2012 with full implementation in September, 2015. In this study, we report the association of the implementation of a Level III NICU with in-hospital neonatal survival at GPHC. Using an observational study design, available data were collected from January 1, 2015 through September 30, 2020. During the study period, there were 30,733 deliveries at GPHC and 4,467 admissions to the NICU at GPHC. There were no significant changes in the numbers of births or NICU admissions during the time of the study. The survival rate for patients admitted to the NICU was ~64% during the first 3 quarters of 2015 with most deaths were caused by sepsis or respiratory failure. By the last quarter of 2015, the NICU survival rate increased dramatically and has been sustained at ~87% (p<0.0001). The inborn mortality rate at GPHC, calculated as a percentage of all live births at GPHC, was 2.9% prior to the full implementation of the NICU and was 1.4% after the full implementation of the NICU (p<0.0001). These findings suggest that the implementation of a Level III NICU at GPHC was associated with an improvement in survival to NICU discharge in a resource limited setting.

Associations Between Adverse Childhood Experiences and Trauma Among Young People Who Offend: A Systematic Literature Review.

This systematic review synthesized current knowledge about the prevalence of adverse childhood experiences (ACEs) among young people known to have offended and examined evidence of associations between ACEs, trauma symptoms, and offending behavior. A systematic search of English-language, peer-reviewed studies published from the year 2000 onwards was conducted. A final pool of 124 studies that reported quantitative data were included in the review. The Cambridge Quality Checklist for the assessment of studies on offending was used to assess methodological quality of included studies. Pooled data indicated that almost 87% of justice-involved young people across 13 countries experienced at least one traumatic event. The odds of experiencing at least one ACE were over 12 times greater for justice-involved young people compared with nonjustice-involved young people. Prevalence of individual ACEs ranged from 12.2% for childhood sexual abuse to 80.4% for parental separation among justice-involved young people. Those who reported both a higher number and multiple types of ACEs were more likely to be diagnosed with post-traumatic stress symptoms. However, when considering only high-quality studies, there was minimal evidence to suggest that a higher incidence of ACEs predicted trauma symptoms or that trauma symptoms mediated the association between ACEs and offending behavior. Further research is needed to elucidate factors that differentiate young people exposed to ACEs who go on to offend from those who do not. This research is essential to understanding whether ACEs and trauma are drivers of offending behavior and for informing prevention and intervention strategies.

A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study.

BACKGROUND: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. METHODS: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. FINDINGS: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0·02). INTERPRETATION: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. FUNDING: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship.

Characteristics and re-offending outcomes of 'limiting-term' forensic patients found unfit to stand trial in New South Wales, Australia.

There are little published data on the characteristics or outcomes of offenders found unfit to stand trial who receive a 'qualified finding of guilt' in a Special Hearing in New South Wales (NSW) and are detained for a 'limiting term' (LT) under the supervision of the NSW Mental Health Review Tribunal (MHRT). We examined NSW MHRT records linked to re-offending data, to report on the characteristics and outcomes of 69 LT patients in a cohort spanning two decades. The most common diagnoses were schizophrenia (54%) and intellectual disability (33%). Patients were detained on average for 4.2 years, which is slightly shorter than the average maximum term imposed. Of the 55 people for whom criminal record data were available, 9.1% were charged with an offence during the first year post-release and 60% overall were charged for at least one post-release offence during a follow-up period ranging from 4.7 to 11.1 years.

Decriminalizing severe mental illness by reducing risk of contact with the criminal justice system, including for forensic patients.

Risk of contact with the criminal justice system (CJS) is greater among those with mental illness, including severe mental illness-an observation that many argue reflects a process of "criminalizing" mental illness. Forensic patients represent a subgroup at one end of a spectrum of such criminalization, typically with histories of serious violence and psychotic illness. Strategies for decriminalizing mental illness in this context should consider a range of approaches, including intervening to prevent CJS contact in those with severe mental illness, particularly in the early or emerging stages of psychosis. However, it may be that even gold standard mental healthcare applied universally is insufficient to address CJS contact risks. While there is now an extensive literature documenting the relatively low rates of repeat CJS contact for forensic patients released from secure care, appropriate comparison groups are lacking and the key ingredients of any benefits of treatment are unknown. The CJS may well have something to learn from forensic mental health systems and services given the abject failure to stem rates of prison-release reoffending internationally. Understanding how to best identify risk and effectively intervene to prevent CJS contact in those with mental illness, whether early in the course of psychosis or following release from secure care, remains a priority for those seeking to address the criminalization of mentally illness in our communities.

Breaking the Cycle: Understanding the Needs of Women Involved in the Criminal Justice System and the Role of Mentoring in Promoting Desistance.

