Successful antenatal treatment of MAGED2-related Bartter syndrome and review of treatment options and efficacy.

A new form of transient antenatal Bartter syndrome (aBS) was recently identified that is associated with the X-linked MAGED2 variant. Case reports demonstrate that this variant leads to severe polyhydramnios that may result in preterm birth or pregnancy loss. There is limited but promising evidence that amnioreductions may improve fetal outcomes in this rare condition. We report a woman with two affected pregnancies. In the first pregnancy, the patient was diagnosed with mild-to-moderate polyhydramnios in the second trimester that ultimately resulted in preterm labor and delivery at 25 weeks with fetal demise. Whole exome sequencing of the amniotic fluid sample resulted after the pregnancy loss and revealed a c.1337G>A MAGED2 variant that was considered diagnostically. The subsequent pregnancy was confirmed by chorionic villi sampling to also be affected by this variant. The pregnancy was managed with frequent ultrasounds and three amnioreductions that resulted in spontaneous vaginal delivery at 37 weeks and 6 days of a viable newborn with no evidence of overt electrolyte abnormalities suggesting complete resolution. A detailed review of the published cases of MAGED2-related transient aBS is provided. Our review focuses on individuals who received antenatal treatment. A total of 31 unique cases of MAGED2-related transient aBS were compiled. Amnioreduction was performed in 23 cases and in 18 cases no amnioreduction was performed. The average gestational age at delivery was significantly lower in cases without serial amnioreduction (28.7 vs. 30.71 weeks, p = 0.03). Neonatal mortality was seen in 5/18 cases without serial amnioreduction, and no mortality was observed in the cases with serial amnioreduction. In cases of second trimester severe polyhydramnios without identifiable cause, whole exome sequencing should be considered. Intensive ultrasound surveillance and serial amnioreduction is recommended for the management of MAGED2-related transient aBS.

A Scoping Review of Complementary and Alternative Medicine for Human Papillomavirus Infections and Cervical Dysplasia.

OBJECTIVE: The goal of this scoping review is to synthesize clinically relevant scientific literature on current complementary and alternative medications that address human papillomavirus (HPV) infections and cervical dysplasia. MATERIALS AND METHODS: A systematic search of published studies was performed December 2021 for the following concepts: human papilloma virus, cervical dysplasia, and complementary and alternative medicine (CAM). Relevant publications were identified by searching Ovid MEDLINE ALL, Embase, Cochrane Library, AMED, and MEDLINE databases, in addition to clinical trial databases. Data were extracted based on specific study selection criteria and analyzed by 3 authors independently using Covidence software. RESULTS: A total of 2324 studies were identified of which 56 met inclusion criteria. Treatment outcomes measured regression of HPV, improvement of cervical cytology, and/or regression of histopathology with varied definitions of success across all studies. The CAM therapies found to have the most clinical benefit and best supporting data via randomized control trials were topical mushroom ( Coriolus versicolor) gel, oral and topical selenium therapies, and oral indol-3-carbinol. Adverse events were reported in only 28/56 (50%) of included studies. CONCLUSIONS: The evidence for treating HPV and cervical dysplasia with CAM is of low quality because of lack of standardized, clinically relevant treatment outcomes, lack of standardization of products, and minimal reporting on adverse and long-term effects. Future large, randomized control trials are needed to further assess efficacy and safety of CAM therapies to address HPV and cervical dysplasia.

Longitudinal Medication Adherence in Older Adults With Multimorbidity and Association With Health Care Utilization: Results From the Irish Longitudinal Study on Ageing.

