Drug-Drug Interactions and Their Association with Adverse Health Outcomes in the Older Community-Dwelling Population: A Prospective Cohort Study.

BACKGROUND: Evidence on associations between drug-drug interactions (DDIs) and health outcomes in the older community-dwelling population is limited. OBJECTIVE: We estimate potentially clinically important DDI prevalence and examine the association between DDIs and (1) adverse drug events (ADEs), (2) emergency hospital attendance and (3) health-related quality of life (HRQoL) in an older community-dwelling population in Ireland. METHODS: This is a prospective cohort study of community-dwelling older adults (N = 904) aged ≥ 70 years from 15 general practices in Ireland recruited in 2010 (wave-1) and followed-up over 2 years (wave-2; 2012-2013), with linked national pharmacy claims data. Individuals dispensed two or more drugs (wave-1: N = 842; wave-2: N = 763) were included. DDI prevalence at baseline, follow-up and 6 months prior to each health outcome was estimated. Multi-level regression was used to model the association between DDI-exposure and health outcomes at follow-up. DDI prevalence, adjusted incidence-rate ratios (aIRR), adjusted odds ratios (aOR), ß coefficients and robust standard error (RSE) from multi-level regression analyses, and 95% confidence intervals (CIs) are reported. RESULTS: At wave-1, n = 196 (23.3% [95% CI 20.5-26.3]), individuals were potentially exposed to ≥ 1 DDI, increasing to n = 345 (45.2% [41.7-48.9]) at wave-2. At 2-year follow-up, the median number of ADEs was 3 (interquartile range [IQR 2-5]); 229 (30.1%) had ≥ 1 emergency hospital attendance, and the mean EQ-5D was 0.74 (± 0.23). Evidence for the association between DDI-exposure and emergency hospital attendance at follow-up was lacking (aOR = 1.38 [0.42-4.53]). DDI-exposure was associated with an increasing number of ADEs (aIRR = 1.26 [1.03-1.55]), and decreasing EQ-5D utility (ß = - 0.07, [-0.11 to -0.04], RSE = 0.02). Aspirin-warfarin, clarithromycin-prednisolone, amiodarone-furosemide, clarithromycin-salbutamol, rosuvastatin-warfarin, amiodarone-bisoprolol, and aspirin-nicorandil were common DDIs 6 months preceding these health outcomes. CONCLUSIONS: We found a two-fold increase in DDI prevalence between wave 1 and 2. DDI exposure was associated with increasing ADEs and declining HRQoL at 2-year follow-up. Common DDIs involved anticoagulants, cardiovascular and antimicrobial drugs, which should be targeted for medicine optimisation.

Autogenic training for chronic health conditions: A service evaluation.

BACKGROUND: Autogenic training (AT) is a structured meditative-style practice, consisting of a sequence of simple mental exercises intended to induce a relaxed state in patients. There is some emerging evidence to suggest that AT can be effective in treating certain chronic conditions, however, further evidence is required. A service evaluation of AT services at the Royal London Hospital for Integrated Medicine was conducted to evaluate the impact of AT on patients with chronic conditions. METHODS: The service evaluation consisted of the completion of validated quantitative outcome measures pre and posttreatment to explore the impact of AT. AT patients were asked to complete the Measure Yourself Medical Outcomes Profile (MYMOP) and Perceived Stress Scale (PSS) at their first hospital appointment (baseline) and then again 8 weeks later following completion of their AT sessions. Pre- and posttreatment scores for each outcome measure were analysed in SPSS using the Wilcoxon signed-rank test. RESULTS: One hundred ninety-nine patients completed both initial and follow-up MYMOP forms and were included in the evaluation. The most common presenting complaints for MYMOP symptom 1 were prolonged anxiety/stress and depression (n = 70, 35.2%), chronic pain and migraine headache (n = 44, 22.1%), chronic insomnia and sleep problems (n = 42, 21.1%) and, long-term exhaustion and fatigue (n = 18, 9%). The change in median score pre- and posttreatment for all MYMOP categories (symptoms, activity and well-being) were statistically highly significant p < 0.001. Anxiety, stress, depression, pain and insomnia were the symptoms that had the largest statistically significant difference between the median score pre- and posttreatment. Fifty-five patients completed the PSS questionnaire at two time points (pre- and posttreatment). It showed a highly statistically significant change in PSS median score in patients experiencing stress (p < 0.001). DISCUSSION: The findings of the evaluation indicate that 8 weeks of AT appears to be effective in improving symptoms of concern to patients and enhancing patients' overall well-being. In particular, AT was found to be beneficial for patients with symptoms of anxiety, stress, depression, pain and insomnia.