An increasingly popular gender-specific intervention to assist women involved in the criminal justice system (e.g., ex-prisoners) is mentoring. However, despite the growing popularity of mentoring, there is a dearth of literature that has explored the intervention's efficacy, particularly as it relates to women involved in the criminal justice system. In the current study, client files of 64 women in a one-to-one mentoring program in Australia were examined to identify (a) the social and practical needs and obstacles faced by women overcoming their involvement with the justice system, and (b) the extent to which mentoring addressed these needs and obstacles. The results show that consistent with previous research, many of the women experienced a range of social and practical difficulties that impeded the desistance process. For a large portion of the women, however, mentoring helped overcome some difficulties by enhancing positive social capital in their lives. These findings are discussed in the context of how mentoring relationships can act as key turning points in the lives of women involved in the criminal justice system.

Pharmacokinetic Profiles of Ticagrelor Orodispersible Tablets in Healthy Western and Japanese Subjects.

BACKGROUND AND OBJECTIVES: Ticagrelor is an antiplatelet agent for patients with acute coronary syndrome or a history of myocardial infarction. Two studies compared pharmacokinetic profiles of orodispersible (OD) ticagrelor tablets versus immediate-release (IR) tablets in Western and Japanese subjects. METHODS: Both studies were open-label, randomized, crossover, single-center trials. Thirty-six healthy subjects (94% white, 6% other race; Western study NCT02400333) and 42 Japanese healthy subjects (Japanese study NCT02436577) received a single 90-mg ticagrelor dose as an OD tablet [with/without water, and via a nasogastric tube (Western study only)], and an IR tablet; washout between treatments was ≥7 days. Assessments included ticagrelor and AR-C124910XX (active metabolite) plasma concentrations for pharmacokinetic analyses, and safety evaluations. RESULTS: In the Western study, the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for ticagrelor and AR-C124910XX maximum plasma concentration (C max) and area under the plasma concentration-time curve (AUC) were within the acceptance interval (80%-125%) for OD tablets (with/without water, via a nasogastric tube) versus the IR tablet; except for an ~15% lowering of ticagrelor C max (90% CI: 76.77%-93.78%) for the OD tablet taken with water. In the Japanese study, 90% CIs of the GMRs for AUC and C max of both ticagrelor and AR-C124910XX were all within the acceptance intervals for the OD (with/without water) versus IR tablet. No new safety issues were identified. CONCLUSIONS: Ticagrelor administered as an OD tablet to Western (without water, and via a nasogastric tube) and Japanese (with/without water) subjects was bioequivalent to the IR tablet.

Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).

BACKGROUND: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). METHODS: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. RESULTS: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. CONCLUSIONS: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

Solid lipid nanoparticles for nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation

In the present study, haloperidol (HP)-loaded solid lipid nanoparticles (SLNs) were prepared to enhance the uptake of HP to brain via intranasal (i.n.) delivery. SLNs were prepared by a modified emulsification-diffusion technique and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release, and stability. All parameters were found to be in an acceptable range. In vitro drug release was found to be 94.16±4.78% after 24 h and was fitted to the Higuchi model with a very high correlation coefficient (R (2)=0.9941). Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography. The brain/blood ratio at 0.5 h for HP-SLNs i.n., HP sol. i.n. and HP sol. i.v. was 1.61, 0.17 and 0.031, respectively, indicating direct nose-to-brain transport, bypassing the blood-brain barrier. The maximum concentration (C max) in brain achieved from i.n. administration of HP-SLNs (329.17±20.89 ng/mL, T max 2 h) was significantly higher than that achieved after i.v. (76.95±7.62 ng/mL, T max 1 h), and i.n. (90.13±6.28 ng/mL, T max 2 h) administration of HP sol. The highest drug-targeting efficiency (2362.43%) and direct transport percentage (95.77%) was found with HP-SLNs as compared to the other formulations. Higher DTE (%) and DTP (%) suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations.

Acid control cannot be improved with a modified-release formulation of a proton pump inhibitor compared with twice-daily dosing of the conventional formulation.

AIM: The aim of this study was to compare acid control with a once-daily (od) modified-release (MR) formulation of esomeprazole vs. the conventional formulation (CF) dosed twice-daily (bid). METHODS: In a randomized, five-way crossover study, 55 healthy volunteers underwent 24-h intragastric pH monitoring after 5-day treatment with MR esomeprazole (40, 60 or 80 mg od) and CF esomeprazole (20 or 40 mg bid). RESULTS: Modified-release 60 and 80 mg od resulted in a significantly longer time with intragastric pH > 4 than MR 40 mg od (77.1 and 79.0% vs. 66.4%, respectively; both p < 0.05). At equivalent total daily doses, CF 20 mg bid led to a significantly longer time with intragastric pH > 4 than MR 40 mg od (72.3 vs. 66.4%; p < 0.05), and CF 40 mg bid led to a significantly longer time with pH > 4 than MR 80 mg od (85.5 vs. 79.0%; p < 0.05). CONCLUSIONS: At equivalent total daily doses, the MR formulation of esomeprazole provides less 24-h acid control than the conventional formulation dosed twice-daily.