BACKGROUND: The association between objectively measured nonadherence and health care utilization in multimorbid older people is unclear. OBJECTIVE: To measure medication adherence across multiple chronic conditions, identify adherence patterns, and estimate the association between adherence and self-reported health care utilization. METHODS: This is a retrospective cohort study of multimorbid participants aged ≥70 years in the Irish LongituDinal Study on Ageing (TILDA). Eligible participants had linked pharmacy claims data and completed TILDA wave 2 (2 years after wave 1). The RxRisk-V tool was used to identify multimorbidity. Average adherence (AA) across RxRisk-V conditions was estimated using the CMA7 function (AdhereR). Group-based trajectory models (GBTMs) identified adherence patterns in the 12 months following wave 1. Negative binomial regression was used to estimate the association between adherence and the rate of subsequent self-reported general practitioner [GP] visits, emergency department (ED) visits, outpatient visits, and hospitalizations in the 12 months following adherence measurement (reported at wave 2). Adjusted Incident Rate Ratios (aIRR) and 95% CIs are presented. RESULTS: Higher AA (CMA7) was associated with a small significant decrease in GP visit rate (aIRR = 0.70; CI = 0.53-0.94) and outpatient visit rate (aIRR = 0.44; CI = 0.23-0.81). GBTM identified 6 adherence groups (n = 1050). Compared with high adherers, group 1 (rapid decline, modest increase) membership (aIRR = 1.72; CI = 1.09-2.73) and group 4 (high adherence, delayed decline) membership (aIRR = 1.92; CI = 1.19-3.05) significantly increased ED visit rate. CONCLUSION AND RELEVANCE: Suboptimal medication adherence in multimorbid older adults is associated with increased health care utilization. Identification of suboptimal adherence groups for medication management interventions may help decrease the health system burden and health care costs.

Identifying Adherence Patterns Across Multiple Medications and Their Association With Health Outcomes in Older Community-Dwelling Adults With Multimorbidity.

OBJECTIVES: To classify older people with multimorbidity according to their adherence patterns and to examine the association between medication adherence and health outcomes. METHODS: This is a secondary analysis of a cohort study. Community-dwelling adults aged ≥70 years were recruited from 15 general practices in Ireland in 2010 (wave 1) and followed up 2 years later (wave 2). Participants had ≥2 RxRisk-V multimorbidity conditions at wave 1 and had ≥2 dispensations of RxRisk-V medications (wave 1-wave 2). Average adherence across RxRisk-V conditions was estimated based on continuous multiple-interval measure of medication availability (CMA7 function in AdhereR). Group-based trajectory models were used to group participants' adherence patterns for RxRisk-V medications. Multilevel regression was used to examine the association between adherence and (1) EuroQol 5-dimension (EQ-5D) utility (linear) and (2) vulnerability, using the Vulnerable Elders Survey (≥3 defined as vulnerable; logistic) at wave 2, controlling for potential confounders. RESULTS: Average adherence (CMA7) was 77% across 501 participants. Group-based trajectory models identified 5 adherence groups: (1) initial low adherers, gradual increase; (2) high adherers, sharp decline; (3) steady adherers, gradual decline; (4) consistent high adherers; and (5) consistent nonadherers. Higher average adherence was associated with a significant increase in EQ-5D utility (adjusted ß = 0.11, robust standard error 0.04). Group 5 was associated with significantly increased vulnerability compared to group 4 (adjusted odds ratio = 1.88; 95% confidence interval 1.01-3.50). CONCLUSION: Increased average adherence was associated with higher EQ-5D utility. Adherence grouping did not significantly impact utility. Suboptimal adherence to multiple medications in older adults with multimorbidity was associated with vulnerability.

The association between medication non-adherence and adverse health outcomes in ageing populations: A systematic review and meta-analysis.