Altered long-range functional connectivity in PTSD: Role of the infraslow oscillations of cortical activity amplitude envelopes.

OBJECTIVE: Coupling between the amplitude envelopes (AEs) of regional cortical activity reflects mechanisms that coordinate the excitability of large-scale cortical networks. We used resting-state MEG recordings to investigate the association between alterations in the coupling of cortical AEs and symptoms of post-traumatic stress disorder (PTSD). METHODS: Participants (n = 96) were service members with combat exposure and various levels of post-traumatic stress severity (PTSS). We assessed the correlation between PTSS and (1) coupling of broadband cortical AEs of beta band activity, (2) coupling of the low- (<0.5 Hz) and high-frequency (>0.5 Hz) components of the AEs, and (3) their time-varying patterns. RESULTS: PTSS was associated with widespread hypoconnectivity assessed from the broadband AE fluctuations, which correlated with subscores for the negative thoughts and feelings/emotional numbing (NTF/EN) and hyperarousal clusters of symptoms. Higher NTF/EN scores were also associated with smaller increases in resting-state functional connectivity (rsFC) with time during the recordings. The distinct patterns of rsFC in PTSD were primarily due to differences in the coupling of low-frequency (infraslow) fluctuations of the AEs of beta band activity. CONCLUSIONS: Our findings implicate the mechanisms underlying the regulation/coupling of infraslow oscillations in the alterations of rsFC assessed from broadband AEs and in PTSD symptomatology. SIGNIFICANCE: Altered coordination of infraslow amplitude fluctuations across large-scale cortical networks can contribute to network dysfunction and may provide a target for treatment in PTSD.

Individualised prediction of resilience and vulnerability to sleep loss using EEG features.

It is well established that individuals differ in their response to sleep loss. However, existing methods to predict an individual's sleep-loss phenotype are not scalable or involve effort-dependent neurobehavioural tests. To overcome these limitations, we sought to predict an individual's level of resilience or vulnerability to sleep loss using electroencephalographic (EEG) features obtained from routine night sleep. To this end, we retrospectively analysed five studies in which 96 healthy young adults (41 women) completed a laboratory baseline-sleep phase followed by a sleep-loss challenge. After classifying subjects into sleep-loss phenotypic groups, we extracted two EEG features from the first sleep cycle (median duration: 1.6 h), slow-wave activity (SWA) power and SWA rise rate, from four channels during the baseline nights. Using these data, we developed two sets of logistic regression classifiers (resilient versus not-resilient and vulnerable versus not-vulnerable) to predict the probability of sleep-loss resilience or vulnerability, respectively, and evaluated model performance using test datasets not used in model development. Consistently, the most predictive features came from the left cerebral hemisphere. For the resilient versus not-resilient classifiers, we obtained an average testing performance of 0.68 for the area under the receiver operating characteristic curve, 0.72 for accuracy, 0.50 for sensitivity, 0.84 for specificity, 0.61 for positive predictive value, and 3.59 for likelihood ratio. We obtained similar performance for the vulnerable versus not-vulnerable classifiers. These results indicate that logistic regression classifiers based on SWA power and SWA rise rate from routine night sleep can largely predict an individual's sleep-loss phenotype.

Potentially Inappropriate Prescribing and Potential Prescribing Omissions and Their Association with Adverse Drug Reaction-Related Hospital Admissions.

