Prescription drugs with potential for misuse in Irish prisons: analysis of national prison prescribing trends, by gender and history of opioid use disorder, 2012 to 2020.

BACKGROUND: Pharmacotherapy is essential for the delivery of an equivalent standard of care in prison. Prescribing can be challenging due to the complex health needs of prisoners and the risk of misuse of prescription drugs. This study examines prescribing trends for drugs with potential for misuse (opioids, benzodiazepines, Z-drugs, and gabapentinoids) in Irish prisons and whether trends vary by gender and history of opioid use disorder (OUD). METHODS: A repeated cross-sectional study between 2012 and 2020 using electronic prescribing records from the Irish Prison Services, covering all prisons in the Republic of Ireland was carried out. Prescribing rates per 1,000 prison population were calculated. Negative binomial (presenting adjusted rate ratios (ARR) per year and 95% confidence intervals) and joinpoint regressions were used to estimate time trends adjusting for gender, and for gender specific analyses of prescribing trends over time by history of OUD. RESULTS: A total of 10,371 individuals were prescribed opioid agonist treatment (OAT), opioids, benzodiazepines, Z-drugs or gabapentinoids during study period. History of OUD was higher in women, with a median rate of 597 per 1,000 female prisoners, compared to 161 per 1,000 male prisoners. Prescribing time trends, adjusted for gender, showed prescribing rates decreased over time for prescription opioids (ARR 0.82, 95% CI 0.80-0.85), benzodiazepines (ARR 0.99, 95% CI 0.98-0.999), Z-drugs (ARR 0.90, 95% CI 0.88-0.92), but increased for gabapentinoids (ARR 1.07, 95% CI 1.05-1.08). However, prescribing rates declined for each drug class between 2019 and 2020. Women were significantly more likely to be prescribed benzodiazepines, Z-drugs and gabapentinoids relative to men. Gender-specific analyses found that men with OUD, relative to men without, were more likely to be prescribed benzodiazepines (ARR 1.49, 95% CI 1.41-1.58), Z-drugs (ARR 10.09, 95% CI 9.0-11.31), gabapentinoids (ARR 2.81, 95% CI 2.66-2.97). For women, history of OUD was associated with reduced gabapentinoid prescribing (ARR 0.33, 95% CI 0.28-0.39). CONCLUSIONS: While the observed reductions in prescription opioid, benzodiazepine and Z-drug prescribing is consistent with guidance for safe prescribing in prisons, the increase in gabapentinoid (primarily pregabalin) prescribing and the high level of prescribing to women is concerning. Our findings suggest targeted interventions may be needed to address prescribing in women, and men with a history of OUD.

A new era of assessment for neonatal-perinatal medicine trainees: milestones 2.0.

To optimize post-graduate competency-based assessment for medical trainees, the Accreditation Council for Graduate Medical Education initiated a sub-specialty-specific revision of the existing Milestones 1.0 assessment framework in 2016. This effort was intended to increase both the effectiveness and accessibility of the assessment tools by incorporating specialty-specific performance expectations for medical knowledge and patient care competencies; decreasing item length and complexity; minimizing inconsistencies across specialties through the development of common "harmonized" milestones; and providing supplemental materials, including examples of expected behaviors at each developmental level, suggested assessment strategies, and relevant resources. This manuscript describes the efforts of the Neonatal-Perinatal Medicine Milestones 2.0 Working Group, outlines the overall intent of Milestones 2.0, compares the novel Milestones to the original version, and details the materials contained in the novel supplemental guide. This new tool should enhance NPM fellow assessment and professional development while maintaining consistent performance expectations across specialties.

Prescription drugs with potential for misuse: protocol for a multi-indicator analysis of supply, detection and the associated health burden in Ireland between 2010 and 2020.

INTRODUCTION: There is an increasing concern about the misuse of prescription drugs. Misuse refers to the intentional repurposing of prescribed drugs and/or the use of illicitly sourced prescription drugs, which may be counterfeit or contaminated. Drugs with the greatest potential for misuse are prescription opioids, gabapentinoids, benzodiazepines, Z-drugs and stimulants. OBJECTIVE: The aim of this study is to provide a comprehensive analysis of the supply, patterns of use and health burden associated with prescription drugs with potential for misuse (PDPM) in Ireland between 2010 and 2020. Three inter-related studies will be carried out. The first study will describe trends in supply of PDPM using law enforcement drug seizures data and national prescription records from national community and prison settings. The second study aims to estimate trends in the detection of PDPM across multiple early warning systems using national forensic toxicology data. The third study aims to quantify the health burden associated with PDPM nationally, using epidemiological indicators of drug-poisoning deaths, non-fatal intentional drug overdose presentations to hospitals and drug treatment demand. METHODS AND ANALYSIS: A retrospective observational study design, with repeated cross-sectional analyses, using negative binomial regression models or, where appropriate, joinpoint regression. ETHICS AND DISSEMINATION: The study has received approval from the RCSI Ethics Committee (REC202202020). Results will be disseminated in peer-reviewed journals, scientific and drug policy meetings and with key stakeholders via research briefs.