AIMS: The aim of this systematic review and meta-analysis was to synthesise the evidence relating to medication non-adherence and its association with health outcomes in people aged ≥50 years. METHODS: Seven databases were searched up to February 2019 for observational studies that measured medication (non-)adherence as a predictor of the following health outcomes in adults aged ≥50 years: healthcare utilisation (hospitalisation, emergency department visits, outpatient visits and general practitioner visits), mortality, adverse clinical events and quality of life. Screening and quality assessment using validated criteria were completed by 2 reviewers independently. Random effects models were used to generate pooled estimates of association using adjusted study results. The full methodological approach was published on PROSPERO (ID: CRD42017077264). RESULTS: Sixty-six studies were identified for qualitative synthesis, with 11 of these studies eligible for meta-analyses. A meta-analysis including 3 studies measuring medication non-adherence in adults aged ≥55 years showed a significant association with all-cause hospitalisation (adjusted odds ratio 1.17, 95% confidence interval [CI] 1.12, 1.21). A meta-analysis including 2 studies showed that medication non-adherence was not significantly associated with an emergency department visit (adjusted odds ratio 1.05, 95% CI 0.90, 1.22). Good adherence was associated with a 21% reduction in long-term mortality risk in comparison to medication non-adherence (adjusted hazard ratio 0.79, 95% CI 0.63, 0.98). CONCLUSION: Medication non-adherence may be significantly associated with all-cause hospitalisation and mortality in older people. Medication adherence should be monitored and addressed in this cohort to minimise hospitalisation, improve clinical outcomes and reduce healthcare costs.

Association between adherence to antihypertensive medications and health outcomes in middle and older aged community dwelling adults; results from the Irish longitudinal study on ageing.

PURPOSE: To examine the association between antihypertensive medication (AHTM) implementation adherence and healthcare utilisation in community-dwelling adults aged ≥ 50 years in Ireland. METHODS: This was a prospective cohort study. The Irish Longitudinal Study on Ageing (TILDA) was linked to pharmacy claims data for participants aged ≥ 50 years. Participants were included if they had ≥ 3 pharmacy claims for one or more AHTM (ATC codes 'C02', 'C03', 'C07', 'C08' or 'C09') within the year preceding the year of self-reported healthcare utilisation outcome occurrence. Outcomes included self-reported general practitioner (GP), emergency department (ED), outpatient department visits and hospital admissions. Implementation adherence was measured using proportion of days covered (PDC), with participants classified as adherent if the average PDC ≥ 0.8. Negative binomial models were used to analyse the association between AHTM adherence and number of GP, ED, outpatient visits and hospitalisations (adjusted IRR and 95% CI are presented). RESULTS: One thousand four hundred thirty-one participants were included. The majority of participants (72.6%) were considered adherent. Good implementation adherence to AHTM was associated with a significant decrease in self-reported GP visits (adjusted IRR 0.91, 95% CI 0.83-0.99). Adherence had no significant impact on the number of ED visits, outpatient visits or hospitalisations reported by TILDA participants. CONCLUSIONS: Good adherence to AHTM was associated with less self-reported GP visits in this population, suggesting improved overall health status. However, the impact of medication non-adherence on the other self-reported healthcare utilisation outcomes (ED, outpatient visits and hospitalisations) was not evident in this study.

Impact of drug burden index on adverse health outcomes in Irish community-dwelling older people: a cohort study.

BACKGROUND: The Drug Burden Index (DBI) quantifies exposure to medications with anticholinergic and/or sedative effects. A consensus list of DBI medications available in Ireland was recently developed for use as a DBI tool. The aim of this study was to validate this DBI tool by examining the association of DBI score with important health outcomes in Irish community-dwelling older people. METHODS: This was a cohort study using data from The Irish Longitudinal Study on Ageing (TILDA) with linked pharmacy claims data. Individuals aged ≥65 years participating in TILDA and enrolled in the General Medical Services scheme were eligible for inclusion. DBI score was determined by applying the DBI tool to participants' medication dispensing data in the year prior to outcome assessment. DBI score was recoded into a categorical variable [none (0), low (> 0 and < 1), and high (≥1)]. Outcome measures included any Activities of Daily Living (ADL) impairment, any Instrumental Activities of Daily Living (IADL) impairment, any self-reported fall in the previous 12 months, any frailty criterion met (Fried Phenotype measure), quality of life (QoL) score (CASP-19 [Control Autonomy Self-realisation Pleasure] measure), and healthcare utilisation (any hospital admission and any emergency department (ED) visit) in the previous 12 months. Statistical analyses included multivariate logistic and linear regression models controlling for potential confounders. RESULTS: 61.3% (n = 1946) of participants received at least one DBI prescription in the year before their outcome assessment. High DBI exposure (DBI score ≥ 1) vs none was significantly associated with impaired function (ADL impairment adjusted OR 1.89, 95% CI 1.25, 2.88; IADL impairment adjusted OR 2.97, 95% CI 1.91, 4.61), self-reported falls (adjusted OR 1.50, 95%CI 1.03, 2.18), frailty (adjusted OR 1.74, 95% CI 1.14, 2.67), and reduced QoL (ß = - 1.84, 95%CI -3.14, - 0.54). There was no significant association between DBI exposure and healthcare utilisation. CONCLUSIONS: The findings validate the use of the DBI tool for predicting risk of functional impairment, falls, frailty and reduced QoL in older people in Ireland, and may be extended to other European countries. Integration of this tool into routine practice may be an appropriate step forward to improve outcomes in older people.