BACKGROUND: This study aimed to determine the prevalence of potentially inappropriate prescribing (PIP) and potential prescribing omissions (PPOs) and their association with ADR-related hospital admissions in patients aged ≥ 65 years admitted acutely to the hospital. METHODS: Information on medications and morbidities was extracted from the Adverse Drug Reactions in an Ageing Population (ADAPT) cohort (N = 798: N = 361 ADR-related admissions; 437 non-ADR-related admissions). PIP and PPOs were assessed using Beers Criteria 2019 and STOPP/START version 2. Multivariable logistic regression (adjusted odds ratios (aOR), 95%CI) was used to examine the association between PIP, PPOs and ADR-related admissions, adjusting for covariates (age, gender, comorbidity, polypharmacy). RESULTS: In total, 715 (90%; 95% CI 87-92%) patients had ≥1 Beers Criteria, 555 (70%; 95% CI 66-73%) had ≥ 1 STOPP criteria and 666 patients (83%; 95% CI 81-86%) had ≥ 1 START criteria. Being prescribed at least one Beers (aOR = 1.66, 95% CI = 1.00-2.77), or meeting STOPP (aOR = 1.07, 95% CI = 0.79-1.45) or START (aOR = 0.72; 95%CI = 0.50-1.06) criteria or the number of PIP/PPO criteria met was not significantly associated with ADR-related admissions. Patients prescribed certain drug classes (e.g., antiplatelet agents, diuretics) per individual PIP criteria were more likely to have an ADR-related admission. CONCLUSION: There was a high prevalence of PIP and PPOs in this cohort but no association with ADR-related admissions.

A novel abuse liability assessment of e-cigarettes in young adults ii: Reinforcement enhancement and follow-up assessment.

A double-blind study was performed to test the abuse liability of electronic nicotine delivery systems (ENDS) in young adults; in particular, the influence of nicotine on reward sensitivity was assessed. A total of 53 healthy nonusers participated in experimental sessions during which they played a video game made available on a progressive ratio schedule of reinforcement and self-administered nicotine via ENDS. Participants were randomized into one of three groups. Two groups received either a dedicated concentration of nicotine (6 and 12 mg) or a placebo, and whether they received the placebo or their dedicated nicotine dose was randomly determined on a session-by-session basis to mask the sequencing of drug administration. The third group received only a 0 mg (placebo) vaping device during all sessions. In comparison to all placebo conditions, nicotine-induced reward sensitization was evidenced on behavioral measures of video game reinforcement, but not subjective appraisals of the vaping experience. A 1-month follow-up survey provided evidence that reinforcement enhancement by nicotine predicts increased abuse liability of ENDS. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Drug-drug interactions and the risk of adverse drug reaction-related hospital admissions in the older population.

AIMS: The aims of this study were to estimate potentially clinically important drug-drug interaction (DDI) prevalence, and the average causal effect of DDI exposure on adverse drug reaction (ADR)-related hospital admission, and to examine differences in health-related quality of life (HRQoL) and length of stay (LOS) per DDI exposure in an older (≥65 years) population acutely hospitalized. METHODS: This was a cross-sectional study conducted among 798 older individuals acutely admitted to hospital in Ireland between 2016 and 2017. Medication (current/recently discontinued/over-the-counter) and clinical data (e.g., creatinine clearance) were available. DDIs were identified using the British National Formulary (BNF) and Stockley's Drug Interactions. Causal inference models for DDI exposure on ADR-related hospital admission were developed using directed acyclic graphs. Multivariable logistic regression was used to estimate the average causal effect. Differences in HRQoL (EQ-5D) and LOS per DDI exposure were examined non-parametrically. DDI prevalence, adjusted odds ratios (aOR), and 95% confidence intervals (CIs) are reported. RESULTS: A total of 782 (98.0%) individuals using two or more drugs were included. Mean age was 80.9 (SD ± 7.5) years (range: 66-105); 52.2% were female; and 45.1% (n = 353) had an ADR-related admission. At admission, 316 (40.4% [95% CI: 37.0-43.9]) patients had at least one DDI. The average causal effect of DDI exposure on ADR-related hospital admission was aOR = 1.21 [95% CI: 0.89-1.64]. This was significantly increased by exposure to: DDIs which increase bleeding risk (aOR = 2.00 [1.26-3.12]); aspirin-warfarin (aOR = 2.78 [1.37-5.65]); and esomeprazole-escitalopram (aOR = 3.22 [1.13-10.25]. DDI-exposed patients had lower HRQoL (mean EQ-5D = 0.49 [±0.39]) compared those non-DDI-exposed (mean EQ-5D = 0.57 [±0.41]), (P = .03); and greater median LOS in hospital (8 [IQR5-16]days) compared those non-DDI-exposed (7 [IQR 4-14] days),(P = .04). CONCLUSIONS: Potentially clinically important DDIs carry an increased average causal effect on ADR-related admission, significantly (two-fold) by exposure to DDIs that increase bleeding risk, which should be targeted for medicine optimization.