Randomized Controlled Trial Examining the Efficacy of Adding Financial Incentives to Best practices for Smoking Cessation Among pregnant and Newly postpartum Women.

We report results from a single-blinded randomized controlled trial examining financial incentives for smoking cessation among 249 pregnant and newly postpartum women. Participants included 169 women assigned to best practices (BP) or BP plus financial incentives (BP + FI) for smoking cessation available through 12-weeks postpartum. A third condition included 80 never-smokers (NS) sociodemographically-matched to women who smoked. Trial setting was Burlington, Vermont, USA, January, 2014 through January, 2020. Outcomes included 7-day point-prevalence abstinence antepartum and postpartum, and birth and other infant outcomes during 1st year of life. Reliability and external validity of results were assessed using pooled results from the current and four prior controlled trials coupled with data on maternal-smoking status and birth outcomes for all 2019 singleton live births in Vermont. Compared to BP, BP + FI significantly increased abstinence early- (AOR = 9.97; 95%CI, 3.32-29.93) and late-pregnancy (primary outcome, AOR = 5.61; 95%CI, 2.37-13.28) and through 12-weeks postpartum (AOR = 2.46; CI,1.05-5.75) although not 24- (AOR = 1.31; CI,0.54-3.17) or 48-weeks postpartum (AOR = 1.33; CI,0.55-3.25). There was a significant effect of trial condition on small-for-gestational-age (SGA) deliveries (χ2 [2] = 9.01, P = .01), with percent SGA deliveries (+SEM) greatest in BP, intermediate in BP + FI, and lowest in NS (17.65 + 4.13, 10.81 + 3.61, and 2.53 + 1.77, respectively). Reliability analyses supported the efficacy of financial incentives for increasing abstinence antepartum and postpartum and decreasing SGA deliveries; external-validity analyses supported relationships between antepartum cessation and SGA risk. Adding financial incentives to Best Practice increases smoking cessation among antepartum and postpartum women and improves other maternal-infant outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02210832.

Essentials of neonatal-perinatal medicine fellowship: innovations in medical education.

Due to the changing complex healthcare environment, educational innovation is essential to meet the needs of current and future neonatal-perinatal medicine (NPM) leaders. Greater clinical demands, decreased academic funding, and expanded graduate medical education program requirements have negatively impacted time for teaching and educational scholarship potentially limiting innovation in the field. By focusing on adult learning principles, embracing technology, and promoting collaboration, today's educators are preparing the next generation of neonatologists. Current innovations include regionalizing simulation boot camps, leveraging virtual learning to increase accessibility, developing niche training opportunities, and incorporating population health principles within existing quality initiatives. Areas in need of additional innovation include faculty and fellow development for teaching skills, expansion of educational networks, and dissemination and financial support of educational scholarship. These efforts and future innovations will require medical institutions and national NPM organizations to further invest in the medical educator as part of their missions.

Indomethacin for symptomatic patent ductus arteriosus in preterm infants.