Long-term patient-reported outcomes after laparoscopic Burch colposuspension.

BACKGROUND: The negative media attention surrounding vaginal mesh procedures has seen a rise in demand for minimally invasive non-mesh options for the treatment of stress urinary incontinence (SUI). The laparoscopic Burch colposuspension (LBC) is a non-mesh alternative to synthetic midurethral slings (MUS) with similar short-term outcomes. However, long-term outcomes are not well established. AIMS: To evaluate the long-term outcomes of LBC for treatment of SUI in women. MATERIAL AND METHODS: One hundred and fifty-one cases of LBC were performed by a single surgeon over two private hospital settings between January 2010 and January 2016. Follow-up subjective outcomes were obtained in 137 cases (90.7%) utilising standardised questionnaires. Primary outcome was successful treatment of SUI, defined as subjective cure or significant improvement of stress incontinence symptoms. Secondary outcomes included new-onset or worsened symptoms of overactive bladder (OAB), voiding dysfunction, prolapse, and perioperative complications. RESULTS: One hundred and thirty-seven patients were analysed with a mean follow-up of 50.6 months (range: 13-89 months). Primary outcome of successful treatment was achieved in 90.5% of women. New-onset or worsened symptoms of OAB was reported in 10.2%, with a further 8.8% of women experiencing symptomatic voiding dysfunction. Sixteen patients (11.7%) reported new-onset or worsening symptoms of prolapse. There were no major surgical complications. CONCLUSIONS: LBC is a safe and effective long-term treatment for SUI, with low failure rates and minimal adverse outcomes. It is a suitable alternative for women with contraindications to mesh or those having concomitant laparoscopic procedures.

The Manchester repair: an instructional video.

OBJECTIVE: The Manchester repair, developed in the UK by Donald, described in 1908, and later modified by Fothergill, is a well-studied and proven surgical treatment for uterovaginal prolapse when uterine preservation is desired. This operation is currently not widely performed in parts of the world (USA) but is becoming increasing popular in Europe. The objective of this video is to demonstrate our surgical technique and recommendations for successful completion of the procedure. METHODS: This patient is a 39-year-old woman with two previous vaginal deliveries who presented with a 1-year history of vaginal protrusion. She had no urinary or bowel symptoms. On examination, she had a grade 2 cystocele and uterine descent. She desired surgical management of her uterovaginal prolapse but wished to retain her uterus. The procedure involves mobilizing the vagina and bladder off the cervix and uterosacral cardinal ligament complex anteriorly and laterally. The cervix is then amputated. The ligaments are clamped, cut, and ligated and attached to the anterior cervical remnant with an overlapping suture. This pulls the cervix backward into the pelvis and results in anteversion of the uterus. A posterior and then anterior Sturmdorf suture is used to reconstruct the cervix by covering the amputated cervix with vaginal mucosa. CONCLUSION: The Manchester repair is an operation worth considering in patients where preservation of the uterus is desired. It uses native tissue and has a low complication rate and good long-term results.

Developmental interneuron subtype deficits after targeted loss of Arx.