Electroencephalographic markers from routine sleep discriminate individuals who are vulnerable or resilient to sleep loss.

Sleep loss impairs cognition; however, individuals differ in their response to sleep loss. Current methods to identify an individual's vulnerability to sleep loss involve time-consuming sleep-loss challenges and neurobehavioural tests. Here, we sought to identify electroencephalographic markers of sleep-loss vulnerability obtained from routine night sleep. We retrospectively analysed four studies in which 50 healthy young adults (21 women) completed a laboratory baseline-sleep phase followed by a sleep-loss challenge. After classifying subjects as resilient or vulnerable to sleep loss, we extracted three electroencephalographic features from four channels during the baseline nights, evaluated the discriminatory power of these features using the first two studies (discovery), and assessed reproducibility of the results using the remaining two studies (reproducibility). In the discovery analysis, we found that, compared to resilient subjects, vulnerable subjects exhibited: (1) higher slow-wave activity power in channel O1 (p < 0.0042, corrected for multiple comparisons) and in channels O2 and C3 (p < 0.05, uncorrected); (2) higher slow-wave activity rise rate in channels O1 and O2 (p < 0.05, uncorrected); and (3) lower sleep spindle frequency in channels C3 and C4 (p < 0.05, uncorrected). Our reproducibility analysis confirmed the discovery results on slow-wave activity power and slow-wave activity rise rate, and for these two electroencephalographic features we observed consistent group-difference trends across all four channels in both analyses. The higher slow-wave activity power and slow-wave activity rise rate in vulnerable individuals suggest that they have a persistently higher sleep pressure under normal rested conditions.

The Benefits and Harms of Pharmacological Treatment for Postradiation Pelvic Pain: A Systematic Review by the European Association of Urology Chronic Pelvic Pain Panel with Recommendations for Clinical Practice.

Context: Radiotherapy of the pelvis is a widely used method for the treatment of malignancies, and local complications including pain following pelvic radiation therapy are acknowledged complications. Objective: The primary objective is to assess the clinical effectiveness and safety of pharmacological therapies on postradiation pelvic pain. Evidence acquisition: A systematic review of the use of different pharmacological treatments in the management of post-radiation pelvic pain was conducted (PROSPERO-ID: CRD42021249026). Comprehensive searches of EMBASE, Medline, and Cochrane library were performed for publications between January 1980 and April 2021. The primary outcomes were improvement in pain and adverse events following treatment. The secondary outcomes included quality of life, bowel function, and urinary function. Evidence synthesis: After screening 1514 abstracts, four randomised controlled trials were identified, enrolling 355 patients with bladder and anorectal subtypes of postradiotherapy chronic pelvic pain (CPP). A narrative synthesis was performed as heterogeneity of included studies precluded a meta-analysis. A single study reported a significant reduction in pain after 6 mo in patients with bladder pain syndrome treated with hyaluronic acid or hyperbaric oxygen. Anorectal pain was reported to be reduced by the application of 4% formalin, but the use of hyperbaric oxygen in postradiotherapy anorectal pain remains controversial. Adverse event reporting was generally poor. Studies looking at medications used routinely in guidelines for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, and duloxetine, were absent or of poor quality when it came to postradiation pelvic pain. Conclusions: Beneficial effects of hyperbaric oxygen or formalin on pain, quality of life, and functional symptoms were seen in patients with certain CPP subtypes, but the current evidence level is too weak to allow recommendations about the use of any pharmacological treatment for postradiation pelvic pain. Patient summary: Different pharmacological treatments are used to treat pain after radiotherapy, but current studies are of insufficient quality to determine whether these should be recommended and many chronic pelvic pain subtypes are not covered. Further research is needed.