BACKGROUND: Symptomatic patent ductus arteriosus (PDA) is associated with mortality and morbidity in preterm infants. In these infants, prophylactic use of indomethacin, a non-selective cyclooxygenase inhibitor, has demonstrated short-term clinical benefits. The effect of indomethacin in preterm infants with a symptomatic PDA remains unexplored. OBJECTIVES: To determine the effectiveness and safety of indomethacin (given by any route) compared to placebo or no treatment in reducing mortality and morbidity in preterm infants with a symptomatic PDA. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 7), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 31 July 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included RCTs and quasi-RCTs that compared indomethacin (any dose, any route) versus placebo or no treatment in preterm infants. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal, with separate evaluation of trial quality and data extraction by at least two review authors. We used the GRADE approach to assess the certainty of evidence for the following outcomes: failure of PDA closure within one week of administration of the first dose of indomethacin; bronchopulmonary dysplasia (BPD) at 28 days' postnatal age and at 36 weeks' postmenstrual age; proportion of infants requiring surgical ligation or transcatheter occlusion; all-cause neonatal mortality; necrotizing enterocolitis (NEC) (≥ Bell stage 2); and mucocutaneous or gastrointestinal bleeding. MAIN RESULTS: We included 14 RCTs (880 preterm infants). Four out of the 14 included studies were judged to have high risk of bias in one or more domains. Indomethacin administration was associated with a large reduction in failure of PDA closure within one week of administration of the first dose (risk ratio (RR) 0.30, 95% confidence interval (CI) 0.23 to 0.38; risk difference (RD) -0.52, 95% CI -0.58 to -0.45; 10 studies, 654 infants; high-certainty evidence). There may be little to no difference in the incidence of BPD (BPD defined as supplemental oxygen need at 28 days' postnatal age: RR 1.45, 95% CI 0.60 to 3.51; 1 study, 55 infants; low-certainty evidence; BPD defined as supplemental oxygen need at 36 weeks' postmenstrual age: RR 0.80, 95% CI 0.41 to 1.55; 1 study, 92 infants; low-certainty evidence) and probably little to no difference in mortality (RR 0.78, 95% CI 0.46 to 1.33; 8 studies, 314 infants; moderate-certainty evidence) with use of indomethacin for symptomatic PDA. No differences were demonstrated in the need for surgical PDA ligation (RR 0.66, 95% CI 0.33 to 1.29; 7 studies, 275 infants; moderate-certainty evidence), in NEC (RR 1.27, 95% CI 0.36 to 4.55; 2 studies, 147 infants; low-certainty evidence), or in mucocutaneous or gastrointestinal bleeding (RR 0.33, 95% CI 0.01 to 7.58; 2 studies, 119 infants; low-certainty evidence) with use of indomethacin compared to placebo or no treatment. Certainty of evidence for BPD, surgical PDA ligation, NEC, and mucocutaneous or gastrointestinal bleeding was downgraded for very serious or serious imprecision. AUTHORS' CONCLUSIONS: High-certainty evidence shows that indomethacin is effective in closing a symptomatic PDA compared to placebo or no treatment in preterm infants. Evidence is insufficient regarding effects of indomethacin on other clinically relevant outcomes and medication-related adverse effects.

A Pilot Randomized, Controlled, Double-Blind Trial of Bumetanide to Treat Neonatal Seizures.

OBJECTIVE: In the absence of controlled trials, treatment of neonatal seizures has changed minimally despite poor drug efficacy. We tested bumetanide added to phenobarbital to treat neonatal seizures in the first trial to include a standard-therapy control group. METHODS: A randomized, double-blind, dose-escalation design was employed. Neonates with postmenstrual age 33 to 44 weeks at risk of or with seizures were eligible. Subjects with electroencephalography (EEG)-confirmed seizures after ≥20 and <40mg/kg phenobarbital were randomized to receive additional phenobarbital with either placebo (control) or 0.1, 0.2, or 0.3mg/kg bumetanide (treatment). Continuous EEG monitoring data from ≥2 hours before to ≥48 hours after study drug administration (SDA) were analyzed for seizures. RESULTS: Subjects were randomized to treatment (n = 27) and control (n = 16) groups. Pharmacokinetics were highly variable among subjects and altered by hypothermia. The only statistically significant adverse event was diuresis in treated subjects (48% vs 13%, p = 0.02). One treated (4%) and 3 control subjects died (19%, p = 0.14). Among survivors, 2 of 26 treated subjects (8%) and 0 of 13 control subjects had hearing impairment, as did 1 nonrandomized subject. Total seizure burden varied widely, with much higher seizure burden in treatment versus control groups (median = 3.1 vs 1.2 min/h, p = 0.006). There was significantly greater reduction in seizure burden 0 to 4 hours and 2 to 4 hours post-SDA (both p < 0.01) compared with 2-hour baseline in treatment versus control groups with adjustment for seizure burden. INTERPRETATION: Although definitive proof of efficacy awaits an appropriately powered phase 3 trial, this randomized, controlled, multicenter trial demonstrated an additional reduction in seizure burden attributable to bumetanide over phenobarbital without increased serious adverse effects. Future trials of bumetanide and other drugs should include a control group and balance seizure severity. ANN NEUROL 2021;89:327-340.

Optimizing High-risk Infant Follow-up in Nonresearch-based Paradigms: The New England Follow-up Network.