BACKGROUND: Aristaless-related homeobox (ARX) is a paired-like homeodomain transcription factor that functions primarily as a transcriptional repressor and has been implicated in neocortical interneuron specification and migration. Given the role interneurons appear to play in numerous human conditions including those associated with ARX mutations, it is essential to understand the consequences of mutations in this gene on neocortical interneurons. Previous studies have examined the effect of germline loss of Arx, or targeted mutations in Arx, on interneuron development. We now present the effect of conditional loss of Arx on interneuron development. RESULTS: To further elucidate the role of Arx in forebrain development we performed a series of anatomical and developmental studies to determine the effect of conditional loss of Arx specifically from developing interneurons in the neocortex and hippocampus. Analysis and cell counts were performed from mouse brains using immunohistochemical and in situ hybridization assays at 4 times points across development. Our data indicate that early in development, instead of a loss of ventral precursors, there is a shift of these precursors to more ventral locations, a deficit that persists in the adult nervous system. The result of this developmental shift is a reduced number of interneurons (all subtypes) at early postnatal and later time periods. In addition, we find that X inactivation is stochastic, and occurs at the level of the neural progenitors. CONCLUSION: These data provide further support that the role of Arx in interneuron development is to direct appropriate migration of ventral neuronal precursors into the dorsal cortex and that the loss of Arx results in a failure of interneurons to reach the cortex and thus a deficiency in interneurons.

Technique of extraperitoneal uterosacral ligament suspension for apical suspension.

AIM OF THE VIDEO/INTRODUCTION: Vaginal vault prolapse can occur alone or in combination with anterior or posterior compartment prolapse. Apical prolapse has shown a strong correlation with anterior wall prolapse and a moderate correlation with posterior wall prolapse. The McCall culdoplasty uses the extraperitoneal vaginal approach to support the vault at the time of hysterectomy. Sacrospinous fixation and ileococcygeus suspension with or without mesh have also been used for the treatment of vaginal vault prolapse. The uterosacral ligaments can also be used to re-suspend the vaginal vault using the extraperitoneal or transperitoneal approach. With the extraperitoneal approach, the peritoneal sac, which can be difficult to access at times, especially when there are dense pelvic adhesions, does not need to be opened. The extraperitoneal approach also carries a lower risk of ureteric injury, as the ureters and the bladder can be retracted from the field using a Breisky-Navratil retractor. METHODS: This video, which documents the surgical treatment of a woman with a complete vaginal eversion and grade 3 pelvic organ prolapse (POP), was recorded in a live workshop during the 2015 Urogynaecology and Reconstructive Pelvic Surgery Conference, held in Chennai, India, in January 2015. It is aimed at educating interested surgeons in the technique of extraperitoneal uterosacral suspension. CONCLUSIONS: This video demonstrates the extraperitoneal approach to uterosacral ligament suspension for apical support in women with vaginal vault prolapse.

Characteristics of Patients Undergoing Fetal Potassium Chloride Injection at a Single Center Over Time.

Changes in the U.S. laws, particularly the Dobbs decision in 2022, altered access to abortions. Fetal potassium chloride (KCl) injections can be used for second- and third-trimester abortions. This descriptive study aims to present the characteristics of patients who received KCl injections in a state with protective laws (Colorado), including pre- and post-Dobbs. Patients undergoing KCl injection at our institution between January 2014 and December 2023 were included. Records were reviewed for demographic data, parity, and procedure details. Distance traveled and area deprivation index (ADI) were determined based on residence data. Group differences pre- and post-Dobbs were analyzed using Chi-squared and Mann-Whitney U tests. Subanalyses were performed to compare in-state and out-of-state (OOS) patients. One hundred and nineteen patients were included: 56 pre-Dobbs and 63 post-Dobbs, representing a 6.4-fold increase in volume post-Dobbs. Patients were from 10 states of residence pre-Dobbs and 17 post-Dobbs. Median distance traveled significantly increased post-Dobbs, 29.8 versus 383.9 miles (p = 0.004). The maximum distance traveled was 855 miles pre-Dobbs and 1,201 miles post-Dobbs. ADI did not vary pre- or post-Dobbs. Singleton procedures increased post-Dobbs for all patients. There was no change in gestational duration at the time of procedure across any comparison. Procedure volume and distance traveled increased for both in-state and OOS patients with minimal change in patient characteristics pre- and post-Dobbs. Our data indicate an increased need for these procedures, even in a state with protective laws.