Point-of-care hemoglobin A1c margin of error alters resident management of Type 2 diabetes when near glycemic target.

AIMS: Point-of-care (POC) HbA1c is frequently used as a surrogate for serum HbA1c. We aimed to determine if resident management of type 2 diabetes changed after accounting for the + 0.5% margin of error associated with POC HbA1c devices. METHODS: Residents were surveyed in an outpatient clinic regarding two of their patients with type 2 diabetes for which they had obtained a POC HbA1c. For one patient, the resident was asked if management would change if the POC HbA1c were 0.5% higher (called the positive case), and for another if management would change if POC HbA1c were 0.5% lower (negative case). RESULTS: Twelve of 58 (21%) cases had a change in management. Of the 27 cases where POC HbA1c was near the glycemic target (defined as POC HbA1c ≥6.0% and <8.0%), 11 (41%) resulted in a change in management while one (3%) of the 31 cases outside that interval had a change in management. CONCLUSION: POC HbA1c testing is well-suited for patients with poorly controlled type 2 diabetes while serum HbA1c testing may be more appropriate when near a patient's personalized HbA1c target since small changes in HbA1c can lead to differences in medical management.

EVALUATING BAITS WITH LUFENURON AND NITENPYRAM FOR FLEA CONTROL ON PRAIRIE DOGS (CYNOMYS SPP.) TO MITIGATE PLAGUE.

Plague, caused by Yersinia pestis, is a widespread threat to endangered black-footed ferrets (Mustela nigripes) and their primary prey, prairie dogs (Cynomys spp.). Wildlife biologists most commonly manage plague using insecticides to control fleas, the primary vectors of Y. pestis. We tested edible baits containing the insecticides lufenuron and/or nitenpyram in prairie dogs. During a laboratory study, we treated 26 white-tailed prairie dogs (Cynomys leucurus) with lufenuron at 300 mg/kg body mass. All animals remained clinically healthy over the 9 wk monitoring period. Although serum lufenuron concentrations were >130 ppb in two treatment groups at week 1, concentrations declined to ≤60 ppb after 3 wk in non-torpid prairie dogs and after 7 wk in torpid prairie dogs. In a field experiment, we tested baits containing a combination of 75 mg lufenuron and 6 mg nitenpyram, respectively, in black-tailed prairie dogs (Cynomys ludovicianus). We uniformly distributed baits at 125 baits/ha on two plots (treated once) and 250 baits/ha on two plots (each treated twice 4.4 wk apart). Following treatments, flea abundance increased on prairie dogs and remained stable in burrows. Our findings indicate that baits containing lufenuron and nitenpyram, at the reported treatment rates, are ineffective tools for flea control on prairie dogs. Future experiments might evaluate efficacy of higher doses of lufenuron and nitenpyram, and repetitive treatments at differing intervals over time to evaluate potentially therapeutic treatments.

Plague mitigation for prairie dog and black-footed ferret conservation: Degree and duration of flea control with 0.005% fipronil grain bait.

Sylvatic plague, a primarily flea-borne zoonosis, is a significant threat to prairie dogs (Cynomys spp., PDs) and their specialized predators, endangered black-footed ferrets (Mustela nigripes, BFFs). Host-fed fipronil baits have proven effective in controlling fleas on PDs for the purposes of plague mitigation and BFF conservation. Currently, annual treatments are the norm. We tested the long-term efficacy of fipronil bait treatments with black-tailed PDs (C. ludovicianus, BTPDs) and BFFs in South Dakota, USA. During 2018-2020, we provided BTPDs on 21 sites with grain bait formula, laced with 0.005% fipronil (50 â€‹mg/kg); 18 non-treated sites functioned as baselines. In 2020-2022, we live-trapped, anesthetized, and combed BTPDs for fleas. Flea control was significant for at least 639-885 days. Flea abundance on the treated sites was < 0.5 fleas/BTPD for ∼750 days. During 2020-2022, we sampled BFFs for fleas on 4 BTPD colonies treated with fipronil grain bait and 8 non-treated colonies. Flea control was significant with BFFs, but flea abundance began to rebound within ∼240 days post-treatment. When feasible, the combination of insecticide treatments, such as fipronil baits, and BFF vaccination against plague provide a "two-pronged" protection approach for these endangered carnivores. If fipronil bait treatments are less effective with predatory BFFs than PDs, as found herein, the "two-pronged" approach might be used to protect BFFs and biennial fipronil bait treatments might be used to protect PDs. If BFF vaccination is not possible, or few BFFs can be vaccinated, annual fipronil bait treatments might be used as a precaution to protect BFFs. Flea densities might be surveyed to determine when/where more frequent treatments seem useful.