OBJECTIVES: To establish the first regional quality improvement collaborative solely dedicated to follow-through care of high-risk infants after Neonatal intensive care unit (NICU) discharge and to characterize extremely low birth weight (ELBW) follow-up in New England. METHODS: Eleven of 14 follow-up programs in New England partnered with the Vermont Oxford Network (VON) ELBW project for an initial data collection project. We collected information about the health status and developmental outcomes of infants born ≤1,000 g or younger than 28 weeks 2014-2016 at the 18-24 months corrected for gestational age (CGA) follow-up visit. VON collected and compiled the data. RESULTS: Of 993 eligible infants, 516 (52.0%) had follow-up visits. The rehospitalization rate was 33.9%, mostly respiratory illness. Ninety-six children (19.3%) had weight less than 10th percentile and 44 (8.9%) had weight less than third percentile at 18-24 months. Only 170 (61.4%) children had recommended hearing screening after NICU discharge. Forty-six (9.1%) had cerebral palsy; 81 of the 441 infants that completed all 3 sections of the Bayley Scales of Infant Development, third edition (18.4%) had any composite score less than 70. Over half of the social and demographic data were missing. CONCLUSION: Most quality initiatives in neonatology stop at NICU discharge. This first project by the New England Follow-up Network showed a low rate for clinical follow-up. It demonstrated many opportunities to improve postdischarge follow-through specific to NICU-based care. Future projects will aim to improve the quality of follow-through services through collaborative learning, data sharing, and comparative outcomes.

Evaluating peer-supported screening as a hepatitis C case-finding model in prisoners.

BACKGROUND: Hepatitis C Virus (HCV) infection is endemic in prison populations, and HCV management in prisons is suboptimal. Incarceration is a public health opportunity to target this cohort. Community peer support increases HCV screening and treatment uptake. Prison peer workers have the potential to support the engagement of prisoners with health services and reduce stigma. This study's primary aim is to evaluate peer-supported screening as a model of active HCV case finding with a secondary aim to describe the HCV cascade among those infected including linkage to care and treatment outcomes. METHODS: An observational study was conducted in a medium-security Irish male prison housing 538 inmates, using a risk-based questionnaire, medical records, peer-supported screening, laboratory-based HCV serology tests and mobile elastography. RESULTS: A prison peer-supported screening initiative engaged large numbers of prisoners in HCV screening (n = 419). The mean age of participants was 32.8 years, 92% were Irish and 33% had a history of injecting drug use. Multiple risk factors for HCV acquisition were identified including needle sharing (16%). On serological testing, 87 (21%) were HCV Ab +ve and 50 (12%) were HCV RNA +ve of whom 80% were fibroscaned (25% showing evidence of liver disease). Eighty-six percent of those with active infection were linked with HCV care, with 33% undergoing or completing treatment. There was a high concordance with HCV disclosure at committal and serological testing (96% for HCV Ab +ve and 89% for HCV Ab -ve). CONCLUSION: Peer-supported screening is an effective active HCV case-finding model to find and link prisoners with untreated active HCV infection to HCV care.

The seroprevalence of untreated chronic hepatitis C virus (HCV) infection and associated risk factors in male Irish prisoners: a cross-sectional study, 2017.

IntroductionData on chronic hepatitis C (HCV) infection prevalence in European prisons are incomplete and impact the public health opportunity that incarceration provides.AimsWe aimed to estimate the seroprevalence of untreated chronic HCV infection and to identify associated risk factors in an Irish male prison.MethodsWe conducted a cross-sectional study involving a researcher-administered questionnaire, review of medical records and HCV serology.ResultsOf 422 prisoners (78.0% of the study population) who participated in the study, 298 (70.6%) completed the questionnaire and 403 (95.5%) were tested for HCV antibodies. Of those tested, 92 (22.8%) were HCV antibody-positive, and of those, 53 (57.6%) were HCV RNA-positive, 23 (25.0%) had spontaneous clearance, 16 (17.4%) had a sustained viral response, 10 (11.0%) were co-infected with HIV and six (6.0%) with HBV. The untreated chronic HCV seroprevalence estimate was 13.1% and the seroprevalence of HCV among prisoners with a history of injecting drug use (IDU) was 79.7%. Risk factors significantly associated with past HCV infection were IDU (p < 0.0001), having received a prison tattoo (p < 0.0001) or a non-sterile community tattoo (p < 0.0001), sharing needles and other drug-taking paraphernalia (p < 0.0001). Small numbers of prisoners had a history of sharing razors (n=10; 3.4%) and toothbrushes (n=3; 1.0%) while incarcerated. On multivariable analysis, history of receiving a non-sterile community tattoo was the only significant risk factor associated with HCV acquisition (after IDU was removed from the model) (p = 0.005, ß = 0.468).ConclusionThe level of untreated chronic HCV infection in Irish prisons is high, with IDU the main associated risk.