Simultaneous Knockouts of the Oxytocin and Vasopressin 1b Receptors in Hippocampal CA2 Impair Social Memory.

Oxytocin (Oxt) and vasopressin (Avp) are two neuropeptides with many central actions related to social cognition. The oxytocin (Oxtr) and vasopressin 1b (Avpr1b) receptors are co-expressed in the pyramidal neurons of the hippocampal subfield CA2 and are known to play a critical role in social memory formation. How the neuropeptides perform this function in this region is not fully understood. Here, we report the behavioral effects of a life-long conditional removal (knockout, KO) of either the Oxtr alone or both Avpr1b and Oxtr from the pyramidal neurons of CA2 as well as the resultant changes in synaptic transmission within the different fields of the hippocampus. Surprisingly, the removal of both receptors results in mice that are unable to habituate to a familiar female presented for short duration over short intervals but are able to recognize and discriminate females when presented for a longer duration over a longer interval. Importantly, these double KO mice were unable to discriminate between a male littermate and a novel male. Synaptic transmission between CA3 and CA2 is enhanced in these mice, suggesting a compensatory mechanism is activated to make up for the loss of the receptors. Overall, our results demonstrate that co-expression of the receptors in CA2 is necessary to allow intact social memory processing.

Obstetric complications in mothers with ADHD.

Background: There is currently limited research on the intersection of pregnancy and ADHD and the unique pregnancy risk factors for mothers with an ADHD diagnosis. With an increased population of patients with ADHD in the recent decades and an increase in ADHD medication use during pregnancy it is important to consider what unique risks mothers with ADHD face during the perinatal period. Objective: Investigate a variety of outcomes in maternal ADHD. Methods: We identified female patients with a diagnosis of pregnancy and ADHD diagnosis. We also further separated the ADHD cohort for separate sub-analyses based on medication type. Odds ratios and relative risk were calculated from outcome incidence within each cohort. Cohorts were balanced on age, sex, and race. Results: We identified 45,737 pregnant females with ADHD. We matched these patients to pregnant females without ADHD, for a total of 42,916 pairs. Compared to the group without ADHD, mothers with ADHD had higher rates of every outcome except for HPV infection, which was statistically insignificant (P = 0.768). The odds ratios ranged from 1.08 for anemia complicating pregnancy to 2.63 for depressive episodes. Most outcomes were between 1.2 and 1.8 times more likely to occur in the cohort with ADHD. Conclusion: This study presents substantial advancements in our knowledge of pregnancy-related ADHD care. Armed with an increased awareness of these potential complications and their relationship with ADHD, obstetricians, psychiatrists, and providers of all specialties may be able to reduce the rate of complications within this specific patient population.

Adverse drug reactions in an ageing PopulaTion (ADAPT) study: Prevalence and risk factors associated with adverse drug reaction-related hospital admissions in older patients.

Background: Older people experience greater morbidity with a corresponding increase in medication use resulting in a potentially higher risk of adverse drug reactions (ADRs). Objectives: The aim of this study was to; 1) determine the prevalence and characteristics of ADR-related hospital admissions among older patients (≥65 years) in Ireland; and 2) identify the risk factors associated with ADR-related hospital admissions. Methods: A cross-sectional study of ADR prevalence in patients aged ≥65 years admitted acutely to hospital in Ireland over a 8 month period (November 2016- June 2017). A multifaceted review of each hospital admission was undertaken to assess the likelihood of an ADR being a reason for admission (cause of admission or contributing to admission) in the context of the patient's medication, clinical conditions, comorbidities and investigations. A number of decision aids were applied by two independent reviewers to assess ADR causality, avoidability and severity. A random sample of patients, determined not to have a suspected ADR on screening, were assigned to a non-ADR control group. Multivariable logistic regression was used to assess the association between potential risk factors for ADR-related admissions compared with non-ADR-related admissions. Results: In total, 3,760 hospital admission episodes (in 3,091 patients) were screened and 377 admissions were considered ADR-related (10.0%, 95% CI 9.1%, 11.0%). 219 (58.1%) ADR-related admissions were caused by an ADR, while ADRs contributed to 158 (41.9%) admissions. 268 (71.1%) of all ADR-related admissions were deemed definitely or possibly preventable/avoidable. 350 (92.8%) ADRs were classified as being of moderate severity, with 27 (7.2%) classified as severe. Antithrombotic agents, mainly aspirin and warfarin, were the drugs most frequently associated with ADR-related admissions (gastrointestinal and vascular haemorrhagic disorders). In multivariable analysis, immobility, frailty, having delirium or ulcer disease and taking anticoagulant and antiplatelet medication on admission were significantly associated with an ADR-related hospital admission. Conclusion: One in ten hospital admissions, among those aged 65 + years, were considered ADR-related, with approximately 70% potentially avoidable. Reliable and validated ADR detection and prediction tools are needed to develop prevention strategies.