Spatial distribution and determinants of childhood vaccination refusal in the United States.

Parental refusal and delay of childhood vaccination has increased in recent years in the United States. This phenomenon challenges maintenance of herd immunity and increases the risk of outbreaks of vaccine-preventable diseases. We examine US county-level vaccine refusal for patients under five years of age collected during the period 2012-2015 from an administrative healthcare dataset. We model these data with a Bayesian zero-inflated negative binomial regression model to capture social and political processes that are associated with vaccine refusal, as well as factors that affect our measurement of vaccine refusal. Our work highlights fine-scale socio-demographic characteristics associated with vaccine refusal nationally, finds that spatial clustering in refusal can be explained by such factors, and has the potential to aid in the development of targeted public health strategies for optimizing vaccine uptake.

LETHAL EFFECTS ON FLEA LARVAE OF FIPRONIL IN HOST FECES: POTENTIAL BENEFITS FOR PLAGUE MITIGATION.

Plague, caused by the bacterium Yersinia pestis, is a zoonotic disease of mammalian hosts and flea vectors. Fipronil baits have been used to suppress adult fleas for plague mitigation. The degree and duration of flea control may increase if fipronil also kills other stages in the flea life cycle. We fed grain treated with 0.005% fipronil by weight, or nontreated grain, to black-tailed prairie dogs (Cynomys ludovicianus), which excrete fipronil and metabolites in their feces after consuming fipronil in their diet. We presented prairie dog feces to 331 larval Oropsylla montana (Siphonaptera: Ceratophyllidae). When exposed to feces lacking fipronil or metabolites, 84% of larvae survived for 24 h. In contrast, survival declined to 42% for larvae contacting feces from fipronil-treated prairie dogs. Just 7% of larvae consuming feces from fipronil-treated prairie dogs survived. Fipronil and metabolites may persist in host feces for several months or longer in prairie dog burrows where flea larvae dwell and forage. The lethal effects of fipronil on adult and larval fleas (and perhaps other life stages) may help to explain why fipronil baits are capable of suppressing fleas on prairie dogs for ≥12 mo.

Prevalence of Drug-Drug Interactions in Older Community-Dwelling Individuals: A Systematic Review and Meta-analysis.

BACKGROUND: Drug-drug interactions (DDIs) can lead to medication-related harm, and the older population is at greatest risk. We conducted a systematic review and meta-analysis to estimate DDI prevalence and identify common DDIs in older community-dwelling adults. METHODS: PubMed and EMBASE were searched for observational studies published between 01/01/2010 and 10/05/2021 reporting DDI prevalence in community-dwelling individuals aged ≥ 65 years. Nursing home and inpatient hospital studies were excluded. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool. Meta-analysis was performed using a random-effects model with logit transformation. Heterogeneity was evaluated using Cochran's Q and I2. DDI prevalence and 95% confidence intervals (CIs) are presented. All analyses were performed in R (version 4.1.2). RESULTS: There were 5144 unique articles identified. Thirty-three studies involving 17,011,291 community-dwelling individuals aged ≥ 65 years met inclusion criteria. Thirty-one studies reported DDI prevalence at the study-participant level, estimates ranged from 0.8% to 90.6%. The pooled DDI prevalence was 28.8% (95% CI 19.3-40.7), with significant heterogeneity (p < 0.10; I2 = 100%; tau2 = 2.13) largely explained by the different DDI identification methods. Therefore, 26 studies were qualitatively synthesised and seven studies were eligible for separate meta-analyses. In a meta-analysis of three studies (N = 1122) using Micromedex®, pooled DDI prevalence was 57.8% (95% CI 52.2-63.2; I2 = 69.6%, p < 0.01). In a meta-analysis of two studies (N = 809,113) using Lexi-Interact®, pooled DDI prevalence was 30.3% (95% CI 30.2-30.4; I2 = 6.8%). In a meta-analysis of two studies (N = 947) using the 2015 American Geriatrics Society Beers criteria®, pooled DDI prevalence was 16.6% (95% CI 5.6-40.2; I2 = 97.5%, p < 0.01). Common DDIs frequently involved cardiovascular drugs, including ACE inhibitor-potassium-sparing diuretic; amiodarone-digoxin; and amiodarone-warfarin. CONCLUSIONS: DDIs are prevalent among older community-dwelling individuals; however, the methodology used to estimate these events varies considerably. A standardised methodology is needed to allow meaningful measurement and comparison of DDI prevalence.