Automatic measurement of interburst interval in premature neonates using range EEG.

OBJECTIVE: To explore the direct measure of EEG amplitude (range EEG, rEEG) for detection of interburst intervals (IBIs) and bursts in neonates. METHODS: Previously described 177 two-channel EEG recordings 3-6h long from 26 preterm infants (median gestational age of 26 weeks) at 23-38 weeks post-menstrual age (PMA) without major abnormalities were used to test four definitions of IBI detection algorithms with various settings of the parameters. RESULTS: As the basis for all four algorithms we developed the aggregation of rEEG signal over the channels by taking its maximum, and method of EEG trace selection at different phases of sleep-wake cycle (with different degree of discontinuity). The two less restrictive algorithms - with one and two amplitude thresholds - turned to be the most promising definitions. There were enough IBI detections for analysis, with no substantial difference in mean and maximum values of intervals. The longest IBI were measured at the location of greater discontinuity. Values of bursts and IBI indices as well as association with PMA were close to the published normative values derived manually. CONCLUSIONS: rEEG as a direct measure of EEG amplitude can be used for detection of bursts and IBI. SIGNIFICANCE: The automatic measurement of IBI based on rEEG provides a basis for improvements in neonatal brain monitoring.

Peak-to-peak amplitude in neonatal brain monitoring of premature infants.

OBJECTIVE: To assess the strength of association between alternative measures of electroencephalographic (EEG) signal peak-to-peak amplitude (ppA) and postmenstrual age (PMA) among a cohort of extremely premature infants. METHODS: 177 Two-channel EEG recordings 3-6h long were collected from 26 infants born before 29weeks of gestation. The raw EEG was converted into four different continuous measures of ppA: amplitude-integrated EEG (aEEG), range-EEG (rEEG), Gotman and Gloor's half-wave decomposition (HWD), and root of mean squares (RMS). For each ppA-measure EEG indices including mean, median, and 5% margins; indices of spread (width, standard deviation, coefficient of variation), and asymmetry were calculated for each 1min epoch. The medians of each index for the entire recording were tested for association with PMA using linear mixed models. RESULTS: The log-transformed values of aEEG and rEEG indices of spread were highly associated with PMA (fixed effects R(ß)(2)=0.84-0.89). CONCLUSIONS: Indices of spread by aEEG or rEEG can be used as indicators of neonatal brain maturation. However, rEEG produces the absolute values that most closely approximate the raw EEG amplitudes. SIGNIFICANCE: The indices of spread and rEEG as a measure of ppA provide a basis for improvements in neonatal EEG monitoring.

Low dose intrathecal morphine facilitates early extubation after cardiac surgery: results of a retrospective continuous quality improvement audit.

PURPOSE: To document one centre's experience with a multimodal analgesic approach, with or without low dose intrathecal morphine (ITM), in facilitating "fast-track" recovery in patients undergoing cardiac surgery. METHODS: Records of 131 consecutive patients who underwent first time elective cardiac surgery during a four-month period in 2000 were reviewed. Patients were divided into two groups: those receiving and those not receiving preoperative low dose ITM (< 5 microgxkg(-1)) as part of a multimodal analgesic technique. Demographic and surgical characteristics, postoperative morphine use, time to extubation and requirement for antiemetics were recorded. RESULTS: Overall, 75% of patients were extubated within two hours, and 93% within six hours. Fifty-five patients received, and 76 did not receive, ITM (mean +/- SD 259 +/- 53 microg) along with a multimodal analgesic technique (parasternal infiltration, acetaminophen and indomethacin, and postoperative i.v. morphine). Anesthetic technique involved modest dose opioids, volatile agent and propofol infusion. The groups were similar with respect to preoperative, intraoperative and anesthetic characteristics. Mean extubation time for fast-track patients receiving vs not receiving ITM was 75 +/- 65 vs 117 +/- 85 min (P = 0.003). Intravenous morphine use for the first 12 hr after surgery was also reduced in the ITM group (4.6 +/- 4.1 vs 10.0 +/- 14.8 mg, P = 0.009). There was no difference in rescue antiemetic or antipruritic requirements, failed fast-tracking, or serious adverse events. CONCLUSIONS: Multimodal postoperative analgesia allowed for uneventful early extubation and low opioid requirements. Low dose ITM further facilitated early extubation, and reduced postoperative analgesic requirements.