Prevalence and Factors Associated with Potential Drug-Drug Interactions in Older Community-Dwelling Adults: A Prospective Cohort Study.

BACKGROUND: Older patients are at increased risk of drug-drug interactions (DDIs) due to polypharmacy. Cardiovascular and central nervous system (CNS) drugs are commonly implicated in serious DDIs. OBJECTIVES: This study aimed to determine the prevalence and factors associated with potential 'severe' cardiovascular and CNS DDIs among older (≥ 70 years) community-dwellers. METHODS: This was a prospective cohort study using linked data from a national pharmacy claims database and waves 1 and 2 of The Irish LongituDinal study on Ageing (TILDA). 'Severe' cardiovascular and CNS DDIs were identified using the British National Formulary 77 and Stockley's Drug Interactions. The prevalence of 'severe' DDIs (any DDI vs. none) was calculated. Logistic regression was used to examine the association between sociodemographic, functional ability, and medication-related factors and the risk of DDI exposure between waves 1 and 2. RESULTS: A total of 1466 patients were included [mean age (standard deviation) = 78 (5.5) years; female n = 795, 54.2%]. In total, 332 community-dwellers aged ≥ 70 years [22.65%, 95% confidence interval (CI) 20.58-24.86] were potentially exposed to at least one 'severe' cardiovascular or CNS DDI, with more than half (54.82%) of this cohort dispensed the same DDI for a prolonged time (≥ 3 consecutive claims). Aspirin-warfarin was the most frequently dispensed (co-prescribed) DDI (n = 34, 10.24%, 95% CI 7.39-14.00), followed by atorvastatin-clarithromycin (n = 19, 5.72%, 95% CI 3.64-8.81). Polypharmacy [≥ 10 vs. < 5 drugs, odds ratio (OR) 13.40, 95% CI 8.22-21.85] and depression (depressed vs. not, OR 2.12, 95% CI 1.34-3.34) were significantly associated with these DDIs, after multivariable adjustment. CONCLUSION: 'Severe' cardiovascular and CNS DDIs are prevalent in older community-dwellers in Ireland, and those with polypharmacy and depression are at a significantly increased risk.

Mapping the use of Group-Based Trajectory Modelling in medication adherence research: A scoping review protocol.

The use of group-based trajectory modelling (GBTM) within the medication adherence literature is rapidly growing. Researchers are adopting enhanced methods to analyse and visualise dynamic behaviours, such as medication adherence, within 'real-world' populations. Application of GBTM based on longitudinal adherence behaviour allows for the identification of adherence trajectories or groups.  A group is conceptually thought of a collection of individuals who follow a similar pattern of adherence behaviour over a period of time. A common obstacle faced by researchers when implementing GBTM is deciding on the number of trajectory groups that may exist within a population. Decision-making can introduce subjectivity, as there is no 'gold standard' for model selection criteria. This study aims to examine the extent and nature of existing evidence on the application of GBTM for medication adherence assessment, providing an overview of the different GBTM techniques used in the literature. The methodological framework will consist of five stages: i) identify the research question(s); ii) identify relevant studies; iii) select studies; iv) chart the data and finally, v) collate, summarise and report the results. Original peer-reviewed articles, published in English, describing observational and interventional studies including both concepts and/or sub-concepts of GBTM and medication adherence or any other similar terms, will be included. The following databases will be queried: PubMed/MEDLINE; Embase (Ovid); SCOPUS; ISI Web of Science and PsychInfo. This scoping review will utilise the PRISMA extension for Scoping Reviews (PRISMA-ScR) tool to report results. This scoping review will collect and schematise different techniques in the application of GBTM for medication adherence assessment available in the literature to date, identifying research and knowledge gaps in this area. This review can represent an important tool for future research, providing methodological support to researchers carrying out a group-based trajectory analysis to assess medication adherence in a real-world context.