A systematic review and meta-analysis of interventions to induce attempts to quit tobacco among adults not ready to quit.

The prevalence of past-year smoking cessation remains below 10% in the U.S. Most who smoke are not ready to quit in the near future. Cessation requires both (a) initiating a quit attempt (QA) and (b) maintaining abstinence. Most research has focused on abstinence among people already motivated to quit. We systematically reviewed interventions to promote QAs among people not motivated to quit tobacco. We searched PubMed, CENTRAL, PsycINFO, Embase, and our personal libraries for randomized trials of tobacco interventions that reported QAs as an outcome among adults not ready to quit. We screened studies and extracted data in duplicate. We pooled findings of the 25 included studies using Mantel-Haenszel random effects meta-analyses when ≥ 2 studies tested the same intervention. Most (24) trials addressed cigarettes and one addressed smokeless tobacco. Substantial heterogeneity among trials resulted in a series of small meta-analyses. Findings indicate varenicline may increase QAs more than no varenicline, n = 320; RR = 1.4, 95% CI [1.1, 1.7]; I² = 0%, and nicotine replacement therapy (NRT) may increase QAs more than no NRT, n = 2,568; RR = 1.1, 95% CI [1.02, 1.3]; I² = 0%. Pooled effects for motivational counseling, reduction counseling, and very low nicotine content cigarettes showed no clear evidence of benefit or harm. The evidence was judged to be of medium to very low certainty due to imprecision, inconsistency, and risk of bias, suggesting that further research is likely to change interpretation of our results. Findings demonstrate the need for more high-quality research on interventions to induce QAs among adults not ready to quit tobacco. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Novel Use of the Penumbra CAT 12 Lightning Aspiration System for the Treatment of a Complex Thrombus.

Debulking procedures using aspiration devices have been previously described in the literature to treat vegetations or thrombi on intracardiac structures such as the tricuspid valve. Transcatheter therapy has also been shown to be an effective alternative to surgical treatment for managing high risk or non-surgical patients. Furthermore, aspiration procedures can help identify the unique etiologies of intracardiac masses which can greatly impact differing treatment modalities. Utilization of aspiration devices combined with blood-loss limiting technologies have led to an increased interest in using aspiration systems to address a wider array of clinical situations that can occur. Herein we describe our experience in using the Penumbra CAT 12 Lightning Aspiration System in addressing and treating a mobile mass attached to the lead of an implantable cardiac device.

Cognitive flexibility in post-traumatic stress disorder: Sustained interference associated with altered modulation of cortical oscillatory activity during task-switching.

Post-traumatic stress disorder (PTSD) is associated with deficits in cognitive flexibility, with evidence suggesting that these deficits may be a risk factor for the development of core PTSD symptoms. Understanding the neurophysiological substrate of this association could aid the development of effective therapies for PTSD. In this study, we investigated the relationship between post-traumatic stress severity (PTSS) in service members with combat exposure and the modulation of cortical oscillatory activity during a test of cognitive flexibility. Participants were assigned to three groups based on PTSS scores: low (well below a threshold consistent with a diagnosis of PTSD, n = 30), moderate (n = 32), and high (n = 29) symptom severity. Magnetoencephalography data were recorded while participants performed a cued rule-switching task in which two matching rules were repeated or switched across consecutive trials. Participants with high PTSS had longer reaction times for both switch and repeat trials, and showed evidence of sustained residual interference during repeat trials. During the cue-stimulus interval, participants with moderate and high PTSS showed higher relative theta power in switch trials over left dorsolateral prefrontal cortex (DLPFC). After test-stimulus onset, participants with high PTSS showed less suppression of beta band activity, which was present over multiple prefrontal, parietal, and temporal regions in switch trials, but it was confined to ventromedial prefrontal cortex in repeat trials. Higher theta band activity is a marker of effortful voluntary shifting of attention, while lower suppression of beta band activity reflects difficulties with inhibition of competing perceptual information and courses of action. These findings are consistent with a role for altered suppression of beta band activity, which can be due to less effective top-down bias signals exerted by DLPFC, in the etiology of cognitive flexibility deficits in PTSD.