Midkine-a functions as a universal regulator of proliferation during epimorphic regeneration in adult zebrafish.

Zebrafish have the ability to regenerate damaged cells and tissues by activating quiescent stem and progenitor cells or reprogramming differentiated cells into regeneration-competent precursors. Proliferation among the cells that will functionally restore injured tissues is a fundamental biological process underlying regeneration. Midkine-a is a cytokine growth factor, whose expression is strongly induced by injury in a variety of tissues across a range of vertebrate classes. Using a zebrafish Midkine-a loss of function mutant, we evaluated regeneration of caudal fin, extraocular muscle and retinal neurons to investigate the function of Midkine-a during epimorphic regeneration. In wildtype zebrafish, injury among these tissues induces robust proliferation and rapid regeneration. In Midkine-a mutants, the initial proliferation in each of these tissues is significantly diminished or absent. Regeneration of the caudal fin and extraocular muscle is delayed; regeneration of the retina is nearly completely absent. These data demonstrate that Midkine-a is universally required in the signaling pathways that convert tissue injury into the initial burst of cell proliferation. Further, these data highlight differences in the molecular mechanisms that regulate epimorphic regeneration in zebrafish.

Anticholinergic and sedative drug burden in community-dwelling older people: a national database study.

OBJECTIVES: The Drug Burden Index (DBI) tool quantifies individual exposure to anticholinergic and sedative medications. The DBI has been internationally validated against adverse health outcomes in older people. DBI exposure has not been reported in the Irish older population. This study aimed to: (1) develop a list of drugs with clinically significant anticholinergic and/or sedative effects (DBI medications) relevant to Ireland; (2) examine, using the DBI formula, the prevalence of exposure to DBI medications in Irish older people and (3) explore patient factors associated DBI exposure. DESIGN: A cross-sectional national pharmacy claims database study. SETTING: Community setting using the General Medical Services (GMS) scheme pharmacy claims database maintained by the Health Service Executive Primary Care Reimbursement Services. PARTICIPANTS: Irish older individuals (aged ≥65 years) enrolled in the GMS scheme and dispensed at least one prescription item in 2016 (n=428 516). MAIN OUTCOME MEASURES: Prevalence of exposure to DBI medications and patient factors associated with DBI exposure. RESULTS: 282 874 (66%) of the GMS population aged ≥65 years were exposed to at least one DBI medication in 2016. Prevalence of exposure to DBI medications was significantly higher in females than males (females 71.6% vs males 58.7%, adjusted OR 1.65, 95% CI 1.63 to 1.68). Prevalence of DBI exposure increased progressively with the number of chronic drugs used, rising from 42.7% of those prescribed 0-4 chronic drugs to 95.4% of those on ≥12 chronic drugs (adjusted OR 27.8, 95% CI 26.7 to 29.0). The most frequently used DBI medications were codeine/paracetamol combination products (20.1% of patients), tramadol (11.5%), zopiclone (9.5%), zolpidem (8.5%), pregabalin (7.9%) and alprazolam (7.8%). CONCLUSIONS: The majority of older people in Ireland are exposed to medications with anticholinergic and/or sedative effects, particularly females and those with multiple comorbidities. The high use of low-dose codeine/paracetamol combination products, Z-drugs and benzodiazepines, suggests there are opportunities for deprescribing.