Evaluating awareness, knowledge and practice of healthcare professionals following implementation of a revised pregnancy prevention programme for isotretinoin in Ireland: A multi-stakeholder cross-sectional study.

PURPOSE: In 2018, following an EU-wide safety review, a revised pregnancy prevention programme (PPP) was introduced for isotretinoin (Roaccutane®). This study aimed to examine awareness, knowledge, and experience implementing the revised isotretinoin PPP in clinical practice across three healthcare professional (HCP) groups in Ireland. METHODS: A cross-sectional study using anonymous online surveys among general practitioners (GPs), community pharmacists, and specialist consultants was undertaken. Descriptive analyses are presented. RESULTS: Across all HCP groups there was high (≥87%) awareness that oral isotretinoin is contraindicated in women of childbearing potential (WCBP) unless the conditions of the PPP are fulfilled, but varying awareness among GPs (54.9%) and community pharmacists (45.9%) that exposure during pregnancy can cause both severe fetal malformations and spontaneous abortions. Implementation of the PPP in clinical practice varied across HCP groups. When initiating isotretinoin in WCBP, 66.7% of specialists and 40.8% of GPs indicated they had considered alternative treatment options, and 71.4% of specialists and 31.6% of GPs reported they first requested a pregnancy test. There was limited provision of the patient reminder card to WCBP, where 26.1% of community pharmacists provide this at each dispensing, while 47.6% of specialists and 11.8% of GPs ensured WCBP had a copy of the card when initiating treatment. Across all HCP groups, there was high (≥81.6%) awareness of the need for urgent consultation and immediate cessation of isotretinoin in the event of an unplanned or suspected pregnancy. CONCLUSIONS: Reinforcement of the provision and utilisation of the isotretinoin patient reminder card may be required, and further targeted education on specific elements of the PPP should be considered for GPs and community pharmacists.

The interactive effects of JUUL flavor and nicotine concentration on addiction potential.

Prior research suggests that flavors can influence the pharmacological effects of nicotine. We used commercially available JUUL pods to examine whether preferred menthol versus tobacco flavor increased the addictive potential of nicotine per se. This study recruited 15 regular JUUL e-cigarette users to complete a 2 × 2 factorial crossover trial using an entirely remote video format. Participants completed a sampling baseline session to identify preferred JUUL flavor (menthol vs. tobacco) followed by four counterbalanced experimental sessions separated by ≥ 48 hr: (a) low-nicotine dose (3% JUUL)/nonpreferred flavor; (b) low dose/preferred flavor; (c) high-nicotine dose (5% JUUL)/nonpreferred flavor; and (d) high dose/preferred flavor. In each experimental session, participants completed a puffing procedure followed by subjective ratings of e-cigarette liking and wanting (ELW), urges, and reinforcement using a JUUL pod purchase task. There was a dose-by-flavor interaction for average ELW (F = 4.58, p = .041) in which ELW was significantly greater for the preferred than the nonpreferred flavor at the low-nicotine dose but not the high-nicotine dose. There were also dose-by-flavor interactions for pre- to post-puffing change in overall urge to vape (F = 5.97, p = .021) and urge strength (F = 4.96, p = .049), with greater reductions in overall urge/strength for the preferred compared to the nonpreferred flavor at the low but not the high dose. We found no significant interaction effects for purchase task outcomes. Using a fully remote experimental puffing procedure, our findings suggest preferred flavors increase the rewarding effects most for lower nicotine e-cigarettes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).